BEACHEM, SHAW, SARGENT, FORTENBAUGH AND SALSBURY
5430
VOl. 81
TABLEI11
REACTIONS OF VARIOUSSULFONATES Sulfonate
Solvent
Cyclohexyl benzeneCyclohexyl p-tolueneCyclohexyl p-tolueneCyclohexyl p-toluene2-Octyl benzene2-Octyl benzene2-Octyl 2-naphthalene2-Octyl benzene-
Dimethyl sulfoxide Dimethyl sulfoxide Hexamethylphosphoramide Dimethylformamide Dimethyl sulfoxide Dimethyl sulfoxide Dimethyi sulfoxide Hexameth ylphosphoramide
sulfonate was heated in pyridine solution. The reaction was considerably slower, and a much lower yield of menthenes was obtained (Table I ) . The olefin composition and degree of racemization of the A3-menthene were similar to those obtained with the other solvents. Hence, it seems likely that pyridine and related bases also promote the decomposition of sulfonate esters by a solvolytic ionization route, although much less effectively. In summary, the available evidence suggests that in the formation of olefins from sulfonate esters of secondary alcohols, dimethyl sulfoxide and hexamethyl phosphoramide function as highly polar non-reacting solvents, and promote the decomposition by an ionic path.
Experimental
Solvolysis of ( - )-Menthyl Benzenesulfonate in Dimethyl Sulfoxide.-A solution of 29.6 g. (0.10 mole) of (-)-menthyl benzenesulfonate in 150 i d . of dimethyl sulfoxide (Stepan Chemical Co.) was heated (solution temperature 89-91') under reflux for 6 hours. On allowing the solution to cool t o room temperature, two layers formed. The mixture was extracted with 50 nil. of ligroin (b.p. 66-75"], which dissolved the upper layer. The lower layer was poured into an equal volume of a mixture of ice and water, and the resulting mixture was extracted with two 50-ml. portions of ligroin. All of the ligroin extracts were combined, washed with two 50-ml. portions of water, 50 ml. of saturated brine and then filtered through anhydrous sodium sulfate. The ligroin was removed by distillation through a 7" L'igreux column and the residue was fractionated with an eficient semi-micro column.l* Five fractions were collected __.___
(14) C. W. Gould, Jr., G. Holzman and C. I'iemann, A n d . C h o n . , 20, 301 (1948).
[CONTRIBUTION FROM ?'NE
Temp., OC
Time, hr.
Product
90-95 90-95 100 100 100-107 100 100 100
2 5 6 5.5 0.75 1 1 3
C yclohexene Cyclohexene Cyclohexene Cyclohexene Octene Octene Octene Octene
7 '0 65 61 62 55 52 58 30 61.5
Yield,
and combined to give 10.5 g . (76%) of mixed menthenes, b.p. 60-61.5" (17-19 mm.), nZD 1.4495 - 1.4500, [CY],D f85" (170 iii CHC18); reported15 for a mixture containing 247, A2-menthene, b.p. 64.565' (22 mm.), n z 5 1.4500, ~ [a]~ $117' (1% in CHCla). The residue (1.53 g.) solidified and a mixture m.p. with ( - )-menthyl benzenesulfonate (m.p. 79-79.5' (cor.)) was 77-79'. The yield of menthenes was 80r0 based on recovered starting material. A 500-mg. sample of the menthenes was racemized with hydrogen chloride in chloroform'z and had [*ID f27' (ly, in CHC11) after raceniization, corresponding to 20.5cjC of Az-menthelie in the original mixture. Solvolysis of p-Cholestanyl Benzenesulfonate in Dimethyl Sulfoxide.-A mixture of 250 mg. (0.46 millimole) of pcholestanyl benzenesulfonate arid 2.5 ml. of dimethyl sulfoxide was heated a t 100' (a clear solution resulted soon after heating) for 150 minutes. When the solution was allowed to cool to room temperature a colorless oil separated which partially solidified on standing. The mixture was added to a mixture of ice and water, this mixture was neutralized with sodium bicarbonate, and the white solid which formed was collected by filtration, washed well with water, and recrystallized from aqueous ethanol. A yield of 139 mg. (8275) of a mixture of A2- and A3-cholestene was obtained, m.p. 69.5-70.5' (cor.).