Benzo thiophene aldehydes

A general route to both benzo[/)]furans and benzo[/>]thiophenes depends upon the cyclodehydration of either 2-hydroxy- or 2-sulfanylbenzyl ketones or aldehydes (Scheme 7.23a). 2-Acetylbenzo[6]furan can be obtained by reacting the sodium salt of 2-formylphenol with chloroace-tone (chloropropanone) (Scheme 7.23b). A similar reaction using sodium 2-formylbenzenethiolate yields 2-acetylbenzo[Z)]thiophene. 

Reaction of 2-benzo[6]thienyllithium (and its 7-methyl derivative 90) with aldehydes 486,5fl4, 620 or ketones 467 483 affords a secondary or tertiary alcohol, respectively. Treatment of 2-benzo[6]thienyl-lithium with acetyl chloride gives mainly l,l-di(2-benzo[6]thienyl)-ethylene.132 Side-chain alcohols in positions other than the 2-position are most easily prepared by reaction of the appropriate benzo[6]-thienylmagnesium halide with aldehydes 460,471 or ketones,186,3o9, 349, 4 7,466,479,498 or foy reaction of a benzo[fe]thiophene aldehyde, ketone, or ester with an alkylmagnesium halide.358,427 465 The preparation of alcohols from 2- and 3-benzo[6]thienylmethyl-magnesium chloride485,528 is discussed in Section VI, D, 4. 

Benzo[6]thiophene aldehydes have also been prepared by oxidation of the corresponding primary alcohol with fer -butyl chromate,518 nitric acid,518 or manganese dioxide,337,565 and by reaction of the... 

Benzo[6]thiophene aldehydes have been condensed with a variety of active methylene compounds, including cyclic511, 644 and open-chain645-647 ketones, aliphatic aldehydes,90 benzyl cyanides,93-436 malononitrile,487 rhodanine,144,648 hippuric acid,477 barbituric acid,487 diethyl malonate,487 and malonic acid (Section VI,M). Aliphatic nitro compounds condense smoothly with most benzo[6]-thiophene aldehydes03,141,337,343, 556,640,650 (except 5-hydroxy- and... 

The most widely used routes to benzo[ >]thiophene-2-carboxylic acids are (a) successive lithiation and carbonation of the parent benzo[ >]thiophene,42,76 90 98,183,477, 481>487,521,685-687 (ft) oxidation of the corresponding aldehyde,90,91,106,189 424, 477,640 (c) hypohalite oxidation of the corresponding methyl ketone,82 °8,189,424 and (d) cyclization reactions (Section IV,D, and E). Acids prepared by these routes are listed in Table XV. Oxidation of aldehydes usually proceeds almost quantitatively with moist silver oxide,90,91,105, 189,424 hut potassium permanganate is satisfactory.477, 640... 

The synthesis of 1,2-benzodithiin has been achieved through cyclisation of the bisthiolate obtained from either phenylacetylene or benzo[ >]thiophene (95TL1421). These yellow solids are more stable than both 1,2-dithiins and can be oxidised at either sulfur atom and also under Swem conditions to give the 3-aldehyde. 

The normal reactions of aldehydes and ketones attached to thiophenes or benzo[ ]thiophenes have been discussed exhaustively in CHEC(1984) and CHEC-II(1996) <1984CHEC(4)741, 1996CHEC-II(2)491>. Only novel reactions, or those leading to products with special applications, are discussed here. 

Treatment of the A, A -diethylthiocarbamate 344 with LDA and then with aldehydes affords (Z)-3-(alkyliden-l-yl)-37/-benzo[ ]thiophen-l-ones 345 as major products along with minor amounts of the ( )-isomers 346 <2004H(63)1813>. 

Electron-withdrawing substituents seem to stabilize the benzo[cjfuran system as they do in the analogous benzo[c]thiophene and benzo [c]indole series. l-Cyano-3-phenylbenzo[c]furan (128) was obtained from the aldehyde 127 as stable yellow needles hydrolysis with base yields the carboxylic acid (129). Catalyzed hydrogenation of these cornpounds leads to 1,3-dihydrobenzo[c]furans (130, R = CH2NH2, COOH = Ph). Increased... 

Ozonolysis of benzo[6]thiophene results in rupture of the hetero ring the aldehydes (154) and (155) are formed (74TL4069). 

Robba and coworkers succeeded in preparing the o-quinonoid thieno[3,4-with hydrazine (equation 35) (67BSF2495). Compound (314) is obtained as yellow crystals with m.p. 135-136 °C. Compared with benzo[c ]thiophene the stability of (314) is considerably increased. Thieno[3,4-prepared from the corresponding aldehydic acids of thiophene and hydrazines. 

Matsuki and Lee 91 have brominated all the isomeric benzo[6]thio-phene aldehydes and obtained solely the 3-bromo compound, except with the 3-aldehyde this observation has been confirmed by other workers in the case of the 2-aldehyde.477 Monobromination of 7-methylbenzo[6]thiophene-2-carboxaldehyde produces mainly the... 

Bromoacetylbenzo[6]thiophene is reduced to 2-(l,2-epoxyethyl)-benzo [6]thiophene by 1 mole of sodium borohydride in alkaline solution.336 2-Chloroacetyl-3-ethylbenzo[6]thiophene and salicyl-aldehyde react together to give 285.132 2-Chloroacetyl-2,3-dihydro-benzo[6]thiophene is readily aromatized by potassium acetate to... 

Esters, amides, and primary alcohols are obtained from benzo[6]-thiophene carboxylic acids by standard procedures.337 481,585 692 093,695 Acid chlorides undergo the Arndt-Eistert reaction,337,568,689 react with diethyl ethoxymagnesium malonate to give the corresponding methyl ketone,144 557 and are reduced to the aldehyde with 1 ithium tri-ferf-butoxy aluminohydride.33 7... 

Finally, SchifTs bases of other heterocyclic aldehydes can also be reacted with p-tolyl-substituted benzo[6]- (see Table III) and naphtho-[2, l-i]thiophenes.38,37,58 Thus, 2-(p-tolyl)naphtho[2,l-A]thiophene (116) gives, on reaction with the anil derived from 3-formyldibenzofuran and p-chloroaniline, the styryl compound 117.36... 

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