7369
Stereochemistry of Sulfur Compounds. I. Stereochemical Reaction Cycles Involving an Open Chain Sulfoxide, Sulfimide, and Sulfoximide'vz Donald J. Cram,* Jack Day, Dennis R. Rayner, Don M. von Schrilt~,~" David J. Duchamp, and Donald C. G a r ~ o o d ~ ~ Contribution N o . 2443 from The Department of Chemistry, The University of California, Los Angeles, California 90024, and from The Upjohn Company, Kalamazoo, Michigan 49001. Received October 29, 1969 Abstract: Treatment of (+)-@)-methyl p-tolyl sulfoxide ((+)@)-I) of maximum rotation with either N-sulfinylp-toluenesulfonamide or N,N'-bis(p-toluenesulfony1)sulfur diimide in pyridine at 0 gave (80 and 95%) (-)-(S)N-(p-tosy1)methyl-p-tolylsulfimide (( -)-(S)-11),which in base at 25 O gave (94%) (+)-(R)-I of 94% optical purity. Imidation of (+)-(R)-I of maximum rotation with tosyl azide gave (70%) (-)-(R)-N-tosylmethyl-p-tolylsulfoximide (( -)-(I?)-111) of 99% maximum rotation. Oxidation of (-)-(,!+I1 of maximum rotation with mchloroperbenzoic acid gave (65%) (-)-@)-I11 of 98% maximum rotation. Hydrolysis of (-)@)-I11 of maximum rotation with concentrated sulfuric acid at 25 gave (99%) (-)-(I?)-methyl-p-tolylsulfoximide(( -)-(I?)-IV)of 99% maximum rotation. Conversion of (-)-(R)-IV of maximum rotation to (-)@)-I11 was accomplished either with pyridine and tosyl chloride (86% yield, 99% maximum rotation) or by treatment of (-)-(R)-IV with first sodium and benzene followed by tosyl chloride (62,97% of maximum rotation). Sulfoximide, (-)-(I?)-IV,of 98% maximum rotation, when treated with a mixture of nitromethane and solid nitrosyl hexafluorophosphate at Oo, gave (75%) (+)-(I?)-I of 97% maximum rotation. Sulfoximide ( -)-(I?)-IV,when treated with cold sodium hypochlois rite, gave (-)-(I?)-N-chloromethyl-p-tolylsulfoximide ((-)-(I?)-V). The absolute configuration of (+)-@)-I already known, and those of (-)-(R)-I11and (-)-(I?)-IVwere determined by X-ray methods. The absolute configuration of (-)-(S)-II was established by comparison of the melting point composition diagram of (-)-I1 and (-)-111, and of (+)-I1 and (-)-111. Clearly the nucleophilic substitution reactions at sulfur, (+)-I a (-)-I& proceed with inversion, and the electrophilic, (+)-I + (-)-I11 and (-)-I1 -P (-)-111, proceed with retention of configuration, as does (-)-IV + (+)-I. Optical rotatory dispersion curves of (+)-I, (-)-11, (-)-111, and (-)-IV exhibit well-defined Cotton effects, and these are correlated with their configurations. In the conversion of (+)-I to (-)-I1 the same reagent appears to donate an imide group and accept an oxygen atom, and thus it is concluded that the sulfur, oxygen, and nitrogen must be included in a ring system that is part of the same transition state and possibly the same intermediate. Kinetic studies of the reaction indicate it to be second order in concentration of the sulfur diimide reagent. Thus, the ring system cannot be any more than six-membered, which is much too small to accommodate a linear arrangement of incoming and leaving groups. An intermediate is proposed that accommodates all data in which the incoming and leaving groups occupy the equatorial positions of a trigonalbipyramid intermediate rather than the classical axial positions. Maps are developed that identify the stereochemical courses of associative substitution reactions on tetrahedra that form trigonal bipyramids and square pyramids capable of undergoing pyramidal reorganization. O
O
In
recent years the mechanisms and especially the stereochemical course of nucleophilic substitution reactions at second-row element centers have elicited considerable attention. Substitution at silicon has been observed to occur with both retention4a and inand these reactions have been interpreted as involving trigonal-bipyramidal transition states in which the entering and leaving groups occupy apiequatorial and apiaxiaP ( r e t e n t i ~ n ) ~or " both apiaxial positions (in~ersion).~~ * To whom correspondence should be addressed at the University of California. (1) This investigation was supported by the U. S. Public Health Service Research Grant No. GM 12640-04 from the Department of Health, Education, and Welfare. (2) Preliminary accounts of portions of this work have appeared: (a) J. Day and D. 3. Cram, J . Amer. Chem. Soc., 87, 4398 (1965); (b) D. R. Rayner, D. M. von Schriltz, J. Day, and D. J. Cram, ibid., 90,2721 (19681. (3) (a) National Institutes of Health Postdoctoral Fellow, 19661967; (b) National Institutes of Health Special Research Fellow, 1969-1970. (4) (a) L. H. Sommer, G. A. Parker, N. C. Lloyd, C. L. Frye, and K. W. Michael, J . Amer. Cbem. Soc., 89,857 (1967); (b) L. H. Sommer, W. D. Korte, and P. G. Rodewald, ibid., 89, 862 (1967). (5) The two types of apexes of a trigonal bipyramid have been variously termed axial, apical, or polar and equatorial, radial, or basal.
