878
RICHARD B. TURNER
Summary 1. An improved method of synthesis of ketimines is reported. 2. six ketimines have been prepared and characterized by their physical constants and derivatives. [CONTRIBUTION FROM THE CONVERSE
Vol. 72
3. Five ketones have been produced by hydrolysis of ketimines. 4. Six primary amines have been prepared by low pressure catalytic reduction of ketimines. RECEIVED AUGUST22, 1949
MEMORIAL LABORATORY OF HARVARD UNIVERSITY]
Stereochemistry of the Peracid Oxidation of Ketones1 BY RICHARD B. TURNER The conversion of cyclic ketones into lactones by the action of persulfuric acid was first observed by Baeyer and Villiger2 in 1899. The general applicability of the reaction has since been demonstrated by many investigators, and numerous examples of the formation of esters from acyclic ketones, both aliphatic and aromatic, are recorded in the literature. Peracetic and perbenzoic acids have been employed successfully in place of persulfuric acid. The stereochemistry of the reaction, however, has not hitherto been explored, and a study of the steric course of the oxidation was undertaken in this Laboratory in conjunction with Gallagher'sa investigation of the behavior of epimeric 17-acetyl steroid derivatives. cis- and trans-1-acetyl-2-methylcyclohexane(I1 and 111) were chosen as suitable model substances. Although only the trans isomer (111) had been prepared previously,' a satisfactory synthesis of the cis derivative was achieved by catalytic
rCHa 'COCH,
hydrogenation of 1-acetyl-2-methyl-A'-cyclohexene (I). The crude hydrogenation product was purified as the semicarbazone (m. p. 182182.5'), from which the ketone was regenerated by steam distillation in the presence of phthalic acid.6 Evidence for the absence of inversion in the latter transformation was provided by reconversion of the purified ketone into a semicarbazone identical in melting point and mixed melting point with the starting material. The cis ketone (11) proved rather stable toward acid, but isomerization could be effected without difficulty by the use of sodium ethoxide. The rearrangement product was likewise purified as the semicarbazone (m. p. 177-178.5', marked depression with the cis semicarbazone), which, after hydrolysis, furnished a pure sample of trans1-acetyl-2-methylcyclohexane (111). Structures assigned to the isomeric ketones are based on the methods of synthesisB*'and on correlation of the physical constantss recorded in Table I. TABLE I Compound
B. p.
OC.
Mm.
dzb
I1 (cis) 67-68 10 0.9169 I11 (trans) 64-65 10 ,8951 VI (cis) 53-53.5 14 .9043 VI1 (trans) 53.5-54 14 .8923 Calcd. 41.59. Calcd. 36.97.
nP5D
1.4532 1.4464 1.4418 1.4383
MZaD
41.36" 41.80 36.91b 37.06
(I
bI\COCH, H
k (IV)
''OCOC~H,CO~H H (VI
(1) This work was supported by funds provided by the American Cancer Society on the recommendation of the Committee on Growth of the National Research Council. (2) Baeyer and Villiger, Bcr.. 91, 3625 (1899); 33, 858 (1900). (3) Gallagher and Kritchevsky, THISJOURNAL, 73, 882 (14501. (4) Darzens. Compf. rend., 144, 1124 (1907).
Both substances (I1 and 111) were subjected to oxidation with perbenzoic acid in chloroform solution according to the procedure employed by Gallagher.3 The products, cis- and truns2-methylcyclohexanyl acetate, were saponified directly and converted into the corresponding acid phthalates, which were separated from the nonalcoholic fraction by extraction with dilute alkali. From cis-1-acetyl-2-methylcyclohexane (11) a product (IV), m. p. 102-103O, was obtained that did not depress the melting point of an authentic sample of cis-2-methylcyclohexanylacid phthal(5) Naves and P.Bachmann, Hclu. Chim. Acta, 26, 2151 (1943). (6) Cf. Linstead, Doering, Davis, Levine and Whetstone, THIS JOURNAL, 64, 1985 (1942). (7) Cf.Hilckel and Goth, B e y . , 68, 447 (1926). (8) Hiickel, "Theoretische Grundlagen der organischen Chemie," 6th ed., Vol. 11. p. 154, Akademische Verlagsgesellxhaft, 1,eipzig. 1548.
