Principal The Merck Index (Version 12.3)

The Merck Index (Version 12.3)

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THE MERCK INDEX OF CHEMICALS, DRUGS, AND BIOLOGICALS A 1, Abamectin, Avermectin if,; 5-0-deniethylaver- mcctin A.a and 5-0-dcmcthyl-25-dc(I-niethyipropy|)-25- (1 -metbylelhyl)avermeciiu A (4:1); MK-936; Affinti: Agrimek; Avomec; Vertimec. Mixture of aver-mectins, q.v., containing at least 807u of avermeelin B,n (CWH7I0[4) and not more than 207" of avermeelin B[b (OrfH^O,^. lsoln from Streptomyces avermititis: G, Albcrs-Schonbcrg a al Ger. pal. 2,717,040; vidvm. U.S. pal. 4,310,519 (1977. 1982 bolh lo Merck & Co.). Separation of components: T. W. Miller et uJ.. Antimicrob. Ag. Chemother. 15, 368 (1979); by semr-p reparative HPLC: C. C. Ku cl al, J. Liq, Chroma ton. 7,2905(1984). Structure dctcrmn: G. Albcrs-Schonbcrg et al. J. Am. Chcm. Sac. 103, 4216 (|9X1). Absolute configuration: J. P. Springer et a!., ibid. 4221. Partial synthesis of B,,: K. C. Nicolaou et at., ibid. 106, 4189 (|984). Total synthesis: S. Hanessian el al, ibid. 108, 2776 (|986). Anthelmintic activity in animals: L. S. Blair, W. C, Campbell, J. Parasitol. 64, 1032 (1978); J. R. ligerlon et at, Antimicrob. Ag. Chemother. 15, 372 0979); K. S. Todd et at,. Am. J. Vet. Res. 45, 976 (1984). Pestieidal activity: I. Putter et al, Ex- perientia 37, 963 (1981); R. A. Dybas, A- St. J, Green, Brit. Crop. Prat. Conf. - Pests Dis. 1984, 947. Control of red imported fire ants: J- A. Greenblalt el al, J. A%r. limomol. 3,233(1986). Interaction with GABA receptors: S. S. Pong et u/., J. Neumchcm. 34, 351 (1980); T. N. Mellin ,-I al. Neuropharmacol 22, 89 (1983); receptor binding studies- S S. Pong, C. C- Wang, ibid. 19, 31 | (1980); G, Drcxler, W. Siegharl. Eur. J. Pharmacol 99, 269 (1984). Fi*te in soil and plants: D. L. Bull et al, J. Agr. Food Chcm. 52, 94 (1984); H. A. Mnye of a!., ibid. 35, 859(1987); M. S. Maynard et al, ibid. 37, 178, 184 (1989). Review: J. R. Babu, '"Avermeciins: Biological and Pesiieidal Activities" in Biologically Active Natural Products. ACS Symp. Series 380, II. Q, Cutler. Ed. (American Chemical Society, Wash; ington, D,c., 1988) pp 91-108. Reviews of modes of aclion: C C Wang, S..S. och. compontaii B|a, R--C2U5 component R][v K —CH Consult (he cross index Ponx. Pros- Clin. Biol. Res. 97, 373-395 (1982); D. J. Wright, Biochcm. Soc. Trans, 15, 65-67 (1987). Review of insecti- cidal activities and use: F. Strong, T. A, Brown, Bull Eut. Res. 77, 357-389 (1987). Odorless, off-while 10 yellow crystals from methanol, mp 150-155° (dec)- [«],, I 55.7° ±2" (c - 0.87 in CHCI3). uv max (methanol): 237, 245, 253 nni (log e 4.48, 4.53, 4.34). Vapor pressure: 1.5 x |0 9 torr. Soly at 21° (ng/l): water 10; (mg/ml): acetone |00; n-butanol 10: chloroform 25; cyckihexane 6; ethauol 20; isopropauol 70; kerosene 0.5; methanol 19,5; toluene 350. Hydrolysis does nol occur in aq solu at pH 3, 5, 7- LDS(I (technical grade) orally in sesame oil in mouse, ral: 13.5, 10.0 mg/kg; dermally in rabbit: > 2000 mg/kg. LDS„ in mallard duck, bobwhiie quail: 84.6, >2000 mg/kg. LC50 (9ft lir) in rainbow Irout, bluegilh 3.6, 9.6 Hg/I; LCM (48 hr) in Duphnia manna ().34 ug/l (Merck Technical Data Sheet). USE: Acaricide; insecticide. l'HERAP CAT (vet): Anthelmintic 2, Abietic Acid. l1R-(1u,4a(i,4hv,U>a„)]-1,2J.4t4u.- 4b,5,<i,IG,IOa-l)ecahydr<i-l,4a-dimethyl-7-(l-methyleth$l)~ ]-phvuanthrviivcarbnxylic acid; 1 .i'isopritpylpfidocarpa-7,1.?- dien-15-oic acid; sylvic acid. C^II^'-V mol wi 302.44. C 79.42%, H 9.997c, O 10.58%. A widely available organic acid, prepared by isomeri/.atkm of rosin: Harris. Sanderson, Org. Syti, coll. vol. IV, 1 (1963); Fieser, Ficser. The Chemistry of Natural Products Related to Phonanthmnc (New York, 3rd cd., 1949). Synthesis from dehydroabietic acid: A. W. Bnrgstahler, F. W. Wortleu, J. Am. Chem. Soc. 83, 2587 (|961); E. Wenkert et al, ibid. 86, 2038 (1964). Chromatographic study: A, G. Douglas, T. G. Powell, J. Chromatog. 43, 241 (1969). Metabolism in rabbits: Y. Asakawa et al. Xenobiotica 16, 753 (1986). Mouoclinie plates from alcohol + water, nip 172-175". [ujjf* - 106°(c - 1 in abs ale), uv max: 235, 241.5, 250 nm (c 19500, 22000. |4300). Insol in water. Sol in ale, benzene, chloroform, ether, acetone, carbon disulfide, dil NaOll sotn. Commercial abietic acid made by healing rosin alone or with acids may be glassy or partly crystalline, usually of yellow color and melting as low as 85°. Methyl ester see methyl abietate. i,"sr.: Manufacture of esters (ester gums), e.g.. methyl, vinyl and glyceryl esters for use in lacquers and varnishes. Manufacture of "metal resinates", soaps, plastics and paper sizes. Assisls growth of lactic and butyric acid bacteria, 3. Abikoviromycin. 7-FJhylidene-Ia.2,3,7-tetrahy- drocycloptntfbfoxirciiofcjpyridinc; 4,4a-epoxy-5-ethyIidene- 2,3,4,4a-letrahydro-5H- I -pyridine; abieoviromycin; latum- before using this section.

Acacic Acid 11 NaOH; slightly sol in dimethyl ether. HC1. Practically insol in dil 7. Absinthin. l3S-(3t*,3a<x,f>fi,f>un.,6b&, 7n, 7a(i,Sn,- 10a&,U(i,i3an,l3bn,l3c(i,l4bp)]-3Ja,4,5,6,6a,6b,7,7a,ti,V,- 10,iQa,I3a,13c,I4h-llexad<:cuhydr<i-6.8-dihydroxy-3,(>,fi,l!,- 14, }5-hexarnethyl-2H-7,13b-ethenopentaieno[!",2':(>, 7; 5",4":6', 7]di(ych>hvpta[t,2-b:r,r-b]difuran-2,l2- (HH)-dione; absinthiin; absynihin. CjpH^O^; mol wt 496.62. C 72.55%, H 8.12%, O 19.33%. Chief bitter principle of wormwood, Artemisia absinthium L., Compdsitae. Isoln by chromatography: Herout ft al., Coll. Czech. Chi-m. Commun. 21, 1485 (1956); see also Chem. & Ind. {London) 1955, 569. Structural studies: Novolny m ul. ibid. 1958, 465: Coll. Czech. Chem. Commun. 25, 1492 (I960); Vokac et al. Tetrahedron Letters 1968, 3855. Structure; J. Bcauhaire et al. ibid. 21, 3191 (1980). Very bitter Orange needles from abs elher, mp 179-180" (dec), y Solvated crystals from benzene, decomp 165". W\\" + 180.0° (c = 1.9 in CHC13). Bitterness threshold 1:70,000. 8. Absinthium, Wormwood; Absinthe; Armoisc, Dried leaves and flowering tops oUArtemisia absinthium 1,., Compositac. Habit. Orows as weed or is cultivated in Europe, U.S., Canada, North and West Asia, Africa. Has been used as stomachic lonie and anthelmintic. Comtit. Absinthin, anabsinthin, dark green or brown volatile oil (chiefly thnjone). F,. Quenther, The Essential Oils, V, 487 (Van Nostrand, New York 1952). Isolation of various constituent: Cekan, Herout, Coll. Czech. Chem. Commun. 21, 79 (1956); Herout et al.. ibid. 1485. Characterization of oil: T. Saceo, F. Chialya, Planta Med. 54, 93 (1988). Very sirong odor, acrid taste. USL: As flavoring in alcoholic beverages, e.g. vermouth, which is a blent! of white wines, contg traces of absinthium and other flavors. Caution: Ingestion of the volatile oil or of the liqueur, absinthe, may cause G.I. symptoms, nervousness, stupor, convulsions, deaili. 9. Acacetin. 5,7-Diltydr<>xy-2-(4-tnethoxypheiiyt). 4II-1 -benzopyraii-4-Dtte; S,7-dihydroxy-4'-methoxyflavotie; apige]]in-4'-m(;thyl ether. C1(1H|j05; mol wt 284.26. C 67.60%, II 4.26%, O 28.1470. The aglycon of linarin, q.Vl, and of acaciin. Isoln from linarin: /,emplen, Bognar, Ber. 74B, 1818 (1941). From acaciin: Hattori. Acta Phytochim. 2, 105 (1925). Isoln from Robinia psvudoacacia L., Legurni- nosae: Nakazawa, Matsuura, J. Pharm. Soc. Japan 73, 481 (1953). Structure: Haker et al. J. Chem. Soc. 1951, 691. Synthesis: Robinson, Venkataraman, ibid. 1926, 2348; Zemplen, Bognar, Ber. 76B, 452 (1943); Narasinihacharj, Seshadri, Proc. Indian Acad. Sei. 30A, 151 (1949): Simpson, Sci. Proc. Roy. Dublin Soc. 27, 111 (1956), C.A. 51, 8082a (1957). Yellow needles from 95% alcohol, mp 263°. Sol in hot ale, practically insol in ether. Sol in alkalies with yellow color. Diacetate, Ca)U1(.07, lustrous needles from ale, mp 203". 7-Rhanmoglueosidc, C;SH120|4. acaciin. From Robinia pseudacacia I,., l.cguminosae: Frcudcnbcrg, Hartmann, Ann. 587, 207 (1954). Structure: Zernplen, Mesler, Magyar Kym. Folyoirat 56, 2 (1950). C.A. 45, 7977d (1951). Needles from pyridine f water, mp 263°. [a] —85.3° (pyridine); —99.5° (glacial acetic acid). Sparingly soluble in cold, more sol in boiling water; slightly sol in organic, solvents- 10. Acacia. Gum Arabic. F.slinialions of mol wt range from about 240.000: Oakley, 7'ratis. I'araday Sot:. 31, 136 (1935), lo 580,000: Anderson et al. Carbohyd. Res. 3, 308 (1967). According to the U.S.P., acacia is the dried gummy exudation from the stems and branches of Acacia Senegal (L.) Willd., I.agumifioxau. or other African species of Acacia. According to C. L. Mantell, The Water-Snluble Gums (New York, 1947), Kordofan gum (hashab geneina), the gum from Acacia verck Cnrill. & 1'err. from plantations in |he Kordolan province (Sudan) is considered the best commercial variety. Grades of Kordofan gum which are clear, white (sun bleached) and tasteless are preferred for food prepns and pharmaceuticals. (There is a close relationship between color and flavor due to the presence of tannins.) Acacia was originally thought to be composed only of ( — )-arabinose, (+)-gsdactose, ( )-rlianitiose, (-J-)-glycu- ronie acid. Revised composition and structural studies: Anderson et u/.. J. Chem. Soc. (C) 1966, 1959. See also Swcnson at al. J. Polym. Sci. Port A.2 6, 1593 (1968). General review: Anderson, Dea, J. Soc. Cosmet. Chem. 22, 61- 76 (1971). Review of use as food additive: D. M. W. Anderson, Food Addit. Contain. 3, 225-230 (1986). Occurs in spheroidal tears up to 32 mm in diameter. Also flakes and powder. Solns of ginn from Acacia verek are levorotatory; other acacia species arc dextrorotatory: flamy, Bull. Sci. Pharmacol. 35, 421 (1928), Specific gravity: 1.35- 1.49 (samples dried at 100" are heavier). Moisture content usually varies from 13-15%.. U.S.p. limit 15%>. Material containing less than 12% chips easily and produces dust dining transportation. Insol in alcohol. Almost completely sol in twice its weigh) of water. 100 grams of a satd soln contains 37 g at 25°; 38 g at 50"; 40 g at 90°: Tafl, Malm, Trans. Kans. Acad. Sci. 32, 49 (1929). Aq soln acid to litmus. Also sol in glycerol and in propylene glycol, hut prolonged heating (several days) may be necessary for complete solution (about 5». Incoinpat. Precipitates or jellies result upon addition of solns of ferric salts, borax, basic lead acetate (lead subace- late, but noi neutral lead acetate), alcohol, sodium silicate, gelatin, arnmoniated tincture of guaiac. USii: As mucilage, excipienl for tablets, size, cmulsifier, thickener, also in candy, other foods; as colloidal stabilizer. In the manufacture of spray-dried "fixed" flavors —stable, powdered flavors used in packaged dry-mix products (puddings, desserts, cake mixes) where flavor stability and long shelf life are important. 11. Acacic Acid, {3(i,lf>ii,2lii)-Trihydroxyoleaii-l2- en-2H-oic acid. C^H^Ojl mol wt 488.68. C 73.73%, H 9.90%,, O 16.37%'. Isoln from pods of Acacia concinna D.C., Leguminosae: Varshney, Shamsnddin, Tetrahedron Letters 1964, 2055; from bark of A. concinna D.C.: R. Uanerji, S. K. Nigam. J. Ind. Chem. Soc. 57, 1043 (1980). Structure and stereochemistry: Varshney ct a/., ibid. 1965, 1187. Revised structure: A. K. Barua et al.. Trans. Bose Res. Inst., Calcutta 39, 61 (1976), C.A. 87, 53460c (1977). H„C CH„ Needles from methanol, mp 280.281°. Methyl ester. CjtH50Os, needles from methanol, mp 223- 224". Diacctyl lactone, C^H^O,,, crystals, mp 235-236". Consult the cross index before using this section. Page 3