Nucleophilic substitution reactions at phosphorus have also been found to occur with both retention and inversion mechanisms. For example, the Wittig reactionBa and alkaline hydrolysis of phosphetanium,6b phospholaniumyBC and alkoxyphosphetaniumad salts all occur with retention. Acyclic phosphonium6" and acyclic a1koxyphosphonium6' salts cleave with inversion upon alkaline hydrolysis. Another typical inversion reaction is the Grignard synthesis of optically active phosphine oxides.' Hydrolyses of phosphorus esters have been demonstrated to proceed through trigonalThe terms axial and equatorial are the most familiar to organic chemists, and their conversion to apiaxial and apiequatorial allows them to be applied to the apexes of bipyramids. Use of the api prefix only once or twice in a paper fixes the context of the terms. The prefix can be dropped from then on unless the positions on a six-membered ring also need to be differentiated. This suggested nomenclature is exemplified here, (6) (a) W. E. McEwen, K. F. Kumli, A. Blade-Font, M. Zanger, and C. A. Vander Werf, J . Amer. Cbem. Soc., 86, 2378 (1964); (b) R. J. Corfield, J. R. Shutt, and S. Trippett, Cbem. Commun., 789 (1969); (c) K. L. Marsi,J. Amer. Cbem. Soc., 91,4724(1969); (d) K. E. DeBruin, G. Zon, K. Naumann, and K. Mislow, ibid., 91, 7027 (1969); (e) G. Zon, K. E. DeBruin, K. Naumann, and K. Mislow, ibid., 91, 7023 (1969). (7) 0. Korpium, R. A. Lewis, J. Chickos, and K. Mislow, ibid., 90, 4842 (1968), and references cited therein.
Cram, et al. / Open Chain Sulfoxide, Su[fimide,and Sulfoximide
7310
bipyramidal intermediates,*awhich undergo pseudorotaas their chiral center make polymers containing such tionEb>'in certain cases before they decompose. chiral centers attractive optically active adsorbants for Fewer studies of the stereochemistry of substitution possible resolution of racemates by chromatography. at sulfur have been reported. Nucleophilic substituIn this paper we report the results of a study of the tions at sulfur for the most part have been observed to stereochemistry of the interconversions of sulfoxides, proceed with inversion.' Thus, sulfinate esters react sulfimides, and sulfoximides.ll In all but one case with Grignard reagents stereospecificallyga to give we used reactions already reported in the literature, but s~lfoxides,'~alkoxysulfonium salts with hydroxide to whose stereochemical course had not been examined, or give sulfoxides," sulfinic esters with lithium amideyd if one had been examined, it had been reported to go with or magnesium amideyereagents to give s ~ l f i n a m i d e s , ~ ~ ~no ' or low stereospecificity. In all cases we searched sulfinamides with Grignard reagents to give sulf~xides,~'~' for conditions that maximized stereospecificity, and in sulfonate esters with Grignard reagents to give sulmost reactions studied, the degree of stereospecificity f o n e ~ , ' ~and ethoxy-3-methylthietanium salts with varied considerably with the reaction conditions. This hydroxide," all with inversion. The first example of initial study centered around optically pure (+)-(R)nucleophilic substitution of sulfoxides that occurs with methyl p-tolyl sulfoxide ((+)-(I?)