NOTES
Feb., 1946 TABLE I1 % excess of
Molar proportion of DiphenoryChloropropane sulfonic acid
1 1 1 1
chlorosulfonic acid
4 5
% yield of
disulfonamide
solvent was reyoved t o leave the crude product (33.0 g.), m. p. 138-142 After recrystallization from ethanol it weighed 30.7 g. (F9% yield) and melted at 143.5-144 (see Table I for analysis).
.
N,N'-Diacety1-~,~-diphenoxypropane4,4'-disulfon-
26
0 25 50 112
337
amide (VI).-A mixture of a.r-di~henoxv~ro~ane-4,4'disulfonamide (31.5 g., 0.0815 mole) -and ac&c anhydride 6 83 (250 cc.) was refluxed one hour then poured onto ice and 8.5 64 allowed t o stand overnight. The solid product (m. p. 163-168') was recrystallized from aqueous acetic acid t o The disulfonamide, after recrystallization from an give the pure diacetyl derivative (25.6 g., 67% yield), m. p. ethanal-methyl ethyl ketone mixture, was in the form of 169-170' (see Table I for analysis). feather-like clusters, m. p. 194.5-195'7 (see Table I for The material crystallizes as a monohydrate and if the analysis). The structure of the material prepared in sample is dried in a vacuum a t not over 80" it analyzes for these Laboratories has been unequivocally proved, as will a monohydrate. be shown in the following paragraph. Z O46.71; : H, N,N,N',N'-Tetramethyl-~~,~~diphenoxypropme4,4'-Anal. Calcd. for C ~ , H ~ & T ~ O & C HC, disulfonamide (IV). A.-A portion of the same chloro- 4.92; N, 5.73. Found: C, 46.73; H , 4.72; N, 5.92. The diacetyl derivative VI (25.0 g., 0.0512 mole of form solution of a,y-diphenoxypropane-4,4'-disulfonyl chloride, of which part had been used to prepare the amide monohydrate) was dissolved in 106 cc. of 0.962 N sodium 111,m. p. 194.5-195", was treated with an excess of aqueous hydroxide (the theoretical amount), the solution was dimethylamine. The resultant solid, after two recrystal- evaporated to a thick paste and the residue was triturated lizations from ethanol, was in the form of flaky crystals, with ethanol to give the white solid disodium salt VI1 (see Table I for analysis). in.p. 191' (see Table I for analysis). B.-A mixture of 4-hydroxybenzenesulfondimethylSummary amide1 (620 mg., 3.1 millimoles), potassium hydroxide (175 mg., 3.1 millimoles), and trimethylene bromide (300 1. a,y-Diphenoxypropane has been converted mg., 1.5 millimoles) in ethanol (10 cc.) was refluxed one hour. The mixture was poured into water and the white by chlorosulfonic acid followed by ammonia into solid formed was recrystallized once ofrom ethanol then the 4,4'-disulfonamide. once from methanol; rn. p. 187-189 . When this sub2. The orientation of the two chlorosulfonyl stance (m. p. 187-189") was mixed with a sample of the groups entering the molecule has been proved by same material (m. p. 191") prepared by procedure A, the showing that an amide prepared from the dimixture melted a t 188-190". 85
N,N'-Diethyl-a,~-diphenoxypropane-4,4'-disulfonamide sulfonyl chloride is identical with that synthesized
(V) .-a,~-Diphenoxypropane-4,4'-disulfonylchloride (42.5 g., 0.10 mole, crude, m. p. 116-117') dissolved in chloroform (200 cc.) was stirred a t room temperature for forty five minutes with aqueous ethylamine (100 g. of 33% solu tion, 0.73 mole), the chloroform was separated and the
(7) A compound of m. p. 245-255' prepared in 44% yield from a,-,-diphenoxypropane with chlorosulfonic acid, and giving satisfactory analyses, was reported by Huntress and Carten.' In the light of results reported in the present paper, however, their product could not have been a,r-diphenoxypropane-4,4'-disiilfonamide.