Acenaphthene 23 phylline and chloroacetic acid in hot dil NaOH: Ger. pat. 352,980 (1922 to E. Merck); Frdl. 14, 1320. Prepn of free acid and sodium salt: Milletti, Virgili, Chimica (Milan) 6, 394 (1951), C.A. 46, 8615h (1952), CH2COOH Crystals from water, mp 271°. Sodium salt, C9H9N4Na04, Aminodal. Silky needles, mp >300*. therap CAT: Diuretic; cardiotonic; bronchodilator. 19. Acefylline Piperazine. l,2,3,6-Tetrahydro-l,3-di- methyl-2,6-dioxo-7H-purine-7-acetic acid compd with piperazine; acepifylline; piperazine theophylline-7-acetate; 7- theophyllineacetic acid piperazine salt; piperazine theophylline ethanoate; Dynaphylline; Etaphydel; Etaphylline; Eta- fillina; Etophylate. Cl3HMN604; mol wt 324.34, C 48.14%, H 6.227c N 25.91%, O 19.73%. Undefined mixture of the 1:1 and 2:1 salts which contains 75-7/8% theophylline acetic acid and 22-25% anhydrous piperazine. Active metabolite is acefylline, q.v. Prepn: Baisse, Bull. Soc. Chim. France 1949, 769. Pharmacokinetics: J..Zuidema, F. W. H. Merkus, Pharm. Weekbl. 113, 605 (1978); S. Sved et al., Biopharm. Drug Dispos. 2, 177 (1981). HPLC determn in serum: J. Zuidema, F. W. H. Merkus, J. Chromatog. 145, 489 (1978). GC determn in urine: J. Zuidema, H. Hilbers, ibid. 182, 445 (1980), CH2COOH HaC H n =« 1 or 2 THERAP cat: Bronchodilator, 20. Aceglatone. D-Glucaric acid di-y -lactone diace- tate; 2,5-di-0-acetyl-D-glucaro-l,4:6,3-dilactone; 2,5-di-O- acetyl -D-glucosaccharo -1,4:6,3 -dilactone; Aceglaton; Glu - caron. C10H10O8; mol wt 258.19. C 46.52%-, H 3.90%, O 49.58%. Prepn and structure: Hirasaka, Umemoto, Chem. Pharm. Bull 13, 325 (1965), C.A. 63, 3024h (1965); Ishidate et al, Japan, pat. 14,956('67) (1967 to Tokyo Biochem. Res. Com.), C.A. 68, 78558m (1968). Pharmacological studies: Iida et al, Japan. J. Pharmacol. 15, 88 (1965), C.A. 63, 5961g (1965). Review and toxicity data: Japan. Med. Gaz. 8(8), 15 (1971). 0=C HC — 0C0CH. "<\. a j .• CH HC HC — OCOCH, C=0 White, odorless and tasteless crystalline powder, mp 185- 186" (Hirasaka); from 2:1 ethanol-ethyl acetate 192° (dec) (Japan. Med. Gaz.). Sol in dimethylformamide, sparingly sol in acetone, slightly sol in dioxane, methanol and ethanol. Practically insol in water. LD50 in mice, rats (g/kg): > 20, > 10 orally; > 20, > 10 s.c; 5.80-6.35, 6.10-6.15 i.p. (Japan. Med. Gaz.). THERAP CAT: Antineoplastic. 21. Aceglutamide. N2-Acetyl-L-glutamine; a-N-ace- tyl-L-glutamine; Acutil-S. C7H12N204; mol wt 188.18. C 44.68%, H 6.43%, N 14.88%, O 34.01%. Prepn: P. Karrer et al, Helv. Chim. Acta 9, 301 (1926); Brit. pat. 792,576 (1958 to Merck & Co.), C.A. 53, 2109a (1959); I. J. Masch- ler, N. Lichtenstein, Biochim. Biophys. Acta 57, 252 (1962). Stability study: G. Sekules, G. Guadagnini, Farmaco Ed. Prat. 21, 22 (1966). NMR study: W. Voelter et al, Z. Na- turforsch. B 26, 213 (1971). Fermentation study: T. Naka- nishi, J. Ferment. Technol. 56, 573 (1978). Prepn of the aluminum complex: T. Kagawa et al, Ger. pat. 2,127,176 corresp to U.S. pat. 3,787,466 (1971, 1974 both to Kyowa). Physico-chemical properties: E. Hayakawa et al, Yakugaku Zasshi 97, 731 (1977), C.A. 87, 141198 (1977). Effect on exptl chronic gastric ulcer: H. Tanaka et al, Oyo Yakuri 7, 1035 (1973), C.A. 81, 33283v (1974). Cytoprotective effect: H. Tanaka, Arzneimittel-Forsch. 36, 1485 (1986). HOOCCHCH0CH0CONH0 NHCOCH., [o]g> -12.5°(c - 2.9 in Crystals from ethanol, mp 197 water). Aluminum complex, C35H59Al3N10O24, pentakis (J^-acetyl- L-glutaminato)tetrahydroxytrialuminum, aceglutamide aluminum, KW-110, Glumal White powder, mp 221° (dec). Sol in water. Practically insol in methanol, ethanol, acetone. LD^j in male mice, rats (g/kg): 14.3, > 14.5 orally; 5.0, 4.2 i.p.; 0.46, 0.40 i.v. (Kagawa). THERAP CAT: Free acid as nootropic; aluminum complex as anti -ulcerative. 22. Acemetacin. l~(4-Chlorobenzoyl)-5-methoxy-2- methyl-lH-indole-3-acetic acid carboxymethyl ester; [[1-(4- chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetoxy]- acetic acid; TV 1322; Acemix; Rantudil; Rheumibis. C21- H,8C1N06; mol wt 415,83. C 60,66%, H 4.36%, CI 8.53%, N 3.37%, O 23.09%. Deriv of indomethacin, q.v. Prepn: K. H. Boltze et al, Ger. pat. 2,234,651 corresp to U.S. pat. 3,910,- 952 (1972, 1975 both to Troponwerke). Series of articles on chemistry, analysis, pharmacodynamics, toxicology and clinical trials: Arzneimittel-Forsch. 30, 1313-1468 (1980). Toxicity data: H. Jacobi, H.-D. Dell, ibid. 1398. CH2COOCH2COOH Very fine pale yellow crystals from petr ether, mp 150- 153°. LD50 in male, female mice, male, female rats (mg/kg): 55.5, 18.42, 24.2, 30.1 orally; 34.1, 51.1, 38.1, 28.3 i.v, (Jacobi, Dell). THERAP CAT: Anti-inflammatory. 23. Acenaphthene. 1,2-Dihydroacenaphthylene; peri- ethylenenaphthalene; 1,8-ethylenenaphthalene. C12H10; mol wt 154,21. C 93.46%, H 6.54%. Occurs in coal tar. Isoln: Ges. f. Teerverwertung, Ger. pat. 277,110; Chem. Zentr. 1914, II, 597. In petroleum residues: Orloff et al, CA. 31, 28009 (1937). By passing ethylene and benzene or naphthalene though a red hot tube: Berthelot, Bull Soc. Chim. [2] 7, 274; 8, 226, 245 (1867). By heating tetrahydroacenaphthene with sulfur to 180°: Braun et al, Ber. 55, 1694 (1922). From acenaph then one or acenaphthenequinone by high pressure hydrogenation in decalin with nickel at 180-240°: Braun, Bayer, Ber. 59, 921, 923 (1926). From acenaphthenone oxime: Morgan, Stanley, J. Soc. Chem. Ind. (London) 44, 494T (1925). Consult the cross index before using this section. Page 5

e -Acetamidocaproic Acid 38 Potassium salt, C4H4KN04S, acesulfame-K, Sunette. mp 250°. Very sol in water, DME^ DMSO. Sol in ale, glycerin - water. USE: Potassium salt as sweetener for foods, cosmetics. 31. Acetal. 1,1-Diethoxyethane; diethylacetal; acetal - dehyde diethyl acetal; ethylidene diethyl ether. C6H1402; mol wt 118.17. C 60.98%, H 11.94%, O 27.08%. CH3CH- (OC2H5)2. Made from acetaldehyde and alcohol in the presence of anhydrous calcium chloride or of small quantities of mineral acid: H. Adkins, B. H. Nissen, J. Am. Chem. Soc. 44, 2750 (1922); eidem. Org. Syn. coll. vol. I, 1 (2nd ed., 1941). Volatile liquid, df 0.8254. bp760 102.7°; bp200 66.3°; bp^ 39.8°; bP4o 31.9°; bp20 19.6°; bpl0 +8.0°; bp5 -2.3°; bpl0 -23°. ng> 1.38193. Flash pt, closed cup: 97°F (36°C). uv spectrum: Purvis, J. Chem. Soc. 127,^9-(1925). 100 g water dissolve 5 g acetal. Misc with alcohol, 60% alcohol, ether. Sol in heptane, methylcyclohexane, propyl-, isopropyl-, butyl-, isobutyl alcohol, an^d ethyl acetate. Tends to polymerize on standing. Stable to alkalies. LD50 orally in rats: 4.57 g/kg, H. F. Smyth et al, J. Ind. Hyg. Toxicol 31, 60 (1949). USE: Solvent; in synthetic perfumes such as jasmine; in organic syntheses. therap cat: Hypnotic. 32. Acetaldehyde. Ethanal; "aldehyde"; acetic aldehyde; ethylaldehyde. C2H40; mol wt 44.05. C 54.53%, H 9.15%, O 36.32%. CH3CHO. Produced by oxidation of alcohol with Na2Cr207 and H2S04; usually from acetylene, dil H2S04 and mercuric oxide as catalyst; also by passing alcohol vapor over a heated metallic catalyst. Lab procedure from ethanol: Wertheim, J. Am. Chem. Soc. 44, 2658 (1922); Fricke, Havestadt, Angew. Chem. 36, 546 (1923); Gattermann-Wielaud, Praxis des organischen Chemikers (de Gruyter, Berlin, 40th ed., 1961) p 180; from acetylene: Gattermann-Wieland, op. cit. 183; from paraldehyde: A. I. Vogel, Practical Organic Chemistry (Longmans, London, 3rd ed., 1959) p 324; by catalytic oxidation of ethylene in aq soln: J. Smidt et al, Angew Chem. 71, 176 (1959); by oxidation of ethylene in fuel cells in the gas phase: K. Otsuka et al, Chem. Commun. 1988, 1272. Manuf: Faith, Keyes & Clark's Industrial Chemicals, F. A. Lowenheim, M. K. Moran, Eds. (Wiley-Interscience, New York, 4th ed., 1975) pp 1 -7. Toxicity data: Smyth, Arch. Ind. Hyg. Occup. Med. 4, 119 (1951). Review: H. J. Hagemeyer in Kirk-Othmer Encyclopedia of Chemical Technology vol. 1 (Wiley-Interscience, New York, 3rd ed., 1978) pp 97-112. Flammable liquid; characteristic, pungent odor. d\6 0.788. mp —123.5°. bp 21°. ng* 1.3316. Flash pt, closed cup: — 36"F (—38°C). Miscible with water, alcohol. Keep cold. Chill thoroughly before opening. LD50 orally in rats: 1930 mg/kg (Smyth). Human Toxicity: General narcotic action. Large doses may cause death by respiratory paralysis. Symptoms of chronic intoxication resemble those of chronic alcoholism, cf. Clinical Toxicology of Commercial Products, R. E. Gosse- lin et al, Eds. (Williams & Wilkins, Baltimore, 4th ed., 1976) Section II, p 124. USE: Manuf paraldehyde, acetic acid, butanol, perfumes, flavors, aniline dyes, plastics, synthetic rubber; silvering mirrors, hardening gelatin fibers. Caution: Irritating to mucous membranes. 33. Acetaldehyde Ammonia. I-Aminoethanol; a-ami- noethyl alcohol; aldehyde ammonia. C2H7NO; mol wt 61.08. C 39.32%, H 11.55%, N 22.937^, O 26.19%. CH3CH- (OH)NH2. Prepd from acetaldehyde and ammonia: Asch- an, Ber. 48, 874 (1915). Crystals; gradually turns yellow to brown in air. mp 97°. bp 110°, partly decomposing. Freely sol in water, slightly in ether. Protect from light and air. use: For preparing pure acetaldehyde; in organic syntheses. Caution: Irritates eyes, mucous membranes. 34. Acetaldehyde Sodium Bisulfite. 1~ Hydroxy ethane- sulfonic acid sodium salt. C2H5Na04S; mol wt 148.11. C 16.22%, H 3.40%, Na 15.52%, O 43.21%, S 21.65%. CH3- CH(OH)S03Na. Hemihydrate, crystals. Decomposed by acids. Freely sol in water; insol in alcohol. USE: Making pure acetaldehyde; in organic synthesis. Caution: Irritates skin, mucous membranes. 35. Acetaldoxime. Acetaldehyde oxime; aldoxime; eth - ylidenehydroxylamine. C2H5NO; mol wt 59.07. C 40.66%, H 8.53%, N 23.72%, O 27.09%. CH3CH-NOH. Prepn: Dunstan, Dymond, J. Chem. Soc. 61, 470 (1892). Manuf: Donaruma, U.S. pat. 2,763,686 (1956 to du Pont). Two crystalline modifications, mp 12° (/3-form), mp 46.5° (a-form), d 0.966. bp 114.5°. ng> 1.415. Dec by aq HC1 into acetaldehyde and hydroxylamine. Very sol in water, alcohol, ether. 36. Acetamide. Acetic acid amide. C2H5NO; mol wt 59.07. C 40.66%, H 8.53%, N 23.72%, O 27.09%. CH3- CONH2. Prepd by fractional distillation of ammonium acetate: Coleman, Alvarado, Org. Syn.; coll. vol. I, 3 (2nd ed., 1941); Gattermann-Wieland, Praxis des organischen Chemikers (40th ed., 1961) p 118; Vogel, Practical Organic Chemistry (3rd ed., 1959) p 401. Prepn from methyl acetate, W. P. Munro et al, U.S. pat. 2,106,697 (1936 to Calco Chem.); from ethyl acetate, Vogel, op. cit, p 403. Studies of acetamide as an ionizing solvent: Jauder, Winkler, J. Inorg. Nucl Chem. 9, 24, 32, 39 (1959). Toxicological study: Weisburger et al, Toxicol. Appl. Pharmacol 14, 163 (1969). Deliquescent hexagonal crystals. Odorless when pure, but frequently has a mousy odor. dj° 1.159. mp 81°. bp760 222°; bp100 158°; bP40 136°; bp20 120°; bp10 105°; bp. 92°. ng 1.4274. Neutral reaction. Kb at 25° = 3.1 X lO"1^ One gram dissolves in 0.5 ml water, 2 ml alcohol, 6 ml pyridine. Sol in chloroform, glycerol, hot benzene. USE: Solvent; molten acetamide is an excellent solvent for many organic and inorganic compounds. Solubilizer; renders sparingly soluble substances more soluble in water by mere addition or by fusion. Plasticizer; stabilizer. Manuf methylamine, denaturing alcohol. In organic syntheses. Caution: Mild irritant. 37. Acetamidine Hydrochloride. Ethanimidamide hydrochloride; ethanamidine hydrochloride; a-amino-a-imino- ethane hydrochloride; ethenylamidine hydrochloride; acedi- amine hydrochloride; SN 4455. C2H7C1N2; mol wt 94.55. C 25.41%, H 7.46%, CI 37.50%, N 29.63%. Prepd by passing HC1 into a soln of acetonitrile in abs alcohol, then passing NH3 into the reaction mixture: Pinner, Ber. 16, 1654 (1883); 17, 178 (1884); Dox, Org. Syn., coll. vol. I, 5 (New York, 2nd ed., 1941). See also Fargher, J. Chem. Soc. 117, 674 (1920). Review: Shriner, Neumann, Chem. Rev. 35, 351 -425 (1944). NH II CH3CNH2HCl Long prisms from alcohol, somewhat deliquescent, mp 174° (Fargher); mp 164-166° (Dox). Very sol in water. Sol in alcohols. Practically insol in acetone, ether. Should be stored in a closed container and in a cool place. If alkali is added to an aq soln, the free base is liberated. Free base, C2H6N2. uv max: 224 nm (e 4000). pK, (25°): 12.1. Has a strong alkaline reaction and on slight warming dissociates into ammonia and acetic acid. use: In the synthesis of imidazoles, pyrimidines, triazines. Caution: Irritates mucous membranes, skin. Avoid tasting, swallowing, inhalation of the dust, skin contact. 38. e -Acetamidocaproic Acid. 6-(Acetylamino)hexa- noic acid; 6-acetamidohexanoic acid; acetaminocaproic acid; acexamic acid; iV-acetyl-6-aminohexanoic acid. C8H15N03; mol wt 173.21. C 55.47%, H 8.73%, N 8.09%, O 27.71%. CH3CONH(CH2)5COOH. Prepn: Offe, Z. Naturforsch. 2b, 182 (1947); Fr. pat. M2332 (1964 to Rowa), CA. 61, 577b (1964). Anti-inflammatory activity of salts: O. Guillard et al, Pharmacology 34, 296 (1987). Clinical comparison with ranitidine in gastroduodenal ulcer: M. J. Varas Lorenzo, Curr. Ther. Res. 39, 19 (1986). Crystals from acetone, mp 104-105.5° (Fr. pat. M2332), mp 112° (Offe). Sodium salt, C8H14NNa03, Plastenan. Consult the cross index before using this section. Page 7