-I) as starting material, retention of configuration to be reportedlo" involved partly because it is easily prepared and because its l60 exchange of (+)-methyl p-tolyl sulfoxide with absolute configuration is e s t a b l i ~ h e d . ~ ~ , ~ ~ W-dimethyl sulfoxide at elevated temperatures. More Results recently, N-phthaloylmethionine sulfoxide has been reported to react with N-sulfinyl-p-toluenesulfonamide to Reactions. The stereochemical courses of the reacyield the corresponding sulfimide with retained contions formulated in Chart I have been examined, and figuration at sulfur .lob Chart I The research reported in this series of papers was initiated for a number of purposes. (1) The stereochemical c TsS=S=O course of a relatively small number of substitution reactions at sulfur had been examined, and we wished to survey a large number of both nucleophilic and electrophilic reactions and extract from the results correlations between stereochemical course and electrical character of the entering and leaving groups. Since knowledge of the stereochemical course of a reaction depends on a determination of maximum rotation and relative configurations of starting materials and prod0 0 ucts, we concentrated our attention on those reaction t \ t sequences that provided cycles of reactions, e.g., A B 4A or A 4B 4 C 4A. ( 2 ) Some of the reactions studied involve a twofold ligand exchange reaction between two substituted sulfur atoms, and examination of the starting material and products suggested that the entering and leaving groups were part of the same ring system at some point along the reaction coordinate of 0 structural change. This feature places certain structural \ t restrictions on the transition states and intermediates in the reaction and provides clues as to mechanism. ( 3 ) Since a variety of stable compounds of sulfur are known in which sulfur carries three or four ligands of widely differing types, study of the mechanism of subhave been found to go under the proper conditions stitution at this element allows a high degree of flexiwith a minimum of 96% stereospecificity as measured bility in choice of substrate structure. For example, before the products were fractionally crystallized. rates and stereochemistry of substitution of both openIn the conversion of sulfoxide I to sulfimide I1 with chain and cyclic sulfoxides can be compared. (4) The either N-sulfinyl-p-toluenesulfonamidel*a~b or N,N'-bisstability and polarity of many compounds with sulfur (p-tosy1)sulfur diirnidel'' (yields of 51 and 95%) the (8) (a) P. C. Haake and F. H. Westheimer, J . Amer. Chem. Soc., 83, 1102 (1961); (b) E. A. Dennis and F. H. Westheimer, ibid., 88, 3432 (1966), ( c ) F. H. Westheimer, Accounts Chem. Res., 1, 70 (1968). (9) (a) I l . ilfcmin.~idv111 with the R factor indicated. The correct enantiomer Figure 4. Melting point composition diagram for the system of is shown in Figure 3. Least-squares refinement was (-)-N-(p-tosy1)methyl-p-tolylsulfimide[( -)-I11 and (-)-N-(p-tosyl)continued with anomalous dispersion effects included. methyl-p-tolylsulfoximide [( -)-1111. The final R for this structure is 0.045. Details of the crystallographic investigation will be published elseThe absolute configuration of the bromoe ~ t a b l i s h e d . ~The ~ ~ ~absolute ~' configurations of chemcamphor portion is in agreement with that found preically interrelated sulfoximides (-)-(R)-111 and (-)viou~ly.~?'~~ (R)-IV were determined as follows. Treatment of (-)The absolute configuration of sulfimide (-)-I1 was IV with (+)-3-endo-bromo-2-oxo-9-bornanesulfonyl chloride gave (+)-N-(3-endo-bromo-2-oxo-9-bornane- determined by the phase-diagram method. 