128
M.
s. KHARASCH AND P. 0.TAWNEY
A reaction took place immediately with the formation of a heavy pale-yellow precipitate and the evolution of heat. The mixture was heated on a steam-bath for one hour with shaking. The precipitate was filtered, washed with dioxane and ether, and dried in a vacuum desiccator. The yield was 13.6 g. (lOOjoo) of pale-yellow crystals melting a t 214.5-215.5' dec. N-p-AcetylsulfanilyI-N'-phenylhydrazine.-Four and five-tenths grams of phenylhydrazine was placed in a beaker containing 5 g. of sodium carbonate dissolved in 100 ml. of cold water. To this was added slowly with stirring 10 g. of $-acetylaminobenzenesulfonyl chloride. The mixture was removed from the ice-bath after all the ehloride had been added and stirred for an additional thirty minutes. The tan precipitate was removed by filtration, washed with water, and dried in a vacuum desiccator. It weighed 11 g. (76% yield). Three recrystallizations from an alcohol-water mixture, using Norit, gave a white crystalline product melting at 157-9" dec N-(N-Thiazolyl) -p-sulfonamidQphenyl-N'-methylthiourea.-Seventeen and seven-tenths grams of sulfathiazole was placed in a small flask with a ground glass joint. To this was added 150 ml. of absolute ethanol and 5 g. of methyl isothiocyanate. The mixture was refluxed on the qteam-bath for twentv-two hours. At the end of this time
Vol. 07
there was a slight residue in the flask. The reaction mixture was cooled in an ice-bath and the crystalline precipitate filtered, washed with ethanol, and dried. The yield was 17 g. (75%). The product was thoroughly ground up and treated with dilute hydrochloric acid t o remove any unreacted sulfathiazole. It was then recrystallized from boiling water using Norit. White needles melting a t 190--193° were obtained.
summary 1. Twelve sulfanilamide derivatives contain-
ing a substituted urea or thiourea grouping in the N' position and fourteen containing a urea or thiourea grouping in the N' position were prepared and described. 2. The preparation of acetylsulfanilylhydrazine and N-p-acetylsulfanilyl-N'-3-nitrophenylhydrazine is described. 3. Methyl isothiocyanate wm found to react with sulfathiazole to give N-(N-thiszolyl)-psulfotmmidophenyl-N'-methylthiourea LAFAYETTE, IND. RECEIVED JUNE22, 1934
[CONTRIBUTION FROM DEPARTMENT OF CHEMISTRY, UNIVERSITY OF CHICAOO]
Factors Influencing the Course and Mechanism of Grignard Reactions. XVI. h Isomer of Isophorone -~~~~-3,5,3-Trimethylcyclohexenone BY M. S. KHARASCH AND P. '3. TAWNEY enol of a cyclic ketone (saturated or unsaturated) has ever been isolated. The absorption spectra of the two compounds in question have, however, since been determined. They indicate condusivety that the new isomer has the keto,*cture (111). That is to say, when methylmagnesium CH3 CHI CHa CHs CHa CHa bromide reacts upoii isophorone in the presence of I/ ' , I small amounts of ferric chloride, it shifts the o = o 6 - O H double bond from the a-@ to the 0-7position. The ultraviolet absorption curves for isoCHI CH3 CHn phorone I and A3~4-3,5,5-trimethylcyclohexenone Isophorone (I) Enol (11) Keto (111) (111) are given in Fig. 1. These curves (as well The following facts favor the enol structure (11): as the infrared absorption curves in Fig. a) were (a) The compound is easily reconverted into iso- obtained through the courtesy of the Stamford phorone, especially in the presence of acid. (b) Research Laboratories of the American CyanThe new compound yields a semicarbazone which amide Company, to whom sincere thanks are here is identical with that of isophorone, since the two expressed. These investigators have also kindly do not depress each other's melting points. The provided an analysis of their findings, from which following facts favor the keto structure (111): some of the following statements are taken. The ultraviolet absorption curve for isophorone (a) The molar refraction of the new compound checks with that calculated for a compound with exhibits an intense broad absorption band with structure (111). (b) Cyclohexylidineacetic acid maxima near 2845, 2975, 3070 and 3700 mm.-'. and cyclohexenylacetic acid are easily converted The band at 4450 mrn.-' indicates the presence into one another as are cyclohexylidine acetone of conjugated unsaturation; the absorption near and cyclohexenyl:icetone.2 By analogy, similar 3700 mm.-' may possihly represent approxibehavior might be expected of the two ketones mately 0.5% of a substance such as compound (11) with two conjugated double bonds in the (I) and (111). A t the time the aforementioned paper was pub- ring. Cooke and Macbeth* have examined the lished, the available data were insufficient to war- ultraviolet absorption spectra of a number of unrant a decision between structures (11) and (111). saturated aldehydes and ketones. The curve Structure (111)was favored, inasmuch as no stable they obtained for piperitone (IV) in hexane very closely approximates that of isophorone (I) in In a previous paper' it was shown that methylmagnesium bromide, in the presence of a small amount of ferric chloride, converts isophorone into an isomeric substance for which the structures (11) and (111) were considered.
a=.
13) Cooke and Macbeth. J Chem. Soc., 1408 (1938).
