Sulfoxide, isopropyl methyl

Figure 3. Effect of temperature on the magnitude of the chemical shift difference between isopropyl methyl sulfoxide enantiomers in the presence of (-)-TFPE in CCI4. Molar ratio of alcohol to sulfoxide to solvent is 2 1 5. Symbols are as in Figure 2. Reprinted with permission from Tetrahedron Lett. 1974,2295-2298.

Other solvents may also be used with similar effects. Isopropyl alcohol has been used for fractionating a polyglucose.72 Examination of the fractions revealed that fractionation according to viscosity and immunological reactivity had occurred.240 The excellent solvent properties of methyl sulfoxide,241 tetramethylene sulfone, pyridine, N, TV-dimethylformamide, and formamide may also prove useful. 

By Methods A and B, isopropyl phenyl sulfoxide was included in crystalline 1 with high ( -enantioselectivity (86 and 87% ee, respectively). Ethyl phenyl sulfoxide formed no inclusion compound by Method A, but the inclusion compound of its (5)-enantiomer was obtained by Method B. The inclusion crystal of (.V)-e(hyl phenyl sulfoxide is isostructural with that of (S)-isopropyl phenyl sulfoxide (Figure 3). As mentioned above, (6>ethyl phenyl sulfoxide was not included by Method A. The lack of one methyl group may make enthalpy (interaction with the inclusion cavity) and entropy disadvantageous in crystal packing to result in no inclusion of ethyl phenyl sulfoxide via Method A. 

Methyl m-tolyl (8), ethyl m-tolyl, methyl n-butyl and methyl n-propyl sulfoxides were obtained in 100% e.e. This method was less successful when applied to methyl phenyl sulfoxide (5% e.e.) or to methyl isobutyl and methyl ethyl sulfoxides (25% e.e.). No complexes were formed between methyl o-tolyl, methyl p-tolyl, methyl 2-butyl and methyl isopropyl sulfoxides so these compounds could not be resolved using 7. A crystal structure of the 1 1 complex formed between 7 and 8 revealed that the partners were linked by OH—OS hydrogen bonds in endless zig-zag chains23. More recently, 2-chloroethyl m-tolyl sulfoxide (9) has been resolved using 724. 

Komori and Nonaka132,133 electrochemically oxidized methyl, isopropyl, n-butyl, isobutyl, r-butyl and cyclohexyl phenyl sulfides (108) and cyclohexyl p-tolyl sulfide (109) to their sulfoxides using a variety of polyamino acid-coated electrodes to obtain the range of e.e. values shown in parentheses. The highest enantiomeric purities were obtained using an electrode doubly coated with polypyrrole and poly(L-valine), an electrode which also proved the most durable of those prepared. 

Tai156 applied MM2 to the ten dialkyl sulfoxides possible when the alkyl groups are restricted to methyl, ethyl, isopropyl and t-butyl, and calculated that only one or two conformations exist in substantial amount (> 20%) for each molecule. 

Mikolajczyk and coworkers have summarized other methods which lead to the desired sulfmate esters These are asymmetric oxidation of sulfenamides, kinetic resolution of racemic sulfmates in transesterification with chiral alcohols, kinetic resolution of racemic sulfinates upon treatment with chiral Grignard reagents, optical resolution via cyclodextrin complexes, and esterification of sulfinyl chlorides with chiral alcohols in the presence of optically active amines. None of these methods is very satisfactory since the esters produced are of low enantiomeric purity. However, the reaction of dialkyl sulfites (33) with t-butylmagnesium chloride in the presence of quinine gave the corresponding methyl, ethyl, n-propyl, isopropyl and n-butyl 2,2-dimethylpropane-l-yl sulfinates (34) of 43 to 73% enantiomeric purity in 50 to 84% yield. This made available sulfinate esters for the synthesis of t-butyl sulfoxides (35). 

Nevertheless, correlations have been found in four j3-hydroxyesters (107), eight aminoesters (108), primary a-deuterioalcohols (109), and secondary carbinols (110). Even in a closely related series, exceptions have been found (110) in search of a predictable pattern. A study of nonequivalence in methyl alkyl sulfoxides with CLSR 54c (48) revealed a diminution of nonequivalence on increasing alkyl bulk with an inversion of sense between n-propyl and isopropyl. Changes in nonequivalence sense in several cases with different CSA-solute ratios were also observed. Presently, these CLSR configurational correlations remain totally empirical. 

Dimethyl sulfoxide Ethanol Ethyl acetate Ethyl ather Ethyl formate Formic acid Heptane Isobutyl acetate Isopropyl acetate Methyl acetate... 

Dehydrochlorination with diethylaniline was explored for the preparation of 4//-thiopyran (7) and its 3-methyl and 4-isopropyl derivatives from 2,6-dichloro-l-thiacyclohexanes7,l9,24 303a (see Section III,B). Chlorosulfone 288b undergoes dehydrochlorination to 289.300 Chloro derivative 296 was similarly dehydrochlorinated with triethylamine to 4//-thiopyran sulfoxide (10).27 On the other hand, debromination of 2,3,5,6-tetrabromo derivative 297 with zinc surprisingly gives 2//-dioxide 9 instead of expected 10,46 probably due to an isomerization of 10 with ZnBr2. 

