The preparation, spectral properties, structures, and ...

The preparation, spectral properties, structures, and base-induced cleavage reactions of some a-halo-P-ketosulfones J. STUART GROSSERT,' PRAMOD K. DUBEY,GLENH. GILL,T. STANLEY CAMERON,' A N D PATRICK A. GARDNER

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Depn~rtt~et~r oJ' C/~etni.s~ty, Dalhousie Ut~iversity,H n l i j u , N.S.. Catladn B3H 4J3 Received March 28, 1983' J. STUART GROSSERT, PRAMOD K. DUBEY, GLENH. GILL.T. STANLEY CAMERON. and PATRICK A. GARDNER. Can. J. Chcm. 62, 798 (1984). The halogenation of P-ketosulfones such as a-methylsulfonylacetophcnone ( I ) and benzenesulfonylacetone (10) can be effected with sulfuryl chloride or pyridinium bromide perbromide. Rcgiochemical control can be achieved by control of stoichiometry and/or thc reaction conditions. Detailed 'H and "C nmr, and mass spectra are recorded for a series of halogenated P-ketosulfones, together with structures by X-ray crystallography for 1, 2-chloro-2-methylsulfonyl-1phenylethanone (2), chloromethyl methyl sulfonc (4). and a-chloroacetophenone (21). Results from these studies are used to suggest a reason for the difficulty associated with substitution reactions of a-halosulfones. J. STUART GROSSERT, PRAMOD K. DUBEY,GLENH. GILL,T. STANLEY CAMERON ct PATRICK A. GARDNER. Can. J. Chem. 62, 798 (1984). L'halogCnation des P-~Ctosulfonescomme I'a-mCthylsulfonylacCtophCnone (1) ct la benzensulfonylacttone (10) peut Ctre effectuke avcc le chlorure de sulfuryle ou le perbromure du bromure dc pyridinium. On peut exercer un contr6le rCgiochimique en controlant la stoichiomCtrie et/ou les conditions de la reaction. On a cnrcgistrk des spectres ddtaillks de la rmn du proton et du carbone-13 ainsi que les spectres de masse d'une strie de P-~Ctosulfoncs;de plus, faisant appel a la diffraction des rayons-X, on a determine les structures de 1, dc la chloro2 n~tthylsulfonyl-2phenylethanone (2), de la chloromtthyl methyl sulfone (4) et de I'a-chloroacttophCnone (21). On utilise les rtsultats de ccs ttudes pour suggtrer une raison pour la difficult6 associCe aux reactions de substitutions des a-halosulfones. [Traduit par le journal]

Introduction The chemistry of P-ketosulfones has not been explored in detail and much of the reported chemistry involves the incorporation of the functionality into directed alkylation sequences from which the sulfone is later discarded (1 -4). Even less has been reported on derivatives such as a-halo-P-ketosulfones (5-7). A systematic study of these functionalities could be useful; for example, it could provide information about halogenation of ketones with an adjacent sulfonyl group which would complement traditional studies on halogenation reactions of ketones with an adjacent electron-withdrawing group (8). However, the potential of these functionalities as precursors of a-sulfenylated-P-ketosulfoneswas of particular interest to US. In this paper we report on the controlled halogenation of two P-ketosulfones together with the alkaline cleavage reactions of the resulting a-halo-P-ketosulfones. The range of polyfunctional sulfones obtained in this study forms a useful series in which to study spectroscopic properties and we have, in addition, determined crystal structures of certain selected compounds by X-ray diffraction techniques. In subsequent papers we will describe reactions of a-halo-P-ketosulfones with nucleophiles having varying degrees of hardness on the HSAB scale,' and report on direct sulfenylation reactions to give a-sulfenylated-P-ketosulfones(9). Results and discussion Preparations and reactions The present study has focussed on the chemistry of two ' ~ u t h o r sto whom correspondence may be addressed; correspondence regarding the X-ray crystallography should be directed to T.S.C. 'Revision received November 24, 1983. 'Preliminary results were presented to the 64th Canadian Chemical Conference in Halifax, N.S., June 1980.

known, structurally isomeric P-ketosulfones, 1 and 10. These were chosen partly for their convenience of preparation, but also to represent the two possible extremes in structure of P-ketosulfones, namely a ketone with a-hydrogens only between the ketone and sulfonyl groups (1) and a ketone with hydrogens both in such a position and also in a methyl group a' to a ketone (10). Monohalogenation of the methylene in 1 was readily achieved using either sulfuryl chloride or pyridinium bromide perbromide, in either neutral or acidic reaction media. The products, provided stoichiometry was controlled, were either the known monochloro compound, 2, or the previously unreported monobromo compound, 3. Compound 2 has been prepared previously by Bohlmann and Haffer, using a different route (7). Both 2 and 3 possess a relatively strongly-acidic

methine proton that is easily abstracted by triethylamine in deuterochloroform solution. Deuterium oxide exchange of these methine protons in a basic solution was extremely rapid but did not occur in deuterochloroform containing ca. 20% trifluoroacetic acid, even after 48 hours at room temperature. Careful examination by "C nmr yielded no detectable en01 formation in an acidic medium and, furthermore, infrared spectroscopy showed no sign of enolization in either chloroform solution or a potassium bromide pellet, the two spectra being

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GROSSERT ET AL.