2.0
3 ."x
'3
1.0
U
-1.0
bonds, but it does show carbonyl absorption in the broad band near 3500 mm.-l. A double bond in the ring, when not conjugated, has a very small -2.0 effect on the absorption. The spectrum for compound (111) may be compared with that of men2800 3200 3600 4000 4400 thone (V)given by Cooke and Macbeths Wave number, rnm.-'. Isophorone shows an infrared absorption band Fig. 1 .-Ultraviolet absorption curves for cyclohexane a t 1670 crn.-l which is characteristic of a carbonyl solutions of. isophorone (I), and Aa*4-3,5,5-trimethyl- qroup conjugated with an olefin double bond. hexenone (111). The spectrum observed is quite parallel to that of mesityl oxide. The new isomer shows no infrared cyclohexane, as may be seen from the following Aata.
The ultraviolet absorption curve of the new isomer shows no evidence for any conjugated double
2300
3400 3000 2600 Frequency in wave numbers, ern.-'. Pig. 2a - .?nfrared ahsorption spectra (thickness 0.02 mm.). -3800
2500 2700 2900 Wave length, A. Fig. 3.-Absorption spectra in ethanol solution: 0 cyclohexanone semicarbazone; 0 , isophorone semicarbazone, 0 . tautomer (TIT) semicarbairnne.
J. H. BILLMAN,T. G. WARDAND P. H. HIDY
130
Vol. 67
The chemical data do not warrant the assignment of a definite structure to the semicarbazone in question, but a comparison of its ultraviolet H"C$S2-C_-H ;c=o absorption curve with that of cyclohexanone __ semicarbazone (Fig. 3) suggests that the semiHz' H-CHB carbazone in question is derived from isophorone i (I) rather than from its isomer (111). If such is CH, the fact, then when the semicarbazone is formed (111) (VI from (111), the double bond is shifted, during K3mo = 0 I17 Kareo = 0.126 the process of formation, from the P,-y to the alp absorption for hydroxyl, either associated or un- position. associated. The carbonyl absorption is that of a Summary normal ketone. 1. Ultraviolet and infrared absorption spectra These data indicate that both the infrared and ultraviolet absorption spectra of the new com- indicate that when isophorone is treated with pound are in accord with the keto structure (111). methylmagnesium bromide in the presence of Structure of the Semicarbazone Formed from small amounts of ferric chloride, the double bond Compounds (I) and (III).-Compounds (I) and in the ring is shifted from the a,p to the ply (111) each yields a semicarbazone which melts position. 2 . In the formation of the semicarbazone of at 186-187O.l Since these semicarbazones do not A3~4-3,5,5-trimethylcyclohexenone, the double depress each other's melting points, they may be concluded to be identical. This conclusion bond is shifted back to the a,@ position and the is supported by their ultraviolet absorption semicarbazone of isophorone is obtained. CHICAGO, ILLINOIS RECEIVED AUGUST28, 1944 curves (Fig. 3).
&
[CONTRIBUTION FROM THE CHEMICAL LABORATORY O F INDIANA cNIVERSITY
i
Antispasmodics and Anticonvulsants. N. N,N'-Substituted a-Aminodiphenylacetamides BY JOHN H. BILLMAN, THELMA G. WARD'AND PHILHARTERHIDY* I n an earlier publicationa it was shown that certain a-aminodiphenylacetamideshaving identical OH I
(1)
OH
O
,
JCBHS)~-C-C-OCHS
phenylacetamide. However, to verify this the following reactions were run
I
0 /I
+ CHJNHZ+(CsH6)2C---C--rU"CH3
radicals attached to both of the nitrogen atoms, possessed anticonvulsant as well as antispasmodic acitivity. It was decided, t4erefore, to synthesize a number of derivatives having dissimilar groups attached to the nitrogens by using a-chlorodiphenylacetyl chloride and two different amines. The a-chlorine atom of an a-chloroacyl chloride is normally much less reactive than the chlorine atom attached to the carbonyl group. Klinger4 has done some work which indicates that cu-chlorodiphenylacetyl chloride when treated with two moles of aniline produces N-phenyl-a-chlorodi(1) Submitted to the Faculty of t h e Graddate School in partial fulfillment of the requirements for the degree, Doctor of Philosophy, in t h e Department of Chemistry, Indiana University (2) Eli Lilly Fellow (3) Billman and Hidy, THISJOURNAL, 66, 700 (1943). (4) Klinger, A n n . , 389, 255 (1912)
+ CHaOH
The diphenylacetic acid derivatives (I) formed in reactions (1) and ( 2 ) were found to be identical. Both products melted a t 146-147' and gave no depression in melting point when fused together. This temperature is approximately 60' below the melting point of the isomeric a-methylaminodiphenylacetic acid.5 Neither product was soluble in alkali or hydrochloric acid. Thus the structure of Compound I1 is established. These results along with the fact that the a-chloroacetamides were obtained in yields of better than seventy per cent. confirm the order and relative ease of replacement of the chlorine atoms in a-chlorodiphenylacetyl chloride. It is this appreciable difference in reactivity which made possible the synthesis of a-aminodiphenylacetamides, with unlike radicals attached to each nitrogen atom, according to the reactions ( 5 ) Biltz and brydel, A J L N, 391, 227 (1912)
