Sulfenyl chlorides cyclizations

Elimination of hydrogen chloride from 2/f perfluoro-2-methylpropane-1 -sulfenyl chloride by the triethylamine-boron trifluoride complex results in cyclization to perfluoro-l,l-dimethylthiirane (perfluoroisobutylene sulfide) [, 9] (equation 9)... 

Benzotrithiadiazepine (12.14, R = H) is obtained as bright-yellow crystals by the reaction of benzo-l,2-bis(sulfenyl chloride) with McsSiNSNSiMcs (Eq. 12.4). The tetrafluoro derivative 12.14 (R = F) has been prepared by a similar procedure. The isomeric 1,2,4,3,5-benzotrithiadiazepine (12.15) is formed in the reaction of PhNSNSiMcs and S2CI2, followed by intramolecular cyclization (Eq. 12.5). " ... 

Cyclization of unsaturated alcohols with sulfenyl chlorides... 

In the reaction of ketones with thionyl chloride the intermediate sulfinyl (or sulfenyl) chloride can cyclize on to an aromatic ring located two carbon atoms away giving benzo[b]thiophenes (48) (Scheme 7).54 Additional... 

When the thiole derivatives are converted into the corresponding sulfenyl chloride such as 56, an addition reaction to styrene or /3-methylstyrene in nitromethane gives regioisomeric mixtures of adducts 57 and 58 (Scheme 11) <2001CHE702> as well as the cyclization products 59 which are generated in 47% (R = H) and 52% (R = OI I () yield, respectively. 

N-Allenylazetidinone 181 rearranges to cephalosporin 182 in the presence of lithium chloride (Eq. 13.62) [70], This is a very unusual reaction that is presumed to be initiated by chloride ion-induced cleavage of the disulfide to give sulfenyl chloride 183. Thiolate attack at the allene sp carbon atom of 183 generates ester enolate 184, which cyclizes to 182. The reactivity of the allene function in 181 ensures the success of the reaction. 

H. Cyclizations, Conversions and Reactions of Sulfenyl Chlorides with Metal Carbonyls. ... 

Thionyl chloride undergoes a cyclization reaction with ketones. Enoli-zation of the intermediate sulfenyl chloride, followed by the base-induced intramolecular nucleophilic displacement reaction, produces the thietanone... 

A recent report on trifluoromethylsulfenylation of (3-keto acids and derivatives describes isolation of 29 in good yield from reaction of 27 with trifluoromethyl-sulfenyl chloride (Scheme 6.10). Mechanistically, this was rationalized via electrophilic attack of trifluoromethylsulfenyl chloride on the enamine tautomer 27a to generate 28 followed by intramolecular cyclization through the imide oxygen with concomitant loss of CF3SH to produce 29. The product was characterized spectroscopically. 

A concerted elimination-cyclization mechansim, involving a sulfenyl halide in a 1,3-butadiene-1-thio system, is the most probable mechanism for the formation of benzo[6 Jthiophenes from cinnamic acids or 4-aryl-2-butanones by treatment with thionyl chloride. The reactions shown in Scheme 5 have been carefully worked out, and the intermediates isolated (75JOC3037). The unique aspect of this synthesis is the reduction of the sulfinyl chloride (a) by thionyl chloride to form the sulfenyl chloride (b). The intermediate (b) was isolated and converted in pyridine to the 3-chlorobenzo[6]thiophene-2-carbonyl chloride in 36% yield (73TL125). The reaction is probably initiated by a sulfenyl ion attack on the aromatic ring, since it is promoted by electron-releasing groups para to the site of ring closure. For example, when X in (36) was N02, a 23% yield of (37), a mixture of 5-and 7-nitro derivatives, was obtained, but when X in (36) was OMe, a 54% yield of (37) was obtained, contaminated with some 3,4-dichloro-5-methoxybenzo[6]thiophene-2-carboxylic acid. 

Trithianes are rare but routes established for the 3-methyl derivative (226) could provide the basis of more general methods. These include the chlorination of diethyl disulfide and the reaction of the sulfenyl chloride (227) with 1,2-ethanedithiol (74MI22601). 1,2,4,5-Tetrathiane (228) has been prepared by the cyclization of two equivalents of the bis sulfenyl chloride CH2Y2 (229 Y = SCI) or the bis Bunte salt CH2Y2 (230 Y = SSQ3Na) using sodium... 

A general method for the preparation of oxathiazoles and dithiazoles with exocyclic conjugation is the cyclization reaction of carboxamides and appropriately substituted sulfenyl chlorides. Most of the known reactions of this... 

