Hughes, Gordon K.; Lions, Francis; Ritchie, Ernest published the artcile< Indoles. VII. Derivatives of 7-nitroindole>, Related Products of 112-63-0, the main research area is .
A number of o-nitrophenylhydrazones were prepared by (a) reacting o-nitrophenylhydrazine with aldehydes and ketones and by (b) applying the Japp-Klingemann reaction, i. e., by coupling diazotized o-O2NC6H4NH2 (I) with the alkali derivatives of monoalkylated acetoacetic esters. The o-nitrophenylhydrazones were then subjected to ring closure by the Fischer indole synthesis, using the following methods: (1) refluxing a solution of o-nitrophenylhydrazone (hereafter designated O. N. P.) in 10 times its weight of glacial AcOH for several hrs.; (2) dissolving the O. N. P. in 10 times its weight of cold concentrated H2SO4 and allowing to stand for 24 h.; (3) passing dry HCl into a hot solution of the O. N. P. in absolute alc. until NH4Cl precipitated; (4) refluxing the O. N. P. in 10 times its weight of dilute H2SO4 (1:1) until no further change occurred; if a solid precipitate remained, it was filtered; if the product was tarry, the acid liquor was decanted and the residue washed with H2O, extracted with hot dilute Na2CO3, and acidified; (5) same as (4) but using concentrated HCl instead of dilute H2SO4; (6) following the method of German pat. 238, 138(C. A. 6, 1659), anhydrous ZnCl2 was added to 1 part O. N. P. in 3 parts cumene and the whole refluxed for 3 h.; (7) dissolving anhydrous ZnCl2 (20 g.) in a solution of the O. N. P. (2 g.) in absolute alc. (16 cc.) and refluxing for 2 h.; (8) dissolving the O. N. P. in 10 times its weight of HBr in glacial AcOH and refluxing 90 min. The reaction product was generally poured into water, collected with ether and purified. The suitable cyclization conditions varied with the intermediates and it was not possible to formulate a set of conditions which invariably lead to success since a method working well in one case was useless in another. The most generally useful reagent was found to be anhydrous ZnCl2 in boiling cumene, but even this failed where, curiously enough, HBr in AcOH or even alc. HCl was effective. Et α-acetylpyruvate (20.5 g.) and diazotized I gave Et pyruvate o-nitrophenylhydrazone, yellow, m. 106°, which failed to cyclize by methods (1), (2) and (3), but by method (5) it was possible to isolate 7-nitroindole-2-carboxylic acid, yellow, m. 231°, the yield being 3 g. from 5 g. of the hydrazone; in cold dilute alc. the latter gives a yellow solution which becomes red on warming; attempts to prepare 7-aminoindole-2-carboxylic acid with FeSO4 and NH3 proved abortive. Decarboxylation of the acid (10 g.) by heating carefully in anhydrous glycerol (100 cc.) to 220° and maintaining that temperature for 3-5 min., followed by cooling and pouring into cold H2O, gave 60% 7-nitroindole, b32 170-5°, orange platelets, m. 113°, from petr. ether. Et α-acetylbutyrate and diazotized I gave 90% Et α-ketobutyrate o-nitrophenylhydrazone (II), yellow, m. 94°; attempts to cyclize this by methods (1) or (3) converted it into a yellow compound (III), m. 68°, probably a geometric isomer since it could be converted to 3-methyl-7-nitroindole-2-carboxylic acid (IV), yellow, m. above 270°, by boiling with concentrated HCl, but the ease of cyclization of III was considerably less than that of isomeric II; cyclization of II by method (2) readily yielded Et 3-methyl-7-nitroindole-2-carboxylate, yellow, m. 115°, while cyclization of either II or III by method (5) gave the corresponding acid (IV). Coupling diazotized I (15 g.) with Et α-acetylvalerate (18 g.) gave Et α-ketovalerate o-nitrophenylhydrazone, as a non-crystallizable, dark red oil (28 g.), which failed to cyclize by method (1) but, by methods (2) or (6), gave Et 3-ethyl-7-nitroindole-2-carboxylate, yellow, m. 85°; method (5) formed 3-ethyl-7-nitroindole-2-carboxylic acid, yellow, m. 245°. Diazotized I (10 g.) was coupled with the K salt of Et α-acetylcaproate, giving Et α-ketocaproate o-phenylhydrazone as a non-crystallizable red oil (15 g.), which failed to couple by method (1) but by methods (2) and (6) yielded Et 3-propyl-7-nitroindole-2-carboxylate, yellow, m. 70°; treatment of the hydrazone by method (5) yielded 3-propyl-7-nitroindole-2-carboxylic acid, yellow, m. 196°. Diazotized I (20 g.) and Et α-acetylphenylpropionate (32 g.) gave Et phenylpyruvate o-nitrophenylhydrazone as a dark red oil (41 g.) which from petr. ether deposited orange prisms, m. 68°, upon slow evaporation at room temperature; cyclization by methods (1), (2), (4), (5) and (6) were of no avail, but methods (3) and (8) gave, resp., 60% and 45% Et 3-phenyl-7-nitroindole-2-carboxylate, yellow, m. 112°; the product by method (3) was much more difficult to purify than that obtained by method (8). Diazotized I (10 g.) and the K salt of Et cyclohexanone-2-carboxylate (12 g.) gave the o-nitrophenylhydrazone of the half-ester of α-ketopimelic acid, yellow, m. 122°, which failed to cyclize by method (2), formed a tar by method (6), but by method (5) gave γ-(2-carboxy-7-nitroindolyl)butyric acid, yellow, m. 171°, from MeOH and benzene, also obtained in small yield (5-10%) by method (7), the product m. 184° from MeOH. The o-nitrophenylhydrazones of the following aldehydes and ketones were prepared and subjected to cyclization experiments: Me2CO, m. 70° (cf. Ekenstein and Blanksma, Rec. trav. chim. 24, 37(1905)), could not be cyclized using methods (5) or (6); Et2CO, m. 60° (cf. E. and K.), failed to cyclize by method (1), but with (5), 2-ethyl-3-methyl-7-nitroindole, orange, m. 104°, was obtained; iso-BuCHO, m. 59°, by method (5) gave a product as orange leaflets, m. 154°, which may be 2,2′-isobutylidenebis(3,3′-dimethyl-7-nitroindolenine), and treatment by method (7) caused indole cyclization but the product was contaminated with tar and could not be purified; cyclopentanone, m. 64°, although cyclized by Perkin and Plant (C. A. 18, 687) with hot dilute H2SO4, failed with methods (2), (4) or (5); PhCOMe, m. 138° (cf. E. and B.), failed to cyclize by methods (2), (5) and (6); PhCOEt, scarlet, m. 120°, failed to cyclize by method (5), but by method (6) gave a mixture of red and orange crystals, the conversion, however, being incomplete even after heating for 6 h.; desoxybenzoin, scarlet, m. 125°, failed to cyclize by methods (5) and (6); β-acetylpyridine, orange, m. 144°, failed to cyclize by methods (5) and (6).
Journal and Proceedings of the Royal Society of New South Wales published new progress about Hydrazones. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Related Products of 112-63-0.
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