@ Solvolysis of Cyclohexyl Benzenesulfonate in Dimethyl Sulfoxide.-A solution of 24 g. (0.10 mole) of cyclohexyl benzenesulfonate in 100 ml. of dimethyl sulfoxide was heated in B distillation flask under a nitrogen atmosphere a t 90-%5' (130-160 mm.) for 2 hours. The receiver was cooled in a Dry Ice-acetone-bath, and when the reaction was complete, the receiver contents were fractionated through a semi-micro distillation c0lutnn.~4 A yield of 5.34 g. (667,) of cyclohexene wa5 obtained, b.p. 81-82.5", 13% 1.44401.4414. -~ ~( 1 3 ) H. IOH12 + 2 C H 3 e H z The reaction of 1,4-bis-(hydroxymethylsulfonyl)butane with aliphatic amines, such as propylamine, diethylamine or pyrrolidine, gave low-melting, hygroscopic solids or oils, whose analyses did not fit the expected compounds, while reaction with amThe syntheses involved adding a methanolic solu- monia resulted in the formation of the diammonium tion of the aromatic amine to a methanolic solution salt of 1,4-butanedisulfinic acid. 1,4-Bis-(hydroxymethylsulfonyl) -butane was also of 1,4-bis-(hydroxymethylsulfony1)-butane. Most treated with urea, acetamide and allylthiourea of the products (Table V) precipitated, within a few minutes, in good yields. The results with N- (Table V). These reactions involve refluxing two ethylaniline and diphenylamine depended on the moles of the amide with one of the bis-hydroxyreaction temperature. At Oo, cream-colored solids methyl sulfone for several hours. The expected were obtained in good yields, whereas reaction a t products resulted in each case. Acknowledgment.-The authors thank -Vrs. room temperature gave oils in both cases. The oils were probably mixtures of several products, Cecilia Jorgensen, Mr. A. Pollara and Mr. G. Weiss since i t has been reported" that p-unsubstituted for the infrared absorption data, hlr. 0. E. Sundaromatic amines can undergo both N- and ring- berg and his associates for the microanalyses, and substitution. T h a t the solid product from the N- Mr. R. L. Cox and Mr. S. P. Kodama for determining the optical properties reported. (11) E. Bader and H . D. Hermann, Chem. Bey., 88, 41 (1955). +
5434
BEACHEM, SHAW, SARGENT, FORTENBAUGH AND SALSBURY
Experimental12 Materials.-Tlie a ,o-disulfonyl chlorides were prepared by oxidative chlorination of the corresponding diisothiuronium saltsi3 by the method of Sprague and Johnson,'4 and then converted to the disodium sulfinate, with sodium sulfite in the presence of sodium bicarbonate.3 1,4-Butanedisulfinic Acid; Preparation from the Zinc Salt.-To a solution of 332 g. (2.63 moles) of sodium sulfite and 453 g. (5.38 moles) of sodium bicarbonate, in 120 ml. of water, 321 g. (1.25 moles) of 1,4-butanedisulfonyl chloride was added, with stirring, a t 45-55' during one hour. The reaction mixture was heated a t 75-85' for 1.5 hr., cooled to room temperature and filtered to separate some insoluble salts. The filtrate was mixed with a solution of 510 g. (3.74 moles) of zinc chloride in 400 ml. of water and the resulting mixture, containing precipitated zinc salt, was stirred for one hour a t room temperature, filtered, and the salt washed with a little water. The product was dissolved in 530 ml. of 20% hydrochloric acid by warming gently on a steam-bath and the mixture filtered, while hot, to remove additional salts. The filtrate was cooled and let stand at 5' for several hours. The colorless crystalline precipitate which separated was collected, washed with two 50-ml. portions of ice-cold water and dried. The product weighed 153 g. (66%) and melted a t 119-122". On recrystallization from water the m.p. was 124-125'. The infrared absorption spectrum showed the sulfinic acid absorption band a t 1047 cm.