THE PREPARATION OF 1-METHYL-1-CYCLOHEXEN-6-ONE FROM

Ketone of satisfactory quality has been obtained by two routes from cyclohexanone, by ... None of the methods described in the literature (Table I) wa...
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BUREAU OF AKIMALINDUSTRY, AGRICULTCRAL RESEARCH ADDEPARTMENT OF AGRICULTURE]

MINISTRATION, U N I T E D STATES

THE PREPARATION OF 1-METHYL-1-CYCLOHEXEN-&ONE FROM 1-METHYLCYCLOHEXENE AND FROM CYCLOHEXANE-l,2-DIONE1 LEWIS W. BUTZ, BENJAMIN L. DAVIS,

AND

ADAM & CADDIS I.

Received July 26, 1946

l-Methyl-l-cyclohexen-6-one,free from l-methyl-l-cyclohexen-3-one,was required for combination with butadiene in the preparation of a methyloctalone (1, 2). Ketone of satisfactory quality has been obtained by two routes from cyclohexanone, by fractionation of the products of the action of selenium dioxide on 1-methylcyclohexenein boiling ethanol and by dehydration of the products of the interaction of cyclohexane-l12-dioneand methylmagnesium iodide. It was difficult to get analytically pure ketone by either method, material with carbon content about one per cent too low being obtained each way in about IS'% yield based on cyclohexanone. This is suitable for the preparation of the methyloctalone (2). None of the methods described in the literature (Table I) was reported to give so large a yield. We have found that the 2 4-dinitrophenylhydrazones of l-methyl-l-cyclohexen-3-one and 1-methyl-1-cyclohexen-&one can be separated quantitatively by differential adsorption on and elution from alumina, and have shown, by this procedure, that the crude products obtained from selenium dioxide and l-methylcyclohexene under the conditions we employed contain about 13% of the Previous investigators of this reaction (6, 9) have not found l-methyl-l-cyclohexen-3-one, 3-01, or 3-yl acetate. The &one and two minor components of the crude oxidation product which give colored derivatives with 2,4-dinitrophenylhydrazine can be removed by heating with about one-fourth mole of butadiene at 200" and fractionating the resulting mixture by distillation. Constants for three of these preparations (J, K, L) are given in Table I. Cyclohexane-112-dione,with any enolic form (11,24), from cyclohexanone and selenium dioxide (12, 13), was allom-ed to react with methylmagnesium iodide t o give 2-hydroxy-2-methylcyclohexanone,or isomeric material, which was converted to semicarbazone without purification. Hydrolysis of the crude semicarbazone with sulfuric acid gave 1-methyl-1-cyclohexen-&one which may contain 7% of unchanged ketol, since the content of carbon is about one per cent too low for enone. Reconversion of such material to semicarbazone, followed by hydrolysis and repeated fractional distillation, gave a specimen of 6-one with the calculated carbon and hydrogen content. Constants for these preparations are given in Table I (M, N, and 0). 1 This work was supported by an allotment from the Special Research Fund (BankheadJones Act of June 29, 1935). Not copyrighted. 2 l-Methyl-l-cyclohexen-3-one, bzo 90-100", n: 1.4920 [Knoevenagel, Ann., 281,94 (189411 was kindly furnished by Mr. W. F. Barthel, Bur. Entomology and Plant Quarantine, for comparison with our material. 122

PREPARATION O F 1-METHYL-1 -CYCLOHEXENE-6-ON E

123

The structure of the main product from the reaction between selenium dioxide and 1-methylcyclohexenein ethanol, and the product of dehydration of the ketol by the following: described here, is established as 1-methyl-1-cyclohexen-6-one The methyl group is a! to the carbonyl group, since it is cy in the methylockalone formed from the ketone by cbmbination with butadiene (2). The carboncarbon double bond is in the ring and is cy,p to the carbonyl group since the ketone gives an angle-methyloctalone with butadiene (2), absorbs in the ultraTABLE I PROPERTIES OF l-METHYL-l-CYCLOHEXEN-6-ONE PBEPN.

--

B.P., T . / M M .

*D

“C.

SOURCE

HzSOa on oxime from nitrosate of l-methyl-

A

178-181

1.4831

20

B

178-179

1.4833

20

C

170-171

1.4646

17

D

178-179/760 69-70/16

1.4820

22

69-70/16

?

E F G

? ?

? ?