3 3 Figure 4 records the melting point composition diagram for sulfony1)methyl-p-tolylsulfoximide ((+)-VIII) (see (-)-I1 and (-)-111, and Figure 5 that of (+)-I1 and Chart 11). The absolute configuration of this sub(-)-111. The shape of Figure 4 shows that (-)-I1 Chart I1 and (-)-I11 are isomorphous (form a series of solid 0 0 solutions with no eutectic) whereas (+)-I1 and (-)-I11 t form a simple eutectic (type 2 behavior33b). The latter diagram shows a straight initial thaw line in the neighborhood of the eutectic. This behavior shows that the solid phases of the two components (+)-I1 and (-)-I11 are immiscible. Other experiments demonstrated that (-)-I1 and (+)-I1 form a series of solid solutions as did (-)-I11 and (A)-111. These experiments taken together establish the absolute configurations of all the compounds of Charts I and 11. Br Spectra. The ultraviolet spectra of sulfoxide I, stance was determined by the X-ray anomalous dissulfimide 11, sulfoximide 111, and tosylamide are repersion technique. The compound crystallized in the (32) (a) J. M. Bijvoet, Endeauour, 14, 71 (1955); (b) in preparation orthorhombic system space group 12), and then was washed with water, dried, and filtered. The solvent was removed under reduced pressure below 50". The residue, 0.929 g, was chromatographed on 100 g of silica gel with elution by acetonitrile. Three products were collected and identified by ir: (a) methyl p-tolyl sulfide, 0.017 g (3.1%); (b) (+)-methyl p-tolyl sulfoxide, 0.222 g (36%) +179.3" ( c 1.084, acetone); and (c) the desired sulfimide, 0.628 g (51.2%), [ c ~ ] ~-323.4' 5 ~ ~ ~ (c 1.646, acetone), >99% OPtically pure. Thus the reaction was highly stereospecific. Hydrolysis of (-))-(S)-N-(p-Tosyl)methyl-p-tolglsulfimide (11) to (+)-Methyl p-Tolyl Sulfoxide (I). Method A. A 0.307% portion (1.0 mrnol) of chromatographed and recrystallized (-1(S)-N-(p-tosyl)methyI-p-tolylsulfimide which was 95% optically Pure, [ ~ Y ] ~ ' 5 4 6-310" (c 1.61, acetone) was added to 135 ml of methanol saturated with potassium hydroxide. The resulting mixture was swirled in a stoppered flask for 2 min at room temperature to dissolve the sulfimide and was then cooled to 15-17" for 24 hr. The methanol solution was poured into a mixture of 35 g of acetic acid (glacial), 125 ml of methanol, 250 ml of dichloromethane, and 500 rnl of water. This mixture was shaken vigorously. The aqueous layer was removed and extracted with dichloromethane. Evaporation of the combined dichloromethane extracts left 0.197 g Of a light yellow solid which was chromatographed on silica gel. The product was eluted with acetonitrile. The desired sulfoxide,
Journal of the American Chemical Society / 92:25 / December 16, 1970
7383 0.145 g (9473, was identified by ir, [aIz5546$167" (c 0.806, acetone), 92.5 % optically pure. The hydrolysis took place with greater than 96 stereospecificity. Hydrolysis of (-)-(S)-N-(p-Tosyl)methyl-p-tolylsulfimide (11) to (+)-Methyl p-Tolyl Sulfoxide (I). Method B. The sulfimide, 0.65 g, [(YIz5546-321" (c 0.900, acetone), was stirred with 10 ml of concentrated sulfuric acid for 2 min a t room temperature. The clear solution was poured into 30 g of sodium carbonate (anhydrous) dissolved in 250 ml of water. The resulting clear solution (pH -8) was extracted with three 50-ml portions of chloroform. The extracts were dried, filtered, and evaporated under reduced pressure to yield an oil which was identified by its ir spectrum as pure methyl p-tolyl sulfoxide, [aIz5546 +54" and [aIz5D +45" (c 1.095, acetone). This rotation corresponds to an optical purity of 30%. N o attempt was made to improve the stereospecificity. Oxidation of (-))-(S)-N-(p-Tosy1)methyl-p-tolylsulfimide(11) with m-Chloroperbenzoic Acid to ( -)-(R)-N-(p-Tosy1)methyl-p-tolylsulfoximide (111). A 0.862-g portion (5.0 mmol) of m-chloroperbenzoic acid, 0.424 g (4.0 mmol) of anhydrous sodium carbonate, and 0.307 g (1 .O rnmol) of (-))-N-(p-tosy1)methyl-p-tolylsulfimide, [aIz5546-320" (c 