+ and none a t 1176 cm.-l, indicative of a sulfonic acid group. Anal. Calcd for C4HloOrSz: C, 25.8; H. 5.38; S, 34.4. Found: C,25.9; H, 5.28; S, 34.4. The following optical properties of 1,4-butanedisulfinic acid were determined: interference figure, biaxial; optical character, negative; optical axial angle (2V), 13 f 1'; extinction, parallel and symmetrical; refractive indices, negative; 13 i 1'; parallel and symmetrical; a = 1.494 f 0.002, p = 1.610 f 0.002, y = 1.612 zt 0.002. The following crystal morphology was observed: crystal system, orthorhombic; crystal habit (recrystallized from water) six-sided plates, also rhombs; optical axial plane, 001; optical orientation, a = y, b = a,c = p. 1,4-Butanedisulfinic Acid, Direct Isolation from the Reaction Solution.-To a solution of 26.5 g. (0.21 mole) of sodium sulfite and 36.1 g. (0.43 mole) of sodium bicarbonate in 100 ml. of water, 25.5 g. (0.1 mole) of 1,4-butanedisulfonyl chloride was added with stirring a t 45-50' over a period of one hour. The solution was stirred a t 70-80' for two hours, cooled to 50" and filtered. The filtrate was cooled to 5O, filtered again to remove additional inorganic solids and acidified by adding 19 ml. of concd. hydrochloric acid. The resulting colorless precipitate was collected and stirred with 30 ml. of water a t room temperture. The colorless crysFlline product weighed 11.25 g. (60.3% yield), m.p. The mixture melting point and infrared spec124-125 trum showed this product to be identical with the one obtained vio the zinc salt. Attempted Isolation of 1,3-Propanedisullinic Acid.-A mixture of the zinc salt of 1,3-propanedisulfinic acid and other salts was prepared by the reduction of 1,3-propanedisulfonyl chloride according to the procedure used in preparing the zinc salt of 1,4-butane-disulfinic acid. A portion of this material, 18.0 g., which contained about 7.2 g. of the zinc salt of 1,3-propanedisulfinic acid, as determined by the > ield of the acrylamide adduct, was dissolved in a solution of 13 nil. of concentrated hydrochloric acid in 20 ml. of water. The solution was filtered and freeze-dried overnight. The residue, 21.2 g. of solid plus some liquid, showed absorption in the infrared a t 1047 and 1176 cm.-l. This material did not form an adduct with acrylamide. 1,5-Pentanedisulfinic Acid.-To a solution of 422 g. (3.35 moles) of sodium sulfite and 563 g. (6.70 moles) of sodium bicarbonate in 1675 ml. of water, 450 g. (1.67 moles) of 1,5-pentanedisulfonyl chloride was added with stirring a t 40-50O over a period of one hour. The reaction mixture was heated a t 75-85' for 1.5 hours, cooled to room temperature and filtered. -4 solution of 479 g. (3.52 moles) of zinc chloride in 500 ml. of water was added to 1525 ml. (707,) of
.
(12) All meltinp points are uncorrected. (13) C H. Grogan. L M. Rice a n d RI X. Sullivan, J. OYE.Chern., 18, 728 (1953). (14) 5. M. Sprague and T. B. Johnson, THISJOGRNAL., 59, 2440
(1937).