Acetimidoquinone 49 ty data: H. H. Anderson, C. D. Leake, Proc. Soc. Exp. Biol, Med. 27, 267 (1930). AsO(OH)2 NHCOCH, [ Stout prisms from water, dec 240-250°; slight acid taste. Slightly sol in water; freely sol in solns of alkalies and alkali carbonates. Stable at ordinary temps. MLD in rabbits, cats (mg/kg): 125-150, 150-175 orally (Anderson, Leake). Calcium salt (with hexosediphosphoric acid), Realphene. Bismuth salt, Bistovol. Diethylamine salt, C12H21AsN2Os, Acetarsin, Acetilarsano, Acetylarsan, Arsaphenan, Golarsyl, Syntharsol. Prepn: Brit. pat. 224,764 (1954 to Rhone-Poulenc). Arecoline salt, see Drocarbil. therap CAT: Antiprotozoal (Trichomonas). Diethylamine salt formerly as antisyphilitic. therap cat (vet): Antiprotozoal (Histomonas) in turkeys. Antibacterial (spirocheticide) in poultry. Has been used as a tonic. 45. Acetazolamide. N-[5-(Aminosulfonyl)-l,3y4-thia- diazol-2-yl]acetamide; 5-acetamido-lf3,4-thiadiazole-2-sul- fonamide; 2 -acetylamino -1,3,4 -thiadiazole-5 -sulfonamide; acetazoleamide; #6063; carbonic anhydrase inhibitor no. 6063; Acetamox; Atenezol; Cidamex; Defiltran; Diacarb; Diamox; Didoc; Diluran; Diureticum -Holzinger; Diuriwas; Diutazol; Donmox; Edemox; Fonurit; Glaupax; Glupax; Natrionex; Nephramid. C4H6N403S2; mol wt 222.25. C 21.61%, H 2.72%, N 25.21%, O 21.60%, S 28.86%. Prepn: Roblin, Clapp, J. Am. Chem. Soc. 72, 4890 (1950); Clapp, Roblin, U.S. pat. 2,554,816 (1951 to Am. Cyanamid); U.S. pat. 2,980,679 (1961 to Omikron-Gagliardi Soc. Fatto). ch3conh S02NH2 Crystals from water, mp 258-259° (effervescence). Weak acid. pKa 7.2. Sparingly sol in cold water. Sodium salt, Vetamox. therap CAT: Carbonic anhydrase inhibitor, diuretic; treatment of glaucoma. therap cat (vet): Diuretic, carbonic anhydrase inhibitor. 46. Acetiamine. Ethanethioic acid S-[l-[2-(acetyl- oxy)ethyl]-2-[[(4-amino-2-methyl-5-pyrimidinyl)methyl]- formylamino]-l-propenyl] ester; thioacetic acid S-ester with N-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-N-(4-hydr- oxy-2-mercapto-l-methyl-l-butenyl)formamide acetate; N- [(4-amino -2 -methyl -5 -pyrimidinyl)methyl]-iV-(4 -hydroxy - 2-mercapto-l -methyl-1 -butenyl)formamide 0,S-diacetate; 3-acetylthio-4-[(4-amino-2-methyl-5-pyrimidinyl)methyl- iV-formylamino]-3-pentenyl acetate; 5-acetoxy-3-acetyl- thio-2-[(4-amino-2-methyl-5-pyrimidinyl)methyl-iV-form- ylamino]-2-pentene; diacethiamine; O.S-diacetylthiamine; Yitamin B, O.S-diacetate; D.A.T.; Thianeuron. C16H22N4- 04S; mol wt 366.45. C 52.44%, H 6.05%, N 15.29%, 0 17.46%, S 8.75%. A fat-soluble deriv. of vitamin Br Prepn: Matsukawa, Kawasaki, J. Pharm. Soc. Japan 23, 705, 709 (1953), C.A. 48, 7017e (1954); Takamizawa et al, Bull Chem. Soc. Japan 36, 1214 (1963). Synthesis and pharmacology: Gauthier et al, Ann. Pharm. Franc. 21, 655 (1963). Clinical studies: Wagner, Wagner, Arzneimittel-Forsch. 16, 1643 (1966); Blum, Thomas, Pharmacol Clin. 2, 177 (1970). C = C — S-COCH. CHO CH2CH2OOCCH3 Colorless prisms from benzene-petr ether, mp 122-123° (dec); from water, mp 123-124°. Soluble in water, methanol, ethanol. Hydrochloride, C16H23C1N404S, Nevriton Comprimes. therap CAT: Vitamin (enzyme cofactor). 47. Acetic Acid Glacial. Aci-Jel. C2H402; mol wt 60.05. C 40.00%, H 6.71%, O 53.29%. CH3COOH. Obtained in the destructive distillation of wood; from acetylene and water, via acetaldehyde by oxidation with air. Manuf processes: Bhattacharyya, Sourirajan, J. Appl Chem. (London) 6, 442 (1956); eidem, ibid. 9, 126 (1959); Elce et al, U.S. pat. 2,800,504 (1957 to Distillers Co.); Wirth, U.S. pat. 2,818,428 (1957 to British Petroleum); McKusick and Hoover, U.S. pats. 2,940,913 and 2,940,914 (both 1960 to Du Pont); Faith, Keyes & Clark's Industrial Chemicals, F. A. Lowenheim, M. K. Moran, Eds. (Wiley-Interscience, New York, 4th ed., 1975) pp 8-15. Toxicity data: H. F. Smyth et al, Arch. Ind. Hyg. Occup. Med. 4, 119 (1951). Review: F. S. Wagner in Kirk-Othmer Encyclopedia of Chemical Technology vol. 1 (Wiley-Interscience, New York, 3rd ed., 1978) pp 124-147. Liquid; pungent odor. Produces burns of the skin! d16-67 (liq) 1.053; d16-60 (solid) 1.266'. dg 1.049. bp 118°. mp 16.7°. n§ 1.3718. Flash pt, closed cup: 103°F (39CC). Caution: Flammable! Contracts slightly on freezing. It is an excellent solvent for many organic compounds; also dissolves phosphorus, sulfur and halogen acids. Miscible with water, alcohol, glycerol, ether, carbon tetrachloride. Practically insol in carbon disulfide. Weakly ionized in aq solns: pKa 4.74. pH of aq solns 1.0M = 2.4; 0.1M = 2.9; 0.01M = 3.4. LD50 in rats (g/kg): 3.53 orally (Smyth). Incompat. Carbonates, hydroxides, many oxides, and phosphates, etc. Caution: Ingestion may cause severe corrosion of mouth and G.I. tract, with vomiting, hematemesis, diarrhea, circulatory collapse, uremia, death. Chronic exposure may cause erosion of dental enamel, bronchitis, eye irritation, cf Patty's Industrial Hygiene and Toxicology vol. 2C, G. D. Clayton, F. E. Clayton, Eds. (Wiley-Interscience, New York, 3rd ed., 1982) p 4909-4911. USE: Manuf various acetates, acetyl compounds, cellulose acetate, acetate rayon, plastics and rubber in tanning; as laundry sour; printing calico and dyeing silk; as acidulant and preservative in foods; solvent for gums, resins, volatile oils and many other substances. Widely used in commercial organic syntheses. Pharmaceutic aid (acidifier). therap cat (vet): Vesicant, caustic, destruction of warts. 48. Acetic Anhydride. Acetic oxide; acetyl oxide. C4H603; mol wt 102.09. C 47.06%, H 5.92%, O 47.02%. (CH3CO)20. Equivalent to 117.64% acetic acid. Made formerly from sod. acetate and acetyl or sulfuryl chloride; now usually obtained from acetaldehyde or acetic acid: Faith, Keyes & Clark's Industrial Chemicals, F. A. Lowenheim, M. K. Moran, Eds. (Wiley-Interscience, New York, 4th ed., 1975) pp 16-20. Of industrial importance is also the ketene process, starting with the thermal decomposition of acetone: Schmidlin, Bergmann, Ber. 43, 2821 (1910). Very refractive liquid; strong acetic odor. Readily combustible. Fire hazard. Flash pt 130°F. dj5 1.080. mp — 73°. bp 139°. n^° 1.3904. Slowly soluble in water, forming acetic acid; with alcohol forms ethyl acetate; sol in chloroform, ether. LD50 orally in rats 1.78 g/kg, H. F. Smyth et al, Arch. Ind. Hyg. Occup. Med. 4, 119 (1951). USE: Manuf acetyl compounds, cellulose acetates. As ace- tulizer and solvent in examining wool fat, glycerol, fatty and volatile oils, resins; detection of rosin. Widely used in organic syntheses, e.g., as dehydrating agent in nitrations, sul- fonations and other reactions where removal of water is necessary. Caution: Produces irritation and necrosis of tissues in liquid or in vapor state. Avoid contact with skin, eyes. 49. Acetimidoquinone. N-(4-oxo-2,5-cyclohexadien- l-ylidene)acetamide; iV-acetyl-p-benzoquinonimine; iV-ace- tylimidoquinone; NAPQI. C8H7N02; mol wt 149.14. C 64.42%, H 4.73%, N 9.39%, O 21.46%. Proposed "ultimate" toxic metabolite of acetaminophen, q.v. Initially prepared by oxidation of acetaminophen with lead tetraacetate and characterized as a Diels-Alder adduct: I. C. Calder et al, J. Med. Chem. 16, 499 (1973). Electrochemical generation in Consult the cross index before using this section. Page 9

V Acetonylacetone 63 464.96. C 41.33%, H 5.20%, Hg 43.15%, O 10.32%. Prepn: Niederl, Shukis, J. Am. Chem. Soc. 66, 844 (1944). HgOOCCH3 CH3CCH2CCH3 CH3 CH3 Crystals, mp 158°. Practically insol in water. Sol in ale, ether, chloroform. Sparingly sol in benzene. Marketed as a 1:1000 soln contg 50% (v/v) ale and 10% (v/v) acetone. therap CAT: Topical anti-infective. 58. Acetone. 2-Propanone; dimethyl ketone; /3-keto- propane; pyroacetic ether. C3HfiO; mol wt 58.08. C 62.04%, H 10.41%, O 27.55%. CH3COCH3. Obtained by fermentation (by-product of butyl alcohol manufacture) or by chemical synthesis from isopropanol (as chief product); from cumene (by-product in phenol manufacture); from propane (by-product of oxidation-cracking); Faith, Keyes & Clark's Industrial Chemicals, F. A. Lowenheim, M. K. Moran, Eds. (Wiley-Interscience, New York, 4th ed., 1975) pp 21-25 . Toxicity: Smyth et al, Ind. Hyg J. 23, 95 (1962). Review: Weiss, Chem. Eng. News 36, 79 (1958); D. L. Nelson, B. P. Webb in Kirk-Othmer Encyclopedia of Chemical Technology vol. 1 (Wiley-Interscience, New York, 3rd ed., 1978) pp 179-191. Volatile, highly flammable liquid; characteristic odor; pungent, sweetish taste. d|| 0.788. bp 56.5°. mp —94°. ng* 1.3591. Flash pt, closed cup: 0°F (— 18°C). Miscible with water, alcohol, dimethylformamide, chloroform, ether, most oils. Keep away from fire! Keep away from plastic eyeglass frames, jewelry, pens and pencils, rayon stockings and other rayon garments. LDS0 in rats: 10.7 ml/kg orally (Smyth). Caution: Prolonged or repeated topical use may cause erythema, dryness. Inhalation may produce headache, fatigue, excitement, bronchial irritation, and, in large amounts, narcosis. Serious poisoning rare. USE: Solvent for fats, oils, waxes, resins, rubber, plastics, lacquers, varnishes, rubber cements. Manuf methyl isobutyl ketone, mesityl oxide, acetic acid (ketene process), diacetone alcohol, chloroform, iodoform, bromoform, explosives, aeroplane dopes, rayon, photographic films, isoprene; storing acetylene gas (takes up about 24 times its vol of the gas); extraction of various principles from animal and plant substances; in paint and varnish removers; purifying paraffin; hardening and dehydrating tissues. Pharmaceutic aid (solvent). 59. Acetone Cyanohydrin. 2-Hydroxy-2-methylpro- panenitrile; 2-methyllactonitrile; a-hydroxyisobutyronitrile. C4H7NO; mol wt 85.10. C 56.45%, H 8.28%, N 16.46%, O 18.80%. (CHj)2C(OH)CN. Prepd by adding acetone to sodium or potassium cyanide in water and treating with H2S04 at below 20°: Welch, Clemo, J. Chem. Soc. 1928, 2629; Cox, Stormont, Org. Syn. coll. vol. II, 7 (1943). Continuous production from HCN and aq acetone: G. Barsky, U.S. pat. 2,731,490 (1956). Liquid; d|5 0.9267; 6\9 0.932. mp —19°. bp15 81°; bp20 88-90°; bp23 82°; bp760 95°. n\9 1.40002; n}? 1.3980. Freely sol in water and in the usual organic solvents but not in petr ether and carbon disulfide. LD50 orally in rats: 0.17 g/kg, H. F. Smyth et al. Am. Ind. Hyg. Assoc. J. 23, 95 (1962). USE: In preparative organic chemistry for transcyanohy- drination, such as preparing the 17-monocyanohydrin of a 3,17-diketo steroid by hydrogen cyanide exchange with the reagent, e.g. Ercoli, de Ruggieri, J. Am. Chem. Soc. 75, 650 (1953). Caution: May be slightly irritating to skin, mucous membranes. Decomposes readily to form hydrogen cyanide, q.v., which is highly toxic. 60. Acetonedicarboxylic Acid. 3-Oxopentanedioic acid; 3-oxoglutaric acid; /3-ketoglutaric acid. C5H6Os; mol wt 146.10. C 41.10%, H 4.14%, O 54.76%. C02HCH2- C0CH2CO2H. Prepd by the action of fuming sulfuric acid on citric acid: Willstatter, Pfannenstiel, Ann. 422, 5 (1921); Ingold, Nickolls, /. Chem. Soc. 121, 1642 (1922); R. Adams et al.. Org. Syn. coll. vol. I, 10 (2nd ed., 1941). By the action of Aspergillus niger on ammonium citrate mixed with some citric acid: Walker et al, J. Chem. Soc. 1927, 3050; also by B. pyocyaneus: Butterworth, Walker, Biochem. J. 23, 931 (1929). Decomposition studies: Wiig, J. Phys. Chem. 32, 961 (1928). Intermediate in synthesis of tropinone: R. Robinson, J. Chem. Soc. Ill, 762 (1917); C. Schopf, G. Lehmann, Ann. 518, 1 (1921). Needles from ethyl acetate, mp 138° (dec). The pure compound may be stored over P2Os for several months. Crude material dec after a few hours. Decomposed by hot water, acids or alkalies to C02 and acetone. K (25°): 7.9 X 10"4. Very sol in water and alcohol; slightly sol in ethyl acetate, ether. Insol in chloroform, ligroin, benzene. use: In organic synthesis. 61. Acetone Sodium Bisulfite. 2-Hydroxy-2-propane- sulfonic acid sodium salt; acetone sulfite. C3H7Na04S; mol wt 162.15. C 22.22%, H 4.35%, Na 14.18%, O 39.47%, S 19.78%. (CH3)2C(OH)S03Na. Crystals, fatty feel, slight S02 odor. Freely sol in water, sparingly in alcohol. Decomposed by acids. USE: In photography; manuf of pure acetone; dyeing and printing texiles; in organic syntheses. 62. Acetonitrile. Methyl cyanide; cyanomethane; eth- anenitrile. C2H3N; mol wt 41.05. C 58.517c H 7.37%, N 34.12%-. CHjCN. Small amounts occur in coal tar. Obtained commercially as a byproduct in manuf of acryloni- trile, q.v.: R. A. Smiley in Kirk-Othmer Encyclopedia of Chemical Technology, vol. 15 (Wiley-Interscience, New York, 3rd ed., 1978) p 896. Prepn by dehydration of acet- amide: Adkins, Nissen, J. Am. Chem. Soc. 46, 143 (1924); A. I. Vogel, Practical Organic Chemistry (Longmans, London, 3rd ed., 1959) p 407; Gattermann-Wieland, Praxis des organischen Chemikers (de Gruyter, Berlin, 40th ed., 1961) p 125; or from acetylene and ammonia: Ger. pat. 365,432; Chem. Zentr. 1924 I, 2398; 1925 II, 1563. Review of purification methods: Techniques of Chemistry, vol. II, Organic Solvents, J. A. Riddick, W. B. Bunger, Eds. (Wiley, 3rd ed., 1970) pp 798-805. Toxicity: H. F. Smyth, C. P. Carpenter, J. Ind. Hyg. Toxicol. 30, 63 (1968). Liquid. Ether-like odor. Poisonous! Burns with a luminous flame. Flash pt 12.8°C (55°F). d]5 0.78745; dj° 0.7138. mp _45°. bp760 81.6°. ng 1.34604, ng> 1.33934. Dielectric constant at 20° = 38.8. Surface tension at 20" = 29.04 dynes/cm. Misc with water, methanol, methyl acetate, ethyl acetate, acetone, ether, acetamide solutions, chloroform, carbon tetrachloride, ethylene chloride and many unsaturated hydrocarbons. Immiscible with many saturated hydrocarbons (petroleum fractions). Dissolves some in organic salts, e.g., silver nitrate, lithium nitrate, magnesium bromide. Constant boiling mixture with water contains 16% H20 and bp 76°. LD50 orally in rats: 3800 mg/kg (Smyth). USE: In organic synthesis as starting material for aceto- phenone, a -naphthaleneacetic acid, thiamine, acetamidine. To remove tars, phenols, and coloring matter from petroleum hydrocarbons which are not soluble in acetonitrile. To extract fatty acids from fish liver oils and other animal and vegetable oils. Can be used to recrystallize steroids. As an indifferent medium in physicochemical investigations. Wherever a polar solvent having a rather high dielectric constant is required. As medium for promoting reactions involving ionization. As a solvent in non-aqueous titrations. As a non-aqueous solvent for inorganic salts. Caution: Avoid breathing vapors. May cause skin irritation. 63. Acetonylacetone. 2,5-Hexanedione; a,/3-diacetyl- ethane. C6H10O2; mol wt 114.14. C 63.13%, H 8.837c O 28.03%». CH3COCH?CHjCOCH3. Prepn by decarboxylation of diacetosuccinic ester (from sodium acetoacetic ester and iodine): Paal, Ber. 18, 58 (1885); Knorr, Ber. 22, 2100 (1889); by hydrolysis of 2,5-dimethylfuran: Perkins, Tou- ssaint, U.S. pat. 2,052,652 (1936 to Union Carbide). Toxicity data: H. F. Smyth, C. P. Carpenter, J. Ind. Hyg. Toxicol. 26, 269 (1944). Liquid, gradually turns yellow. d|° 0.970. mp —9°. bp 188°, n{J> 1.449. Misc with water, alcohol, ether. LD50 orally in rats: 2.7 g/kg (Smyth, Carpenter). Consult the cross index before using this section. Page 11