quite similar. Similar deuterium oxide exchange of the methylene protons in 1 was observed. Halogenation of ketones in neutral or acidic media proceeds by way of reaction between the en01 and a source of positive halogen (8, 10). Hence when 1 is halogenated in this manner, enolization of 2 or 3 does not occur, and further halogenation is thus not possible. We have examined reactions of 2 and 3 involving attack by hydroxide or alkoxides, and found that in both cases reactions are exclusively at the carbonyl with subsequent displacement of the halosulfonyl carbon. This reaction has potential as a synthesis of halomethylsulfones (RS02CH2Xor RSO?CHX,, X = C1 or Br), although the dibromomethyl sulfones tended to be readily reduced to monobromoethyl compounds. Thus, for example, aqueous alkaline hydrolysis of 2 gave the known (I 1) chloromethyl methyl sulfone (4) and benzoic acid, whereas ethanolic sodium ethoxide alcoholysis gave 4 and ethyl benzoate. Similar reactions with 3 gave 5 and benzoic acid or ethyl benzoate. Dichlorination of 1 was accomplished readily with sulfuryl chloride in a basic reaction medium to give 6 which was accessible also by similar chlorination of 2. Saponification of 6 gave 7 and benzoic acid only, no traces of 4 being detectable. Dibromination of 1 gave the expected dibromo-P-ketosulfone (8)

together with a small amount of the dibromosulfone 9. This small amount of 9 was most likely formed by hydrolysis of 8 during work-up of the reaction. Aqueous alkaline treatment of the reaction products resulted in both hydrolysis and reduction, with 5 being the only isolable sulfone product; it is known that a,&-dibromosulfones are readily reduced ( 12). We have found that compounds such as 4, 5 , and dimethyl sulfone have appreciable water solubility, which complicated their isolation in high yields during work-up of reactions from the saponification process. Halogenation of 1, under the conditions we have employed, was possible only at a single center. By contrast, halogenation of 10 presented a more interesting problem for regiocontrol of reaction. Bromination of 10 with one mole equivalent of pyridinium bromide perbromide in dichloromethane - acetic acid led to the formation, in high yield, of the previously unreported, crystalline a' monobromo compound, 11. By changing the solvent to pyridine-dichloromethane, either compounds 12 (a-monobromo) or 14 (a,&-dibromo) could be obtained, depending on the reaction stoichiometry. Spectral characterization of these was followed by cold aqueous alkaline hydrolysis to the respective brominated phenyl sulfones, PhSOzCHzBr (13) and 15, although 14 always yielded a mixture of 15 and its reduction product 13. It should be noted that both the tribromo- and triiodomethyl phenyl sulfones have been reported (13), apparently as stable products, from haloform reactions on 10. Chlorination of 10 with sulfuryl chloride has been reported previously (14) as yielding a-chloro-a-phenylsulfonylacetone (16). We have been unable to obtain 16 in a pure form; the best chlorination conditions involved chlorination with sulfuryl chloride in acetic acid - methylene chloride and the products

799

were shown by nmr spectroscopy to be 16, always contaminated with about 20% of its regioisomer, 17. Chlorination of 10 in the presence of triethylamine gave the unstable dichlorocompound 18, which could be saponified readily to dichloromethyl phenyl sulfone (19).

These reactions demonstrate clearly that the sulfonyl group exerts a powerful directing effect on the course of P-ketosulfone reactions. The regiochemistry of halogenation parallels that of a-haloketones (8). In addition, the a-halo-P-ketosulfones show a strongly electrophilic carbonyl group and the major reaction that we have described is the alkoxide-induced bond, undoubtedly due to the stacleavage of the C,-CO bilization of -:CHCl .S02R which is a good leaving group. This trend is evident even in 1 , which is slowly hydrolyzed in alkaline solution. It has been shown previously (15) that a-halosulfones are reduced by attack of alkoxide at halogen. In all the cases described here, except 14, the a-halo-P-ketosulfones were attacked at the carbonyl rather than at halogen and were cleaved, but were not reduced. Precise delineation of the relative activation energies for these competing reactions remains to be made.

Mass spectra Although some of the compounds reported in this paper have been described previously, they have invariably not been fully characterized by modem spectroscopic techniques. Exceptions are the P-ketosulfone (1) and its monochloro derivative (2), mass spectra for which have been reported by Bohlmann and Haffer (7). The fragmentation patterns of compounds 4 , 5, 7 , and 9 are all similar and are in agreement with the fragmentations of simple sulfones (16). The mass spectra of 11 and 12 are similar to those of 1-3 in that predominant fragmentations occur either by McLafferty rearrangement or by a-cleavage, in this latter case, however, to ~ h S 0 ~ 1as' compared to phCOlt for 1-3, indicative of the controlling influence exerted by the phenyl group. These fragmentations are outlined in Scheme 1. It is interesting to note that ions of m / z 94 were not observed in these spectra, which indicates that the rearrangement processes operating in simple phenylsulfonyl sulfones (16) are not important in these compounds. Nztclear magrzetic resonance spectra The 'H nmr spectra of these compounds were all quite routine, especially in that the observed chemical shifts all fall within the ranges normally expected. The methylsulfonyl compounds 1-3 showed 4-bond, proton-proton couplings of less than 1 Hz across the sulfonyl group. This has been observed previously in similar cases (17, 18). These couplings are appar-

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C A N . J . CHEM. VOL. 62. 1984

TABLE I. The "C nuclear magnetic resonance spectral parameters of substituted sulfones and P-ketosulfones'" 6 CH3

Compound

6 CH2

37.79 (q) ('JCH= 139.1 HZ)

42.40 (t) (IJcl., = 160.4 HZ)

. PhCO .CC1,. S02CH,, 611

PhCO CHC1. S02CH3,2

PhCO .CHBr.SOaCH,, 3

41.62 (q) ('J,, = 139.2 Hz

60.97 (t) (I.lCH= 137.1 HZ)

36.73 ('JCH= 139.9 Hz) -

~

)

PhSO,. CH2.COCH2Br, 11

.