0.682, acetone), 98% optically pure, were added to 8 ml of acetone, The heterogenous mixture was stirred for 24 hr a t room temperature. A 2.0-g portion of sodium thiosulfate and 25 ml of water was then added. After stirring for 10 min, a slight excess of 6 N sulfuric acid was added. After another 10 min of stirring, the mixture was made alkaline with 6 N sodium hydroxide (pH >12) and extracted with two 50-ml portions of dichloromethane. The combined extracts were washed with water and dried over magnesium sulfate. An off-white solid, 0.349 g, was obtained upon evaporation of the solvent. This product was chromatographed on 20 g of silica gel with elution by ether-pentane mixtures. A white solid was eluted, 0.21 g (65%), which proved to be the desired sulfoximide, [a]25546-168.5 (c 0.894, acetone), 97.6 % optically pure. Recrystallization from dichloromethaneether gave a white crystalline product: mp 159-160.5; [aIz5546 -172.5' (c 0.798, acetone). The oxidation thus took place with greater than 98 % stereospecificity. An nmr spectrum of the product showed the S-methyl peak at 7 6.60 (3 H), two p-CH3Ar peaks at 7.55 and 7.61 (6 H), and an aromatic multiplet centered about 2.4 (8 H). Anal. Calcd for Cl5Hl7NO3SZ:C, 55.70; H, 5.30; S , 19.83. Found: C, 55.44; H, 5.34; S, 19.63. Preparation of ( -)-(R)-N-(p-Tosy1)meth yl - p tolylsulfoximide (111) by the Method of Kwart and Kahn.I8 Optically pure (+)methyl p-tolyl sulfoxide, 18 g (0.117 mol), was dissolved in 100 ml of methanol, and 39 g (0.2 mol) ofp-tosyl azide in 50 ml of methanol was added. Freshly precipitated copper powder (prepared from Zn and C u S 0 4 .5H20), which had been washed with dilute sulfuric acid, water, and methanol, 12.6 g (0.2 mol), was then added. The mixture was refluxed for 1 hr. An additional 20 g (0.1 mol) of p-tosyl azide and 12.6 g of copper powder was then added. Another 20 g (0.1 mol) ofp-tosyl azide was added after 2 hr of reflux. The reactants were refluxed for an additional 2.5 hr. The sulfoximide crystallized from the filtered, hot methanol solution in which it is only slightly soluble. The product was continuously extracted with acetone overnight. Upon evaporation a total of 26.5 g of nonfractionally crystallized sulfoximide was obtained (70 Z), [aIz5546- 170°, [CUIz5D -140" ( c 1.165, acetone). The sulfoximide was recrystallized from acetone: mp 160-162"; [aIz5546 - 172"; [aIz5D- 142" (c 1.060, acetone). The reaction is thus 99% stereospecific. Hydrolysis of (-)-(R)-N-(p-Tosy1)methyl-p-tolylsulfoximide (111) to (-))-(R)-Methyl-p-tolylsulfoximide (IV). Optically pure (-))-(R)-N-(ptosy1)methyl-p-tolylsulfoximide,3.70 g (0.015 mol), was stirred with 20 ml of concentrated sulfuric acid for 15 min a t room temperature. The resulting clear colorless solution was poured into 200 ml of water and made basic by addition of solid sodium carbonate (pH 9). The mixture was extracted with three 100-ml portions of chloroform. The combined extracts were dried, filtered, and evaporated under reduced pressure. The light yellow oil obtained crystallized on cooling and weighed 1.92 g (99 % yield): mp Of 53-59'; [~t]~~546 -39.7'; [(rIz5D-33.1" ( C 1.105, acetone). The product was then recrystallized from acetone-ether : mp 56-60", [(YIz5546-39.9", [a]% -33.4" (c 2.275, acetone). The product (-)-(R)-methyl-p-tolylsulfoximide is hygroscopic and was sublimed, 50" (0.05 mm), to obtain an analytical sample: mp 5961"; [cY]25546-38.9", [ a I 2 b -32.4" (c 0.885, acetone). The hydrolysis was 99 % stereospecific. Anal. Calcd for C8HllNOS: C, 56.77; H, 6.55; S, 18.95. Found: C, 56.65; H, 6.31; S, 18.85.
