Approaches to benzo[ b ]thiophenes by gas-phase pyrolysis of methyl 2-(alkylthio)cinnamates

Flash vacuum pyrolysis (FVP) of 3-[2-(t-butylthio)phenyl]propenoate 7 at 700 °C (0.01 Torr) unexpectedly gave a mixture of benzo[ b ]thiophene derivatives 5 (15%) and 8 (21%), and thiocoumarin 9 (28%). Control experiments show that thiophenoxyls ( e.g. 15 ) cyclise efficiently to benzo[ b ]thiophene 5 under similar conditions. It follows that FVP of S -t-butyl derivatives of thiophenols, is not an efficient means of generating thiophenoxyl radicals owing to competing hydrogen capture processes.


Introduction
We have shown that benzo[b]furans 4 can be generated by flash vacuum pyrolysis (FVP) of 2-(benzyloxy)-or 2-(allyloxy)-cinnamate esters 3 (X = O); these precursors act as sources of the corresponding phenoxyl radical by homolysis of the weak O-benzyl and O-allyl bonds respectively (Scheme 1). 1,2Often, phenoxyls and thiophenoxyls show very different properties in the gas-phase 3,4 and so it was of interest to explore whether the strategy could be extended to benzo[b]thiophene 5 synthesis.The methods we previously used to prepare benzo[b]furan precursors, from salicylaldehyde 1, are inapplicable in this case because of the poor stability of 2-mercaptobenzaldehyde 5 2 and so, in the first part of this paper, we discuss whether the S-tbutyl group can act as a thiophenoxyl radical generator in the gas-phase.Because this aspect of the work was only partially successful, we also present the results of a short feasibility study exploring the use of 2-(benzylthio)cinnamates in this application.‡

Results and Discussion
In order to probe the effectiveness of S-t-butyl groups as gas-phase thiophenoxyl radical generators, the cinnamate 7 was readily made under standard Wittig conditions from the commercially available aldehyde 6.The X-ray crystal structure of 7 has been reported. 6The electron impact (EI) mass spectrum of 7 apparently provides benzothiophenium species as the base-peak cluster (in agreement with the anticipated thermal behaviour), though the mechanism of formation under EI conditions appears to involve a multi-step process (Scheme 2).

Scheme 2
Under FVP conditions, cleavage of the S-t-butyl group of 7 required a marginally higher furnace temperature (700 °C in our apparatus) than S-allyl-or S-benzyl-derivatives (650 °C), but the product mixture was more complex than expected.Benzo[b]thiophene 5 was indeed formed, though only in 15% yield and the major products were the dihydrobenzothiophene 8 (21%) and the thiocoumarin (benzothiopyran-2-one) 9 (28%) (Scheme 3).Compounds 5, 8 and 9 are known and were identified by their spectra (see Experimental section).The possibility of a rearrangement leading to the isomeric thiochromone (benzothiopyran-4-one) system was readily excluded, since the 1 H NMR spectra of thiocoumarins and thiochromones are characteristic. 7hus, signals of simple thiocoumarins generally occur at δ H <8.0 p.p.m whereas thiochromones show a peak at δ H ca. 8.5 p.p.m., due to H (5)

Scheme 3
At this stage in the study it was not clear whether the anomalous thermal behaviour of 7 was due to the t-butyl group acting as an inefficient radical generator, or whether the thiophenoxyl, once generated, behaves differently from the corresponding phenoxyl and is inefficient at cyclising onto propenoate groups.It was therefore important to establish this point by the synthesis and FVP of the allyl-or benzyl-compounds 10 or 11 respectively.At the time this work was carried out, the aldehyde precursor to the allylthio compound 10 was unknown, but 2-benzylthiobenzaldehyde 12 could be made by 5-step synthesis, the key step of which was the McFadyen-Stevens degradation of the hydrazide 13 (see Experimental section). 13With the aldehyde 12 in hand, Wittig reaction provided the cinnamate 11 (82%) and Knoevenagel condensation gave the cyano-derivative 14 (23%).Small-scale FVP of 11 and 14 both gave pyrolysates consisting of bibenzyl and a single cyclised product, viz the benzothiophenes 5 and 17 respectively.The thiophenoxyls 15 and 16 therefore behave in the same manner as the corresponding phenoxyl to provide the 5-membered ring heterocycles (Scheme 4).The results are therefore clear; the anomalous thermal behaviour of 7 is due to the poor generation of thiophenoxyls from such S-t-butyl derivatives.

Scheme 4
We rationalise the formation of products 5, 8 and 9 from FVP of the t-butyl derivative 7, as shown in Scheme 5.After initial homolysis of the S-t-butyl bond, some thiophenoxyl 15 is able to undergo standard cyclisation to provide the benzothiophene 5 obtained in this experiment.
The formation of reduced derivatives such as 8 is unusual under FVP conditions, which normally favour products at high oxidation level.It seems likely that the key intermediate 18 can be diverted, prior to elimination, by hydrogen atom capture to provide 8.The hydrogen atom flux is provided by the decomposition of the t-butyl radicals to 2-methylpropene.It is also known that FVP of 2-hydroxycinnamates is a good synthetic route to coumarins 14 so we propose that the thiocoumarin 9 is formed from the thiophenol 19 by an analogous mechanism (Scheme 5).The thiophenol 19 itself may be obtained directly by intramolecular decomposition of the precursor 7, or by hydrogen capture by the thiophenoxyl 15 prior to cyclisation.

19 Scheme 5 Experimental Section General Procedures
13H and13C NMR spectra are recorded at 250 (or 200) and 63 (or 50) MHz respectively for solutions in [ 2 H]chloroform unless otherwise stated. Cling constants are quoted in Hz;13C NMR signals refer to one CH resonance unless otherwise stated.