H

172-176 176-1?8/754

1 ,4803 1,4865

21

KQ

63-69/14

1. a 5 5

20

LQ

65/14

1.4850

19.(

1.4528

20.(

Ja

Ma

176-178

c yclohexene HzSOl on oxime from nitrosochloride of 1-methylcyclohexene Quinoline on 2-chloro-2-methylcyclohexanone

CrOoon an alcohol from l-methylcyclohexene and SeOz KHSO, on a ketol from 1,2-cyclohexanedione and CHJMgI 1-Methglcyrlohexene and 02 SeOz on 1-methylcyclohexene in AcOH AcZO CrOI on 1-methylcyclohexene SeOz on 1-methylcyclohexene. Contains 1-methyl-1-cyclohexen-3-one SeOz on 1-methylcyelohexene, then heated with butadiene K redistilled. See exptl. part for anal. and ultraviolet abs’n HzSOIon scbzone. of ketol. See exptl. part for anal. and UV abs’n HzSO, on scbaone. of ketol. See exptl. part for anal. and UV abs’n S redistilled. dnal. and ultraviolet abs’n in exptl. part

+

Nn

66-66.5/14

1.4849

19.1

0“

66.9j14

1.4854

22.:

0

Present work.

violet like an a ,&enone, and is different from 2-methylenecyclohexanone (14). Confirmation is provided by the identity of the 2,4-dinitrophenylhydrazoncw with the 2,4-dinitrophenylhydrazonefrom the ketone from the nitrosochloride of 1-methylcyclohexene, which we prepared according to the procedure of Wallach (4). 2-Hydroxy-2-methylcyclohexanone, prepared from cyclohexane-l,2-dione and methylmagnesium iodide, has been reported t o be a distillable liquid (15, 7). The crude ketol used in the present work is liquid and consists chieflyof material

124

BUTZ, DAVIS, AND GADDIS

boiling within the previously reported boiling ranges. However, it contains or is readily changed into two other compounds isomeric with hydroxymethylcyclohexanone. One of these is a solid, m. 173.4-174.4’, which crystallizes from distillates of the crude ketol when they have been stored for a week or more, and from distillates recovered after unsuccessful dehydration experiments in which heat and acids were employed. The other isomer, which we have not obtained pure, is a liquid which b. 190-202’ a t atmospheric pressure. This may have been formed from hydroxymethylcyclohexanone at the temperature required for the distillation (bath 240-250”) , but it also might be formed during distillations a t lower temperatures, or even be present in the product from the Grignard reaction. It is suggested, on the basis of comparison with the properties of related ketols (16, 17), that the solid is a dimer and that the liquid b. 190-202’ is chiefly 1,2-epoxy-2-methylcyclohexanol. Conversion of the “ketol” blF 80-95’ to enone was attempted by a number of common dehydration procedures, all of which failed. Although some enone was usually formed, much of the “ketol” was recovered unchanged. This stability is understandable if it be assumed that much of the “ketol” exists as the epoxide isomer. The semicarbaaone of 2-hydroxy-2-methylcyclohexanone(15) was obtained from crude undistilled “ketol”, from “ketol” which had b16 80-95’, and from the solid isomer. The 2,4-dinitrophenylhydrazoneof l-methyl-l-cyclohexen-6one was obtained, by the usual procedure, from the solid isomer, and from many distillates from the “ketol”. These observations suggested the procedure for the preparation of l-methyl-l-cyclohexen-&one from cyclohexane-1,2-dione which was finally developed, hydrolysis of the semicarbazone from undistilled “ketol”.

EXPERIMENTAL^ 1-Methyl-f -cyclohexenS-onefrom 1-melhylcyclohexene. Previous investigators of the reaction between l-methylcyclohexene and selenium dioxide have used less than one mole of selenium dioxide in ethanol (6) or in a mixture of acetic acid and acetic anhydride (9) and or the acetate as the chief product. No mention have obtained l-methyl-l-cyclohexen-6-01 was made of the 3-01 or the %one. I n the present work 96 g. of methylcyclohexene, b. 110-114”, made from cyclohexanone and methylmagnesium iodide, 250 ml. of ethanol (commercial absolute or recovered from previous batches), and 111g. of powdered selenium dioxide were mixed and shaken occasionally a t 30“ in a flask with a reflux condenser. Addition of the dioxide in small portions appeared to give no advantage. The mixture warmed up spontaneously in a few minutes. Sometimes the flask was cooled with water at about 20°, but the reaction could usually be controlled without this. Most of the selenium dioxide did not dissolve. After about an hour, when the mixture had cooled, i t was refluxed for four hours in a boiling water-bath. Refluxing was continued for three hours more on the following day. The mixture was filtered, the solids washed with ethanol, and the ethanol (with so’me recoverable 6-one) was removed a t the water-pump with a column and bath at 60’. Rapid distillation of the residue gave 63 g., b14-1662-102”. Redistillation at 14 m. gave {he following fractions: (A) b. 34-66’, 2 g.; (B) b. 66-76’, n:“ 1.4856, 30 g.; (C) b. 1.5150,15 g. The content of compounds re76-82’, n:‘ 1.4900, 3 g.; (D) b. 82-105”, a All melting points are corrected. Microanalyses by Arlington Laboratories, Fairfax, Virginia.