-
-
Conversion of (-)-(R)-Methyl-p-tolylsulfoximide (IV) to (- )-
(R)-N-(p-Tolylsulfoximide (111). The compound, (-)-methyl-ptolylsulfoximide, 0.17 g (1 mmol) ([(uIz5546-39.9'), was refluxed with 0.05 g of sodium in 25 ml of dry benzene for 6 hr. The unreacted sodium was removed by filtration and 0.19 g (1 mmol) of p-tosyl chloride was added to the filtrate. The resulting solution was refluxed for 1 hr. The benzene solution was then washed with water, dried over magnesium sulfate, filtered, and evaporated leaving 0.20 g (62%) of solid product. The crude product was chromatographed on silica gel. After development of the column with benzene, the product was eluted with 1 : 1 benzene-ether, [01]25546- 166.3", [ a ] z 6 ~- 137.3 (c 0.875, acetone). The N-tosylsulfoximide obtained was 97% optically pure and was identical with authentic material by nmr and ir spectra. Conversion of ( -)-(R)-Methyl-p-tolylsulfoximide (IV) to ( -)(R)-N-(p-Tosy1)methyI-p-tolylsulfoximide (111). The compound, (-)-(R)-methyl-p-tolylsulfoximide, 0.5 g (0.003 mol), [aIz5546 -39.7" (c 2.275, acetone), was dissolved in 20 ml of dry pyridine. Tosyl chloride, 0.96 g (0.005 mol), was then added to the above stirred solution. The stirring was continued for 0.5 hr a t room temperature, and then the light yellow reaction mixture was poured into 150 ml of water. The precipitated product was filtered, washed with water, and oven-dried to give 0.82 g (86% yield) of dry N-tosylsulfoximide: mp 159.5-160.5'; [~2]'~546 -171.3", [ a I z 5~ 141.6" (c 0.885, acetone). The product, crystallized from acetone-methanol, weighed 0.60 g: mp 159.5-160.5'; [(YIz5546- 172.5'; [aIz5D- 142.7" (c 0.825, acetone). The reaction was 99 stereospecific based on the highest observed rotation for (-))-(R)-N-(p-tosy1)methyl-p-tolylsulfoximide. This result also confirms the optical purity of (-)-(R)-methyl-p-tolylsulfoximide. Preparation of (+)-(R),-N-(3-endo-Bromo-2-oxo-9-bornanesulfonyl)methyl-p-tolylsulfoximide ((+)-VIII). A solution of ( -)(R)-methyl-p-tolylsulfoximide, 0.2 g (0.0012 mol), [alZ5518- 39.9 (c 2.275, acetone) and 0.4 g (0.0012 mol) of optically pure (+)-3endo-bromo-2-oxo-9-bornanesulfonyl chloride,48 [aIz6D 128O (c 0.605, CHC13) in 5 ml of dry pyridine was stirred at room temperature for 18 hr. The reaction mixture was poured into 50 ml of water and adjusted to pH 7 with 10% HC1. The colorless solid product was filtered, washed with water, and dried to give 0.45 g (83 % yield) of sulfoximide VI11 which was recrystallized from ether to a constant melting point: mp 155-156"; [ a I z 5+4.32"; ~ [(YIz5546 +8.92" (c 0.740, acetone). Anal. Calcd for C I ~ H Z ~ B ~ N O ~ S Z : C, 46.75; H, 5.23; S, 13.89. Found: C, 46.81; H, 5.32; S, 13.88. Conversion of (-))-(R)-Methyl-p-tolylsulfoximide (IV) to (+)(R)-Methyl ~ - T o l y lSulfoxide (I). The sulfoximide, 1.6 g (0.01 mol), [(YIz5546-39.1 (c 1.2, acetone) (98% optical purity), was dissolved in 25 ml of nitromethane (dried over molecular sieves 4A). A 1.75-g portion (0.01 mol) of solid nitrosyl hexafluorophosphate was added to the stirred solution. A n exothermic reaction ensued which evolved gas. The reactants were stirred for a n additional 5 min. The nitromethane solution was poured into dilute sodium bicarbonate which was then extracted with chloroform. The chloroform extracts were dried, filtered, and evaporated (rotatory evaporator). The residual oil crystallized. The crude product was then chromatographed on silica gel. The product was eluted with 1 : l ether-benzene: 0.25 g (20%); mp 71-75'; [a]25546 +175"; [aIz5D +134". Since the starting sulfoximide was 98% optically pure and the product is 97% optically pure, the reaction occurred with 99 % retention of configuration. The ir spectrum of this material was identical with that of known (+)-methyl p-tolyl sulfoxide. Subsequent preparations indicated that the greater yields could be obtained (75%) if the reaction was conducted a t 0" and if excess NO+PF6- was used. Preparation of (-))-(R)-N-Chloromethyl-ptolylsulfoximide (V). The compound, (-)-(R)-methyl-p-tolylsulfoximide ([aIz5546- 39", 98% optically pure), 0.85 g (0.005 mol), was dissolved in 10 ml of water. This solution was added to a stirred solution of 50 ml of cold sodium hypochlorite. The reactants were stirred for 5 min before the oily product was extracted into chloroform, The solution was dried, filtered, and evaporated to yield 0.6 g (60%) of a viscous yellow oil, which crystallized on standing: mp 66-68"; [a]25546 -266"; [alz5D -221" (c 1.35, acetone). This product was recrystallized from ether-n-hexane: mp 67-68"; [U]"j46 - 264", [aIz5D -222" (c 0.63, acetone). Recrystallization from the same solvent mixture gave mp 67-68'; [a]25546-264O; [a]26~-220"
+
(48) (a) The sulfonyl chloride was generously provided by Dr. Edward C. Olson of The Upjohn Company; (b) F. S. Kipping and W. J. Pope, J . Chem. Soc., 63, 576 (1893).