Vol. 81
the filtrate. The copious precipitate was diluted with 400 ml. of water and stirred for one hour. After the product was filtered and dried a t BS", a portion of this material, 270 g., was dissolved in IS0 ml. of 13% hydrochloric acid by warming on a steam-bath. The resulting solution was filtered, cooled to - 10' and the colorless crystalline precipitate which separated was collected. After two recrystallizations from the minimum amount of 13% hydrochloric acid the product melted a t 86-95'. A third recrystallization yielded a fine white crystalline solid melting a t 92-95'. After drying over phosphorus pentoxide in Z J U C U O . this material became very waxy and the melting point changed to 72-86'. The infrared absorption spectrum of this waxy material showed strong absorption band a t 1047 cxn.-' and no absorDtion band a t 1175 cm.+ to indicate the uresence of the sulfonic acid group. Anal. Calcd. for C6Hl;O&: C, 30.01 H,6.00; S, 31.9. Found: C,29.6; H,e.OO; S, 31.9. 1,6-Hexanedisulfinic Acid.-To a solution of 26.5 .g. (0.21 mole) of sodium sulfite and 36.2 g. (0.43 mole) of sod'lum bicarbonate in 100 ml. of water, 37.4 g. (0.10 mole) of 1,shexanedisulfonyl bromide was added with stirring a t 40-50' over a period of one hour. The reaction was heated a t 7585' for 1.5 hours and then filtered. The filtrate was cooled to 10" and acidified by the dropwise addition of 33 ml. of 6 N hydrochloric acid. The colorless crystalline precipitate was collected and washed with 30 ml. of ice-water. After drying in vacuo overnight, the product weighed 25.0 g An amount of 10.0 g. of this material was recrystallized from 10 ml. of water and dried in vacuo overnight. The infrared absorption spectrum of the recrystallized product showed the sulfinic acid absorption band a t 1047 ern.-'. This material was used directly for the preparation of the acrylamide adduct. 1,lO-Decanedisulfinic Acid.-To a solution of 108.3 g. (1.29 moles) of sodium bicarbonate and 79.5 g. (0.63 mole) of sodium sulfite in 300 ml. of water, 105 g. (0.31 mole) of 1,lo-decanedisulfonyl chloride was added a t 45-55' with stirring over a period of one hour. The reaction mixture was heated a t 75-86' for 1.5 hours, cooled to room temperature and filtered. The clear filtrate was added to a solution of 200 ml. of concentrated hydrochloric acid in 200 ml. of water and resulting colorless precipitate w ~ collected s and dried; 65 g. (77% crude yield), m.p. 91-101 . The infrared absorption spectrum of the crude product showed the characteristic sulfinic acid band a t 1047 cm.-l. No absorption band a t 1175 ern.-', due to the presence of sulfonic acid groups, was found. This material was used without further purification for the preparation of the acrylarnide adduct. Preparation of Adducts of a,p-Unsaturated Compounds.Unless otherwise noted, the general procedure was to reduce the disulfonyl chloride and acidify the reduction filtrate with concentrated hydrochloric acid. The acidified solution was treated with a 20yo molar excess of the appropriate a,@unsaturated compound based on the initial charge of disulfonyl chloride. The solution was stirred overnight a t room temperature and the precipitated adduct was collected, washed a i t h water and recrystallized from water. In the case of 1,4-butanedisulfinic acid, the free acid was isolated, recrystallized from water and then used to prepare the desired adducts. 3,3 '-( Trimethylenedisulfony1)-bis-( N-hydroxyme thylpropionamide).