PREPARATION OF l-METHYL-l-CYCLOHEXENE-6-ONE

125

acting with 2,4-dinitrophenylhydrazinein these fractions, calculated as dinitrophenylhydraaones (DNPH's) of carbonyl compounds, C7H100, is about as follows: (B) 89%, (C) 91%, (D) 40%. These values were obtained from the weights of the DNPH's by adding a correction of 57, for incomplete precipitation. The value of the correction was estimated by titrating a typical fraction with hydroxylamine (19). Separation of the products from B and 1.2 equivalents of 2,4-dinitrophenylhydrazineon a, column of alumina (see below) and weighing the several eluted components indicated a content of 67.2% 6-one, 12.97, of carbonyl compound II,9.5% of carbonyl compound 111,and 10.4% of non-carbonyl material. I n similar work on another fraction which contained only two carbonyl compounds (see below) it was shown that the minor component is l-methyl-l-cyclohexen-3-one.2The yields of material corresponding to B from the next eleven batches mere higher, amounting to from 36 to 44 g. Fraction B mixed with similar cuts, 60.8 g., 6 g. of butadiene, and a few crystals of hydroquinone were heated in a sealed tube under nitrogen for forty hours a t 200". Fractional distillation of the products gave 27.3 g. of l-methyl-l-cyclohexen-6-one, bl7 67-74", (corrected) pure by the gravimetric DNPH method and free from other carbonyl conipounds (alumina column). Finally the distillates from two one-mole batches of selenium dioxide on methylcyclohexene were combined before fractional distillation and a single C above, was taken for purification with butadiene; 85g. fraction, corresponding to B of B C gave 45.3 g., b13 62-69'. nt 1.4850, yield 18% on cyclohexanone (17% recovered at this point, to which is added 1%recovered from other fractions; 1-methylcyclohexene from cyclohexanone, 80%). 1-Methyl-1-cyclohexen-6-oneof this degree of purity gives the maximum yields of methyloctalone (a 9-methyl-1-octalone with the C-C double bond probably a t C-6) and maximum recoveries of unchanged &one, thus far observed, when heated with further portions of butadiene (2). Siniilar material from anbther batch, b14 63-69', nt 1.4855 (K, Table I), was twice fractionated by distillation to give: (E) blr 63-65', nAga 1.4837; (F) (L, Table Ibb14 65", nh9 E 1.4850, ultraviolet absorption X,,,2355 d ( E 9200), Xmln 2780 d ( E 9), Amax 3180 A ( E 42);4 (G) b 65-66', n:' 1.4862.

+

+

Anal. of Fraction F. Calc'd for C?HloO: C, 76.3; H, 0.15. Found : C, 74.3; H, 9.1 Found, by a modification of Iddles' (18) (see below) gravimetric DKPH method : methylcyclohexenone, 96.5%. Estimution of carbonyl compounds CrHlaO in the various fractions. The estimation was usually made by Method 1,which consisted in taking 0.2 g. of the fraction, 28 ml. of ethanol and 0.44 g. (1.2 equivalents) of 3,4-dinitrophenylhydrazine,mixing, bringing to boiling, adding 0.6 ml. of concentrated hydrochloric acid, boiling for ten minutes, allowing to cool, filtering with suction, drying without washing, and weighing. The values so obtained were checked, for eome fractions, by two other methods which gave higher values and, therefore, corrections Mere sometimes applied as already indicated. Method 2 was a modification of that of Iddles (18). About 0.2 g. of the fraction was dissolved in 10 ml. of ethanol and the solution was dropped with sn irling into a lukewarm solution of 0.72 g. of 2,4-dinitrophenylhydrazine in 150 ml. of 2 *V hydrochloric acid. Three more ml. of ethanol was used t o complete the transfer of material. Finally 50 ml. more of 2 Y hydrochloric acid was added and the mixture was allowed to stand a t room temperature for four days. The precipitate was filtered, washed with 2 iV hydrochloric acid and water, and dried a t 110-120". Method 3 was that of Stillman and Reed (19) in which hydroxylamine is employed. A fraction, which gave a precipitate by Method 1 which could not be separated into components on alumina (IC, Table I), was found to contain 92% of niethylcyclohexenone by Method 1 and 95.1% by Method 2. Fraction J (Table I) contained, by Method 1, 94% of 4 We are indebted to Mr. Harry Bastron of this Bureau for all the ultraviolet absorption data in this paper.

