Thiophene-2-carboxylate

Thiophene-4-carboxylic acid, 3-bromo-debromination, 4, 78 Thiophenecarboxylic acids acidity, 4, 71... 

Wynberg and Feijen prepared d-methylhexanoic acid (236) by desulfurization of thieno[3,4-6]thiophene-2-carboxylic (93) and 6-carboxylic (197) acids [Eq. (80)]. The analogous reaction with thieno-[3,4-A]thiophene-4-carboxylic acid (196) produce 3-ethylpentanoic acid (237) [Eq. (81)]. 

Decarboxylation of 5,7-dimethyl-8-oxo-6-aza-8//-indeno[2,1 - ]thiophene-4-carboxylic acid could be effected by heating an admixture of it and copper powder <87H(26)1535). Direct sublimation in vacuo afforded the desired product (58%). 9-Chloro-2- and 3-methyltriazolo[4,5-/]quinoline-7-carboxylic acids are decarboxylated under similar conditions <93H(36)259>. The cyano group of 8-cyano-7-oxo-4,5,6,7-tetrahydrothiazolo[4,5-/]quinolines can be converted into an amino group by cone. HC1 mediated hydrolysis to the amide, followed by Hofmann rearrangement <89H(29)I517>. 

Three phenalenothiophens (521)—(523) have been synthesized by unambiguous methods from the corresponding phenalenothiophenones (524)— (526), which in turn were prepared by electrophilic ring-closure of the corresponding 3-(a-naphthyl)thiophen-2-carboxylic acid, 2-(a-naphthyl)-thiophen-3-carboxylic acid, and 3-(a-naphthyl)thiophen-4-carboxylic acid. The reaction of (527) with glycerol, sulphuric acid, and iron leads to the... 

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-ainino-2-thiophene carboxylate can be used as intermediate for herbicidal sulfonylureas (67) and various thiophenic stmctures (68). 

The dianions derived from furan- and thiophene-carboxylic acids by deprotonation with LDA have been reacted with various electrophiles (Scheme 64). The oxygen dianions reacted efficiently with aldehydes and ketones but not so efficiently with alkyl halides or epoxides. The sulfur dianions reacted with allyl bromide, a reaction which failed in the case of the dianions derived from furancarboxylic acids, and are therefore judged to be the softer nucleophiles (81JCS(Pl)1125,80TL505l). 

Finally, certain 3-substituted compounds can be prepared by utilizing the - meta) directing powet (cf. Section IV,B) of some groups in the 2-position which afterward can be removed. 3-Nitrothiophene is prepared by nitration of 2-thiophenesulfonyl chloride and by removal of the sulfonic acid group of the 4-nitro-2-sulfonyl chloride formed with superheated steam. Another approach to 3-nitrothio-phene is to nitrate 2-cyanothiophene, separate the 4-nitro-2-cyano-thiophene from the 5-isomer, hydrolyze, and decarboxylate. A final method of preparation of 3-nitrothiophene is by simultaneous de-bromination and decarboxylation of 5-bromo-4-nitro-2-thiophene-carboxylic acid obtained through the nitration of methyl 5-bromo-2-thiophenecarboxylate. 

In —I—M-substituted aminothiophenes, the possibility of coupling during diazotization is eliminated. Thus ethyl 5-amino-2-thiophene-carboxylate and 5-amino-2-thiophenesulfonic acid and its amide- have been diazotized and coupled with various reagents. 

Replacement of a benzene ring by its isostere, thiophene, is one of the more venerable practices in medicinal chemistry. Application of this stratagem to the NSAID piroxicam, gives tenoxicam, 136, a drug with substantially the same activity, nie synthesis of this compound starts by a multi-step conversion of hydroxy thiophene carboxylic ester 130, to the sulfonyl chloride 133. Reaction of that with N-methylglycinc ethyl ester, gives the sulfonamide 134. Base-catalyzed Claisen type condensation serves to cyclize that intermediate to the p-keto ester 135 (shown as the enol tautomer). The final product tenoxicam (136) is obtained by heating the ester with 2-aminopyridine [22]. 