PhSO,. CHCI COCH,, 16

27.97 (q)

6 CO

-

-

-

68.23 (d) (IJCH= 157.5 Hz)

37.61 37.58 (q of d) (1jCH= 140.4 ~

-

78.45 (d) = 185.1 Hz)

34.42 (q) ('.ICH = 140.4 HZ) PhCO .CH2SOZCH3, I$$

6 CH

-

187.23 185.16

55.82 (d) ('JCH= 156.9 Hz)

g

-SO,CH,63.94 (t) -CH2Br 34.18 (t)

-

-S02CH263.87 (t) -CH2CI 48.64 (t)

-

-

75.90 (d)

193.60

*The chemical shifts are reported with respect to TMS, G("CDC1,) = 76.90 (23). ?Abbreviations: d = doublet; q = quartet; t = triplet. $'Jo = 0.4 Hz. S3JCH= 0.7 Hz. +$All aryl carbons exhibited absorptions within the expected range (ref. 20, pp. 375-376 and refs. therein) of chemical shifts. IThe quarternary carbon bearing two chlorine atoms was observed at 6 92.08. **Not observed.

I I I

ently dependent on the oxidation level of the sulfur atom, as we have not observed them to be present across sulfenyl sulfur atoms (19). Also of note is the remarkably precise chemical shift coincidence of the two methylene sets in 17, although this is an agreement with a Strehlow-type calculation of chemical shifts (20) using a value of S(6) = 2.0 for a PhSO, group at position 2. Whenever possible, "C nmr spectra of the compounds described were measured also, although in some cases compounds were not sufficiently stable to permit accumulation of an adequate number of transients. Parameters from these spectra, which were recorded under conditions described previously (19), are given in Table 1. The chemical shifts of carbons in all

the compounds studied fall within acceptable ranges but several observations are noteworthy. The series provides for interesting comparisons of y-effects in acyclic compounds, and these are highlighted in Table 2. The values observed for A6 are intermediate between those reported (21) for acyclic and for rigid cyclic compounds. For example, the motionally averaged y-effect for acyclic chlorine is a 4-ppm upfield shift (21), whereas y-gauche effects for chlorine range from -6.88 ppm4 on methylene carbons in conformationally rigid cyclohexanes (21) to -5.72 ppm for the axial methyl and -3.45 ppm for the equatorial methyl in 4The negative sign denotes an upfield shift

GROSSERT ET AL.

TABLE2. y-Effects in the ''c chemical shifts of certain methyl sulfoncs and ketones S CH3

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Compound CH3S02CH3 BrCH2S02CH3 CICH2S02CH3 CI,CHS02CH, PhCO .CH,S02CH, PhCO .CHBr .S02CH, PhCO .CHCI .SOzCHi PhCO .CClr .SOICH, PhS02. CH2. COCH, PhS02. CHC1. COCH3

20

5 4 7 1

3 2

6 10 16

42.33 37.79 37.45 34.32 41.62 37.58 36.73 37.62 31.18 27.97

AS -

-4.54 -4.88 -6.01 -0.7 1 -4.04" -4.89" -4.00'" -

-3.21

W i t h respect to the chemical shift of the rnethyl carbon in 1.

2-chloro- I , I-dimethylcyclohexane (22). These authors caution that whereas distinctions between g a ~ i c h eand anti geometries can be made using y-shielding effects, there is no general, precise correlation between the y-effect and dihedral angles. From the magnitude of the effects exhibited by 2 and 4 , it is likely that the methyls and chlorines are largely in a g a u c l ~ e orientation, which are the conformations adopted by 2 and 4 in the solid state (vide infr-a). Similar conclusions concerning both the solid- and liquid-state conformations of sulfones with polar groups in the a-position have been reached by Engberts, Exner, and Vos (23). Study of a model of 2 leads to the conclusion that the solid-state conformation is likely to be adopted by the molecule (at least in solutions of low or moderate polarity) due to the considerable steric demands by the benzoyl and sulfonyl groups. One might then expect the y-effect in 6 to parallel that in 7 , yet such is not the case, indicating again (22) that the origins of the effect d o not lend themselves to simple explanations. Finally, it is reasonable to assume a smaller steric demand by a carbonyl group versus a sulfonyl group, with a resulting greater freedom of rotation likely in 1 6 versus 2; the y-effect in 1 6 is 1.68 ppm less than that in 2. Also of interest in this series of compounds are the chemical shifts of the carbonyl carbons. Using acetophenone as a base model for 1 , we have observed an upfield shift of -9.0 ppm due to the replacement of a hydrogen atom by a methylsulfonyl group.' The carbonyl absorption in a-chloroacetophenone (21) is at 6 190.9 (24), which therefore shows an upfield shift of -7.2 ppm due to the replacement of a hydrogen by a chlorine. As seen in Table 1, further halogenation (compounds 2 , 3 , and 6) results in further upfield shifting of the carbonyl absorption, albeit not in a linear manner. It was possible in a number of cases to record the "C nmr spectra under conditions of gated decoupling. From these spectra, values for 'JcHwere measured and are recorded in Table 1. The values obtained are in general agreement with trends recorded in the literature (ref. 20, pp. 375-376 and references therein). W e had previously reported sizeable 3-bond carbon-proton couplings across sulfenyl sulfur (19). Such couplings have apparently not been reported across sulfonyl groups and we have not observed them previously. However, by careful recording of spectra and data processing using the spectrometer computer, we were able to observe small, 3-bond proton-carbon couplings for both the methyl and methylene carbons in 4 , and for the methyl carbon only in 3. The obser-

We have measured SCO in acetophenone as 198.1 ppm.