126

BUTZ, DAVIS, AND GADDIS

TABLE I1 ULTRAVIOLET ABSORPTION OF FRACTIONS CONTAINING MORE 1-METHYL-l-CYCLOHEXEN-6-ONEu SOURCE

90%

SOLVENT

Nitrosochloride of I-methylcyclohexene (4) I-Methylcyclohexene and SeOzc I-Methylcyclohexene and SeOzc 1-Methylcyclohexene and SeOz (L, Table I) Semicarbazone of 2-hydroxy-2-methylcyclohexanone (M, Table I) (K,Table I) (0,Table I) (I

THAN

Hexanes Hexanes Water Ethanol Ethanol

2280 2270 2400 2355

Ethanol Ethanol Ethanol

2360 2355 2350

10600 9600

11OOo 9200

9500 loo00 9300

Measurements by Mr. Bastron. n: 1.4812. Kot

FIG. 1. ABSORPTION SPECTRUM

OF 1-METHYL-1-CYCLOHEXEN-6-ONE(95-98%

PURE)

IN

ETHANOL compounds reacting with 2,4-dinitrophenylhydrazine calculated as DNPH's of CrHloO; by Method 3,989-99.3% of carbonyl compounds calculated as C7H100. DNPH of 1-methyl-1-cyclohexend-one fyom the products of the interaction of i-methylcyclohexene and selenium dioxide. The material employed for the identification of the two

PREPARATION OF 1-METHYL-1-CYCLOHEXEXE-6-ONE

127

ketones was obtained by a procedure somewhat different from the preparative procedure already described. The selenium dioxide (111 g.) was added gradually during one hour t o 96 g. of 1-methylcyclohexenein 250 ml. of ethanol at 28'. Heat was then applied, cautiously a t first, thereafter in amount sufficient to maintain a steady refluxing for six hours. Steam distillation of the products gave four fractions: I, about 300 ml., containing much ethanol; 11,about one 1.; 111,about one 1.; and IV, the distillate obtained by taking the residue from I11 to dryness. After removal of ethanol (and probably 1-methylcyclohexene) from fraction I at SO mm. and bath 50°, the several fractions were worked up separately by extraction with ether. Thirty-six g. of material b2.5 77-80' and 20.5 g., b2590-115" were obtained. The lower-boiling fraction was combined with another portion (32 g.) of similar material. This mas twice fractionated by distillation at 754 mm. to give 53 g., b. 176-178" (J,Table I). T n o ml. of J and 1.5 g. of 2,4-dinitrophenylhydrazinegave by Method 1, modified by taking an excess of ketones, 95% of mixed DNPH's, ni. 176-175". Recrystallization from ethanol gave the DKPH of 1-methyl-1-cyclohexen-6-one(6-DNPH), m. 207-210'; mixture with 2.4-dinitrophenylhydrazine(m. 198-199"), m. 173-180". Anal. Calc'd for C13HlaS404: C, 53.8; H, 4.9; N , 19.3. Found: C, 53.95; H , 5.0; S,19.2. This 6-DSPH was identical with 6-DKPH from the mixture of isomers of 2-hydroxy-2methylcyclohexanone (see below) on-the basis of mixture melting-point and properties of the crystals.6 It was also identical with the DXPH from 1-methyl-1-cyclohexen-6-one prepared by the method of Wallach (4) (by F. L. Schmehl). Separataon of the DKPH's of 1-methyl-1 -cyclohexen-3-one and I-methyl-2-cyclohexen-6-one o n alumina. Mixtures of DNPH's were resolved by differential adsorption by Strain (20). An interesting application is the separation of the DSPH's of estrone and equilenin on gave the DNPH, m. 117-173"; Marvel and alumina (21). 1-Methyl-1-cyclohexen-3-one2 Levesque (22) found m. 172.5-173". A solution of 5.6 mg. of this 3-DSPH and 14.6 mg. of 6-DKPH in 75 ml. of petroleum ether (redistilled Skellysolve "B", essentially n-hexane, b. 60-70") was poured on a column of 15 g. of alumina (Merck's according to Brockmann), 8 mm. wide. I t formed a band 115 mm. long. Separation into two bands was observed after 150 nil. more Skellysolve "B" had been added. When 175 ml. in all had been added, the lower band reached the bottom of the column. Elution of the two bands separately 11-ith Skellysolve "B" was possible. A nirxture of the 3-DNPH with DXPH (yield 92y0 by method 1; corrected value for ketone content of source fraction, 977') from the fraction, bl, 67-74', obtained from the products of the reaction of 1-methylcyclohexene and selenium dioxide by removal of some minor components by heating with butadiene as described before, exhibited the same phenomena when dissolved in Skellysolve "B" and chromatographed on alumina. A solution of 3.4 mg. of 3-DXPH and 15.6 mg. of this 6-DNPH in 60 ml. of Skellysolve "B" mas poured onto a column of 15 g. of alumina, 6 x 460 mm. Development with Skellysolve "B" for about ten hoars gave tlvo bands; upper, 113 mm., lower, 176 mm. Elution of the lower band with the same solvent gave 17.1 mg. (6-DSPH, less strongly adsorbed!). Elution of the upper band gave 4.1 nig. of 3-DXPH Other things being the same. a somewhat longer column is required to effect the resolution \Then the 3-DSPH and 6-DSPH are present in about equal amounts. Howiogenezty of the fraction recocered after heating wzth butadiene. An experiment was carried out, similar to that described in the preceding paragraph, but with omission of the 3-DSPII. A solution of 20.7 mg. of the DNPH frorn the fraction b17 67-74' in 60 ml. of Skellysolve "B" was taken. After passing solvent through the column for sixteen hours, there was a single band at the bottom of the column, 304 mm. long. Elution of this material ~