Acetylcarnitine 78 CH2OCOCH3 Needles from acetone. Becomes opaque at about 80° or on prolonged standing, mp 184-185°. Very slightly sol in ether, in pentane; sol in chloroform, toluene. The esterified keto group is relatively stable to the action of chromic acid in cold and to such reducing agents as potassium iodide or zinc. On heating with aluminum isopropoxide in isopropyl alcohol it is reduced to 5-pregnene-3,20,21-triol. therap CAT: Anti -inflammatory. 71. Acetozone. Acetyl benzoyl peroxide; benzoyl acetyl peroxide; benzozone. C9H804; mol wt 180.15. C 60.00%, H 4.48%, O 35.52%. Prepd from benzaldehyde and acetic anhydride in the presence of O-contg gas and dibenzoyl peroxide: Carruthers, U.S. pat. 1,985,886 (1935 to Carbide & Carbon Chemicals); Appell, U.S. pat. 3,397,245 (1968 to Koppers). 6 5 -0 —O —CCH, Crystals, mp 36-37°. bp19 130°. Decomposes on contact with moisture or in a warm place. Soluble in carbon tetrachloride, chloroform, ether, oils. Marketed as a mixture with an equal part of an absorbent powder. Incompat. Water, alkalies, heat. USE: Germicide; in bleaching of flour and food oils. Caution: Strong oxidizing agent. Can cause severe skin burns. 72. Acetrizoate Sodium. 3-(Acetylamino)-2,4,6-triio- dobenzoic acid sodium salt; 3-acetamido-2,4,6-triiodobenzoic acid sodium salt; acetrizoic acid sodium salt; Acetiodone; Bronchoselectan; Cystokon; Diaginol; Iodopaque; Pyelo- kon-R," Salpix; Thixokon; Tri-Abrodil; Triopac; Triurol; Urokon Sodium; Vesamin; Visotrast. C9H5I3NNa03; mol wt 578.90. C 18.67%, H 0.87%, I 65.77%, N 2.42%, Na 3.97%, 0 8.29%. Prepn: Wallingford et al, J. Am. Chem. Soc. 74, 4365 (1952); Wallingford, J. Am. Pharm. Assoc, Sci. Ed. 42, 721(1953). Toxicity data: J. O. Hoppe et al, J. Pharmacol. Exp. Ther. 116, 394 (1956). COONa NHCOCH. Not isolated from soln. Marketed as a sterile 30% aq soln, d about 1,200, pH between 4.8 and 5.2. The free acid is a white powder, decompn 278-283°. Sol in alcohol. Solubility in water at 25°: 94.2 g/100 ml. Very slightly sol in chloroform. Practically insol in benzene. LD50 in rabbits, cats, dogs (mg/kg): 5200, 5600, 6300 i.v. (Hoppe). Opacoron is a mixture of acetrizoate sodium and meglumine acetrizoate, q.v. therap CAT: Diagnostic aid (radiopaque medium). 73. Acetulan®. Acetylated lanolin alcohols. Prepn: Conrad, Motiuk, /. Soc. Cosmet. Chem. 6, 344 (1955); eidem, U.S. pat. 2,725,334 (1955 to American Cholesterol Prod.). Pale yellow, practically odorless liquid. Sp gr at 25°: 0.867. Neutral to litmus. Acid no. 0.35. Hydroxyl no. 2.0. Saponification no. 190.0. Hydrophobic, practically insol in water with no emulsification. Miscible with mineral oil, castor oil, vegetable oils, isopropanol, 95% ethanol, isopropyl myristate, isopropyl palmitate, butyl stearate. USE: In cosmetic formulations and shampoo. 74. Aceturic Acid. N-Acetylglycine; acetamidoacetic acid; acetylaminoacetic acid; acetylglycocoll; ethanoylami- noethanoic acid. C4H7N03; mol wt 117.10. C 41.02%, H 6.03%, N 11.96%, O 40.99%. CH3CONHCH2COOH. Prepd by warming glycine with a slight excess of acetic anhydride in benzene: Radenhausen, J. Prakt. Chem. [2] 52, 437 (1895); by warming glycine in glacial acetic acid with the stoichiometric amount of acetic anhydride: Dakin, J. Biol Chem. 82, 443 (1929). Long needles from water, mp 206-208°. K at 25° = 2.3 X 10"4. Sol in water at 15° = 2.7%. Moderately soluble in alcohol. Slightly sol in acetone, chloroform, glacial acetic acid. Practically insol in ether, benzene. Forms stable salts with organic bases. 75. Acetylacetone. 2,4-Pentanedione; diacetylmethane. C5Hs02; mol wt 100.11. C 59.98%, H 8.06%, O 31.96%. CH3COCH2COCH3. Made by the action of sodium on ethyl acetate and acetone or by the action of anhydrous aluminum chloride on acetyl chloride in the presence of an inert solvent: Combes, Compt. Rend. 103, 814 (1886); Ann. Chim. (Paris) 12, 199 (1887); Claisen, Ber. 38, 695 (1905); Hunt, U.S. pat. 2,737,528 (1956 to Shawinigan Chem.); Georgieff, U.S. pat. 2,834,811 (1958); Gattermann-Wieland, Praxis des Organischen Chemikers (de Gruyter, Berlin, 40th ed, 1961) p 219. Colorless or slightly yellow, flammable liquid; pleasant odor, d 0.976. bp 140.5°. mp — 23°. ng 1.4512. One part dissolves in about 8 parts of water. Miscible with alcohol, benzene, chloroform, ether, acetone, glacial acetic acid. LC50 (4 hrs) in rats: 1000 ppm: Carpenter, J. Ind. Hyg. Toxicol 31, 343 (1949). USE: Forms organometallic complexes which are used as gasoline additives, lubricant additives, driers for varnishes and printer's inks, fungicides, insecticides, colors. Caution: Mild irritant to skin, mucous membranes. 76. Acetyl Bromide. C2H3BrO; mol wt 122.96. C 19.54%, H 2.46%, Br 64.99%, O 13.01%. CH3COBr. Prepd from phosphorus tribromide and glacial acetic acid or acetic anhydride: Burton, Degering, J. Am. Chem. Soc. 62, 227 (1940). Fuming liquid; irritating to the eyes, bp 76°. d9 1.52. mp — 96°. Violently decomposed by water, or by alcohol; miscible with ether, chloroform, benzene. Protect from water. 77. a-Acetylbutyrolactone. 3-Acetyldihydro-2(3H)- furanone; a-(2-hydroxyethyl)acetoacetic acid 7-lactone; a-acetyl-7-hydroxybutyric acid 7-lactone; a-acetobutyro- lactone. C6Hs03; mol wt 128.12. C 56.24%, H 6.29%, O 37.46%. Prepn from sodium acetoacetate and ethylene oxide in abs alcohol: Knunyantz et al, Compt. Rend. Acad. Sci. (U.R.S.S.) [N.S.] 1, 312 (1934), C.A. 28, 4383 (1934); Feo- filaktov, Onishchenko, J. Gen. Chem. USSR 9, 304 (1939), C.A. 34, 378 (1940); Forman; Johnson, U.S. pats. 2,397,134 and 2,443,827 (1946, 1948, both to U.S. Industrial Chemicals); see also Matukawa et al, Japan, pat. 134,284; C.A. 35, 7421 (1941). COCH. Liquid; ester-like odor. Solubility in water 20% v/v; soly of water in lactone 12% v/v. df 1.1846; dg 1.185-1.189; bp30 142-143°; bp18 130-132°; bp5 107-108°. n§ 1.4562 (Knunyantz et al); njj 1.4590 (Feofilaktov et al). Acquires a blue to bluish-purple color when in contact with iron. use: In synthesis of 3,4-disubstituted pyridines; of 5-(/3- hydroxethyl)-4-methylthiazole. Caution: Irritating to skin, mucous membranes. 78. Acetylcarnitine. 2-(Acetyloxy)~3-carboxy-N,NfN- trimethyl-1-propanaminium hydroxide inner salt; (3-carb- oxy-2-hydroxypropyl)trimethylammonium hydroxide inner salt acetate; carnitine acetyl ester; vitamin BT acetate. C9H17N04; mol wt 203.24. C 53.19%, H 8.43%, N 6.89%, O 31.49%. (CH3)3N + CH2CH(OCOCH3)CH2COO-. O-Acetyl deriv of carnitine, q.v. Prepn of racemate: R. Engeland, Ber. 42, 2457 (1909); of L-form: R. Krimberg, W. Wittandt, Consult the cross index before using this section. Page 13

Acetylpheneturide 94 dibromoethylene; sym-dibromoethylene. C2H2Br2; mol wt 185.87. C 12.92%, H 1.09%, Br 85.99%. BrCH=-CHBr. Prepd by reaction of tetrabromoethylene with Zn and ale followed by sepn of cis- and Trans-forms by fractional distillation: Noyes et al, J. Am. Chem. Soc. 72, 33 (1950). Liquid, gradually decomposed by air, moisture, or light. dj7 2.21. n$ 1.5428. Practically insol in water; sol in many organic solvents. LD50 in rats: 117 mg/kg orally. ds-Form, ri$ 1.5370. rrans-Form, n^5 1.5440. Caution: Narcotic in high conens. 86. Acetylene Dichloride. 1,2-Dichloroethene; l,2-di~ chloroethylene; sym-dichloroethylene; Dioform. C2H2C12; mol wt 96.95. C 24.78%, H 2.08%, CI 73.14%. C1CH = CH- Cl. Prepn: Bordner, U.S. pat. 2,504,919 (1950 to du Pont). Prepn of irans-form: Adler, U.S. pat. 2,440,997 (1948 to Stockholms Superfosfot Fabriks Aktiebolag). Sepn of cis- and trans-forms by fractional distillation: Wood, Dickinson, /. Am. Chem. Soc. 61, 3259 (1939); Johnsen, Fitzpatrick, Rec. Trav. Chim. 70, 823 (1951); Truce, Barney, J. Org. Chem. 27, 128 (1962). Toxicity: D. Gradiski et al, Eur. J. Toxicol. 7, 247 (1974); K. J. Freundt et al, Toxicology 7, 141 (1977). Review: V. L. Stevens in Kirk-Othmer Encyclopedia of Chemical Technology, Vol. 5 (Wiley -Interscience, New York, 3rd ed., 1979) pp 742-745. Liquid; ethereal, slightly acrid odor; gradually decom- and moisture, forming HC1. d about Insol in water. Sol in ale, ether and -2150 posed by air, light 1.28. bp about 55° most other organic solvents. LDS0 i.p. in mice: mg/kg (Gradiski). ds-Form, mp —81.5°. bp745 59.6°, bp760 60°. njf 1.4435. rrans-Form, mp —49.4°. bp745 47.2 to air oxidation. LD50 in rats (ml/kg): Noticeably subject 1.0 orally; 60 i.p.; in mice (ml/kg): 3.2 i.p. (Freundt). Caution: May cause respiratory irritation, narcosis: Patty's Industrial Hygiene & Toxicology Vol. 2B, G. D. Clayton, F. E. Clayton, Eds. (Wiley-Interscience, New York, 3rd ed., 1981) pp 3550-3553. USE: Solvent for fats, phenol, camphor, etc. 87. Acetyleneurea. Tetrahydroimidazo[4,5-d]imida- zole-2,5-(lH,3H)-dione; glycoluril; acetylenediureine; glyox- aldiureine; acetylene carbamide. C4H6N402; mol wt 142.12. C 33.80%, H 4.26%, N 39.42%, O 22.52%. Prepd by the sodium amalgam reduction of allantoin; Biltz, Schiemann, /. Prakt. Chem. 113, 77 (1926); from glyoxal and urea: Reibnitz, U.S. pat. 2,731,472 (1956 to BASF). Crystals, dec at about 300". Slightly sol in cold, more sol in hot water; sol in warm mineral acids, warm ammonia. 88. Acetyl Iodide. C2H3IO; mol wt 169.96. C 14.13%, H 1.78%, I 74.68%, O 9.41%. CH3COI. Prepd from acetyl chloride and HI: Gustus, Stevens, J. Am Chem. Soc. 55, 374 (1933). Liquid; suffocating odor; fumes and turns brown in air. bp 108°, bp735 104-106°; dj° 2.0674; ng> 1.5491. Dec by water or alcohol; sol in benzene, ether. Keep tightly closed and protected from light. Caution: A strong irritant. Avoid contact with skin. Vapors can cause pulmonary edema. 89. Acetylleucine Monoethanolamine. N-Acetyl-DL- leucine compound with 2-aminoethanol (1:1); monoethanolamine DL-acetylleucinate; DL-acetylleucine monoethanolamine salt; monoethanolamine salt of a-acetamidoisocaproic acid; RP 7452; Tanganil. C,0H22N2O4; mol wt 234.29. C 51.26%, H 9.46%, N 11.96%, O 27.32%. Prepn: Gailliot et al, U.S. pat. 2,941,924 (1960 to Rhone-Poulenc). (CH3)2CHCH2CHC0OH,H2NCH2CH20H NHCOCH3 Crystals, mp about 150°. Soly in water: > 20%; slight soly in alcohol: ~1%. pH of 10% aq soln: about 6. therap CAT: Antivertigo agent. 90. W-Acetylmethionine. C7H13no3S; mol wt 191.26. C 43.96%, H 6.85%, N 7.33%, O 25.10%, S 16.77%. CH3S- CH2CH2CH(NHCOCHj)COOH. Prepn of racemic mixture: Wheeler, Ingersoll, J. Am. Chem. Soc. 73, 4604 (1951); Cal- lanan, Patton, U.S. pat. 2,745,873 (1956 to Distillers Products). Resolution: Wheeler, Ingersoll, loc. cit.; Gillingham, U.S. pat. 3,028,395 (1962 to Parke, Davis); Tullar, U.S. pat. 3,056,799 (1962 to Sterling Drug); Brit. pat. 1,072,876 (1967 to Tanabe Seiyaku), CA. 67, 114015x (1967). DL-Form, Methionamine. Crystals from water, mp 114- 115°. D( + )-Form, crystals from water or ethyl acetate, mp 104-105°. [o]g +20.3° (c - 4 in water). l( — )-Form, crystals, mp 104°. [a]g —20.3°. THERAP CAT: DL-Form as lipotropic. 91. 5 -Acetyl -2 -methoxybenzaldehyde. 3 -Acetyl -6 - methoxybenzaldehyde. C10Hl0O3; mol wt 178.18. C 67.40%, H 5.66%, O 26.94%. A natural plant growth inhibitor found in the leaves of Encelia farinosa A. Gray, Compositae. Isoln and synthesis from 3-acetyl-6-methoxybenzonitrile: Gray, Bonner, J. Am. Chem. Soc. 70, 1249 (1948). CH0 COCH. Needles from alcohol or ether, mp 144°. Sublimes without decomp. Emits fragrant odor on prolonged heating. Sol in hot water, warm ether, alcohol, benzene, chloroform; practically insol in cold water, 5% HC1, 5% NaOH, petr ether, carbon tetrachloride; sol with orange color in coned mineral acids. 92. Acetyl Nitrate. Acetic acid anhydride with nitric acid. C2H3N04; mol wt 105.05. C 22.87%, H 2.88%, N 13.33%, O 60.92%. CH3COON02. Prepn from acetic anhydride and N2Os: Boh, Annates de Chimie [11] 20, 437 (1945). Fuming, mobile, hygroscopic liquid. Should be colorless. d]5 1.24. bp70 22°. Although it may be stored in the dark over P2Os for the weekend, it should be used in statu nascen- di to avoid explosions. Always explodes when heated sud - denly over 60° or when in contact with HgO. Explosions have occurred upon contact with ground glass surfaces: K6- nig, Angew. Chem. 67, 157 (1955). USE: In nitrations, especially to introduce a single nitro group in an ortho position on an aromatic ring. Caution: Irritant, corrosive. 93. N-Acetylpenicillamine. N-Acetyl-3-mercapto-D - valine. C7Hl3N03S; mol wt 191.25. C 43.96%, H 6.857c N 7.337c O 25.10%, S 16.76%. Prepn: Crooks in The Chemistry of Penicillin (Princeton Univ. Press, 1949) p 470; Sheehan et al, U.S. pats. 2,477,148 and 2,496,416 (1949, 1950, both to Merck & Co.). CH, ch3c CHCOOH SH NHCOCH, a7-Form, crystals from hot water, mp 183°. d-Form, crystals from water, mp 189-190° (50% ethanol). MS 25 94. Acetylpheneturide. N-[(Acetylamino)carbonyl]-a - ethylbenzeneacetamide; l-acetyl-3-(2~phenylbutyryl)urea; iV-(a-ethylphenylacetyl)-iV'-acetylurea; Crampol. C13H]6- mol wt 248.27. C 62.897c H 6.50%>, N 11.287c O N2Q3; Consult the cross index before using this section. Page 15

