1.3- Dihydrobenzo thiophene 2-oxide

Biocatalytic asymmetric oxidation of 2,3-dihydrobenzo[. ]thiophene to (—)-(lJ)-sulfoxide in excellent yield has been reported. The enzyme used is a chloroperoxidase from the marine fungus Caldariomycesfumago. This enzyme is relatively stable and does not require any cofactor. Hydrogen peroxide was the oxygen source. Using this system, 2,3-dihydro-benzo[. ]thiophene was converted to the (—)-(i )-sulfoxide in 99.5% yield, with an ee of 99%. Similarly, 1,3-dihydro-benzo[f]thiophene could be oxidized to the corresponding sulfoxide in 80% yield <1998CH246>. 

Substituted 1,4-dihydrobenzothiin 3-oxides (sultines), which are stable at room temperature, can be obtained from the isomeric l,3-dihydrobenzo[/>]thiophene... 

Although sodium sulphide reacts readily with haloalkanes [2] and activated aryl halides (see Chapter 2) [e.g. 3-5] in the presence of a quaternary ammonium catalyst to form symmetrical thioethers (Table 4.1), a major side reaction results in the formation of disulphides owing to the oxidation of the intermediate thiols under the basic conditions. Consequently, little use has been made of this procedure for the synthesis of thioethers [3, 6], but the corresponding reaction of the a,(0-dihaloalkanes to yield cyclic thioethers has proved to be a valuable procedure for the synthesis of thietanes [7] (Table 4.2). The ring closure with the secondary dihaloalkanes is considerably more difficult to effect than is the reaction of the primary dihaloalkanes. 1,3-Dihydrobenzo[c]thiophene (89%) is produced in the reaction of 1,2-bis(bromomethyl)benzene with sodium sulphide (Scheme 4.1) [8]. The direct... 

For benzo[Z ]thiophene the heterocycle is rather more resistant to ring opening and oxidation with hydrogen peroxide in acetic acid at 95 C, for example, gives the 1,1-dioxide (Scheme 7.22) reduction with either sodium and ethanol or triethylsilane in trifluoroacetic acid affords 2,3-dihydrobenzo[Z)]thiophene. Electrophiles give mainly 3-substituted benzo[Z ]thiophenes, although these products are often accompanied by smaller amounts of the 2-isomers. 

H-NMR spectra of the dihydrobenzo[c]thiophene 5-oxides 5 have been investigated in various solvents510. The a-proton resonates at lower frequency when it is cis to the sulfoxide oxygen compared to the trans orientation. 

The configurations of cis- 2,3- dihydrobenzo[6]thiophene- 3 -carboxylic acid 1-oxide (25) and its trans isomer have been assigned by chemical methods and by use of NMR spectra and ionization constants.221... 

Dihydrobenzo[6]thiophene 426 and its 2-methyl derivative182 are readily dehydrogenated with sulfur to the corresponding benzo[ ]-thiophene. 2,3-Dihydrobenzo[6]thiophenes are oxidized by peracetic acid to the corresponding sulfones (Section VI, P, 2), and give crystalline complexes with mercuric chloride. 

Methyl- and 2-ethylbenzo[6]thiophene are most conveniently prepared by treatment of 2-benzo[6]thienyllithium with the appropriate dialkyl sulfate (Section VII). Mono- and dimethyl-2,3-dihydrobenzo[6]thiophene-l-oxides (Section VI, P, 1) are dehydrated by acetic anhydride to give the corresponding benzo [6]thiophenes.2 80... 

Since hydrobenzo[c]thiophenes are often used as intermediates for the preparation of benzo[c]thiophene and its derivatives, it is convenient to review the chemistry of these compounds first. Hydro-benzo[c]thiophene 2-oxides and 2,2-dioxides are reviewed in Section VI and l,3-dihydrobenzo[c]thiophen-I-one and l,3-dihydrobenzo[c]-thiophen-l,3-dione are covered in Section VII. 

Benzo[c]thiophene may be prepared by low-pressure (20 mm) vapor-phase catalytic dehydrogenation of l,3-dihydrobenzo[c]thio-phene (Section III,A) at 330° under nitrogen,5,8 by decarboxylation of benzo[c]thiophene-1 -carboxylic acid (Section III,C) with copper in quinoline16,38 or by dehydration of l,3-dihydrobenzo[c]thiophene 2-oxide (Section VI,A) in acetic anhydride or over aluminum oxide at 20 mm Hg and 100°-125° in a sublimation tube.52 A trace of water appears to be beneficial to the first reaction, and it has been suggested53... 

Several l,3-dihydrobenzo[c]thiophenes have been oxidized to the corresponding sulfoxides (Table VI) with peracetic acid,43,44 /-butyl hydroperoxide,9 sodium periodate in aqueous ethanol,52,55,56 or... 

We have discussed the preparation of benzo[c]thiophene and its derivatives from l,3-dihydrobenzo[c]thiophene 2-oxides in Section IV. 

Dihydrobenzo[c]thiophene may be oxidized to its sulfone (Table VII) with peracetic acid,28,69,87,88 aqueous hydrogen peroxide,9 or potassium permanganate,21 and when benzocyclobutene and 1,2-diphenylbenzocyclobutene are heated with sulfur dioxide, they give l,3-dihydrobenzo[c]thiophene 2,2-dioxide89 and its cis-1,3-diphenyl derivative (83),69,90 respectively [Eq. (5)]. 1,3-Dihydro-benzo[c]thiophene 2,2-dioxide also arises when the thiadiazepine (17b) is heated just above its melting point (175°-180°).34a When sulfur dioxide is passed into a solution of diphenyldiazo-... 

The catalysis cycle comprises the following steps oxidative addition of H2 to the metal coordination of the benzothiophene in the 77 -mode hydride migration and, finally, elimination of dihydrobenzo[3]thiophene by reductive coupling of the hydride and dihydrobenzothienyl ligands (Scheme 73). Based on this, various ruthenium and rhodium complexes have been developed, which exibit good catalytic activity. 

A similar mercaptoacetate addition reaction to 5-acyl-4,7-dioxo-4,7-dihydrobenzo[i]thiophene-2-carboxylates followed by cyclization and oxidation to give benzo[ 1,2-6 5,4-ft ]dithiophene-4,8-dione derivatives 29 has been shown <03H1689>. Nitrogen bridged heterocycles, 3-(benzylthio)thieno[3,4-6]indolizine derivatives 30 have been synthesized and intramolecular arene-arene interactions within these compounds were reported <03CPB75>. The arene-arene interaction leads to significant shifts in the proton NMR signals and red shifts in the absorption maxima. 

Sulfoxide dehydration. When a mixture of the sulfoxide l,3-dihydrobenzo[f]-thiophene 2-oxide and grade 1 neutral alumina (Woelm) is heated under 25-mm. pressure at 12U-130° in a sublimer, almost pure benzo[c]thiophcnc (2) condenses on the... 

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