~

~~

We are indebted to Mr. F. L. Schmehl for the examination of the crystals. It was found that 6-DXP€I, 3-DNPH and 2,4-dinitrophenylhydrazine are readily distinguished under a polarizing microscope. 6

128

BUTZ, DAVIS, A S D GADDIS

in many small portions, and readsorbing these portions on the column in the order of elution, followed by development with solvent, gave again only one band. Partly resolved mixtures cf 3-DKPH and 6-DXPH could be completely resolved by elution and repassage through the colump in this way. Heating with butadiene has therefore removed from rraterial similar to fraction B all compounds giving insoluble colored products with 2,4dinitrophenylhydrazine excepting 1-methyl-1-cyclohexen-6-one.The other data presented indicate that this product, which is typical of the material which has been used for the preparation of the methyloctalone, contains about 570 of non-carbonyl compounds and 95% of 1-methyl-1-cyclohexen-6-one. Demonstration of 2 -methyl-I-cyclohexen-3-one in fraction J (Table I ) f r o m l-methylcyclohezene a n d selenium dzoxide. A solution of 21.3 mg. of the DNPH from fraction J, not recrystallized, in 75 ml. of Skellysolve "B" was poured onto a column of 15 g. of alumina, 8 mni. wide, through which 25 ml. of solvent had previously beenpassed. Development with 300 ml. of Skellysolve "B" gave two bands; the upper, 126 mm., the lower, 152 mm. long. Elution of the lower band with the same solvent gave 15.3 mg.; the upper band gave 5.9 mg. "lie solution of the eluate from the lower band was concentrated and passed through a second column of alumina. There was no further resolution. The solution of the eluate from the upper band was concentrated and to i t was added 4.8 mg. of 3-DNPH. This was poured onto a column of alumina and the colored band was brought to the bottom of the column with 800 ml. of Skellysolve "B". There was no separation; hence the upper band from the DKPH's from fraction J consisted of 3-DNPH. Fraction J consists almost and 1-methyl-1-cyclohexen-3-one in the ratio of entirely of 1-methyl-1-cyclohexen-6-one three t o one. Cyclohexane-2 ,I-dione (mixture of tautomers 2 ) . Cyclohexane-l,2-dione (enol), m. 38-40' (11). Cyclohexane-l,2-dione (mixture of tautomers ?), b26 96-97', pale green liquid, was obtained from cyclohexanone and selenium dioxide (12, 13) in 19% yield calculated on cyclohexanone taken (these investigators calculated the yield on selenium dioxide taken, to be 35Y0). This liquid product was obtained after unchanged cyclohexanone had been removed by dissolving the dione in aqueous potassium hydroxide and reprecipitating with hydrochloric acid. I n the present work the cyclohexanedione for reaction with methylmagnesium iodide was prepared by mixing 112 g. (one mole) of finely ground selenium dioxide, 500 ml. of ethanol (commercial absolute) and 105 ml. (one mole) of cyclohexanone, shaking thoroughly every half hour for three hours, letting stand sixteen t o forty hours, refluxing for four hours, removing the solids by filtration, removing ethanol at 45" with a water-pump through an 85-mm. column, and distilling. Alkali and mineral acid \%-erenot used in the purification. Reliance was placed on fractional distillation for removal of most of the cyclohexanone. The fractions b,, 78-100" crystallized soon after condensing or when kept at 5" overnight. Redistillation of three such fractions from one-mole batches combined gave 110 g., b17 78-loo", n: 1.5069. The higher-boiling fractions remained liquid. When these were kept several months and then distilled, about half was recovered as solid (perhaps solid tautomer forms on standing or under conditions of distillation) ; yield, 36m0 on cyclohexanone. The refractive index of these fractions, taken before crystallization, was sometimes as l o a as n: 1.4955. The yield stated was obtained several times. Yields of 3C-33Y0 were obtained many times. For the preparation of one batch of l-methyl-lcyclohexen-6-one, once distilled dione was used. This bla 80-100", n: 1.4995, 103.5 g. from two one-mole batches (46%). I-Hydroxy-I-met1:ylcyclohexanoneor isomers. To the Grignard reagent from 52.6 g. of magnesium and 298 g. of methyl iodide in 800 ml. of ether, which had been refluxed for two hours, a solution of 112 g. of redistilled solid cyclohexane-1,2-dione in 400 ml. of ether was added slowly during trro hours, and the mixture was refluxed for two hours more. The next day i t was poured onto ice, acidified with hydrochloric acid, and stirred until clear. On the t t i r d day the ether layer was separated and the water layer was saturated with sodium chloride and extracted with 6 portions of ether, 125 ml. each. After concentration to about 400 ml. the combined ether solutions were washed twice with saturated