Chemicals and Standard Solutions. Cyclohexanone, cyclohexanol, 1,3,5-trichlorobenzene, 1,2,4-trichlorobenzene, phenol, 4-methylphenol, 4-chloro-phenol, 1,2,3,4-tetrahydroisoquinoline, 1-chlorohexane, 1-chlorododecane, and 1-chlorooctadecane were obtained from Aldrich. Acetone, tetrahydrofuran, ethyl acetate, toluene, dimethyl sulfoxide, and methanol were obtained from J. T. Baker. Distilled-in-glass isooctane, methylene chloride, ethyl ether, and pentane were obtained from Burdick and Jackson. Analytical standard kits from Analabs provided methyl ethyl ketone, isopropyl alcohol, ethanol, methyl isobutyl ketone, tetrachloroethylene, dodecane, dimethylformamide, 1,2-dichlorobenzene, 1-octanol, nitrobenzene, 2,4-dichlorophenol, and 2,5-dichlorophenol. All chemicals obtained from the vendors were of the highest purity available and were used without further purification. High-purity water... 

With regard to the phosphorus stereochemistry, a new stereospecific synthesis of chiral 0,0-dialkyl thiophosphoric acids (6,7) has been developed which is based on the Horner-Wittig reaction of the optically active phosphonothionate carbanions containing the sulfoxide or dithioacetal moieties. The transformation of (R)-(+) 0-methyl 0-isopropyl methanephosphonothionate (10)(8) into (R)-(-) 0-isopropyl phosphorothioic acid (H) best Illustrates this method. 

The P-addition of alkyl radicals to 4-methyl-2-(arylsulfinyl)-2-cyclopentenone 117 has been shown to occur in a completely stereocontrolled manner. Of a mixture of (4/ )- and (45)-117, only (4R)-117 reacts with t-Bu and i-Pr radicals to give the trans adducts 119a and 119b in 99% yield, while (45)-117 remained entirely unreacted. The stereochemical outcome of the reaction shows that the alkyl radical approaches from the side opposite to the aryl moiety in an antiperiplanar orientation to the carbonyl and sulfoxide bond. The 2,4,6-triisopropylphenyl group on sulfur plays a critical role, as it effectively shields the olefin face at the P-position by one of the isopropyl groups. This was confirmed by the 1 1 diastereomeric mixture obtained in the reaction of 4-methyl-2-(p-tolylsulfmyl)-2-cyclopentanone with the tert-butyl radical. 

Ac, acetyl AIBN, azobis(isobutanonitrile) All, allyl AR, aryl Bn, benzyl f-BOC, ferf-butoxycarbonyl Bu, Butyl Bz, benzoyl CAN, ceric ammonium nitrate Cbz, benzyloxycarbonyl m-CPBA, m-chloroperoxybenzoic acid DAST, diethylaminosulfur trifluoride DBU, l,8-diazabicyclo[5.4.0]undec-7-ene DCC, /V. /V - d i eye I oh e x y I c ar bo -diimide DCM, dichloromethyl DCMME, dichloromethyl methyl ether DDQ, 2,3-dichloro-5,6-dicyano-l,4-benzoquinone DEAD, diethyl azodicarboxylate l-(+)-DET, L-(+)-diethyl tartrate l-DIPT, L-diisopropyl tartrate d-DIPT, D-diisopropyl tartrate DMAP, 4-dimethylaminopyridine DME, 1,2-dimethoxyethane DMF, /V./V-dimethylformamide DMP, 2,2-dimethoxypropane Et, ethyl Im, imidazole KHMDS, potassium hexamethyldisilazane Me, methyl Me2SO, dimethyl sulfoxide MOM, methoxymethyl MOMC1, methoxymethyl chloride Ms, methylsulfonyl MS, molecular sieves NBS, N-bromosuccinimide NIS, /V-iodosuccinimide NMO, /V-methylmorpho-line N-oxide PCC, pyridinium chlorochromate Ph, phenyl PMB, / -methoxvbenzyl PPTs, pyridiniump-toluenesulfonate i-Pr, isopropyl Py, pyridine rt, room temperature TBAF, tetrabutylammonium fluoride TBS, ferf-butyl dimethylsilyl TBDMSC1, f-butylchlorodimethylsilane Tf, trifhioromethylsulfonyl Tf20, trifluoromethylsulfonic anhydride TFA, trifluoroacetic acid THF, tetrahydrofuran TMS, trimethylsilyl TPAP, tetra-n-propylammonium perruthenate / -TsOH. / -toluenesulfonic acid... 

Apart from this classic approach, it would be possible to improve the properties of known CWs, e.g. microencapsulation so that less stable or highly volatile substances can be used. Nanotechnology offers new possibilities, as described recently by Price and Peterson (2008). The other option is to improve penetration using known enhancers like dimethyl sulfoxide (DMSO). While the percutaneous toxicity (expressed as LD50 in rats) of one of the toxic organophosphates - O-isopropyl 5-2-diisopropylaminoethyl methyl phosphnothiolate - is 59.1 P-g/kg, in mixture with DMSO this value is decreased to 10.1 pg/kg (Bajgar, 1989). 

The typical example of one-stage derivatization of amino acids is their treatment by isopropyl bromide in presence LiH with the formation of N-isopropy-lated isopropyl esters. Unfortunately, this reaction can take place only in high-boiling aprotic bipolar solvents like dimethyl sulfoxide (DMSO, = 189°C, RInonpoiar 90 18) tWs is a significant restriction for its application, in practice. A more important method is based on the reaction of amino acids with methyl or phenyl isothiocyanates with the formation of 3-methyl (phenyl) hydantoins ... 

Studies conducted in rabbit liver microsomes on the metabolism of methyl, ethyl, isopropyl and propyl thiols show that rabbit liver catalyses the S-methylation of short-chain alkane thiols to yield the corresponding methyl sulfides. The coenzyme in this process is S-adenosyl-L-methionine. The resulting methyl sulfides are further metabolized by formation of the corresponding sulfoxide and sulfone (Holloway et al., 1979). The methylation of short-chain alkyl thiols to methylthioethers acts as a detoxication mechanism for the reactive sulfhydryl group (Holloway et al., 1979),... 

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