-An amount of 7.8 g. (0.025 mole of 3,3'(trimethylenedisulfony1)-his-propionamide was added to a solution of 24.2 g. (0.3 mole) of formalin (377,) which had been previously adjusted to p H 11.6 with 1070 sodium hydroxide. The solution was heated a t 80' for three hours and, a t the end of this time, the p H was adjusted to 8 by the addition of 10% sodium hydroxide, the reaction mixture was cooled to 60" and filtered. The filtrate on cooling deposited a solid which weighed 3.5 g. (37% yield), m.p. 167-168'; recrystallized from aqueous dimethylformamide, m.p. 172174'. Anal. Calcd. for C,,HZ~N~O&: CH20,16.1. Found: CH20, 16.7. Preparation of Disu1fones.-The disulfone derivatives were prepared by treating either sodium or potassium 1,4butanedisulfinate with an equivalent amount of the appropriate alkyl or aryl halide in methanol. The reaction conditions are indicated in Table IV. 1,4-Bis- hydroxymethysulfony1)-butane.-To a stirred solution o 6.88 g. (0.086 mole) of 37% formaldehyde was added 5.7 g. (0.031 mole) of 1,4-butanedisulfinic acid. The temperature rose spontaneously to about 50' and was held within the range of 40-50' by external cooling. When the
6
THESTEREOCHEMISTRY OF
Oct. 20, 1959
exothermic reaction subsided, the white slurry was stirred and heated for an additional five minutes a t 40-50'. In an attempt to obtain complete solution a t this temperature, 6.8 g. of 37% formaldehyde was added t o the mixture; no solution resulted. After stirring a t the same temperature, for five minutes, the mixture was cooled, filtered and the product was air-dried overnight; 5.8 g. (77% yield), m.p. 143144O. Anal. Calcd. for CeHirO&: C, 29.2; H, 5.72; S, 26.1. Found: C. 29.1; H, 5.59; S, 26.1. This product was also obtained in an over-all yield of 70% by treating the reduction filtrate from 14-butanedisulfonyl chloride with formalin a t a PH of 2-3, but our attempts to prepare the bis-(hydroxymethyl) sulfones from thecorresponding 1,2-ethane-disulfonyl chloride,ls 1,3-propanedisulfonyi chloridela and 1,5-pentanedisulfonyl chloride'? in the same way were not successful. 1,4-Bis-( a-hydroxypropylsulfony1)-butane.-To a stirred solution of 1.86 g. (0.01 mole) of 1,4-butanedisulfinic acid in 20 ml. of water was added 1.16 g. (0.02 mole) of propional(15) T. B. Johnson and J. M. Sprague, THISJOURNAL,68, 1348 (1936). (16) F . Asinger, F. Ebeneder and E. Back, Bey., TSB,42 (1942). (17) P. W. Clutterbuck and J. B. Cohen, J . Chem. Soc., 120 (1922).
[CONTRIBUTION FROM
THE
CONJUGATE
ADDITIONS
5435
dehyde and the colorless precipitate which formed was diluted with 10 ml. of water. The precipitate was stirred for 15 minutes, collected, and washed successively with water, ethanol and ether. The product weighed 1.4 g., 46% vield. m.D. 117-120": recrvstallized from a mixture of 20 k l . of w 2 e r and 10 ml. of propionaldehyde, m.p. 114-116'. Anal. Calcd. for CIOHZ~O~SZ: C, 39.8; H, 7.35. Found: C, 39.2; H. 7.20. 1,4-Bis-( acetoxymethylsulfony1)-butane.-A mixture of 50 ml. of acetic anhydride and 9.84 g. (0.04 mole) of 1,4-bis(hydroxymethylsulfony1)-butanewas heated on the steambath for 15 minutes with 10 drops of concentrated sulfuric. The solution was cooled to room temperature, chilled, filtered and the precipitate was washed with ether; 12.5 g., m.p. 104-113'. Recrystallization from ethyl acetate gave 9.4 g., 71.5% yield, m.p. 122-125'. Anal. Calcd. for CIOHI~O~S?: C,36.35; H , 5.46; S, 19.4. Found: C,36.35; H, 5.51, S, 19.4. Preparation of 1,4-Bis-( N-substituted)-aminomethylsulfonyl-butanes.-The general procedure involved the addition of a methanolic solution of the amine or amide to a methanolic solution of 1,4-bis-( hydroxymethy1)-sulfonyl-butane. The reaction conditions are indicated in Table V. BOCNDBROOK,N. J.