Cram, et al. J Open Chain Sulfoxide, SulJimide, and Sulfoximide
7384 Table V. Polarimetric Data for a Typical Kinetic Run Time, min
Rotation, deg
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
+O. 249 +O. 177 +o. 108 +0.048 -0,013 -0,070 -0.123 -0.173 -0.221 -0.270 -0.308 -0.346 -0.384 -0.420 -0,455 -0,486 -0.517 -0.546 -0,574 -0.600 -0.625
(c 1.01, acetone). An nmr spectrum of the N-chlorosulfoximide in CDC13, showed the -S-CH, group at r 6.76. Anal. Calcd for CsHloCINOS: C, 47.17; H , 4.95; C1, 17.41. Found: C, 47.25; H, 4.97; C1, 17.49. Melting Point-Composition Diagrams. Optically pure (+)N-(p-tosy1)methyl-p-tolylsulfimide, [ C Y ]+326" ~ ~ ~(c~ 0.785, ~ acetone), mp 125.3-125.6", was obtained by reaction of ( - ) - ( S ) methyl p-tolyl sulfoxide (from reaction of (+)-/-menthyl p-toluenesulfinate with methylmagnesium iodidegb,49) with N-sulfinyl-ptoluenesulfonamide in pyridine at 0". Physical properties of the other compounds used for melting point determinations were: ( -)-N-(p-tosy1)methyl-p-tolylsulfimide,(-)-II, CY]^^ - 326" (c 1.36, acetone), mp 124-125"; (-))-N-(p-tosy1)methyl-p-tolylsulfoximide. (-)-I11 (recrystallized to optical purity from ethyl acetate), CY]^^^^^ - 172" (c 0.665, acetone), mp 159.5-160.5"; racemic sulfimide 11. mp 123.5-124.5" (recrystallized from /I-hexane-acetone); racemic sulfoximide 111, mp 145-146" (from ethyl acetate). Samples were weighed on a Cahn electrobalance (precision of about 0.01 mg), were ground together in a small agate mortar, and were dissolved in dichloromethane. The solvent was evaporated under a stream of dry air, and the residue was ground again. Melting points were determined using the capillary method (silicone oil bath, capillary melting point apparatus made by Arthur H. Thomas Co., Philadelphia) and are accurate to within about k0.5". The bath temperature was raised at a constant rate of I-2"/min. The initial thawing temperature and the final melting temperature were noted. Duplicate mixture melting point determinations were made for each sample. The resulting phase diagrams are shown in Figures 4 and 5 for the system (-)-I1 and (-)-I11 and for (+)-I1 and (-)-HI, respectively. Kinetics. Kinetic runs were made with (+)-(R)-I of maximum rotation in dry pyridine (distilled from barium oxide and stored over molecular sieves 4A) at 25". The other reagent was either sulfur diimide VI1 or the N-sulfinyl compound VI which in pyridine is quickly converted to VII. The conversion of (+)-(R)-I to (-1(S)-II was followed polarimetrically. The solutions were prepared and sealed in a jacketed polarimeter tube (1.00 cm) in a drybox and transferred to a Perkin-Elmer Model 141 polarimeter fitted with a (49) M. M. Green, M. Axelrod, and I