Aclacinomycins 108 volatile oil may vary depending on origin of plant. Identification of constituents: Pailer, Kump, Monatsh. 90, 395 (1959); eidem, Arch. Pharm. 293, 646 (1960); A. J. Falk et al, J, Nat. Prod. 37, 598 (1974); R. F. Chandler et al, J. Pharm. Sci. 71, 690 (1982). Isoln of anti-inflammatory constituents: A. S. Goldberg, J. Pharm. Sci. 58, 938 (1969). Phytopharmacology: J. P. Tewari et al, Ind. J. Med. Set 28, 331 (1974). Review of medicinal uses and composition: R. F. Chandler et al, Econ. Bot. 36, 203-223 (1982). 103. Acid Fuchsin. 2-Amino-5~[(4~amino-3-sulfo- phenyl)(4-imino-3-sulfo-2,5-cyclohexadien-l-ylidene)meth- yl]-3-methylbenzenesulfonic acid disodium salt; C.I. Acid Violet 19; C.I. 42685; 2-amino-a5-(4-amino-3-sulfophenyl)- as-(4-imino-3-sulfo-2,5-cyclohexadien-l -ylidene)-3,5-xy- lenesulfonic acid disodium salt; acid magenta; acid rubin; fuchsin(e) acid; acid roseine. C20H17N3Na2O9S3; mol wt 585.54. C 41.02%, H 2.93%, N 7.18%, Na 7.85%, O 24.59%, S 16.43%. The trisulfonic acid disodium salt of magenta I, q.v. Prepn: Colour Index vol. 4 (3rd ed., 1971) p 4399. Brief review: H. J. Conn's Biological Stains, R. D. Lillie, Ed. (Williams & Wilkins, Baltimore, 9th ed., 1977) pp 285-286. NaOgS S03Na Olive to dark olive-green coarse powder. Absorption max: 540-545 nm (10 mg/1 of 0.01% HC1). One gram dissolves in 7 ml water. Slightly sol in ale. Dil aq solns are purplish red. Very dil aq solns (-1:10,000) are decolorized by drops of coned aq NaOH solns, but not returned by coned HC1. The decolorized soln neutralized with NaOH is called the Andrade indicator. Changes from red to colorless at pH 12-14. USE: As pH indicator; biological stain. 104. Acid Violet 7B. N-[4-[Bis[4-[ethyl(3-sulfophenyl)- amino]phenyl]tnethylene]-2,5-cyclohexadien-l-ylidene]-N- methylmethanaminium hydroxide inner salt monosodium salt; C.I. Acid Violet 25; C.I. 42745. C37H36N3Na06S2; mol wt 705.81. C 62.96%, H 5.14%, N 5.95%, Na 3.26%, O 13.60%, S 9.09%. Prepd by sulfonation of the condensation product from p-dimethylaminobenzoyl chloride with N- ethyldiphenylamine: Miiller, Ger. pat. 34,463; Frdl. 1, 88; U.S. pat. 353,266; Turnbull, Evans, U.S. pat. 1,402,195. See also: Colour Index vol. 4 (3rd ed., 1971) p 4401. SO Na (CH3)2N Violet powder. Sol in water, alcohol with deep blue color and violet tinge. Insol in ether. Absorption max (water): 607.5 nm. USE: As dye; in inks and stains. 105. Acifluorfen. 5-[2-Chloro-4-(trifluoromethyl)~ phenoxy]-2-nitrobenzoic acid. C14H7ClF3NOs; mol wt 361.66. C 46.49%, H 1.94%, CI 9.82%, F 15.76%, N 3.87%, O 22.12%. Selective pre- and post-emergence herbicide. Prepn: H. O. Bayer et al, Ger. pat. 2,311,638 corresp to H. O. Bayer, R. Y. Yih, U.S. pats. 3,928,416, 4,063,929 (1973, 1975, 1977, all to Rohm & Haas). Synthesis and activity: W. O. Johnson et al., J. Agr. Food Chem. 26, 285 (1978). COOH Off-white solid, mp 151.5-157°. Sodium salt, C14H6CIF3NNaOs, RH 6201, scifluorfen, Blazer. White powder, mp 124-125°. Soly in water > 25%. LD50 orally in rats: 1300 mg/kg, W. O. Johnson et al, loc. cit. USE: Herbicide. Caution: Skin and eye irritant. "Do not incorporate in soil. Do not mix with oils, surfactants, liquid fertilizers or other pesticides". 106. Acipimox. 5-Methylpyrazinecarboxylic acid 4- oxide; 2-carboxy-5-methylpyrazine 4-oxide; K 9321; Olbe- mox; Olbetam. C6H6N203; mol wt 154.13. C 46.76%, H 3.93%, N 18.17%, O 31.14%-- Prepn: V. Ambrogi et al, Ger. pat. 2,319,834; eidem, U.S. pat. 4,002,750 (1973, 1977 both to Carlo Erba). Prepn and toxicology: eidem, Eur. J. Med. Chem. 15, 157 (1980). Pharmacological profile: P. P. Lovi- solo et al, Pharmacol Res. Commun. 13, 151, 163 (1981). Pharmacokinetics: L. M. Fuccella et al, Clin. Pharmacol Ther. 28, 790 (1980); L. Musatti et al, J. Int. Med. Res. 9, 381 (1981). Mechanism of action: K. Aktories et al, Arz- neimittel-Forsch. 33, 1525 (1983). N. H3C'/^N' COOH O Crystals from water, mp 177-180°. LD50 orally in mice: 3500 mg/kg (Ambrogi). THERAP CAT: Antihyperlipoproteinemic. 107. Acitretin. (all-E)-9-(4-Methoxy-2,3,6-trimethyl- phenyl)-3f7-dimethyl-2,4,6,8-nonatetraenoic acid; etretin; Ro 10-1670; Neotigason; Soriatane. C21H2603; mol wt 326.44. C 77.27%, H 8.03%, O 14.70%. Synthetic retinoid; free acid form and major metabolite of etretinate, q.v. Prepn: W. Bollag et al, Ger. pat. 2,414,619; eidem, U.S. pat. 4,105,681 (1974, 1978 both to Hoffmann-La Roche). Teratogenicity study: A. Kistler, H. Hummler, Arch. Toxicol. 58, 50 (1985). HPLC determn in plasma: N. R. Al-Mallah et al, Anal. Letters 21, 1603 (1988). Pharmacokinetics in humans: F. G. Larsen et al, Pharmacol Toxicol 62, 159 (1988). Clinical evaluation in cutaneous lupus erythematosus: T. Ruzicka et al, Arch. Dermatol 124, 897 (1988). Review of clinical pharmacology: A. Vahlquist, O. Rollman, Dermato- logica 175, Suppl. 1, 20-27 (1987). Review of clinical studies in psoriatic and nonpsoriatic dermatoses: J.-M. Geiger, B. M. Czarnetzki, ibid. 176, 182-190 (1988). H-.C CH.O COOH Crystals from hexane, mp 228-230°. LD50 i.p. in mice (mg/kg): >4000 (1 day), 700 (10 days), 700 (20 days) (Bollag, 1978). THErAP CAT: Antipsoriatic. 108. Aclacinomycins. Antitumor antibiotic complex of the anthracycline group, produced by Streptomyces galilaeus. Thirteen yellow and seven red-colored components have been identified. Isoln of the major components, aclacinomycins A and B: H. Umezawa et al, Ger. pat. 3,532,568 corresp to U.S. pat. 3,988,315 (1974, 1976 both to Microbio- chem. Res. Found.). See also: T. Oki et al, J. Antibiot. 28, 830 (1975). Structure, taxonomy, production, properties: Consult the cross index before using this section. Page 17

Acridine 117 tubers of Aconitum napellus L., Ranunculaceae, in various species of Achillea (Compositae) and Equisetum (Equiseta- ceae), in beet root, and in sugar cane. Can be prepd commercially from calcium magnesium aconitate recovered from sugar cane juice: McCalip, Seibert, Ind. Eng. Chem. 33, 637 (1941); from molasses: Regna, Bruins, ibid. 48, 1268 (1956). Most of the commercial aconitic acid is, however, manufactured by sulfuric acid dehydration of citric acid: Bruce, Org. Syn. coll. vol. II, p 12 (1943); by using methanesulfonic acid instead of sulfuric: Cranston, U.S. pat. 2,727,066 (1955 to Daniel F. Kelly). Aconitic acid prepd by any of the above methods has the rrans-configuration which is the form described here. HOOC COOH CHgCOOH Leaflets, plates from water. Decompn 198-199° (capillary inserted in oil bath at 190°); decompn 204-205° (capillary in oil bath at 195°); decompn 209° (electrically heated bar). K^ at 25° = 1.58 X 10"3; K2 = 3.5 X 105. One gram dissolves in 5.5 ml water at 13°, in 2 ml water at 25". Soluble in 2 parts of 88% alcohol at 12°. Slightly sol in ether. Triethyl ester, bps 155°. Tributyl ester, bp3 190°. USE: Manuf itaconic acid. As plasticizer for buna rubber and plastics. Used in form of triethyl or tributyl ester. 113. Aconitine. (la,3at6a,14a,15aJ6{3)-20-Ethyl-l,6,- 16-trimethoxy-4-(methoxymethyl)aconitane-3,8,13,14,15- pentol 8-acetate 14-benzoate. C^H^NO,,; mol wt 645.72. C 63.24%, H 7.34%, N 2.17%, O 21.26%. Several isomers from Aconitum napellus L., Ranunculaceae and other aconites. Majima et al, Ber. 57, 1456 (1924); Proc. Imp. Acad. Tokyo 5, 415 (1929); Freudenberg, Ber. 69, 1964 (1936); Swanson et al, Aconite, A. Ph. A. Monograph no. 1 (1938); Methods of Analysis, A.O.A.C., 8th ed., 598, 651 (1955). Structure: Wiesner et al. Coll. Czech. Chem. Commun. 28, 2462 (1963); Wiesner et al. Can. J. Chem. 47, 2734 (1969). Stereochemistry: Bachelor et al, Tetrahedron Letters 1960, no. 10, 1; Gilman, Marion, ibid. 1961, 923; Tsuda, Marion, Can. J. Chem. 41, 1634 (1963); Birnbaum et al, Tetrahedron Letters 1971, 867. Toxicity: Dybing et al, Acta Pharmacol Toxicol. 7, 337(1951). OCOCgHc CH3CR2 Hexagonal plates, mp 204°. [a]D +17.3° (chloroform). Aq soln is alkaline to litmus. pK 5.88. K 1.3 X 10"6. One gram dissolves in 2 ml chloroform, 7 ml benzene, 28 ml abs alcohol, 50 ml ether, 3300 ml water. Slightly sol in petr ether. Poisonous! LD50 in mice (mg/kg): 0.166 i.v.; 0.328 i.p.; approx 1 orally (Dybing). Hydrobromide hemipentahydrate, C^H^BrNOjj.2^1-120, hexagonal tablets from water, mp 200-207° (sinters at 160°). Amorphous form mp 115-120°. Also crystallizes from ethane-] -f ether with !^H20, mp 206-207°; [a]D —30.8°. Violent poison! Ref: Paech, Tracey, Modern Methods of Plant Analysis vol. IV (Springer-Verlag, Berlin, 1955) p 375. Hydrochloride hemipentahydrate, C34H48C1N01].21/^H20, crystals, mp 149-153°. mp 194-5° (dry). [o]D—30.9°. Violent poison! Ref: Paech, Tracey, loc. cit. Nitrate, C^H^N^^, crystals, mp about 200° (dec). [a]jj — 35° (c = 2 in water). Violent poison! One gram dissolves in 10 ml boiling water. Less sol in cold water. Sol in alcohol. USE: Used in producing heart arrhythmia in experimental animals: Boyadzhiev, CA. 73, 86256e (1970). therap cat: Antipyretic. 114. Aconitine, Amorphous. Mild aconitine. Mixture of amorphous alkaloids from Aconitum napellus L., Ranunculaceae. Contains aconitine, mesaconitine, hypaconitine, neopelline, /-ephedrine, sparteine, neoline and napelline. Ref: Rogers, Freudenberg, Ber. 70, 349 (1937); eidem, J. Am. Chem. Soc. 59, 2572 (1937). Yellowish-white, amorphous powder. Violent poison! Insol in water; sol in alcohol, chloroform, ether, dil acids. MLD s.c. in rats: 0.175 mg/kg, Handbook of Toxicology Vol. 1, W. S. Spector, Ed. (Saunders, Philadelphia, 1956) PP 12-13. Caution: A highly toxic alkaloid. Can be absorbed through skin. 115. Aconitum Ferox. Indian aconite; bish; visha; bish- ma; bikhroot. Tuber of Aconitum. ferox Wall., Ranunculaceae. Habit. Nepal, Himalaya Mountains, India. Constit. Pseudoaconitine, q.v. Most powerful of all the aconites. Used by natives as arrow poison in big game hunting; in neuralgia and rheumatism. Ref: Aconite, A. Ph. A. Monograph no. 1, p 78 and passim (Am. Pharm. Assoc, Washington, D.C., 1938); N. B. Dutt, Indian J. Pharm. 1, 81-84 (1939); CA. 34, 6768 (1940). Caution: Extremely toxic. A very small dose can cause fatal cardiac depression. 116. Acranil. l-[(6-Chloro-2-methoxy-9-acridinyl)- amino]-3-(diethylamino)-2-propanol dihydrochloride; 5 -[(>- diethylamino -(3 -hydroxypropyl)amino] -3 -methoxy -8 -chlo - roacridine dihydrochloride; SKF 16214-A2; SN 186. C21- H28C13N302; mol wt 460.82. C 54.74%, H 6.12%, CI 23.08%, N 9.12%, O 6.94%. Prepn: Mietzsch, Mauss, Ger. pat. 553,072, Frdl 19, 1167; Brit. pat. 363,392; U.S. pat. 2,113,- 357 (1930, 1930, 1938 all to I. G. Farben.); Maghidson, Grigorovski, Ber. 69, 396 (1936); J. Gen. Chem. (USSR) 6, 806 (1936). Antiviral activity: T. E. Glaz et al, Antimicrob. Ag. Chemother. 3, 537 (1973). Interferon induction and radioprotective activity: T. E. Glaz, M. Talas, Arch. Virol 48, 375 (1975); M. Talas, E. Szolgay, ibid. 56, 309 (1978). OH CH2CHCH2N(C2H5)2 OCH, .2HC1 Bitter, yellow crystals, mp 237-239° (dec). Sol in water. Free base, C21H26C1N302, yellow crystals, mp 105-107°. Sparingly sol in ether. THERAP CAT: Antiprotozoal (Giardia). 117. Acridine. Dibenzo[6,e]pyridine; 10-azaanthra- cene. C13H9N; mol wt 179.21. C 87.12%, H 5.06%, N 7.82%. Occurs in coal tar. Isoln: Graebe, Caro, Ann. 158, 265 (1871); from high boiling tar oils: Wirth, Ger. pat. 440,771 (1926). Prepn from iV-phenylanthranilic acid: Per- kin, Clemo, Brit. pat. 214,756 (1923); from Ca -anthranilate: Koller, Krakauer, Monatsh. 50, 51 (1928); by passing benz- ylaniline vapor over red-hot platinum wire: Meyer, Hof- mann, ibid. 37, 698 (1916); cf Ullmann, Ber. 40, 2521 (1907). Absorption spectrum: Pinnow, J. Prakt. Chem. [2] 66, 276 (1902). Toxicity: S. D. Rubbo, Brit. J. Exp. Pathol 28, 1 (1947). Reviews: A. Albert, The Acridines (St. Martin's Press, New York, 2nd ed., 1966); R. M. Acheson, Acridines (Interscience, New York, 2nd ed., 1973). Orthorhombic plates, needles from diluted alcohol. There Consult the cross index before using this section. Page 19

