2- Amino-5- thiophene intermediate

Peseke and co-workers investigated the effect of incorporating a thienopyrimidine moiety into C-nucleoside analogues to increase cell membrane permeability and antimicrobial and anti-tumor activity. The C-nucleoside derivatives were constructed through the Gewald amino thiophene synthesis in 55% yield under standard conditions. The thiophene intermediate was further converted into a thienopyrimidine to produce the desired compound. 

The intermediates of type (8), wherein G is an electron withdrawing group, which are used in the dyestuffs industry, are usually produced by the user companies themselves and used direcdy. The type (9) amino ester is another product from the SCL range of thiophene derivatives, produced in metric ton quantities for specific outlets. 

Dyestuffs. The use of thiophene-based dyestuffs has been largely the result of the access of 2-amino-3-substituted thiophenes via new cycHzation chemistry techniques (61). Intermediates of type (8) are available from development of this work. Such intermediates act as the azo-component and, when coupled with pyrazolones, aminopyrazoles, phenols, 2,6-dihydropyridines, etc, have produced numerous monoazo disperse dyes. These dyes impart yeUow—green, red—green, or violet—green colorations to synthetic fibers, with exceUent fastness to light as weU as to wet- and dry-heat treatments (62-64). 

Fusion of an additional heterocyclic ring onto a benzodiazepine is well known to considerably increase potency. This increase in potency is apparently maintained when the benzene ring is replaced by thiophene. Thiophene aminoketone 161 is converted to the benzodiazepine analogue 164 via chloroacetamide 162 and then glycine derivative 163 by the same sequence as that used in the benzene series. Treatment of the product 164 with phosphorus pentasulfide gives the thio-amide 165 reaction of that intermediate with hydrazine leads to the amino amidine 166. Conden-... 

Addition of amines to a,/J-unsaturated sulfones has been used in synthesis of key intermediates of biotin. In this reaction, benzylamine serves first as a base in the reaction with 60 to afford thiophene 1,1-dioxide (61) and also as a nucleophile to introduce two amino groups (equation 57)49. 

Diamino-3,4-dicyanothiophene is thus converted by NaOH to 2-amino-3,4-dicyano-5-mercaptopyrrole (Scheme 132) (58JA2822). Here, prior to the recyclization of the intermediate (396), a rotation around the 4,5-bond has occurred. With other substrates such as (397), recyclization results in a thiophene, different from the precursor. Here the 3-substituent is involved in the cyclization and so a rotation around the 3,4-bond is mandatory. One can therefore postulate an intermediate of the type (398) in such reactions ring closure of this will lead to a thiophene-3-carbonitrile which could be either (399) or (400). Some examples are shown in Scheme 133 (75JPR861, 77JCR(S)294). 

A simple two-step synthesis of 4-arylthieno[3,2-c]pyridine-6-carboxylic acids has recently been presented by Eweiss (Scheme 74) (B-81MI31703). The condensation of thiophene-2-carbaldehyde with an N -aroylated a-amino acid yields a thienylidene azlactone (281) which on treatment with AICI3 is converted to a thieno[3,2-c]pyridine (283). A nitrilium ion (282) resulting from a vinyl-oxygen fission is probably involved as an intermediate. Sandberg s method already mentioned in the previous section has also been applied to the synthesis of thieno[3,2-c]pyridines (Scheme 75). 

Many desirable meat flavor volatiles are synthesized by heating water-soluble precursors such as amino acids and carbohydrates. These latter constituents interact to form intermediates which are converted to meat flavor compounds by oxidation, decarboxylation, condensation and cyclization. 0-, N-, and S-heterocyclics including furans, furanones, pyrazines, thiophenes, thiazoles, thiazolines and cyclic polysulfides contribute significantly to the overall desirable aroma impression of meat. The Maillard reaction, including formation of Strecker aldehydes, hydrogen sulfide and ammonia, is important in the mechanism of formation of these compounds. 

Pharmaceuticals and Agrochemicals. ThioglycoHc acid and its esters are useful as a raw material to obtain biologically active molecules. In cephalosporine syntheses, (4-pyridyl)thioacetic acid [10351-19-8] (65) and trifluoromethane (ethyl) thioglycolate [75-92-9] (66) are used as intermediates. Methyl-3-amino-2-thiophene carboxylate can be used as intermediate for berbicidal sulfonylureas (67) and various thiophenic structures (68). 

The presence of pesticidal activity among benzo[6]thiophene derivatives is well documented. The compound 4-A-methylcarbamoylbenzo[Z>]thiophene (372) has been marketed under the name Mobam as an effective insecticide. The anticholinesterase and insecticidal properties of the 3-, 5-, 6- and 7-isomers of (372) in the housefly have been reported. The 4- and 7-isomers were most active, the 5-isomer intermediate, and the 3- and 6-isomers least active. Broad pesticidal activity was claimed for a series of 2-amino-3,4-dihydro-2i/-[ 1 ]benzothieno[3,2-Z>]pyrans (373). 

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