80 1

vation of these long-range couplings, the origins of which are complex (21), is of interest but their value is limited by their small magnitude and the consequent difficulties of observing them. Struct~imlstliciies Only a few structures of acyclic sulfones with a polar group in the a position have been determined (23,25-28). Given this fact a n d the complexities of nucleophilic displacement reactions in these compounds (vicle itlfi-a), we wished to determine structural parameters for some of the compounds made available by this study. In particular, a comparison of solid-state and solution structural parameters for 2 was thought to be worth obtaining, with a long-term view of potential correlations between such sulfone structures and their reactivity. Structures were determined for PhCOCH,SOIMe ( I ) , for its a-chlorinated derivative, 2 , and for the hydrolysis product of 2 , CH2C1S02Me (4). The structure of a-chloroacetophenone (PhCOCH,CI) (21) was also included in order to compare bond distances, bond angles, and torsional angles involving the benzoyl group when the sulfonyl group is not present. Preparation .~ data of of the crystals is described under E ~ p e r i m e n t a lCrystal the four compounds are presented in Table 3 , dimensions of the molecules are given in Table 4 ; pictures of the molecules are shown in Figs. I to 4 , selected torsional angles are given in Fig. 5 , and the packing of the molecules in their unit cells is given in Figs. 6-9.' A CAD-4 four-circle diffractometer with an w/20 scan was used for all crystals to establish unit-cell dimensions and to collect intensities. Since a-chloroacetophenone proved to be unstable at room temperature, intensities for this crystal alone were collected at - 140°C. Reflection data were reduced by routine procedures which are described in ref. 29. Lorenz, polarization, but not absorption corrections were applied; two reflections were omitted from the data for compound 4 because of extinction. Scattering factors were taken from ref. 30. Partial structures were determined from the E-maps in each case, using direct centrosymmetric methods for compounds 2 and 4 and by applying the multisolution tangent formula for compounds 1 and 21. Other atoms were found on subsequent Fourier maps. Full matrix least-squares refinements (WAF' = min) were carred out with anisotropic temperature factors o n the non-hydrogen atoms and isotropic temperature factors on the hydrogens. The SHELX 7 6 system was used for all calculations (3 1). The structure of a-chloroacetophenone (21) was reported in 1966 (32) based on 327 visually estimated intensities. A poor R value of 0.16 prompted us to repeat the structure determination at - 140°C. This gave similar cell parameters and the same space group but a different arrangement of the molecules in the unit cell. W e were unable to confirm the structure as reported in 1966 since adequate reflection data could not be obtained at room temperature. Molecular geotnetries The principal bond distances, bond angles, and torsional "A commercial samplc of 21 (Aldrich) was recrystallized to constant nlp (54-55°C). 7A completc list of atomic parameters, distances, angles, and torsional angles (Table 4), a list of structure factors (Tables 5-8). and unit cell packing diagrams (Figs. 6-9) are available from the Depository of Unpublished Data, CISTI, National Research Council of Canada, Ottawa, Ont., Canada KIA OS2.

CAN. J .

CHEM. VOL. 62. 1984

TABLE3. Crystal data for PhCOCH2S0,Me ( I ) , PhCOCHClS0,Me (2), C1CH2S02Me (4), and PhCOCHzCl (21) Compound Parameter -

-

Formula weight a,

A

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b, A c, A a,deg P? deg Y7 deg d, g.cm-j Space group F (000) F*

Reflections: counted unique used

969 914 8 1 1 (>3 esd)

1857 1788 812 (>3 esd)

904 712 376 (>3 esd)

1216 1024 436 (> 1 esd)

Temperature pt R R,,,

* MoK,

( A = 0.70926 A). t Weight = [cr2(F) + pF']

TABLE4. Bond lengths,* bond angles,t and torsional anglesf for PhCOCH2S02Me( I ) , PhCOCHClS02Me (2), ClCHzS02Me (4), and PhCOCH2C1 (21) (refer to Fig. 5) Compound PhCOCH2SOzMe

PhCOCHClS02Me

CICH2S02Me

S-C,

1.787(4)

1.815(4)

1.781(9)

S-Me S-0, S-O2

1.759(4) 1.425(3) 1.441(3) 1.525(5)

1.760(5) 1.434(3) 1.430(4) 1.553(6) 1.754(4) 1.473(6) 1,203(6)

1.765(9) 1.424(7) 1.445(8)

104.1(2) 109.2(3) 108.8(2) 118.0(4) 118.8(4) 112.3(3) 118.2(2)

105.2(5)

Bonds

ca-c~ C,-CI C,-Ph Cp-0

1.474(5) 1.216(5)

1.761(8)

PhCOCH2C1$

1.55(3)$ 1.70(3)$ 1.43(3)$ 1.20(3)$

Angles Me-S-C, S-C,-Cp S-C,-CI C,-Cp-Ph C,-C,-0 Cl-C,-C, 0-S-0

104.7(2) 112.3(3) 119.9(3) 117.8(3) 118.3(2)

11 1.6(5) 119(2)$ 118(2)$ 1 14(2)$ 119.1(4)

Torsional angles Me-S-C,-C, Me-S-C,-CI S-Ca-C,-0 S-C,-CB-Ph C1-C,-Cp-Ph

-72.9(3) 80.0(3) -98.6(3)

- 172.6(3) 64.5(3) -92.4(4) 86.1(4) - 153.1(3)

-59.4(6)

*Bond lengths are reported in A. t Bond and torsional angles are reported in degrees. S C, for this compound is defined as the chloromethyl carbon, and Cp as the carbonyl carbon.