Feb., 1950
STEREOCHEMISTRY OF THE PERACID OXIDATIONOF KETONES
879
ate.g The derivative V obtained from trans-l- ler12 reported that catalytic hydrogenation of acetyl-2-methylcyclohexane(111) melted a t 123- 2-methylcyclopentanone affords a mixture of 124’ and showed no melting point depression stereoisomeric alcohols, from which 3,5-dinitrowhen mixed with trans-2-methylcyclohexanyl benzoates melting a t 124’ and a t 64’ can be acid ~ h t h a l a t e . ~The cis and trans products were isolated in approximately equal amounts. Hyisolated in sterically pure condition in yields of drolysis of these derivatives after reduction of the 63 and 55%, respectively, based on ketone nitro groups furnished free alcohols, the densities utilized. No other components could be ob- and refractive indices of which were in fair agreetained from the alcoholic fractions. The results ment with the values reported by Godchot and provide conclusive evidence for the retention of Bedos. Reduction of 2-methylcyclopentanone configuration a t C-1 in the perbenzoic acid oxida- with sodium and alcohol likewise yielded a mixture, from which the dinitrobenzoate melting at tion. Similar experiments were conducted with the 64’ was subsequently isolated as the major component, though in a yield of only about 30%. cis- and trans-l-acetyl-2-methyl~yclopentanes~~ On the basis of this evidence a trans structure with analogous results. The former product was obtained by catalytic hydrogenation of 1- was assigned to the dinitrobenzoate, m. p. 64’) and acetyl-2-methyl- A’-cyclopentene, and the latter a cis structure to the higher melting material. by base-catalyzed isomerization of the cis deriva- Hiickel and Kindler12 further noted that the tive. The densities and refractivities of the two p-toluenesulfonate derived from “cis”-Bmethylproducts (Table I) support structures deduced cyclopentanol was decomposed in refluxing methafor these substances from the methods employed nol a t a faster rate than was the corresponding derivative of the “trans’)form. The p-toluenesulin their preparation. Oxidation of the cis and trans ketones (VI and fonates were not obtained in crystalline condition, VII) with perbenzoic acid was carried out as and no attempt was made to identify the methabefore. The alcohols resulting from saponifica- nolysis products. tion of the crude oxidation mixtures were isolated In an effort to resolve the inconsistencies beas the 3,5-dinitrobenzoates (VIII and IX), tween our work and that of Hiickel and Kindler, which melted a t 66-67’ and a t 84-85’, respec- we have reinvestigated the catalytic hydrogenatively. The relation of the products to the start- tion (Pt) of 2-methylcyclopentanone. Treating materials is shown in the accompanying chart. ment of the crude hydrogenation product with 3,5-dinitrobenzoyl chloride and pyridine furnished H H a mixture, from which 3,5-dinitrobenzoates melting a t 67’ and a t 85’ could be isolated. These products did not depress the melting points of the /\COCHa corresponding derivatives (VIII and IX) obtained by the reactions of cis- and trans-1-acetyl-2-methylH H cyclopentane, respectively, with perbenzoic acid. (VI) WI) In no case were we able to isolate a product melting a t 124’. The claim of Godchot and Bedosll that the H reaction of cyclopentene oxide with methylmagnesium iodide affords cis-2-methylcyclopentanol is also apparently in error, for the analogous reaction of cyclohexene oxide with methylmagnesium iodide, which was originally reported by m. p. 66-67” m. p. 84-85’ these authors13 to yield cis-2-methylcyclohexanol, (VIII) (1x1 was subsequently shown to involve rearrangement Synthesis of the stereoisomeric 2-methylcyclo- with ring contraction.14 Moreover, Bartlett and pentanols was claimed in 1926 by Godchot and Berry15 have demonstrated that treatment of Bedos,” who obtained a “cis” product from the cyclohexene oxide with dimethylmagnesium in the reaction of cyclopentene oxide with methyl- absence of magnesium halide leads to the formamagnesium iodide, and a “trans” derivative by tion of the expected trans-2-methylcyclohexanol. Our efforts to obtain a dinitrobenzoate correreduction of 2-methylcyclopentanone with sodium and moist ether. These investigators prepared sponding either to VI11 or to I X by reaction of the phenylurethans and allophanates of their cyclopentene oxide with methylmagnesium iodide products, but the melting points of the “cis” under mild conditions and treatment of the prodand “trans” derivatives in each series were so uct with dinitrobenzoyl chloride were unsuccessclose that differentiation by this means was (12) Hiickel and Kindler, Bcr., 80,202 (1947). (13) Godchot and Bedos, B d . SOC. chim., 37, 1451 (1925). impracticable. &fore recently Hfickel and Kind(14) Godchot and Cauquil, Comfif. rend., 186, 375, 955 (1928);
VH3J.
c?I;H3 J.
(\I/CHJ
(9) Hiickel and Hagenguth, Bcr., 64, 2892 (1931). (10) Colman and Perkin, J . Chcm. Soc., 63,200 (1888). (11) Godchot and Bedos, Compr. rend., 18P, 393 (1926).
Vavon and Mitchovitch, ibid., 186, 702 (1928); Bedos, ibid., 189, 255 (1929). (15) Bartlett and Berry, THISJOURNAL, 66, 2683 (1934).
880
RICHARD B. TURNER
Vol. 72
ful. The only crystalline compound that could be authors for the formation of X is not unique, isolated was identified by analysis as the 3,5- an alternate pathway being dinitrobenzoate of cyclopentene iodohydrin, formed by the action of magnesium iodide on OH+ + :>