ACTH 127 USE: Manuf colloidal forms of metals; making plastics, perfumes; warning agent in methyl chloride refrigerant. Has been used in military poison gas mixtures. Used in organic syntheses. Aquatic herbicide. dj° 1.122. 123. Acrylamide. 2-Propenamide. C3H5NO; mol wt 71.08. C 50.69%, H 7.09%, N 19.717c O 22.51%. CH2=CHCONH2. Prepd from acrylonitrile by treatment with H2S04 or HCl: Bayer, Angew. Chem. 61, 240 (1949); Weisgerber, U.S. pat. 2,535,245 (1950 to Hercules). Reviews: Carpenter, Davis, J. Appl. Chem, (London) 7, 671 (1957); D. C MacWilliams in Kirk-Othmer, Encyclopedia of Chemical Technology vol. 1 (Wiley -Interscience, New York, 3rded„ 1978) pp 298-311. Toxicity: R. E. Peterson, N. K. Sheth, Toxicol Appl. Pharmacol 33, 142 (1975). Monomer, flake-like crystals from benzene, mp 84.5°. bp2 87°; bp5 103°; bp25 125°. Solubilities in g/100 ml solvent at 30°: water 215.5; methanol 155; ethanol 86.2; acetone 63.1; ethyl acetate 12.6; chloroform 2.66; benzene 0.346; heptane 0.0068. The solid may be stored in a cool, dark place. Readily polymerizes at the mp or under uv light. Commercial solns of the monomer may be stabilized with hydroquinone, rerr-butylpyrocatechol, A/-phenyl-2-naph- thylamine or other antioxidants. LD50 i.p. in mice: 170 mg/kg (Peterson, Sheth). Polymer, various forms, sol and insol in water, are obtained by heating with various polymerization catalysts: C. E. Schildknecht, Vinyl and Related Polymers (Wiley, New York, 1952) pp 314-322. Caution: Highly toxic and irritant. Causes CNS paralysis. Can be absorbed through unbroken skin. 124. Acrylic Acid. 2-Propenoic acid; vinylformic acid. C3H402; mol wt 72.06. C 50.00%, H 5.60%-, O 44.40%. CH2=CHC02H. Prepd by hydrolysis of acrylonitrile: Kaszuba, J. Am. Chem. Soc. 67, 1227 (1945) or by oxidation of acrolein: U.S. pats. 1,911,219 (1933 to Rohm & Haas); 2,288,566 (1942 to Acrolein Corp.); 2,341,339 (1944 to Distillers). Various other syntheses, see Org. Syn. coll. vol. Ill, 30-34 (1955). Review: J. W. Nemec, W. Bauer in Kirk- Othmer Encyclopedia of Chemical Technology vol. 1 (Wiley- Interscience, New York, 3rd ed., 1978) pp 330-354. Corrosive liquid; acrid odor and fumes, d]6 1.0621. mp 14°. bp 141.0°; bp^ 122.0°; bp200 103.3°; bp100 86.1°; bp^ 66.2°; bp10 39.0°; bp5 27.3°. ng> 1.4224.Flash pt, open cup: 155°F (68°C). K at 25° = 5.6 X 105, Miscible with water, ale, ether. Polymerizes readily in the presence of oxygen. LD Hyg. Assoc. J. 23, 95 (1962). use: In the manuf of plastics. Caution: Strong irritant. so orally in rats: 2.59 g/kg, H. F. Smyth et ah, Am. Ind. 125. Acrylonitrile. 2-Propenenitrile; vinyl cyanide; cyanoethylene; Acritet; Fumigrain; Ventox. C3H3N; mol wt 53.06. C 67.90%, H 5.70%, N 26.40%. CH2=CHCN. Prepn by dehydration of ethylene cyanohydrin or acrylamide: Moureu, Ann. Chem. Phys. [7] 2, 186 (1893). Manuf by ammoxidation of propylene: Faith, Keyes & Clark's Industrial Chemicals, F. A. Lowenheim, M. K. Moran, Eds. (Wiley-Interscience, New York, 4th ed., 1975) pp 46-49. Toxicity: H. F. Smyth, C. P. Carpenter, J. Ind. Hyg. Toxicol. 30, 63 (1948). Causes acute and chronic adrenocortical insufficiency: S. Szabo et al, Lab. Invest. 42, 533 (1980); eidem, J. Appl. Toxicol. 4, 131 (1984). Review of carcinogenicity studies: IARC Monographs 19, 73-133 (1979). Comprehensive review and bibliography: The Chemistry of Acrylonitrile (Am. Cyanamid, New York, 2nd ed., 1959) 272 pp; L. T. Groet in Kirk-Othmer Encyclopedia of Chemical Technology vol. 1 (Wiley-Interscience, New York, 3rd ed., 1978) pp 414-426. Explosive, flammable and toxic liquid. Should be stored and used in closed systems whenever possible. Work areas should be adequately ventilated, and should be free from open lights, flames, and equipment that is not explosion- proof. Handle in hood. May polymerize spontaneously, particularly in the absence of oxygen or on exposure to visible light. Polymerizes violently in the presence of concentrated alkali. On standing may slowly develop a yellow color particularly after excessive exposure to light. bp760 77.3°; bp 500 64'7°; bP250 455°' bPlOO S a «nn/i »25 23.6°; bp50 8.7°. mp 83.55°. dj° 0.8060; df 0.8004. ng 1.3888. Flash pt, open cup: 32°F (0°C). Explosive mixtures in air at 25°: 3.05% low limit; 17.0% upper limit. At 20° 7.35 parts dissolve in 100 parts water and 3.1 parts water dissolve in 100 parts acrylonitrile. Miscible with most organic solvents. LDS0 orally in rats: 0.093 g/kg (Smyth, Carpenter). Caution: Highly toxic through cyanide effect; irritating to eyes and skin: Clinical Toxicology of Commercial Products, R. E. Gosselin et al, Eds. (Williams & Wilkins, Baltimore, 5th ed., 1984) Section II, p 215. This substance may reasonably be anticipated to be a carcinogen: Fourth Annual Report on Carcinogens (NTP 85-002, 1985) p 15. USE: Manufacture of acrylic fibers. In the plastics, surface coatings, and adhesives industries. As a chemical intermediate in the synthesis of antioxidants, pharmaceuticals, dyes, surface-active agents, etc. In organic synthesis to introduce a cyanoethyl group. As a modifier for natural polymers. As a pesticide fumigant for stored grain. Experimentally to induce adrenal hemorrhagic necrosis in rats. 126. Actaplanins. A-4696; Kamoran. Complex of glycopeptide antibiotics produced by Actinoplanes missouri- ensis. Six actaplanins (A, Bp B2, B3, Cr G) have been isolated and characterized as having a central peptide core with the amino sugar ristosamine and up to four neutral sugars attached. Isoln: R. L. Hamill et al., Ger. pat. 2,209,018 (1972 to Lilly), CA. 77, 138338n (1972); A. P. Raun, U.S. pat. 3,816,618; R. L. Hamill et al, U.S. pat. 4,115,552 (1974, 1978 to Lilly). Chemical characterization: M. Debo- no et al, J. Antibiot. 37, 85 (1984). 'H NMR studies and structures: A. H. Hunt et al, J. Org. Chem. 49, 635 (1984); eidem, ibid. 641. Growth promotant activity: C. Tsaltos et al, Bull Hellenic Vet. Med. Soc. 33, 139 (1982). Use to increase milk production in ruminants: C. C. Scheifinger, Eur. pat. Appl. 63,491 corresp to U.S. pat. 4,430,328 (1982, 1984 to Eli Lilly). Determn in milk: K. H. Hahne et al, Milch- wissenschaft 39, 473 (1984). Rl R2 Aciaplanin A : B2 = B3: Ci: G : maimosyl glucose rhamnosyl glucose glucose maimosyl glucose rhamnosyl glucose glucose mannose mannose mannose H H H Hydrochloride, white cryst solid, mp > 220°. Approx mol wt 1158. [<x]£ —42.3° (c = 1 in water), uv max (acidic and neutral solns): 276 nm ( E{^, 65). Sol in water. Insol in most organic solvents. Stable over pH 1.0 to 10.0 up to 27°. therap CAT (vet): Growth stimulant. 127. ACTH. Corticotropin; adrenocorticotrop(h)in; corticotrophin; adrenocorticotrop(h)ic hormone of the pituitary gland; Acethropan; Acortan; Acorto; Acthar; Acton; Actonar; Adrenomone; Alfatrofin; Cibacthen; Corstiline; Cortiphyson; Cortrophin; Isactid; Reacthin; Solacthyl; Tubex. Pituitary hormone which stimulates the secretion of adrenal cortical steroids and induces growth of the adrenal cortex. Occurs also in female human urine and in serum of pregnant mares. Isoln procedure from swine pituitaries: Sayers et al, J Biol. Chem. 149, 425 (1943); Proc. Soc. Exp. Biol. Med. 52, 199 (1943); from sheep pituitaries: Li et al, J. Biol. Chem. 149, 413 (1943); Li, J. Am. Chem. Soc. 74, 2124 (1952); from human pituitaries: Pickering et al, Biochim. Biophys. Acta 74, 763 (1963). Purification: Johnson, U.S. Consult the crass index before using this section. Page 21

aqueous solns pH > 7. uv max: 262 nm (0.1 AT HC1); 288 nm (OAN NaOH). LD50 in mice, rats (nig/kg): 800 ±27, 1550 ±26 i.v. (Pittillo). Acetate, C1SH24N208, needles from ethanol; softens at 130°, resolidifies at 145°, melts at 263-266°. [«]f,6 +58°. pKa: 4.6, 7.5, 8.8. Very sol in water; sol in warm methanol, ethanol, acetone; sparingly sol in ethyl acetate, uv max.- 264 nm (pH 7 phosphate buffer). Hydrochloride, C13H2.C1N206, hygroscopic. [a]^2 +59° (c = 0.41) (natural); [ajg +55° (c = 0.47) (synthetic). 131. Actinodaphnine. 6,7,7a,8-Tetrahydro-ll-meth- oxy-5H-benzo[g]-l,3-benzodioxolo[6,5,4-de]quinolin-10-ol; 10-methoxy-l,2-(methylenedioxy)-6aa-noraporphin-9-ol; 1,2-methylenedioxy -9 -hydroxy -10-methoxynoraporphine. C]8H17N04; mol wt 311.32. C 69.44%, H 5.50%, N 4.50%, O 20.56%. In bark of Actinodaphne hookeri Meissn., Laura- ceae. Isoln: Krishna, Ghose, J. Indian Chem. Soc. 9, 429 (1932). Structure: Ghose et al, Helv. Chim. Acta 17, 919 (1934). Photolytic synthesis: M. S. Premila et ah, Indian J. Chem. 13, 945 (1975). Needles from alcohol, mp 211°. [a]g> +33° (ethanol). Sol in acetone, alcohol, benzene, chloroform. Moderately sol in ether. Practically insol in water. Hydrochloride, C18H17N04.HC1, needles from alcohol - ether, mp 281° (dec). [a]D° +9°. Methyl ether, C19H,9N04, needles from ether + ale, mp 114-115°. Synthesis: Hey, Lobo, J. Chem. Soc. 1954, 2246. 132. Actinomycetin. Bacteriolytic cell-free fluid of culture filtrates of actinomycetes. Produced by most species of Streptomyces; studied mostly in Streptomyces albus. Protein- like in nature. Stated to consist of a bactericidal fatty acid fraction and an enzyme: Welsch, J. Bacterial 42, 801 (1941); 44, 571 (1942); 53, 101 (1947). Dissolves dead gram-negative, and, with more difficulty, dead gram-positive organisms. Also dissolves living organisms in aq suspensions, such as Staph, aureus. In answer to the question whether actinomycetin deserves the name "antibiotic", see the polemic between Hoogerheide and Welsch, Bot. Rev. 10, 599 (1944) and J. Bacteriol 53, 101 (1947). Purification and prepn from Streptomyces albus: Ghuysen, Belg. pats. 517,- 191 and 521,114 (both 1953 to Soc. Beige de 1'Azote), C.A. 53, 5600g, 12593e (1959). Review: Caltrider in Antibiotics vol. 1, D. Gottlieb, P. D. Shaw, Eds. (Springer Verlag, New York, 1967) pp 681-683. Sol in water. Pptd by alcohol, acetone, ammonium sulfate and other protein precipitants. Destroyed by strong acid. More stable at pH 10 than at pH 4. Rapidly inactivated by heat, 60-70° destroys activity. 133. Actinomycin Fr Actinomycin KS4; KS4. An antibiotic produced by cultures of actinomycin C-elaborat- ing strains of Streptomyces, such as Streptomyces BOP 476 (NRRL 2580) and Streptomyces chrysomallus (NRRL 2250). Considered to be a derivative of actinomycin C2; amino acid analysis indicates that the prolines present in actinomycin C2 are substituted by sarcosine in actinomycin F,. Production by controlled biosynthesis: Schmidt-Kastner, Naturwiss. 43, 131 (1956); idem, Ann. N.Y. Acad. Sci. 89, 299 (1960); Schmidt-Kastner, Hackmann, U.S. pat. 3,219,544 (1965 to Bayer). therap CAT: Antineoplastic. 134. Actinoquinol. 8-Ethoxy-5-quinolinesulfonic acid. CI1HuN04S; mol wt 253.29. C 52.16%, H 4.38%, N 5.53%, 0 25.28%, S 12.66%. Prepn: Orlov, Bogdanov, J. Appl. Chem. USSR 5, 803 (1932), C.A. 27, 7248 (1933); Ghosh, Roy, J. Indian Chem. Soc. 22, 39 (1945); Doner et ai, Trav. Consult the cross index ins 137 Soc. Pharm. Montpellier 14(3), 152 (1954), C.A. 50, 1011a (1956). so3h Brown needles from water, mp 286-288° (dec). Sol in dil NaHC03. Sodium salt, CnH10NNaO4S, sodium etoquinol, etoquinol sodiumf Corodenin, Uviban. THERAP CAT: Sodium salt as ultraviolet screen. 135. Actinorhodine. C32H260,4; mol wt 634.56. C 60.57%, H 4.13%, O 35.30%. Antibiotic pigment produced by Streptomyces coelicolor, found in woods near Gdttingen, Germany: Brockmann, Pini, Naturwiss. 34, 190 (1947); Brockmann et al., Ber. 83, 161 (1950). Tentative structure: Brockmann, Hieronymus, Ber. 88, 1379 (1955); Brockmann et al, Naturwiss. 49, 131 (1962). Structure: Brockmann, Angew. Chem. 76, 863 (1964); Brockmann et al, Ann. 698, 209(1966). Stereochemistry: Zeeck, Christiansen, Ann. 724, 172 (1969). Biosynthesis and determn of point of dimeriza- tion: C. P. Gorst-Allman et ai, J. Org. Chem. 46, 455 (1981). Fine red needles from dioxane, dec 270°. Absorption max (dioxane): 560, 523 nm. Sol in pyridine, piperidine, tetrahy- drofuran, dioxane, phenol; slightly sol in alcohol, acetic acid, acetone. Red soln with acetone, blue soln with pyridine. Practically insol in aq acid; sol in aq alkali with bright blue color. 136. Actiphenol. 4-[2-(2~Hydroxy-3,5~dimethylphen- yl)-2-oxoethyl]-2,6-piperidinedione; 3-(2-hydroxy-3,5-di- methylphenacyl)glutarimide; /3-(3,5-dimethyl -2-hydroxy- benzoylmethyUglutarimide; C-73. Cl5H17N04; mol wt 275.29. C 65.44%, H 6.22%, N 5.09%, O 23.25%. Metabolic product found in culture filtrates of cycloheximide-producing actinomycetes (Streptomyces albulas): Highet, Prelog, Helv. Chim. Acta 42, 1523 (1959); Rao, J. Org. Chem. 25, 661 (1960). Synthesis: Johnson, ibid. 27, 3658 (1962). May be prepd from cycloheximide: Highet, Prelog, loc. cit. Structure-activity studies: Ennis, Biochem. Pharmacol 17, 1197 (1968). OH O H-jC ' O N ' O H Fluffy needles from methylene chloride + methanol, mp 200-202°. Pure crystals are white or colorless, uv max: 262, 345 nm (e 10,870, 4550). Exhibits bright yellow fluorescence under u.v. Soluble in aqueous NaOH (forming bright yellow solns), in anhydr alcohol, tetrahydrofuran. Insol in aq solns of sodium bicarbonate. Acetate, C17Hl9N05, crystals from methylene chloride + ether, mp 155.5°. 137. Activins. Polypeptide hormone, identified in ovarian follicular fluid, which selectively stimulates secretion of FSH, q.v. Dimer composed of 0 subunits of inhibin, q.v. (either £A or /3B), mol wt 24,000 daltons. Isolation and ehar- Page 23 before using this section.