177(2)$

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GROSSERT ET AL

FIG.3. 'The crystal structure of C1CH2S0,CH3, (4).

The crystal structure of PhC0.CH2S02CH3,(I).

FIG.4. The crystal structure of PhC0.CH2CI, (21)

FIG.2. The crystal structure of PhCO .CHC1. S02CH3,(2). angles are listed in Table 4 and presented graphically in Fig. 5. The main features can be summarized as follows. The S-C, distances ia compounds 1 , 2, and 4 are 1.787(4), 1.815(4), and 1.781(9) A. The lengthening of this bond in 2 is a consequence of the substitution of hydrogen by the electron-

withdrawing chlorine, which also causes the C,-cp bond to be longer in 2 than in 1 (1.525(5), 1; 1.553(6) A , 2). The S-C, bond in 4 should be shorter than that of 2, since 4 lacks the benzoyl group, but it should be jonger than the S-C bond in dimethyl sulfone (20) (1.774(3) A) (26); the S-C, distance observed in 4 (1.781(9) A) falls within this range but it could not be determined very accurately. 'The C-C1 distances in 2, 4, and 21, 1.754(4), 1.761 (S), and 1.70(3) respectively, are not significantly different and compare with those in vinyl chloride (1.728(7) A) and methyl chloride (1.784(3) A) (33), both values having been determined by electron diffraction techniques. The S-Me distances in 1, 2, and 4 (1.759(4), 1.760(5), 1.765(9) A) are equivalent and similar to a previously reported compound (34), yet possibly significan!ly shorter than those observed in dimethyl sulfone (1.774(3) A) (26). The structural results for 21 gave a clear picture of the molecular conformation in the crystalline state (Fig. 5), but the molecular dimensions could not be determined sufficiently accurately to merit detailed comment.

CAN. I. CHEM. VOL. 6 2 . 1984

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Along S - C a Bond

Along Ccc-CP Bond

COPh

FIG.5 . Torsional angles for PhCOCHZSOzCH3( I ) , PhCOCHCIS02CH3(2), CICHISO2CH, (4) and PhCOCHzCl (21).

The two S-0 distances in a sulfone are normally equivalent (23, 26-28, 34, 35), the mean of some reported values being 1.439(14) A, (26). The S-0 distances in 1, 2, and 4 range from 1.425(3) to 1.445(8) with a mean of 1.433(8). The two S-0 distances in 1 are significantly different, although the causes of this are obscure. The electron-withdrawing property of the chlorine atom also shows in a slight closure of the S-C,-C, angle from 112.3(3)" in 1 to 109.2(3)" in 2; the same effect is less marked at the C,-Cp-Ph angle which decreases slightly from 119.9(3) to 118.0(4)". Loss of the benzoyl group from the a-chloro-P-ketosulfone (2) increases the angle between chloangle in 4 was rine and sulfur at the a-carbon: the S-C,-CI 11 1.6(5)" as compared to 108.8(2)" in 2. Electron repulsion also explains an apparent widening of the C1-C,-C, angle of 112.3(3)" when the methylsulfonyl group in 2 is replaced by a hydrogen, although the 114(2)" figure for a-chloroaceto-

phenone (21) is not very precise. The compounds 1, 2, 4 comprise a series that permits useful structural comparisons to be made between sulfonyl groups with polar substituents at an a-carbon. These results can then be compared with those from the carbonyl compound, 21. Two a-bromosulfones have been reported as having a bromine gauche to both sulfonyl oxygens (25). However, sulfones with a polar group at C, usually adopt a conformation in the crystalline state in which the polar group is gauche to only one of the sulfonyl oxygens (23,27,28,34). Dipole moment evidence by Exner and Engberts suggests that this same conformation is predominant in solution (the gallche effect) although in such molecules the causes of this phenomenon are obviously more complex than in simple molecules like 1,2-dihaloethanes or dialkyl disulfides (23). It was thus gratifying to find that the methyl group and chlorine in both 2 and 4 were in a gauche orientation about the S-C, bond (Fig. 5). This same con-

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formation was apparently predominant in solutions of these molecules (vide supra). A more subtle conformational effect was observed by examtorsional angles7 in 1 and 2 and ining the S-C,-C,-Ph comparing these with the CI-C-C-Ph angle in 21 (Fig. 5). It was found that the chloro and carbonyl groups in 21 were almost synperiplanar; such conformations of a-haloketones have been studied by infrared spectroscopy (36). Presumably this synperiplanar arrangement of the chloro and carbonyl groups derives from the fact that the electron density in the carbonyl group is rather different from that in a polar group involving only u bonds. Furthermore, since the phenyl and carbonyl groups must be coplanar, a gauche orientation of the carbonyl and chlorine in 21 would produce severe nonbonded repulsion between a hydrogen of the chloromethyl group and one of the ortho hydrogens on the phenyl ring. The corresponding projection of 1 was quite different from that of 21, reflecting the much greater bulk of a methylsulfonyl versus a angle in 2 was 12.5" less chloro group. The S-C,-C,-Ph than the corresponding angle in 1, thus permitting the chloro and carbonyl groups to be in closer proximity to each other.