Chamical Nama 4-Methyl-3-[ [ 1 -oxo-2-(propylamino) propyl] amino]-2-thiophene carboxylic acid methyl ester... 

The N -(5 -nitro-2 -thenoyl)hydrazide is prepared by reacting hydrazine with ethyl 5-nitro-2-thiophene carboxylate. 

Both R and MMA radicals are found to be responsible for the photoinitiation process. Chaturvedi and coworkers [54,55] introduced phenyl dimethyl sulfonium-ylide cupric chloride and chromium thiophene carboxylate as the photoinitiator of styrene and MMA. No reaction mechanism was given for these systems. 

A thermophilic strain M. goodii X7B was reported to carry out desulfurization of BT and DBT [38], The growth of the strain on various sulfur substrates including DBT, BT, 4,6-dimethyl DBT, 5-methyl BT, 2-thiophene carboxylic acid and propylmercaptan was studied at 45°C and varying degree of growth was observed. A mechanism of sulfur removal was proposed for BT based on metabolites identified by GC-MS (Fig. 7 [125]). 

The authors showed that it was possible to perform this reaction in a multimode microwave oven [19] in a few minutes on a large scale in water containing a slight excess of potassium hydroxide but without cosolvent. Under the action of classical heating the major problem with these syntheses is the instability of the thiophene o-amino acids, which readily decarboxylate at room temperature to give aminothio-phenes which are themselves unstable [20 a] and have to be used as soon as they are prepared. With large quantities of reactants, moreover, the hydrolysis step is not easy to perform because of the low reactivity of thiophene carboxylates 39 and 42 [20 b]. 

The reaction of butadiene with the sulfone of 3-benzo[6]thiophene-carboxylic acid under Diels-Alder conditions gives the adduct (32). Catalytic reduction over platinum oxide removes the 2,3-double bond. 

Metallation of dibenzothiophene 5-oxide with three equivalents of butyllithium followed by carbonation gave a mixture of 4-dibenzo-thiophene carboxylic acid (36 /o) and dibenzothiophene (10%). The reduction or even elimination of sulfoxide groups in the presence of... 

Polymers of thiophene carboxylic acids (9) undergo different chromatic transitions upon the addition of a variety of cations (McCullough et al. 1997). Although the acid form of the polymer was not water soluble, addition of various ammonium or metal... 

This synthetic fiexibility was put to use in the preparation of " C-labeled isotopomers of duloxetine (3) for further biological studies (Scheme 14.12). Labeled thiophene carboxylic acid 40 was readily converted to radioactive intermediate 43a, which was then converted to duloxetine-[3- " C] hydrochloride (3a ) via route A. In contrast, 43b was submitted to route B, utilizing labeled [l- C]-naphthalene, to provide duloxetine-[l-naphthalene- " C] hydrochloride (3b ). 

In a related report, ruthenium-catalyzed enantioselective hydrogenation of 3-keto esters was utilized to prepare the crucial alcohol intermediate 36 (Scheme 14.16). The required (3-keto ester 49 was readily prepared from commercial thiophene carboxylic acid 40. Hydrogenation of 49 then led to the desired (S)-alcohol 50 in quantitative yield and 90% enantiomeric excess, catalyzed by a chiral diphosphine-ruthenium complex generated in situ. Catalyst-substrate ratios used were as low as 1/20,000, rendering this approach amenable to industrial application. Alcohol 50 was then converted to known intermediate 36 in three steps and 60% overall yield. 

The maleimide group can undergo a variety of chemical reactions. The reactivity of the double bond is a consequence of the electron withdrawing nature of the two adjacent carbonyl groups which create a very electron-deficient double bond, and therefore is susceptible to homo- and copolymerizations. Such polymerizations may be induced by free radicals or anions. Nucleophiles such as primary and secondary amines, phenates, thiophenates, carboxylates, etc. may react via the classical Michael addition mechanism. The maleimide group furthermore is a very reactive dienophile and can therefore be employed in a variety of Diels Alder reactions. Bisdienes such as divinylbenzene, bis(vinylbenzyl) compounds, bis(propenylphenoxy) compounds and bis(benzocyclobutenes) are very attractive Diels Alder comonomers and therefore some are used as constituents for BMI resin formulations. An important chemical reaction of the maleimide group is the ENE reaction with allylphenyl compounds. The most attractive comonomer of this family is DABA particularly when tough bismaleimide resins are desired. 