Adenosine Triphosphate 145 W^-dimethylpteroylglutamic acid. C^H-^NgOg; mol wt 468.48. C 53.84%, H 5.16%, N 23.92%, O 17.08%. Prepn: Hultquist et al, J. Am. Chem. Soc. 71, 619 (1949); Hultquist, Smith, Brit. pat. 667,098 (1952 to Am. Cyanamid). COOH HOOCCH2CH2CHNIlC CII.j N CH ' CII. ;t •N-. ,-N. NH. NH, Dihydrate, yellow-orange microcrystals. uv max (OAN NaOH): 255, 306, 369 nm (e 25,000, 25,000, 9000); (0.1 AT HC1): 244, 316 nm (e 22,000, 14,000). 143. Adenosine. 9-{3-D-Ribofuranosyl-9H-purin-6- amine; 6-amino-9-£-D-ribofuranosyl-9H-purine; 9-/3-D- ribofuranosidoadenine; adenine riboside; Adenocard. CI0- H13Ns04; mol wt 267.24. C 44.94%, H 4.90%, N 26.21%, O 23.95%. Nucleoside; widely distributed in nature. From yeast nucleic acid: Levene and Bass, Nucleic Acids (New York, 1931) p 163. Structure: Levene, Tipson, J. Biol. Chem. 94, 809 (1932); Bredereck, Ber. 66, 198 (1933); Z. Physiol. Chem. 223, 61 (1934); Gulland, Holiday, J. Chem. Soc. 1936, 765. Cf. Szent-Gybrgyi, J. Physiol. 68, 213 (1930); Lythgoe et al, J. Chem. Soc. 1947, 355; 1948, 965. Synthesis: Davoll et al, ibid. 1948, 967; H. Vorbrueggen, K. Krolikiewicz, Angew. Chem. Intl. Ed. 14, 421 (1975). Crystal structure: T. F. Lai, R. E. Marsh, Acta Crystallogr. B28, 1982 (1972). Conformational properties: D. B. Davies, A. Rabczenko, J. Chem. Soc. Perkin Trans. 2 1975, 1703. Symposium on cardiac electrophysiology, pharmacology and clinical efficacy in supraventricular tachycardia: Prog. Clin. Biol. Res. 230, 1-395 (1987). Reviews: see Adenine; Nucleic Acids. Crystals from water, mp 234-235°. [a] J,1 —61.7° (c = 0.706 in water); [o:]^ —58.2° (c = 0.658 in water), uv max: 260 nm (e 15100). Practically insol in alcohol. therap cat: Anti-arrhythmic. 144. Adenosine Diphosphate. Adenosine 5' -(trihydrogen diphosphate); ADP; adenosine 5'-pyrophosphoric acid; 5'-adenylphosphoric acid; adenosinediphosphoric acid. C10H15N5O10P2; mol wt 427.22. C 28.11%, H 3.54%, N 16.39%, O 37.45%, P 14.50%. Formed from ATP in the muscle by the enzyme adenosinetriphosphatase upon stimulation of the muscle unless hydrolysis is prevented by injection of magnesium sulfate. Prepd by hydrolysis of ATP by means of adenosinetriphosphatase from lobster or rabbit muscle: LePage, Biochem. Prepns. I, 1 (1949). Synthesis: Chambers et al, J. Am. Chem. Soc. 82, 970 (1960). See also the ref and data under Adenosine Triphosphate. Barium salt, Ba3(C10H12N5O10P2)2. The purity of the prepns can be checked by analyses for nitrogen, ribose (or- cinol reaction), total phosphorus, easily hydrolyzable phosphorus, and inorganic phosphorus. ADP should give a ratio of 2:1 for total organic phosphorus to easily hydrolyzable phosphorus, see LePage, loc. cit. aM (molar absorbancy of pure ADP): 15.4 X 103 at 259 nm and pH 7.0. 145. Adenosine Triphosphate. Adenosine 5'-(tetrahy- drogen triphosphate); ATP; adenosine 5'-triphosphoric acid; Adephos; Adetol; Atipi; Atriphos; Striadyne; Triadenyl; Triphosaden. C10H16N5O13P3; mol wt 507.21. C 23.68%, H 3.18%-, N 13.81%, O 41.01%, P 18.32%. Coenzyme valuable in the transfer of phosphate bond energy. Mammalian skeletal muscle at rest contains 350-400 mg ATP per 100 g. Upon stimulation of the muscle the ATP is hydrolyzed to ADP by the myosin-actin complex unless hydrolysis is prevented by injection of magnesium sulfate. Isoln from rabbit muscle: LePage, Biochem. Prepn. 1, 5 (1949); cf. Fiske, Subbarow, Science 70, 381 (1929); Lohmann, Biochem. Z. 223, 460 (1931); 254, 381 (1932); Barrenscheen, Filz, ibid 250, 281 (1932); Kerr, J. Biol. Chem. 139, 121 (1941); Need- ham, Biochem. J. 36, 113 (1942). Synthetic routes: Tanaka, Honjo, U.S. pat. 3,079,379 (1963 to Takeda). Reviews of biosynthesis: Racker, Advan. Enzymol 23, 323-399 (1961); Deamer, J. Chem. Ed. 46, 198-206 (1971). Reviews of nucleotide coenzymes: Bock in The Enzymes vol. 2A, P. D. Boyer et al, Eds. (Academic Press, New York, 2nd ed., 1960) pp 3-38; A. M. Michelson, The Chemistry of Nucleosides and Nucleotides (Academic Press, New York, 1963) pp 153-250; D. W. Hutchinson, Nucleotides and Coenzymes (John Wiley, New York, 1964) pp 36-82. NH, N OH OH OH N" HO-P — 0—P-O-P-0 —CH II II It 0 0 0 OH OH Free ATP, isolated as a glass (by treatment of the Ba salt with H2S04 and treating the coned aq soln with acetone). [«]" —26.7° (c = 3.095). aM(molar absorbancy): 15.4 x lO^at 259 nm and pH 7.0. Freely sol in water. A 1% aq soln has a pH of about 2 and is stable at 0° for several hrs. ATP is a tetrabasic acid and after hydrolytic cleavage it is hexabasic. It is usually pptd as the dibarium salt with 4 or 6 mols of water of crystn which can be removed by prolonged drying at 100° over P2Os and in a vacuum. The anhydr salt is stable, but the hydrated salt slowly decomp forming 5'- adenylic acid and barium pyrophosphate. For use the barium salt is converted to the sodium or potassium salt by treatment with sodium or potassium sulfate in HC1 soln. At pH 6.8-7.4 the Na salt is stable in aq soln provided the product is pure. Ba2+ catalyzes breakdown. Injectable solns of the disodium salt are marketed as Trinosin, Adet- phosy Circulen "Kyorin", Atetien. USE: In biochemical research. To inhibit enzymatic Consult the cross index before using this section. Page 25

Adlumidine 154 4H-[l,2,4]triazolo[4,3-a][l y4]benzodiazepine~l-methan~ amine; 8 -chloro -1 -[(dimethylamino)methyl] -6 -phenyl -4H- s-triazolo[4,3-a][l,4]benzodiazepine; U-41123. CI9H18C1N5; mol wt 351.84. C 64.86%, H 5.16%, CI 10.08%, N 19.90%. Triazolobenzodiazepine with antidepressant and anxiolytic properties. Dimethylamino derivative of alprazolam, q.v. Prepn: H. Allgeier, A. Gagneux, Ger. pat. 2,201,210 corresp to Brit. pat. 1,393,256 (1972, 1975 both to Ciba-Geigy); J. B. Hester, Jr., U.S. pat. 4,250,094 (1984 to Upjohn); idem, J. Heterocyclic Chem. 17, 575 (1980). Chromatographic de- termn in human plasma: G. W. Peng, J. Pharm. Sci. 73, 1173 (1984). Pharmacological profile: R. A. Lahti et al, Neuropharmacology 22, 1277 (1983). Biological activity and metabolism: V. H. Sethy et al., J. Pharm. Pharmacol 36, 546 (1984). Use as antipsychotic; R. Lahti, R. E. Pyke, Ger. pat. 3,401,290 corresp to U.S. pat. 4,472,397 (both 1984 to Upjohn). Preliminary clinical study in severe depression: R. E. Pyke et al, Psyehopharmacol Bull 19, 96 (1983). (CH3)2NCI12 C,H5 Crystals from ethyl acetate, mp 171-172.5° (Hester, U.S. pat.). Also reported as mp 165-166° (Allgeier, Gagneaux). Monomethanesulfonate, C20H22ClN5O3S, adinazolam mesylate, Deracyn. Crystals from methanol-ether, mp 230- 244°. therap CAT: Antidepressant. 151. Adiphenine Hydrochloride. a-Phenylbenzeneace- tk acid 2-(diethylamino)ethyl ester hydrochloride; 2-diethyl- aminoethyl diphenylacetate hydrochloride; diphenylacetyldi- ethylaminoethanol hydrochloride; Trasentine hydrochloride; Diphacil hydrochloride; Spasmolytin; Difacil hydrochloride; Patrovina. C20H26ClNO2; mol wt 347.87. C 69.05%, H 7.53%, CI 10.19%, N 4.03%, O 9.20%. Antimuscarinic antispasmodic. Prepd by the action of diphenylacetyl chloride or diphenyl ketene on diethylaminoethanol: Swiss pat. 190,541 (1937 to Ciba); Ger. pats. 626,539; 653,778 (1937). Crystal and molecular structure: Guy, Hamor, J. Chem. Soc. Perkin Trans. II 1973, 942. COOCH2CH2N(C2H5) 2.HC! Crystals, mp 113-114°. Freely sol in water; very sparingly sol in alcohol, ether. A 5% aq soln is neutral to litmus. Methyl bromide, C21H28BrN02, Lunal. LD50 i.v. in rabbits: 22.5-27.5 mg/kg. therap cat: Anticholinergic. 152. Adipic Acid. Hexanedioic acid; 1,4-butanedicarb- oxylic acid. C6H,0O4; mol wt 146.14. C 49.31%, H 6.90%, O 43.79%. HOOC(CH2)4COOH. Found in beet juice. Prepn from cyclohexanol: Bouveault, Locquin, Bull. Soc. Chim. [4] 3,438 (1908); Ellis, Org. Syn. coll. vol. I, 18 (2nd ed., 1941); Feagen, Copenhaver, J. Am. Chem. Soc. 62, 869 (1940); U.S. pats. 2,191,786 (1940); 2,196,357 (1940); Zilberman et al, J. Appl. Chem. (USSR) 29, 621 (1956). Convenient lab prepn from cyclohexanone: L. F. Fieser, Organic Experiments (Heath, Boston, 1964) pp 106-108. Prepn by one-step oxidation of cyclohexane: Onopchenko, Schulz, J. Org. Chem. 38, 3729 (1973); Tanaka, 167th Am. Chem. Soc. Meet. (Los Angeles, March-April, 1974) Abstracts of Papers, p 29. Manuf: Faith, Keyes & Clark's Industrial Chemicals, F. A. Lowenheim, M. K. Moran, Eds. (Wiley-Interscience, New York, 4th ed., 1975) pp 50-54. Review: D. E. Danly, C. R. Campbell in Kirk-Othmer Encyclopedia of Chemical Technology vol. 1 (Wiley-Interscience, New York, 3rd ed., 1978) pp 510-531. Monoclinic prisms from ethyl acetate, from water or from acetone + petr ether, dj5 1.360. mp 152°. bp760 337.5°; bpI00 265°; bp^ 240.5°; bp20 222°; bp10 205.5°; bps 191°; bPl0 159.5°. K, (25°) = 3.90 X 10 5; K2 = 5.29 X 10 6. Absorption spectrum: Ramart-Lucas, Salmon-Legagneur, Compt. Rend. 189, 916 (1929). Freely soluble in methanol, ethanol; sol in acetone. 100 ml of a satd aq soln contains 1.44 g; 100 ml of boiling water dissolves 160 g; 100 parts of ether dissolve 0.633 parts (w/w) at 19°. Slightly sol in cyclohexane. Practically insol in benzene, petr ether. pH of satd aq soln at 25° = 2.7; pH of 0.1% soln = 3.2. Dimethyl ester, C„H1404, liquid, solidifies at 0°, bp,0 112°. Diethyl ester, CI0H|8O4, ethyl adipate. Liquid, bp 240- 245°. d20 1.009. Insol in water; sol in alcohol and many other organic solvents. USE: Manuf artificial resins, plastics (nylon), urethan foams. Used as acidulant in baking powders instead of tartaric acid, cream of tartar, and phosphates because adipic acid is not hygroscopic. As an intermediate in lubricating oil additives. 153. Adipsin. Serine protease homolog synthesized by mammalian adipocytes and secreted into the bloodstream; also produced by sciatic nerve. Dcvelopmentally regulated glycoprotein; mol wt ranges from 37-44 kilodaltons depending on the degree of glycosylation. Circulating levels of adipsin protein are reduced in certain genetic and experimental models of obesity. Originally identified as a 28 kDa protein encoded by a cDNA clone corresponding to messenger RNA specifically induced during adipocyte differentiation: B. M. Spiegelman et al, J. Biol Chem. 258, 10083 (1983). Nucleotide analysis and predicted amino acid sequence: K. S. Cook et al, Proc. Nat. Acad. Sci. USA 82, 6480 (1985). Structure of adipsin gene: H. Y. Min, B. M. Spiegelman, Nucleic Acids Res. 14, 8879 (1986). Isoln from adipose tissue, reportedly the primary site of synthesis, and from sciatic nerve: K. S. Cook et al, Science 237, 402 (1987). Studies in murine obesity models and potential biological role: J. S. Flier et al, ibid. 405. 154. Adlumidine. [S-(R*,R*)]-6-{5,6,7,8-Tetrahydro- 6-methyl-l,3-dioxolo[4f5-g]isoquinolin-5-yl)furo[3,4-e]-l,3- benzodioxol-8(6H)-one. C20H!7NO6; mol wt 367.34. C 65.39%, H 4.66%, N 3.81%, O 26.13%. An alkaloid present in the d-form in the entire plant of Adlumia fungosa (Ait.) Greene (A. cirrhosa Raf.), Corydalis thalictrifolia Franch. and C incisa (Thumb.) Pers., Fumariaceae. Schlotterbeck, Wat- kins, J. Am. Chem. Soc. 25, 596 (1903); R. H. F. Manske, Can. J. Res. 21B, 111 (1943). /-Adlumidine was isolated from Corydalis sempervirens (L.) Pers., C. scouleri Hook., and C. crystallina Engelm., Fumariaceae: R. H. F. Manske, ibid. 8, 407 (1932); 14B, 347 (1936); 17B, 57 (1939). Structure: idem, J. Am. Chem. Soc. 72, 3207 (1950). Stereochemistry: Blaha et al, Coll. Czech. Chem. Commun. 29, 2328 (1964); Snatzke et al, Tetrahedron 25, 5059 (1969). Review: Stanek, Manske in The Alkaloids vol. IV, R. H. F. Manske, H. L. Holmes, Eds. (Academic Press, New York, 1954) pp 167-198. Stereoisomer of bicuculline, q.v. d-adlumldlne Rhombic plates from chloroform + methanol, nip 236- 237°. [a]g +116.2° (c = 22 in chloroform). pKa 4.27. Practically insol in water. Very sparingly sol in alcohol, ether, hexane. /-Adlumidine, capnoidine. Stout prisms from chloroform Consult the cross index before using this section. Page 27