PREPARATION OF 1-METHYL-1-CYCLOHEXENE-6-OND

129

sodium chloride solution (total, 50 ml.) and dried with sodium sulfate. After evaporation of the ether, distillation at 15 mm. gave 95 g., b. 80-95", n;" 1.4644, and 15 g. of material with higher boiling range and refractive index. The yield of material, bls 80-95', in two later runs was only 75 g. This point was not investigated because in the subsequent work the without crude "ketol" was converted to semicarbazone and 1-methyl-1-cyclohexen-6-one distilling. A n a l . Calc'd for C7Hl2O2:C, 65.6; H, 9.4. Found, fraction bls 80-95': C,66.6; H, 9.7. This fraction gave the 3,5-dinitrobenzoate, colorless (after Filter-Cel), m. 154-la", obtained by Wilson and Read (15). The semicarbazone, m. 203-203.5' (15), was prepared by recrystallization of the semicarbazone from crude undistilled "ketol". A n a l . Calc'd for C8H16N302:N, 22.7. Found: N, 22.6. One g. of the fraction bl5 80-95", 1.8 g. of 2,4-dinitrophenylhydrazine,and 50 ml. of ethanol were heated to boiling and the solution was made clear by the addition of one ml. of concentrated hydrochloric acid. Boiling was then resumed. No precipitate formed during the first three minutes (in contrast to l-methyl-l-cyclohexen-6-one), but after five minutes of boiling there was a heavy precipitate of the 2,4-dinitrophenylhydrazone of 1-methyl-1-cyclohexen-6-one; 2 g., after standing two days, m. 19&203", mixed m.p. with material from products of selenium dioxide on 1-methylcyclohexene, 199-203'. Recrystallized for analysis, m. 205-207'.

Anal. Calc'd for CI,HlaNaOc: C, 53.8; H, 4.9; N, 19.3. Found: C, 53.8; H, 5.0; N, 19.1. Attempts fo dehydrate the distilled "ketol". The fraction b16 80-95", described in the preceding section, was subjected to a large number of dehydration procedures which did not give 1-methyl-1-cyclohexen-6-one in satisfactory yield. Some reagents gave, along with much unchanged (refractive index) material, products with refractive index aa high as 1.500 ( n enone, ~ see Table I). It is possible that the conditions were so extreme that 0-cresol was formed. The indices were especially high when iodine was employed for the dehydration. When 45 g. of "ketol" and 2.5 g. of potassium bisulfate were heated in a bath at 250" for one hour and the products were distilled, it was possible t o recover about half the material taken in one fraction, bls 80-go", n;" 1.4663, Xmax (ultraviolet) 2680 d (e 180), Xmin 2500 d ( E 105) i n hexanes. I n another trial 30 g. of "ketol" was refluxed with 60 ml. of water and 30 g. of oxalic acid for three hours. All of the "ketol" dissolved and the solution remained nearly colorless. Steam distillation, extraction of the distillate and residue with ether, and fractional distillation of the dried residue from ether gave five fractions (5 ml. each), bla 74-93", n:" 1.4608-1.4685. A middle fraction, bla 86-87", n:" 1.4669, was shown by analysis to be nearly pure "ketol". This b. 190-202' at atmospheric pressure; n:' 1.4668. A n a l . Calc'd for CrHlzOz: C, 65.6; H, 9.4. Found: C , 66.0; H, 9.2. Absorption i n ultraviolet: A,, 2350 d ( E 270); Xmm 2500 d (e 210); Am,, 2720 h (e 330) in ethanol. Xmax 2745 A ( e 128) has been found (23) for 2-hydroxy-3-methyl-6-isopropylcyclohexanone. T h e crystalline isomer of .3-hydroxy-B-methylcyclohexanone.A number of " ketol" preparations, both before and after being subjected t o dehydration procedures such as heating with potassium bisulfate, deposited crystals when allowed t o stand for a week or more. One fraction b12 74-87", n: 1.4650, deposited crystals after eight days a t 0". The crystalline

130

BUTZ, DAVIS, AND GADDIS

solid from 66 g. (n: of residual liquid w m 1.4690) was filtered, washed with Skellysolve “F!’, and recrystallized from Skellysolve “B”; 3.5 g., m. 172.4-173.4’.

