Chloromethyl sulfoxides

A novel synthesis of a-unsaturated sulfines has been introduced by Bra-verman et al. [99]. Et3N or DABCO treatment of allylic and benzylic tri-chloromethyl sulfoxides triggered the elimination of chloroform and formation of the sulfines. It must be stressed that these sulfines are thermally relatively stable, and this stands in high contrast to the corresponding thio-carbonyl compounds unsaturated thioaldehydes cannot be monitored under the same experimental conditions and have to be used at very low temperature or trapped in situ. The first synthesis of thioacrolein S-oxide was achieved by flash vacuum thermolysis of an anthracene allyl sulfoxide [100], and both isomers in a (Z E) ratio of 78 22 were characterised by NMR spectroscopy at -60 °C. 

An alternate route to a -thiomethyl methyl sulfoxides involves substitution of an a-chloromethyl sulfoxide with sodium thiomethoxide. ... 

OL-CUoro aUfoxUesJ Diazoraethanc reacts readily with sulflnyl chlorides to form chloromethyl sulfoxides in high yield ... 

Finkelsteim reaction. lodomethyl sulfoxides can be prepared in 80-85% yield by reaction of chloromethyl sulfoxides with K1 in DMSO at 100-110°. Cleavage of acemaphtheneqmmame. This reaction was originally carried out... 

Dithietanef Bis(chloromethyl) sulfoxide (1) reacts with aqueous sodium sulfide in the presence of 1 equiv. of this phase-transfer catalyst to form 1,3-thietane 1-oxide (2) in 36% yield. Bis(chloromethyl) sulfide does not undergo this reaction. However, the product (3) that would have been formed can be obtained by reduction of (2) with borane-tetrahydrofurane (5, 48). The microwave spectra... 

Allenyl chloromethyl sulfoxide (57) reacts with m-CPBA to furnish allenyl chloromethyl sulfone (58) (eq 21). The enethi-olizahle thioketone (59) has been oxidized to the ( )-sulfine (60) (eq 22). The 2 -deoxy-4-pyrimidinone (62) has been prepared by reacting the 2-thiop3Timidine nucleoside (61) with m-CPBA (eq 23). Thioamides have been transformed to the amides in high yields. ... 

Addition of BuLi to a 0.3 M solution of chloromethyl phenyl sulfoxide in THF at — 78 "C yields an immediate bright-yellow solution containing the lithio derivative which is stable for at least 2 h at —78 rC. Decomposition occurs rapidly above —20 C with the solution becoming turbid and the color changing to dark brown. Reaction of the lithiated solution of chloromethyl phenyl sulfoxide with cyclohexanone, acetone, or ben/ophenone for 10 min at —78 °C followed by 30 min at —20 rC yields one diastereomeT in 79, 75 and 68 % yields, respectively, after hydrolysis of the corresponding adducts. 

E. Reduction of Halomethyl Phenyl Sulfones and Chloromethyl Phenyl Sulfoxide by Fluorenide Anions... 

A similar condensation of 177b with chloromethyl phosphonic dichloride gave 2-chloromethyl-l,3,2-oxazaphospholidine-2-oxide 182 which was converted into the cyano derivative 183 by reaction with potassium cyanide in anhydrous dimethyl-sulfoxide (Scheme 51) [82],... 

The synthesis of the benzoimidazo[l,2- ][l,2,3]thiadiazole 61 can be explained using the same mechanistic model to that used for the Hurd-Mori reaction. The amino benzimidazole 58 when treated with thionyl chloride at reflux affords the benzoimidazo[l,2-r ][l,2,3]thiadiazole 61. If, however, the reactant 58 is treated with thionyl chloride at room temperature, the chloromethyl derivative 59 is formed. This derivative was then transformed into product 61 on reflux with thionyl chloride. The proposed mechanism for the formation of product 61 is for the initial formation of the sulfoxide 60, which then undergoes a Pummerer-like rearrangement, followed by loss of SO2 and HC1 to give the c-fused 1,2,3-thiadiazole 61 (Scheme 7) <2003TL6635>. 

Aldicarb degrades rapidly in the chlorination of drinking water forming aldicarb sulfoxide which subsequently degrades to aldicarb sulfone, (chloromethyl)sulfonyl species and A-chloro-aldicarb sulfoxide (Miles, 1991). 

