Indole cyclization of camphor phenylhydrazone. Isolation of interesting collateral products. Sparatore, Fabio. Univ. Genoa,
Gazzetta Chimica Italiana (1958), 88 755-68. CODEN: GCITA9 ISSN: 0016-5603. Journal language unavailable. CAN 53:122385 AN 1959:122385
CAPLUS
Abstract
To clarify the mechanism of the Fischer indole synthesis various secondary products reported in the cyclization of camphor phenylhydrazone (I)
(Kuroda, C.A. 17, 3031) were reinvestigated. I (5 g.), prepd. according to Agostinelli (C.A. 7, 1882), freshly distd. in vacuo, triturated with 15 g.
anhyd. ZnCl2, the mixt. heated 30 min. at 100 (preheated metal bath) then 4 min. at 180 (2nd preheated metal bath), the cooled mass taken up in H2O,
the aq. layer extd. with Et2O, the residual resin taken up in the Et2O ext., the filtered soln. shaken with 0.5N HCl and H2O, the aq. washings united
with the acid ext. (II), the dried Et2O ext. evapd., and the residue distd. at 0.2 mm. gave a small amt. of campholenonitrile, b0.2 100, some camphor
(sublimation on the cold wall), and a heavy dark oil, b0.2 170. The oil fractionated in C6H14 gave a cryst. product (III), m. 153-4 (C6H6), and the
C6H14 filtrate refrigerated yielded the known camphoindole, m. 92-4, giving an intense rose-purple color with Ehrlich reagent. III gave no Ehrlich
reaction and no color with FeCl3 in MeOH. III (30 mg.) heated 3 hrs. on a steam bath in 5 ml. 0.5N NaOH, the cooled soln. extd. with Et2O, the washed
and dried ext. concd., and refrigerated gave a 2nd neutral substance, m. 215-18, insol. in dil. alkali and in dil. acid, giving no color with FeCl3 in
MeOH. II made alk. with NH4OH, extd. with Et2O, the washed and dried ext. evapd., and the product distd. at 0.2 mm. gave clear yellow oily PhNH2; a
2nd fraction, b0.2 90-110, recrystd. (C6H14) gave authentic .omicron.-C6H4(NH2)2 (IV), m. 103, .lambda. 237, 265 (min.), 294 m.mu. (log .epsilon.
3.78, 2.70, 3.45)(Grammaticakis, C.A. 46, 3401g), and a 3rd fraction, b0.2 160-80, washed with Et2O and the residue sublimed at 150-60/0.2 mm. to give
a benzimidazole deriv. (V), C16H22N2, m. 208-10, .lambda. 243, 274, 280 m.mu. (log .epsilon. 3.79, 3.80, 3.86, alc.), 236, 268, 275 m.mu. (log
.epsilon. 3.64, 3.90, 3.95, N HCl), entirely superimposable on the curve of 2-methylbenzimidazole (Leandri, et al., C.A. 50, 2291i).
The possibility of the passage from camphor phenylenediamine to V was confirmed by condensation of IV with the more active pernitrosocamphor (VI).
IV (1 g.) in 2 ml. alc. heated on a steam bath with 2 g. VI to cessation of evolution of N2O, the alc. evapd. in vacuo, the residue heated 5 min. at
180-90 (metal bath), and the product distd. at 0.2 mm. gave, in addn. to campholenonitrile and unchanged IV, a heavy orange-yellow oil, b0.2 115-40,
cleaving in dil. HCl to camphor and IV, and a cryst. fraction, b0.2 150-70, which washed with Et2O and sublimed in vacuo gave authentic V.
Indolic cyclization of camphor phenylhydrazone. II. Sparatore, Fabio. Univ. Genoa, Gazzetta Chimica Italiana (1962), 92
596-605. CODEN: GCITA9 ISSN: 0016-5603. Journal language unavailable. CAN 58:66619 AN 1963:66619 CAPLUS
Abstract
cf. CA 53, 22054d. To clarify the structure of secondary products, the cyclization of camphor phenylhydrazone (I) was reinvestigated. Thus, 16 g. I
heated at 100 and mixed with anhyd. ZnCl2, the mixt. kept 30 min. at 100 and 5 min. at 180, cooled, treated with 2N HCl, extd. with Et2O, the aq.
soln. (A) stored, the org. layer dried (Na2SO4), the solvent evapd. and the residue (6.6 g.) distd. gave a first fraction, b0.2 100-50, from which, by
chromatography on Al2O3, 2.3 g. of crude campholenonitrile (C6H6 as eluent) and 0.6 g. .beta.-campholenic amide (II) (C6H6-5% EtOH as eluent) were
isolated. II m. 90-1 (C6H6-petr. ether). A second fraction (1.8 g.), b0.2 150-80, purified by chromatography on Al2O3, yielded 1 g.
camphoindole(III), m. 92 (petr. ether). The soln. A, decolorized with C and basified with NH3, was extd. with Et2O and the ext. dried (Na2SO4) and
evapd. to give 5.9 g. residue which was distd. to give PhNH2 as fore-run, then a fraction (a), b0.2 90-120 and a fraction (b), b0.2 160-85. Fraction
(a) on standing sepd. a cryst. product, m. 139-40, identified as .alpha.-(camphor)-aminocamphor (IV), .lambda. 302 m.mu. (log .epsilon. 2.30). In the
oily residue o-C6H4(NH2)2 was identified. Fraction (b) on standing sepd. the benzimidazole deriv. (V), m. 197-8 (dil. EtOH). The isolation of IV
suggested a reaction mechanism involving a break of the N-N bond of I to give free radicals which may condense in different ways to III-V.
Indolic cyclization of camphor phenylhydrazone. III. Structure of so-called camphorindole. Sparatore, Fabio; Pirisino, Gerolamo.
Univ. Sassari, Sardinia, Gazzetta Chimica Italiana (1965), 95(5), 546-55. CODEN: GCITA9 ISSN: 0016-5603. Journal written in Italian.
CAN 63:46392 AN 1965:446392 CAPLUS
Abstract
cf. CA 11404h; Kuroda, CA 17, 3031. Camphor phenylhydrazone in contact with anhyd. ZnCl2 at 180 reacts yielding the compd. C16H19N (I), which is
called camphorindole. Assumed structure of I yields a strong violet color reaction with the Ehrlich reagent. Tetrahydrocarbazole (II) having a very
similar structure does not undergo the same reaction. Also uv absorption spectra of I and II show a clear difference: therefore structure I appears
to be not suitable. The only possible exact structure for compd. I is III. A compd. which has indubitably structure III has been prepd. by
cyclization of .beta.-campholenic aldehyde phenylhydrazone. The latter was prepd. by reduction of N-methylanilide of .beta.-campholenic acid.
Complete identity of compd. prepared by this way and so-called camphorindole is a definite proof that structure III is the true structure of
camphorindole.
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