Conclusions A consideration of the above conformational effects offers the possibility of some intriguing speculation concerning the fact that the intermolecular displacement of a leaving group from a carbon adjacent to a sulfonyl group is a difficult and often complex process (2, 15, 37, 38). Among displacement reactions, a small number of efficient substitutions involving the reaction of thiolate anions with chloromethyl sulfones are known (15, 39), but the mechanism of these substitution reactions has not been unequivocally established. More commonly, nucleophiles reduce a-halosulfones which must require attack at halogen rather than at carbon. This is in contrast to a-haloketones which generally (37, 40), although not always (41), undergo facile nucleophilic substitution reactions at carbon. A regular SN2-type mechanism has only been demonstrated to operate when sulfones with exceptionally powerful adjacent leaving groups (triflate and -Nzt) are attacked by nucleophiles (42). If the predominant conformation of an a-halosulfone is that in which the halogen is gauche to only one of the sulfonyl oxygens, then the other oxygen must be anti. Thus the trajectory of attack at carbon by a nucleophile must approach close to this other oxygen, and furthermore the nucleophile must pass parallel to the polar S-0 bond (see Fig. 10). Such a conformation and trajectory would undoubtedly result in a greater activation energy for an SN2-type displacement in a-halosulfones as compared to one, for example, in alkyl halide^.^ In fact, if the activation energy for attack at carbon becomes sufficiently large, substitution reactions would then preferentially occur in a two-step process, initiated by attack at halogen."ince thiolate anions are the only nucleophiles that have been reported to give substitution products from a-halosulfones, it is indeed likely that attack at halogen rather 'It should be noted that these speculations assume reaction through the major conformer. Obviously, the Curtin-Hammett principle (43) needs to be considered in making such a postulation. 'This possibility has been considered previously (15). but ruled out due to the high reactivity of a-sulfonyl carbanions with hydroxylic solvents. However, it is possible for reaction between the a-sulfonyl carbanions and the intermediate sulfenyl halide to occur before the latter has diffused out of the solvent cage.

FIG. 10. 'The postulated path of attack by a nucleophile on carbon in an a-halosulfone.

than at carbon is the lower energy pathway. W e are actively engaged in studies to cast light on these speculations.

Experimental General Thin-layer chromatographic analyses were carried out on Eastrnan silica sheets, containing a fluorescent indicator, and developed with EtOAc-ligroin, bp 40-60°C ( I : I) or i-PrOH - toluene ( 1 :9). Infrared spectra were run in chloroform solution on a P-E 237 spectrometer. Other details have been reported previously (19). All "C spectral results are collected in Table 1; conditions for recording spectra have been reported previously (19). Preparatiorz of 2-methylsulfo~z)~l-I -phenyletharzorze, 1 This preparation was carried out with ethyl benzoate (50 mmol), sodium hydride (100 mmol), and dimethyl sulfone (I00 mmol) using the procedure developed by Corey and Chaykovsky (44). Residual amounts of dimethyl sulfone were removed by washing the final dichloromethane extract thoroughly with water to give 1 in 85% yield. After 2 recrystallizations (toluene), 1 was tlc pure and had mp 106- 107°C (lit. (45) mp 107.5- 108"C, (3) mp 104- 106°C); ir: 3030 (m), 1670 (s), 1590 (m), 1320 (vs), 1155 (s); 'H nrnr, 6: 3.15 (3H, t , J = 0 . 8 H z ) , 4 . 6 0 ( 2 H , q , J = 0.8 Hz),7.43-8.07(m, 5H). Preparatiorz of 2-chloro-2-methyls~iIfo1~~l-I-phetzyletlznrzo1~e, 2 Sulfuryl chloride (1.6 mL, 20 mmol) was dropped into an ice-cold solution of 1 (3.96 g, 20 mmol) in CHzClz(25 mL), which was then stirred for 4 h at 25°C. Rotary evaporation gave a crude solid, a CH2Cl2solution of which was washed (water, 5% NaHCO?, water), dried, and evaporated to give 2 (3.95 g, 86%). Two recrystallizations (ether) gave the pure 2, mp 103- 104°C (lit. (7) mp 105°C); ir: 3040 (w), 3015 (w), 2985 (m), 2940 (w), 1690 (s), 1590 (m), 1315 (s), 1130(s); ' H n m r 6 : 3 . 2 2 ( 3 H , d , J = 0.7 H z ) . 5 . 9 8 ( l H , q , J = 0.7 Hz) 7.53-8.08 (5H, m); ms, m / z : 234 (1.0), 232 (2.4). 156 (2), 154 (6), 127 (1 I), 125 (31), 106 (42), 105 (loo), 90 (9), 89 (20). 78 (22), 77 (loo), 63 (26), 51 (73). Preparation of 2-bro~t~o-2-r~~ethylsulforzylI -phenyletharzorze, 3 A solution of 1 (3.96 g, 20 mmol) in CHzClz(100 mL) was added to a solution of pyridinium bromide perbromide (PyHBr?) (7.00 g, 22 mmol) in CH2Cl2(600 mL) and glacial HOAc(5O mL). After stirring (4 h at 25"C), the solution was washed and worked up (as above for 2) to give 3 (5.0 g, 90%). Two recrystallizations (ether) gave 3 as prisms, mp 90-91°C; ir: 3040 (m) 1680 (vs), 1590 (m), 1320 (vs), 1270 (vs); ' H nmr, 6: 3.35 (3H, s), 6.13 (IH, s), 7.5-8.2 (5H, m); ms, m / z : 278(1) 276(1) M+', 198(1.5), 171(3), 169(3), 106(10), lO5(lOO), 90(5), 89(4), 79(2), 77(26), 63(27). Anal. calcd. for C9H,Br03S: C 39.01, H 3.27, Br 28.8, S 11.57%; found: C 38.93, H 3.27, Br 27.7, S 11.14%. Hydrolyses of 2 or 3 in aqlieolrs alkali A mixture of either 2 or 3 (10 mmol) and 10% aqueous NaOH (100 mL) was stirred at room temperature for 2 h. Extraction with