Dihydrothieno[3,4-Z ]thiophene (131) was prepared by two methods. In the first (Scheme 8), chloromethylation of methyl thiophene-2-carboxylate (132) forms methyl 2,3-bischloromethyl-thiophene-5-carboxylate (133) (85%) cyclization of 133 with sodium sulfide in methanol yields (66%) methyl 4,6-dihydrothieno[3,4-i]-thiophene-2-carboxylate (134). Peroxide oxidation of 134 gives 2-methoxycarbonyl-4,6-dihydrothieno[3,4-h]thiophene 5,5-dioxide (135) and hydrolysis of 134 followed by metaperiodate oxidation furnishes the sulfoxide (91). Thienothiophene (131) was produced by hydrolysis and decarboxylation of 134. As indicated above, the sulfoxide (91) was used for the synthesis of thieno[3,4-6]thiophene (3). 

A very interesting synthetic method of bicyclo[n.l.O]alkanes from cychc ketones via this 1,3-C,H insertion of magnesium carbenoid as a key reaction was reported (equation 22) . 1-Chlorovinyl p-tolyl sulfoxide (76) was synthesized from cyclopentadecanone and chloromethyl p-tolyl sulfoxide in three steps in high overall yield. Lithium enolate of tert-butyl acetate was added to 76 to give the adduct 77 in quantitative yield. a-Chlorosulfoxide (77) in a toluene solution was treated with i-PrMgCl in ether at —78 °C and the reaction mixture was slowly warmed to 0°C to afford the bicyclo[13.1.0]hexadecane derivative 79 in 96% yield through the reaction of the intermediate magnesium carbenoid 78. 

In 1993, Satoh and coworkers reported the preparation of lithium- and magnesium-aUtylidene carbenoids from 1-chlorovinyl phenyl sulfoxides by sulfoxide-metal exchange reaction at low temperature (Scheme 6). 1-Chlorovinyl phenyl sulfoxide (128) is easily synthesized from the corresponding aldehyde and chloromethyl phenyl sulfoxide in high yield. Sulfoxide 128 was treated with f-BuLi in THF at —78 °C to give the terminal alkyne 131. Obviously, the intermediate of this reaction was the alkylidene carbenoid 129. 

Analogously, (/ )-(—)-chloromethyl p-tolyl sulfoxide has been prepared with 97% e.e. and used for the enantioselective synthesis of epoxides [394],... 

Methyl-l-penten-3-one-l-ol 1 and glacial acetic acid in benzene was added to pyrrolidine to give 2-methyl-l-pen ten-1-[N-pyrrolidinyl]-3-one 2. Compound 2 when treated with oxalyl chloride and methanol was added, 3,5-dimethyl-2-methoxycarbonyl-4-pyrone 3 was produced. Treatment of compound 3 with sodium borohydride in methanol gives 3,5-dimethyl-2-hydroxymethyl-4-pyrone 4. Compound 4 was converted to 3,5-dimethyl-2-hydroxymethyl-4-pyridone 5 by heating compound 4 with aqueous ammonia in a sealed flask. Compound 5 was converted to 4-chloro-2-chloromethyl-3,5-dimethyl pyridine 6 by treatment with phosphorous oxychloride. Treatment of compound 6 with 5-methoxy-2-mer-captobenzimidazole in tetrahydrofuran gave 2-[2-(4-chloro-3,5-dimethyl pyridinyl)methylthio]-5-methoxy benzimidazole 7. When compound 7 was treated with potassium hydroxide in dimethyl sulfoxide containing methanol, 2-[2-(3,5-dimethyl-4-methoxypyridinyl)methylthio]-5-methoxy... 

The lithium anion of chloromethyl phenyl sulfoxide reacts with tetrahydrofuran-2-ones 1011 to afford a diastereo-meric mixture of hemiacetal adducts 1012, the potassium enolate of which is treated with /-BuLi followed by addition of a proton source leading to to-hydroxyalkyl ketenes 1013, which themselves cyclize to 6-substituted tetrahydropyran-2-ones in excellent overall yield (Scheme 263) <1998TL9215>. 

Ketone synthesis. The reaction of NaScQ.H, (excess) with a,p-cpoxy sulfoxides, available by reaction ol aldehydes or ketones with the anion of chloromethyl phenyl sulfoxide (8, 94-95), results in a-substituted ketones and diphenyl disclenide. 

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