Anal. Calc’d for C ~ H Z OC, ~ :65.6; H, 9.4. Found: C, 65.6; H, 9.5. This compound dissolved in ethanol was transparent t o ultraviolet light, thus indicating the absence of carbonyl and or-keto1 groups. Two hundred mg. of the solid C1H~202,500mg. of hydroxylamine hydrochloride, 3 ml. of water, and 2 ml. of 10% sodium hydroxide solution were added t o enough ethanol t o dissolve nearly all of the solid. The mixture was heated at 100” for one hour. The crystals which separated on cooling consisted of unchanged compound, m. 173.4-174.4”. No oxime was found Twenty-two ml. of ethanol containing 219 mg. of the solid C7H1202 and 420 mg. of 2,4dinitrophenylhydrazine was brought to boiling, 0.5 ml. of concentrated hydrochloric acid was added, the mixture boiled again, then cooled. The DXPH of 1-methyl-1-cyclohexen-6one Q-asobtained in 96% yield, m. 207-209”. Acetylation of d-hydroxy-2-methylcyclohexanone. “Ketol”, b13 69-81’, n! 1.461-1.466, 25.4 g., and 200 nil. of acetic anhydride were heated at 100”for eleven hours. After removal of acetic anhydride and acetic acid, 22.2 g. of material b14 100-130” (66% calculated as acetate) was recovered. Some solid C7H1202,m. 173.5-174.5”, separated from this distillate, indicating resistance to acetylation. Fractional distillation of the acetylation products gave a cut blb 115-llSo, n! 1.4570.

.

Anal. Calc’d for C~H1403:C, 63.5; H, 8.3. Found: C, 63.9; H, 8.7. Attempts to convert the acetate to 1-methyl-1-cyclohexen-6-onein satisfactory yield were not successful. I-iwethyl-1 -cyclohexen-6-one from cyclohexane-1,%&one without purification of intermediates. Redistilled solid cyclohexane-l,2-dione, b18 7&110”, n! E 1.5069 (110 g.), and methylmagnesium iodide were allowed to react as already described. The products, however, were worked up to the drying of the ether solution inclusive on the second day and a few crystals of sodium thiosulfate were added t o the saturated sodium chloride solution used for washing i n order to remove traces of iodine. Evaporation of the ether gave 121 g. of crude “ketol”, which was dissolved in 120 ml. of ethanol, mixed with 107 g. of semicarbazide hydrochloride and 161 g. of anhydrous sodium acetate in 292 ml. of n;ater, and the mixture was shaken vigorously. Semicarbazone was precipitated almost immediately. Filtration and strong suction on the following day gave about 170 g. which was mixed with one 1. of 10% aqueous sulfuric acid and distilled in steam. The distillate was exhaustively extracted with ether, the extract was washed with saturated sodium bicarbonate solution and dried with sodium sulfate, and the ether was evaporated on a steam-bath. Distillation of the residue gave 62 g . (50%), b14 67-69’, n t ‘ 1.4826, which was combined with 52 g. of similar material and the whole distilled a t atmospheric pressure with an eight-inch column. Two cuts of the distillate were examined: (I) 65 g., b. 176-178”, n;” 1.4828; and (11) 32 g., b. 178-180”, n; 1.4838. The ultraviolet absorption data for these and other fractions are given in Table II.* C, 76.3; H, 9.15. Anal. Calc’d for C~HIOO: Found: (I) C, 75.6; H, 9.4. (11) C, 75.8; H, 9.2. These values for carbon and hydrogen content correspond t o a mixture of 93% methylcyclohexenone and 7% hydroxymethylcyclohexanone. Redistillation of fraction I disclosed that the material was not homogeneous. Accordingly it seems likely that purer specimens of 1-methyl-1-cyclohexen-&onemight be obtained if the conditions of decomposition of the semicarbazone were altered. A few