Affinin 167 COCH2NHCH3 Needles, dec 235-236°. Sparingly sol in water, ale, ether. Hydrochloride, C9H12C1N03, Stryphnonasal. Crystals, mp 243°. Freely sol in water; sol in alcohol. Insol in ether. Aq solns are neutral to litmus. THERAP CAT: Hemostatic. 162. Adrenochrome. 2,3-Dihydro-3-hydroxy-l- methyl-1 H~indole-5,6-dione; 3-hydroxy-l-methyl-5, 6- indolinedione. C9H9N03; mol wt 179.17, C 60.33%, H 5.06%, N 7.82%, O 26.79%. Pigment obtained by the oxidation of epinephrine. Prepn using Ag20 as oxidizing agent: MacCarthy, Chim. Ind. Paris 55, 435 (1946). Structure: Green, Richter, Biochem. J. 31, 596 (1937); Harley-Mason, Experientia 4, 307 (1948). Probably has the zwitterionic quinonimine structure shown here. Review; Heacock, Chem. Rev. 59, 181-237 (1959). Review, as a psychotomimetic agent: Heacock, Chim. Ther. 6, 300 (1971). "OH Hemihydrate, brilliant red crystals from methanol-formic acid. Dec 115-120°. Absorption max: 220, 302, 485 nm (EfSi 5-53' 2-45' 0. Well-formed and well-dried crystals can be kept in a vacuum desiccator for several weeks. Easily oxidized to melanin. Freely sol in water; fairly sol in alcohol. Almost insol in benzene and ether. Solns are unstable. Optimum pH of water soln 4.0. Oxime, C9H10N2O3, sesquihydrate, orange needles from water, mp 278°. Much more stable than adrenochrome. Monosemicarbazone, Cl0H12N4O3, carbazochrome, Adren- oxyl, Cromadrenal, Cromosil. Orange-red crystals from dil alcohol, mp 203° (dec). Prepn: Dechamps et al, U.S. pat. 2,506,294 (1950 to Societe" Beige de l'Azote). See also Carbazochrome Salicylate. Thiosemicarbazone, mp 215-220°. Description: Fleisch- hacker, Barsel, U.S. pat. 2,712,024 (1955 to International Hormones). therap CAT: Monosemicarbazone "as hemostatic. 163. Adrenoglomerulotropin. 2,3,4>9-Tetrahydro-6- methoxy-l-methyl-lH-pyrido[3,4-b]indole; aldosterone - stimulating hormone; ASH; 1 -methyl-6-methoxy-l,2,3,4- tetrahydro-2-carboline. Cl3H16N20; mol wt 216.27. C 72.19%, H 7.46%, N 12.95%, O 7.40%. Found in extracts of pineal gland tissue: Farrell, Circulation 21, 1009 (1960); Farrell, Mclsaac, Arch. Biochem. Biophys. 94, 543 (1961). Synthesis from 5-methoxytryptamine and acetaldehyde: Mclsaac, Biochim. Biophys. Acta 52, 607 (1961); Meek et al., Chem. & Ind. (London) 1964, 622. Crystals, mp 150-151°. uv max (ethanol): 225, 280 nm (log c 4.34, 3.86); (0.1N HC1): 220, 273 nm (log e 4.40, 3.86). 164. Adrenolutin. l-Methyl-lH-indole-3y5,6-triol; N-methyl -5,6 -dihydroxyindoxyl; 3,5,6-trihydroxy -ZV-meth - ylindole. C9H9N03; mol wt 179.17. C 60.33%, H 5.06%, N 7.82%, O 26.79%. Alkaline rearrangement product of adrenochrome. Isoln and identification: Lund, Acta Pharmacol. Toxicol. 5, 75 (1949). Structure and synthesis: Balsinger et al, Helv. Chim. Acta 36, 708 (1953); Heacock, Mahon, Can. J. Chem. 36, 1550 (1958). NMR studies and its existence in the ketonic form in solution: Powell, Heacock, Chim. Ther. 7, 133 (1972). Monohydrate, bright yellow prisms from water, mp 236" (decompn); mp 195" (Balsinger loc. cit.). Anhydrous, bright yellow prisms, mp 245°. 165. Adrenosterone. Androst-4-ene-3,ll,17-trione; Reichstein's substance G. C19H2403; mol wt 300.38. C 75.97%, H 8.05%, O 15.98%. Prepn: Reichstein, Helv. Chim. Acta 19, 29, 1107 (1936); Kendall et al, J. Biol Chem. 116, 267 (1936); Reichstein, Helv. Chim. Acta 20, 817, 953 (1937). Total synthesis: Velluz et al, Compt. Rend. 250, 1293 (1960). Crystal structure: Ohrt et al, Acta Cryst. 19, 479 (1965). Metabolism: Bradlow et al, Steroids 10, 233 (1967). Needles from alcohol, mp 220-224°. Sublimes in high vacuum. Soly in water: 9.85 (23°), 15.2 (37°) mg/100 ml. Sol in alcohol, acetone, ether. [«]d° +262° (abs alcohol); [**]546i +364° ± 5° (c = 0.18 in abs ale), uv max: 235 nm. 166. AET. Carbamimidothioic acid 2-aminoethyl ester dihydrobromide; 2-(2-aminoethyl)-2-thiopseudourea dihy- drobromide; S-(2-aminoethyl)isothiuronium bromide hydro- bromide; /3-aminoethylisothiuronium bromide hydrobro- mide; Antirad; Surrectan; Antiradon. C3HnBr2N3S; mol wt 281.04. C 12.82%, H 3.95%, Br 56.87%, N 14.95%, S 11.41%. Prepd by refluxing thiourea with 2-bromoethyl- amine HBr in isopropanol: Clinton et al, J. Am. Chem. Soc. 70, 950 (1948); Funahashi, Miyano, J. Agr. Chem. Soc. Japan 27, 775 (1953), CA. 49, 15737b (1955); Doherty et al, J. Am. Chem. Soc. 79, 5667 (1957). H3NCH2CH2SC > NH, NH, 2Br" Crystals from abs ethanol + ethyl acetate, mp 194-195°. Hygroscopic, cakes together, and is converted in significant amounts of 2-aminothiazolinc, a transformation that can be detected by a drop in melting point by as much as 30°. The animal organism appears to convert it to 2-mercaptoethyl- guanidine hydrobromide. LD50 in mice i.v., s.c, i.p., orally: 100, 280, 480, 1600 mg/kg, CA. 67, 72261s (1967). THF.rap CAT: Radioprotective agent. 167. Affinin. N-(2-Methylpropyl)-2,6,8-decatrienamide; N-isobutyl-2,6,8-decatrienamide; N-isobutyldeca-frans-2- cis-6-trans-8-trienamide; spilanthol. Cl4H23NO; mol wt 221.33. C 15.91%, H 10.47%-, N 6.33%, O 7.23%. lnsecti- cidal lipid amide isolated from Heliopsis longipes (A. Gray) Blake, Compositae. Isoln and structure: Acree et al, J. Org. Chem. 10, 236, 449 (1945). Identity with spilanthol: Jacob- son, Chem. & Ind. (London) 1957, 50. Stereochemistry and synthesis: Crombie, Krasinski, ibid. 1962, 983; Crombie et al, J. Chem. Soc. 1963, 4970. Consult the cross index before using this section. Page 29

Agmatine 176 Aflatoxin Mt. C17H1207. 2,3,6a,9a-Tetrahydro-9a-hydr- oxy-4-methoxycyclopenta[c]furo[3',2':4f5]furo[2,3-h][l]ben~ zopyran-l,ll-dione; 4-hydroxyaflatoxin Bt. Crystals from methanol, mp 299° (dec). Exhibits blue-violet fluorescence. [a]D -280° (c = 0.1 in DMF). uv max (ethanol): 226, 265, 357 nm (e 23100, 11600, 19000). LD50 orally in day old Pekin ducklings: 16.6 ^g/duckling (Holzapfel, Steyn). Aflatoxin M2. C17HI407. 2,3,6a,8,9,9a-Ilexahydro-9a~hy- droxy-4-methoxycyclopenta[c]furo[3',2':4,5]furo[2y3-h][l]- benzopyran-l,ll-dione; 4-hydroxyaflatoxin B2. The 8,9-di- hydro deriv of aflatoxin M,. Exhibits violet fluorescence. Crystals from methanol-chloroform, mp 293 (dec), uv max (ethanol): 221, 264, 357 nm (c 20000, 10900, 21000). LD50 orally in day old Pekin ducklings: 62 ^g/duckling (Holzapfel, Steyn). Note: The aflatoxins may reasonably be anticipated to be carcinogens: Fourth Annual Report on Carcinogens (NTP 85-002, 1985) p 18. 171. Afloqualone. 6-Amino-2-(fluoromethyl)-3-(2- methylphenyl)-4(3If)-quinazolinone; 6-amino-2-fluoro- methyl-3-(o-to]yl)-4(3/0-quinazolinone; HQ 495; Aroft; Arofuto. CI6HI4FN30; mol wt 283.30. C 67.83%, H 4.98%, F 6.71%, N 14.83%, O 5.65%. A centrally acting muscle relaxant. Prepn: I. Inoue et ai, Ger. pat. 2,449,113; eidem, U.S. pat. 3,966,731 (1975, 1976 to Tanabe); J. Tani et al, J. Med. Chem. 22, 95 (1979). Pharmacology: T. Ochiai, R. Ishida, Japan. J. Pharmacol. 31, 491 (1981); 32, 427 (1982). Metabolism: N. Otsuka et al, J. Phannacobio-Dyn. 5, S-59 (1982); S. Furuuchi et ai, Drug Metah. Dispos. 11, 371 (1983). c\uv II,CV Pale yellow prisms from 2-propanol, mp 195-196°. LD5() in mice (mg/kg): 315.1 i.p. (Tani). THKKAP CAT: Muscle relaxant (skeletal). 172. Agar. Agar-agar; gelose; Japan agar; Bengal isinglass; Ceylon isinglass; Chinese isinglass; Japan isinglass; Layor Carang. A polysaccharide complex extracted from the agarocytes of algae of the Rhodophyceae. Predominant agar-producing genera are Gelidium, Gracilaria, Acanthopel- lis, Ceramium, Pterocladia found in the Pacific and Indian Oceans and Japan Sea. Can be separated into a neutral gelling fraction, agarose, and a sulfated non -gelling fraction, agaropectin: Araki, J. Chem. Soc. Japan 58, 1338 (1937). Structure believed to be a complex range of polysaccaride chains having alternating a-(l --3) and /3-(l —4) linkages and varying in total charge content; three extremes of structure noted, namely neutral agarose, pyruvated agarose having little sulfation, and a sulfated galactan: Duckworth et u/., Carbohyd. Res. 16, 189, 435, 446 (1971). Reviews; V. J. Chapman, Seaweeds and Their Uses (Pitman Publ., New York, 1952) pp 89-123; Humm, Econ, Bot. 1, 317 (1947); Mori, Advan. Carbohyd. Chem. 8, 317 (1953); Selby, Wynne, in Industrial Gums, R. L. Whistler, Ed. (Academic Press, N.Y., 2nd ed., 1973) pp 29-48. Transparent, odorless, tasteless strips or coarse or fine powder. Insol in cold water, ale; slowly sol in hot water to a viscid soln. A 1% soln forms a stiff jelly on cooling. use: Substitute for gelatin, isinglass, etc. in making emulsions including photographic, gels in cosmetics, and as thickening agent in foods esp. confectionaries and dairy products; in meat canning; in production of medicinal encapsulations and ointments; as dental impression mold base; as corrosion inhibitor; sizing for silks and paper; in the dyeing and printing of fabrics and textiles; in adhesives. In nutrient media for bacterial cultures. thf.rap CAT: Cathartic. THi-RAi' cat (vet): Laxative in dogs, cats. Demulcent. 173. Agaric. Larch agaric: touch wood; white agaric; purging agaric; amadou; German fungus. The dried fruit body of Fomes laricis (Jacq.) Murrill (Polyporus officinalis Fries), Polyporaceae, deprived of its outer rind. Habit. European and Asiatic Russia. Grows upon various species of Pinus, Larix, and Picea. Constit. 14-16'% Agaricic acid; agaricoresin, agaricol, phytosterin, ricinoleic acid, cetyl alcohol, glucose, malic acid, carbohydrates. Isoln and separation of some constituents: Valentin, Kniittcr, Pharm. Zentralhalle 96, 478 (1957). Impregnated with potassium nitrate and dried, it constitutes punk or tinder. Light, fibrous, grayish-white to pale brown, spongy, friable pieces of irregular shape," feeble odor and bitter, acrid, yet somewhat sweetish taste. use: Anhidrotic. 174. Agaricic Acid. 2-Hydroxy~l,2,3-nonadecanetri- carboxylic acid; agaric acid; agaricin; agaricinic acid; laricic acid; n-hexadecylcitric acid; tx-cetylcitric acid. C^H^O?; mol wt 416.56. C 63.437c, H 9.68%, O 26.89%>. Active principle of Fomes laricis (Jacq.) Murrill (Polyporus officinalis Fries), Polyporaceae: Thorns, Vogelsang, Ann. 357, 145 (1907). Attempted syntheses: Evans, J. Chem. Soc. 1959, 1313; Graf, Liu, Arch. Pharm. 306, 366 (1973). Activity studies: Bacchi et ai, J. Bacterial. 98, 23 (1969). COOH HOOCCH0 — C — CHCOOH 2 I I 0H C16H33 Sesquihydrate, odorless, almost tasteless, crystalline powder. Anhydrous, mp 142° (dec). [a]D9 —9° (NaOH). Slightly sol in cold water, chloroform or ether; freely sol in boiling water, alkalies, hot glacial acetic acid. One gram dissolves in 180 ml cold, 10 ml boiling alcohol. Note: The name agaric acid has also been used for a lano- stane-like mixture [CA. 68, 29894J (1968)]. USE: Has been used as antiperspirant. 175. Agar it inc. ^-Glutamic acid 5-[2-[4-(hydroxymeth- yl)phenyl]hydrazide]; /3-N-[7-l( + ) -glutamyl] -4-hydroxy- methylphenylhydrazine. Cl2H17N304; mol wt 267.28. C 53.92%, H 6.41%, N 15.72%, O 23.94%. Constituent of the commercial, edible mushroom Agaricus bisporus (Lange) Sing. [Psalliota hortensis Cooke var. bispora], Agaricaceae (Agaricales). Isoln and structure: Levenberg, Fed. Proc. 19, 6 (I960); J. Am. Chem. Soc. 83, 503 (1961); Daniels et al, ibid. 3333; see also Levenberg in Methods Enzymol 17 (Part A), 877 (1970). Synthesis: Kelly et ai, J. Org. Chem. 27, 3229 (1962); Hinman, Kelly, U.S. pats. 3,274,232; 3,288,848 (both 1966 to Upjohn). HOCII Nil, NHNHCOCHgCH CHCOO- Glistening crystals from dil alcohol, dee 205-209°. [a]fi + 7° (c = 0.8). uv max (water): 237.5, 280 nm (e 12,000, 1,400). Very freely sol in water, practically insol in the usual anhydr organic solvents. pKa in water: 3.4 and 8.86. 176. Agmatine. 4-(Aminobutyl)guanidine; l-amino-4- guanidobutane. C5H14N4; mol wt 130.19. C 46.12%, II 10.84%, N 43.04%. Deearboxylated arginine. Found in pollen of Ambrosia artemisifolia L., Compositac, in ergot, in sponges, in herring sperm, in octopus muscle: lleyl, J. Am. Chem. Soc. 41, 681 (1919); Kossel, Z. Physiol. Chem. 66, 257 (1910); Irvin, Wilson, J. Biol. Chem. 127, 565 (1939). Prepn of salts: Ger. pat. 463,576 (1928 to Schering-Kahlbaum AG). Synthesis: Kossel, Z. Physiol Chem. 68, 170 (1910); Odo, ./. Chem. Soc. Japan 67, 132 (1946); Dose, Ber. 90, 1251 (1957). H2NCNH(CH2)4NH NH C5HI4N4.H2S04, needles from dil methanol, mp 23 1' Fairly sol in water, nearly insol in alcohol. Consult the cross index before using this section. Page 31

Aklomide 188 Prisms from dil alcohol, mp 172°.