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CHzClz (3 x 50 mL) gave, after routine processing, chloromethyl methyl sulfone, 4 (0.86 g, 68% from 2) or bromomethyl methyl sulfone 5 (1.20 g, 70% from 3); 4 had mp (from ether) 56°C (lit. (I I ) mp 57.2-58.2"C); 'H nrnr (CDCI,) 6: 3.07 (s, 3H), 4.50 (s, 2H); 5 had mp (from ether) 34°C (lit. (46) mp 35°C); 'H nrnr (CDCI,) 6: 3.17 (s, 3H), 4.48 (s, 2H); ms, m/z: 174 (7), 172 (7), 159 (4), 157 (4), 95 (88), 93 (97), 79 (11). 63 (loo), 48 ( I l ) , 45 (12). The aqueous alkaline solutions from these reactions were acidified (HCI); routine processing gave pure (by 'H nmr) benzoic acid (1.01 g, 82% from 2; 1.03 g, 83% from 3) which was recrystallized for comparison with an authentic sample. Reactiorz of 1 with s~rlfitrylchloride - trie~h~~larnir~e Sulfuryl chloride (0.32 mL, 4 mmol) was cautiously dropped into an ice-cooled solution of 1 (396 mg, 2 mmol) and Et,N (0.6 mL, 4 mmol) in CHzClz(25 mL). The solution was allowed to warm to room temperature and was then stirred for 12 h. Work-up, as described for the preparation of 2, gave oily 2,2-dichloro-2-methylsulfonyl-1phenylethanone, 6, 490 mg (91%); 'H nrnr (CDCI,) 6: 3.47 (s, 3H), 7.4-8.4 (m, 5H); the mass spectrum could not be recorded as the spectrum changed continually with time as the compound decomposed under electron impact. Aqueous alkaline hydrolysis of the crude 6, as described above, gave benzoic acid (184 mg, 82%) and dichloromethyl methyl sulfone. 7 (0.266 g, 88%); mp (ex CC14)69-71°C (lit. (1 I ) mp 72.0-72.3"C); ir: 3030 (m), 2960 (w), 2940 (w), 1340 (vs), 1330 (sh); 'H nrnr (CDC13) 6: 3.20 (s, 3H), 6.23 (s, IH); ms, m/z: 164 (3.8), 162 (5.0), 149 (12), 147 (16), 85 (648), 83 (1000). 79 (102), 63 (143), 48 (372). Reactiorz of 1 with pyriditziurn bromide perbromide - pyridine A solution of 1 (396 mg, 2 mmol), and dry pyridine (2 mL) in CH1CI1 (25 mL) was added slowly to PyHBr, (1.32 g, 4.13 mmol) in CH2C12(50 mL). The mixture was stirred at 25'C for 12 h and then worked up as described for 2 to give an unstable crude product (567 mg, 88%) that was a mixture of 8 (0.58 mmol) and 9 (1.17 mmol) in a ratio of 1 :2 respectively, from ' H nrnr (CDCI,) 6: 3.30 (s, Br2CHSO2CH3),3.37 (s, PhCOCBr2SO2CH3),6.30 (s, BrZCHS02CH3), 7.47-8.47 (m, 5H). The total crude mixture was hydrolyzed in aqueous alkali as described above to give benzoic acid (87 mg, 0.7 1 mmol, 6170 based on 8) as the only alkali-soluble product and 5 (132 mg, 4370 based on 8 and 9) as the only isolable neutral product. Preparation of I-methyl-2-p/1enylsuIfo1zylerhn,1one, 10 Sodium benzenesulfinate and chloroacetone were reacted (47) in refluxing ethanol to give 10, which was crystallized from ether to give plates, mp 53.3-55°C (lit. (47) mp 57-58°C); ir: 3030 (m), 17 15 (s), I585 (w), 1445 (m), 1325 (s), 1230 (s); 'H nrnr (CDCI3) 6: 2.40 (s, 3H), 4.15 (s, 2H), 7.55-7.96 (m, 5H); ms, m / i : 198 (7), 156 (13), 141 (20), 134 (45), 125 (13), 91 (39). 77 (100). Preparation of I-bromorne~h~~l-2-phen~lsulforzylethat~otze, 11 A solution of 10 (396 mg, 2 mmol) in CHZCIZ(10 mL) was added to a solution of PyHBr, (700 mg. 2.2 mmol) in CH2Clz (60 mL) and glacial acetic acid (10 mL). After stirring the orange-red solution at 25°C for 5 h, work-up as described abovc gave 11 (500 mg. 90%), mp (colourless needles from ether) 90.0-90.5"C; ir: 3030 (m), 2940 (w), 1730 (s), 1580 (w), 1330 (s), 1300 (sh); 'H nmr (CDCI,) 6: 4.16 (s, S02-CHZ-CO-), 4.41 (s, -CH,Br), 7.6-8.2 (m, 5H); ms, mlz: 278 (3), 276 (3), 214 (I), 212 (I), 197 (6). 183 (16), 141 (49), 125 (9), 95 (3), 93 (3), 91 (6), 77 (loo), 51 (41), 42 (11). Preparation of 2-brotno-I-methyl-2-phet1yIsuIfot~ylethanone, 12 Bromination of 10 (2 mmol) with PyHBr, (2.2 mmol) in CHzClz (60 mL) containing pyridine (2 mL) gave 12 (503 mg, 90%) as a brown oil which could not be purified, 'H nmr (CDCI,) 6: 2.60 (s, 3H), 5.18 (s, IH), 7.6-8.2 (m, 5H); ms, mlz: 278 (13), 276 (13), 236 (IS), 234 (18). 171 (5), 169 (5), 141 (44), 125 (7), 77 (100). Hydrolysis of 12 in aqueous alkali (vide supra) gave bromomethyl phenyl sulfone, 13 (390 mg, 91%), mp (ether-hexane) 49-50°C (lit. (48) mp 50-52°C); 'H nrnr (CDC13) 6: 4.50 (s, 2H), 7.60-8.27 (m, 5H).