PREPARATION O F 1-METHYL-1-CYCLOHEXENE-6-ONE

131

variations were tried, including refluxing for one hour before steam distillation, without substantial difference in the result. Material from four such experiments, blc 64-72', n: 1.4807 (1.4754-1.4830), was therefore reconverted to semicarbazone and this semicarbaeone (largely of methylcyclohexenone) (semicarbazone of 2-hydroxy-2-methylcyclohexanone is white, semicarbaeone of 1-methyl-1-cyclohexen-6-one is yellow) again hydrolyzed. Fifty-seven g. in 57 ml. of ethanol was mixed with 61 g. of semicarbazide hydrochloride and 92 g. of anhydrous sodium acetate i n 166 ml. of water. The mixture was vigorously shaken, let stand overnight at room temperature, then one day more i n the refrigerator. The semicarbazone and 600 ml. of 10% sulfuric acid was refluxed for a half hour, let stand overnight, and distilled in steam. After working up as alreadydescribed, distillation a t 14 mm. gave : i l l ) 2 ml., b. 63-65', ng 1.4803, tB) 5 ml., b. 65-66", n: 1.4820. iC) 38 ml., b. 66-66.5', ng 1.4849 (N,Table (D) 3 ml., b. 66.5", ng 1.4862

I)

A n a l . Calc'd for CTH~OO: C, 76.3; €1,9.15. Found: (C) C, 75.55; H, 9.6. Thirty-four g. of this fraction C was distilled twice. The spread of n~ after the first distillation, in xhich six equal cuts were taken, was 1.4842-1.4858. The four highest boiling cuts were then distilled and four equal cuts (20 ml. in all) were taken. The four all b. 66.7-66.9" and the spread of nD was 1.4850-1.4857, A fraction, n:" 1.4854, was analyzed. Six n-eeks later the refractive index had risen to n: 1.4892. The solution for ultraviolet spectrum was prepared a t this later time. Several other fractions exhibited similar increases in refractive index. A n a l . Calc'd for C;HloO: C, 76.3; H, 9.15. Found: C, 76.5; H, 9.4. SUMMARY

1. Slightly impure 1-methyl-1-cyclohexen-&one has been prepared by two routes from cyclohexanone in 18% yield. 2. The 2,4-dinitrophenylhydrazone of 1-methyl-1-cyclohexen-6-one(a new compound) can be separated from the 2,4-dinitrophenylhydrazoneof l-methyl1-cyclohexen-3-oneby chromatography. 3. Oxidation of 1-methylcyclohexenewith selenium dioxide gives l-methyl-lcyclohexen-6-one, l-methyl-l-cyclohexen-3-one,and other products not yet identified. 4. Two compounds isomeric with and closely related to 2-hydroxy-2-methylThe other cyclohexanone have been prepared. One of these m. 173.4-174.4'. is a liquid which boils a t about 200" under atmospheric pressure. BELTSVILLE, LID. REFERENCES (1) NUDENBERG AND BUTZ,J. Am. Chem. SOC., 66, 1436 (1943). AND BUTZ,J. Am. Chem. SOC., in press. (2) GADDIS Ber., 36,2824 (1902); Ann., 329,373 (1903). (3) WALLACH, (4) WALLACH,Ann., 369, 303 (1908). AND BEDOS,Compt. rend., 181,919 (1925). (5) GODCHOT (6) URION,Compt. rend., 199, 363 (1934). (7) GODCHOT AND CAUQUIL, Bull. SOC. chim., (5) 2, 1100 (1935).

132 (8) (9) (10) (11) (12) (13) (14) (15) (16) (17) (18) (19) (20) (21) (22) (23) (24)

BUTZ, DAVIS, AND GADDIS

DUPONT, Bull. SOC. chim. Belg., 46, 57 (1936). GUILLEMONAT, Ann. chim., (11) 11, 33 (1939). WHITMORE AND PEDLOW, J. Am. Chem. ~ o c . 63, , 758 (1941). WALLACH AND WEISSENBORN, Ann., 437, 172 (1924). J. Chem. SOC.,1875 (1932). RILEY,MORLEY,AND FRIEND. RAUH,SMITH, BANKS, AND DIEEL, J. Org. Chem., 10, 199 (1945). Ber., 74, 554 (1941). MANNICH, WILSON AND READ,J. Chem. 8 O C . , 1269 (1935). (a) BERGMANN AND GIERTH,Ann., 448, 48 (1926); (b) BERGMANN AND MIEKELEY, Ber., 62, 2297 (1929). STAUDINGER AND RUZICKA, Helv. Chim. Acta, 7, 377 (1924). IDDLES, Ind. Eng. Chem., Anal. Ed., 11, 102 (1939). STILLMAN AND REED,Perfumery and Essential Oil Record, 23, 278 (1932). STRAIN,J . Am. Chem. SOC.,67,758 (1935). VEITSCHAND MILONE,J. Biol. Chem., 167,417 (1945). AND LEVESQUE, J. Am. Chem. SOC.,60,280 (1938). MARVEL WALKER AND READ,J . Chem. Soc., 240 (1934). URION,Compt. rend., 192, 1662 (1931).