directly from the corresponding 4-hydroxybenzenesulfonamide and trimethylene bromide. 3. The following four other N-substituted disulfonamides were prepared : dimethyl, ethyl acetyl, and sodio-acetyl. 4. None of these compounds have trypanocidal activity. RENSSELAER, NEWYORE RECEIVED NOVEMBER 1, 1944
NOTES Mechanism of the Reaction between Hindered . Allyl Esters and Grignard Reagents
An experimental result obtained over a year ago has forced us to make some drastic alterations BY RICHARDT. ARNOLDAND R. WINSTONLIGGETT' in the mechanism proposed earlier.2 I t has bee? found that the olefin produced when phenylmagIn two previous publications from this Labora- nesium bromide is allowed to react with n-crotyl t ~ r yit.was ~ . ~shown that allylic esters of hindered mesitoate is pure n-crotylbenzene (I) and apparcarboxylic acids react with Grignard reagents to ently contains none of the isomeric isocrotylgive hydrocarbons and halomagnesium salts benzene. according t o the following equation. //O 2,4,6-(CH8)3CsHlCOCHzCH=CHCH3 4- Cd&MgBr + R-C
+
//O R'MgX -~OCH~CH=CH~
+
(1) Dupont Post Doctorate Fellow 1941-1942.
(2) Arnold, Bank and Liggett, THISJOURNAL, 63, 3444 (1941). (3) Arnold and Liggett, ibid., 64, 2875 (1942).
+ CBI-ISCHZCH=CHCHI
2,4,6-(CHa)3C6H&02MgBr
I
This seems of especial interest since it is well known that either of the pure isomeric crotyl halides gives a mixture of isomeric hydrocarbons when treated with the Grignard reagent. We believe that the hew mechanism outlined
338
NOTES
Vol. 67
acetone derivatives of d- and 1-mannitol. The key position of these two compounds is illustrated by the fact that they have become essential intermediates in the synthesis of d( +) a-glycerophosphate,' I( - ) a-glycerophosphate,2 the normal alir X 1 phatic cu-mon~glycerides,~~~ ol,fi-digly~erides,~ triglyceride~,~ batyl chimyl alcohol, and selachyl a l ~ o h o l . ~Since the number of applications call be expected to increase, the importance of finding an improved method of preparing these I1 mannitol derivatives is obvious when one con,0-MgX siders the labor involved in the older methods. Rn-C KCH&H=CHK' XO The first synthesis and description of 1,2,5,6By inspection of I1 i t can be seen that group R diacetone d-mannitol was given by E. Fischer and (from RMgX) is one element of a quasi six-mein- Rund in 1916.* They obtained the substance on bered ring and because of this fact it is geo- acetonation of d-mannitol with acetone and metrically in a position such that i t must attack hydrochloric acid, but in a yield of 2% only. By only the a-carbon atom of the allylic system changing the solvent used for extracting the product from the reaction mixture Fischer and a S r (--CHr-CH=CH-R') when the redistribution Baer in 11)349succeeded in raising the yield of this of electrons (as indicated by the arrows) is com- process to approximately 6%. An entirely differpleted. We regard the breaking and formation ent procedure was reported by von Vargha,'O who of bonds in the decomposition of I1 as occurring conducted the acetonation with concd. sulfuric acid in the presence of boric acid. The resulting simultaneously. When conditions permit, a systematic investi- boric acid ester (4.5) of 1,2-acetone d-mannitol gation to prove or disprove this newly proposed was freed from boric acid by alcoholysis and the second acetone introduced by acetonation with mechanism will be undertaken. copper sulfate. 'The yield was still very low Experimental n-Crotyl Mesibate.