Preparation of 2,2-clibrottzo-I -ttzethyl-2-pher1pIs~1y'o11~~lerhar1or 14 Bromination of 10 (2 mmol) with PyHBa (4.4 mmol) in CHZCl2 (60 mL) and pyridine (2 mL) gave 14 (677 mg, 95%) as an unstablc brown-tinged syrup; 'H nrnr (CDCI,) 6: 2.78 (s, 3H), 7.47-8.17 (m, 5H); M" at tn/z 358, 356, and 354 (39:87:41). Hydrolysis of this oil in aqueous alkali (same conditions as above) gave a mixture of 13 and 15 (510 mg) in a ratio of 56:44 (by nmr); 'H nrnr (CDCI,) 6: 4.50 (s. -CH2Br), 6.33 (s.-CHBr?), 7.62-8.62 (m, 5H). Reactiorz of 10 with suIfur-\'l chloride it1 clichlorotnetl~ane- acetic acid Sulfuryl chloride (0.2 mL, 2.5 mmol) was dropped into an ice-cold solution of 10 (396 mg, 2 mmol) in CHZCI2-HOAc (20 mL, 1 : 1). After stirring at 25'C for 4 h the reaction mixture was worked up as before to give an oily mixture of products (430 mg) which consisted of 16 and 17 (9:2, by nmr); 'H nrnr (CDC13)6: 2.55 (s, -COCH,), 4.42 (s, -CH2-CO-CH2CI), 5.22 (s, -SO,-CHCI-CO-), 7.25-8.25 (m, 5H). Preparatiorl of 2,2-dichloro-l-1~1ethyl-2-phenyls~1Ifot1~lerhnr1orle, 18 An ice-cold solution of 10 (2 mmol) in CH,CI, (30 mL), containing Et3N (0.6 mL, 4 mmol) was chlorinatcd for 3 h with S02CI, (0.32 mL, 4 mmol). Work-up as before gave 18 as an unstable, brown-tinged oil (509 mg, 95%), 'H nmr (CDCI,) 6: 2.73 (s, 3H), 7.55-8.12 (m, 5H). The crude 18 was hydrolyzed with aqueous alkali (vide s~cpra)to give dichloromethyl phenyl sulfone, 19 (331 mg, 77%), mp (CH2C11-hexane) 79-81°C (lit. (49) mp 81 .5-83.O0C); 'H nrnr (CDCI,) 6: 6.10 (s, IH). 7.5-8.1 (m, 5H); ms, m/z: 226 (0.8), 224 (1.1), 191 (0.5), 189 (0.8), 162 (2.0), 160 (4.0), 156 (3), 141 (54), 125 (9), 85 (6). 83 (9), 77 (100).

Acknowledgements W e thank the Natural Sciences and Engineering Research Council of Canada for financial support (to J . S . G . and T.S.C.) and an undergraduate summer award (to G . H . G . ) . T h e Government of India awarded a scholarship for overseas study (to P.K.D.), Dr. D . L. Hooper kindly provided nmr spectra, and K. Jochem gave technical assistance. 1. P. D. MAGNUS. Tetrahedron, 33, 2019 (1977). 2. T. DURST.III Comprehensive organic chemistry. Vol. 3. Edited by D. N . Jones. Pergamon, Oxford. 1979. pp. 197-213. 3. H. 0 . HOUSEand J. K. LARSON.J. Org. Chem. 33. 61 (1968). 4. B. M. TROSTand J. E. VINCENT. J . Am. Chem. Soc. 102,5680 (1980); B. M. TROSTand B. R. ADAMS.J. Am. Chem. Soc. 105, 4849 (1983). 5. D. DILLERand F. BERGMANN. J. Org. Chem. 37, 2147 (1972). 6. J. FlClNl and G. STORK.Bull. Soc. Chim. Fr. 723 (1964). 7. F. BOHLMANN and G. HAFFER.Chem. Ber. 102, 4017 (1969). 8. A. J. WARING.111 Comprehensive organic chemistry. Val. 1. Edited by J. F. Stoddart. Pergamon, Oxford. 1979. pp. 1036- 1039. 9. J. S. GROSSERT and P. K. DUBEY.J. Chem. Soc. Chem. Commun. 1183 (1982). 10. L. F. FIESERand M. FIESER.Reagents for organic synthesis. 1 , 967 (1967); 5, 568 (1975). 11. W. E. TRUCE,B. H. BIRUM,and E. T. MCBEE.J. Am. Chem. SOC.74, 3594 (1952). 12. L. A. PAQUETTE. Org. React. 25, 28 (1977); F. G. BORDWELL, E. B. HOYT,JR., B. B. JARVIS,and J. M. WILLIAMS, JR. J. Org. Chem. 33, 2030 (1968). 13. P. DEL BUTTERO and S. MAIORANA. Gazz. Chim. Ital. 103, 809 (1973). and G. ZECCHI.Synthesis. 603 (1978). 14. L. CHIODINI, L. GARANTI, and B. B. JARVIS. J. Org. Chem. 33, 1182 15. F. G . BORDWELL ( 1 968). 16. J. H. BOWIE,D. H. WILLIAMS, S.-0. LAWESSON, J. 0 . MADSEN, C. NOLDE, and G. SCHROLL. Tetrahedron, 22, 3515 (1966);

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