Symmetrical 3,5-dialkyl-l,2,4-trithiolanes (178) can be synthesized in reasonable yield by chlorination of dialkyl disulfides (175) to a-chiloroalkyl sulfenyl chlorides (176), which are then reacted with potassium iodide to give di-a-chloroalkyl disulfides (177). Subsequent cyclization with sodium sulfide gave (178) (72T3489). When (176) was treated with one molar equivalent of sodium sulfide, the reductive dimerization and cyclization was effected in one step (78HCA1404). Treatment of perfluoropropene with sodium hydrogen sulfide in THF resulted in the formation of 3,5-bis(2,2,2-trifluoroethyl)-l,2,4-trithiolane (179) (72IZV2517). 

Cyclizations involving sulfenyl chlorides must be designed carefully, since these reagents can also react with alcohols, amines and other nucleophiles. Benzenesulfenyl chloride has been used to cyclize a... 

Cyclizations involving sulfenyl chlorides must be designed carefully, since these reagents can also react with alcohols, amines and other nucleophiles. Benzenesulfenyl chloride has been used to cyclize a 1,4-diene. For example, diene (4) cyclizes in good yield to tricyclic heptane product (5). This material was then further elaterated to a cyclosativene precursor (6 equation 4). ... 

Phthalimide-N-sulfenyl chloride, 375 Phthaloylamino acids, 212 Phthaloyl-L-valine, 212 Phytuberin, 197 Phytyl chloride, 499, 500 Picrotoxinin, 265, 430 Pictei-Spengler cyclization, 308 Pinacol-typc reduction, 513 -Pinene, 346, 367 Piperidine acetate, 318 Piperidinium acetate, 375-376 Polonovski reaction, 484 Polyaminolactams, 378-379 Polycyclic phenols, 102 Polyene cyclization, 291-292 Polyethylene glycols, 360, 376 Polyketides, 302 Polyphosphate ester, 376-377 Polyprenylation, 499-500 Potassium-Ammonia, 273, 377 Potassium-t-Butylamine-18-Crown-6, 377-378... 

The preparation of isothiazolopyrimidine 366 (R = H) is based on the same procedure, and is obtained in good yield (81%) by oxidation of the stable thioaldehyde 365 with Pb(OAc)4 in AcOH <1996T9971>. Isothiazole 368 can be obtained by intramolecular cyclization of the thermally labile /3-cyano-sulfenyl chlorides 367 (R = CE3, R = Cl). In an analogous way, 367 (R = E, R = /-Bu) readily reacts with sulfuryl chloride affording isothiazoline 369... 

The more frequently used methods for construction of isothiazoles (and its partially or completely saturated analogs) consist of cyclization of compounds containing preformed N-C-C-C-S fragments with a S-N bond coimection. For example, 4,6-dinitrobenzisothiazole 225 is prepared from sulfenyl chloride 224 upon treatment with ammonia <05MC200>. Further functionalization at 4-position is achieved by nucleophilic replacement at the 4-nitro group. 

The ortho-benzylthio derivatives 110 were treated with sulfuryl chloride in di-chloroethane and intermediate compounds sulfenyl chlorides 111 were apparently formed, which underwent intramolecular cyclization due to the interaction of S-Cl fragment with the C = N bond. This pathway results in the formation of 2-aryl-4,6-dinitro-l,2-benzisothiazolium chlorides 112a-d even at room temperature. The structure of salts 112 was established by an NOE method (04MC207, Scheme 36). 

All of the synthetic routes reviewed so far have primarily involved the use of sulfur as a nucleophile. Sulfur can also act as an electrophile in the formation of precursors of the benzothiazine ring system. Reaction of sulfenyl chloride with ketones gives / -keto sulfides. The acetophenone adduct 90 has been cyclized with stannous chloride and hydrogen chloride in acetic acid to give 3-phenyl-6-chloro-2H-1,4-benzothiazine (91).135... 

Tetrahydro-l,3-oxazin-2-ones (368) can be obtained by the reaction of arylthiols with N-bromo-A-cinnamylcarbamates (367). Presumably a sulfenyl bromide, or its equivalent, is formed initially which then acts as an electrophilic agent to promote the cyclization step (Equation (44)). However, should sulfenyl chlorides be reacted with A-alkyl-A-cinnamylcarbamates (369) then the regioselectivity is changed and oxazolidinones (370) are formed instead (Equation (45)) <86JPR173>. 

Fluorothiiranes are also prepared by cyclization of open-chain precursors. Treatment of sulfenyl chloride 92 with the triethylamine-boron triiluoride complex gave thiirane 30 in 68% yield. Tris(diethylamino)phosphine transformed disulfide 94, prepared from alkene 93 and sulfur monochloride, into thiirane 95. An indirect route from a chlorodisulfide that has the advantage of utilizing both halves of the molecule is exemplified by the transformation of 96 into thiirane 97. ... 

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