DEPARTMENT OF CHEMISTRY, CARNECIE INSTITUTE OF T E C H N O L O G Y ]
The Stereochemistry of Conjugate Additions. Convergent Configuration Control in Additions of Morpholine and N-Bromomorpholine to cis- and trans-a,P-Unsaturated Ketones BY PHILIPL. SOUTHWICK AND RAYMOND J. SIIOZDA' RECEIVEDMARCH20, 1959 Addition of N-bromomorpholine yields the same a-bromo-p-morpholino-p-nitrobenzylacetophenone(form B ) from either cis- or trans-4-nitrochalcone. This product is the diastereoisomer of the compound (form A) produced by adding benzomorpholine t o either cis- or trans-a-bromo-4-nitrochalcone. Likewise, 3-bromo-2-keto-4-morpholino-4-phenylbutyl ate was obtained in only one of the two possible configurations by addition of morpholine to the cis- or trans-3-bromo-2keto-4-phenyl-3-butenyl benzoates. In the cases of the a-bromo-8-morpholinobenzylacetophenones and the a-bromo-8morpholino-p-nitrobenzylacetophenonesthe diastereoisomer produced by the morpholine addition (form A) was converted by heating or by standing in solution into the apparently more stable diastereoisomer (form E), produced by X-bromomorpholine addition. The two diastereoisomeric a-bromo-p-morpholinobeiizylacetophenones differ in their behavior when heated in methanol; form B undergoes solvolysis with rearrangement, but form A undergoes only rearrangement to give one of the 8-bromo-a-morpholinobenzylacetophenones.These observations may indicate that form A has the threo configuration, form 13 the erythro. A mechanism involving protonation or bromination of a chelated enolic intermediate from the less hindered direction is advanced as a possible explanation of the observed convergent configuration control in these conjugate additions of morpholine and K-bromomorpholine.
I n a previous investigation*" it was shown (see pholine adduct might be determined by the cis or Chart I) that N-bromomorpholine adds to the ole- trans configuration of the a,P-unsaturated ketone to finic bond of trans-chalcone (Ia) to yield chiefly which the addition occurred; (2) which of the dithe a-bromo-P-morpholinobenzylacetophenone (Va) astereoisomeric adducts represents the thermally (form B) which is the diastereoisomer of the com- stable configuration; and (3) whether a comparison pound (VIa) (form A) obtained by the addition of of reactivities might make i t possible to establish morpholine to the cis or trans forms (IVa or IIIa) of erythro and threo configurations for the form A and cu-bromochalcone.334 The present investigation rep- form B adducts. The results of these experiments, resents an effort to discover the basis for the con- which are described in the sections to follow, have figuration control which has permitted these two delineated the major requirements for any theory conjugate addition reactions each to yield a dif- which could account for the kind of configuration ferent diastereoisomer. To this end, new experi- control peculiar to these conjugate additions. ments have been performed for the purpose of anComparison of Additions to cis and trans Isoswering the following questions : (1) whether the mers.-It had been suggested that in the Nconfiguration (erythro or threo) of an N-bromomor- bromomorpholine addition to trans-chalcone the steric outcome might reflect some kind of concerted (1) h-ational Science Foundation Fellow, 1956-1957. This paper trans addition process.2 This view of of the reacis based on a thesis submitted by Raymond J. Shozda in partial fulfillment of the requirements for the degree of Doctor of Philosophy tion implied that i t might be possible to demonat the Carnegie Institute of Technology, June, 1957. strate that addition of N-bromomorpholine to a (2) (a) P. L. Southwick and W. L. Walsh, TEXISJOURNAL, 7 7 , 405 cis-a,o-unsaturated ketone would yield an addition (1955); (b) P. L. Southwick and D. R. Christman, ibid., 76, 629 (1953). product diastereoisomeric with that obtained from (3) N. H. Cromwell, ibid., 69, 2897 (1940). addition of N-bromomorpholine to the corre(4) R. H. Jordan, R. E. Lutz and D. F. Hinkley, Jr., J . Org. Chem., sponding trans compound. This question has now 16, 1442 (1951).