-This ester was prepared from (14%); moreover, the outcome of the synthesis pure n a o t y l alcohol, mesitoyl chloride and pyridine in was unpredictable. With the chemicals then cold chloroform sofution as described earlier in other ex- (1934) available in Rase1 (Switzerland) we sucamples; yield 58%; b. p. 160-165' (17 mm.). ceeded only twice out of many trials in obtaining Anal. Calcd. for C14Hfa02: C, 77.0; H, 8.3. Found: any yield of diacetone d-mannitol. It is possible C, 76.8; H, 8.7. that some reactant in the successful preparations The ester on ozonolysis gave acetaldehyde as the sole contained a contaminant which acted as a catalyst volatile aldehyde. n-Crotylbe&ene.-Cleavage of n-crotyl mesitoate with for the condensation. phenylrnagnesium bromide as described earlier* for other The successful application of zinc chloride as examples gave a hydrocarbon; yield 75.5%; b p . 81 83" catalyst in other acetonation reactions [Fischer and (22 mm.). (Reported 81-82' (18 mm.) ;) Taube,ll Fischer and 13aer12]prompted a study of Anal. Calcd. for CloHlZ: C, 90.9; H, 9.1. Found: its use for the preparation of the diacetone manniC, 91.0; H, 9.15. This hydrocarbon gave acetaldehyde as the ouly identi- tols. These studies resulted in 1939 in the developfiable volatile aldehyde. Catalytic hydrogenation gave a ment of a quite satisfactory method (Baer and non-olefinic hydrocarbon whose vapor pressure curve was F i ~ c h e r ~ ~the ~ Jyields ~ ~ ) being , raised to 56%, but identical with pure It-butylbenzene and quite different owing to the labor involved in the removal of large from that of s-butylbenzene. amounts of zinc chloride and solvents the method (4) Auwers, Roth and Eisenlohr, Anti., 983,108 (1311J. as described then was still cumbersome and only applicable to small scale preparation. The conseSCHOOL OF CHEMISTRY UNIVERSITY OF MINNESOTA quent necessity of repeating the synthesis a t frebelow offersan accurate description of the reaction which is under investigation in these Laboratories.
+
MINNEAPOLIS, MINNESOTA RECEIVED OCTOBER 23, 1944
1,2,5,6-Diacetone a!-Mannitol and 112,5,6-Di-
acetone 2-Mannitol BY ERICHBAER
The chemical synthesis of pure enantiomorphs of optically active compounds of biological interest often involves the use of difficultly accessible intermediates. The recently described syntheses of the enantiomorphs of a number of unsymmetrically substituted glycerols have been laborious because of the commercial unavailability and the lack of an efficient synthesis of the 1,2,5,6-di-
(1) 1s. Baer a n d H. 0. L. Fischer, J . Biol. C h c m . , 136, 321 (I!MOl. (2) P;. Baer and H.0 . L. Fischer, ibid., 148,491 (1939). (3) E. Baer axid 13. 0. L. Fischer, ibid., 128, 475 (1939). (41 E. Baer and IX. 0. L. Fischer. communication in preparation for THISJ O U R N A L . ( 5 ) 5. C. Sowden and H. 0. L. Fischer, THISJOURNAL, 63, 3244 ( 194 1J . (61 E. Baer a n d H. 0. L. Fischer, J. B i d . Chem., 140, 397 (1941). (7J E. Baer, L. Rubin and H. 0. L.Fischer, i b i d . , 166, 447 (1944). (8) E. Fischer and C. Rund, Ber., 49, 9 1 (1916). (91 H. 0. L. Fischer and E. Baer. Hclo. Chim. Acta. 17, 622 (1934). (10) L. von Varghr, Bcr., 66, 1394 (1933). (111 H.0. L. Fischer and C. Taube, i b i d . , 60, 485 (1927). ( 1 2 ) H. 0. L. Fischer and E. Baer, ibid., 63, 1749 (1930). (131 (a) E. Baer and H. 0. I,. Fischer, J . B i d . Ckem., la%,463 (193oI. (b) E. h e r and H. 0. L. Fischer. THISJOURNAL, 61, 761 (193!J).