Pyrrole-2-carboxylic acid easily loses the carboxylic group thermally. Pyrrole-3-carboxylic acid and furan-2- and -3-carboxylic acids also readily decarboxylate on heating to about 200°C. Thiophene-carboxylic acids require higher temperatures or a copper-quinoline catalyst. In furans, 2-carboxylic acid groups are lost more readily than 3-carboxylic acid groups (Scheme 64). 

Thiophene- and benzo[6]thiophene-carboxylic acids undergo all the normal reactions of an aromatic carboxylic acid (63AHC(1)1, 70AHC(11)177). They can be converted to acid chlorides, amides and esters the esters can be used to make hydrazides. Benzo[6]thiophene-2-carboxylic acid chloride has been converted to the methyl ketone with dimethylcadmium and to the diazoketone with diazomethane. Bromodecarboxylation of the silver salts (Hunsdiecker reaction) has been used to prepare the dibromo compounds (340) and (341). 

A chloroacetylbenzo[6]thiophene is readily converted into the corresponding benzo[6]thiophene carboxylic acid by alkaline hydrolysis of its pyridinium salt.132 464... 

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... 

Benzo[6]thiophene carboxylic acids have been decarboxylated byT heating them with oxalic acid,254 by heating the ester with IN NaOH in dioxane,441 by heating the barium salt with barium hydroxide in vacuo,162, by heating them in quinoline with copper chromite347, 352.353 or> preferably, with copper,109 185 189,298 315 343 344 351 412 422, 638 an(j py heating them alone in quinoline54 or pyridine.114... 

Carboxylic acids, acyl chlorides, and sulfonyl chlorides used for deri-vatization of 4-aminophenylalanine and >-4-am i n op h e ny I a I a n i n e are as follows 5-hydantoinacetic acid, / ran, v - 4 - co t i n i n ec a r b o xy I i c acid, isonicotinic acid, 3-pyridinepropionic acid, 4-hydroxyphenylacetic acid, 2-butynoic acid, 2-pyrazinecarboxylic acid, cyclopropanecarboxylic acid, 3-hydroxy-2-qui-noxaline carboxylic acid, 5-bromovaleric acid, propargyl chloroformate, 3,4-dimethoxybenzoyl chloride, 2-thiophenesulfonyl chloride, 3-thiophene-carboxylic acid, 2-thiophenecarboxylic acid, 2-methylbutyric acid, 2-thio-pheneacetyl chloride, benzoic acid, furylacrylic acid, 4-nitrophenyl acetic acid, 2,5-dimethoxyphenylacetic acid, p-toluenesulfonyl chloride, 4-(di-methylamino)phenylacetic acid, 3-indolepropionic acid, phenoxyacetic acid, 3-(dimethylamino)benzoic acid, cyclohexanecarboxylic acid, naphtha-lenesulfonyl chloride, 4-bromophenylacetic acid, 4-bromobenzoic acid, 2-phenoxybutyric acid, 3,4-dichlorophenylacetic acid, (l-naphthoxy)acetic acid. 

D-Arg H2N,COOH L. n nh2 NH Isonicotinic acid COOH 3-Thiophene carboxylic acid COOH Q... 

D-Arg h2N,co°h C n, nh2 NH Isonicotinic acid Cl COOH 2-Thiophene carboxylic acid C3 -cOOH... 

Ckbp" y) hiT nIj--cooh o Isonicotinic acid Cl - XOOH 3-Thiophene carboxylic acid COOH 0... 

HjO / pH - 5) are 2- and 3-mercaptopropionic-, furan-, and thiophene carboxylic acids, which amount to 40 to 80 % of the volatile Maillard products. The furan- and thiophene carboxylic acids are formed via 3-deoxyosone and the mercaptoacids via 1-deoxyosone (Figure 6). By dehydration, addition of H 0 (or by Strecker degradation of Cys) and reduction of the carbonyl group, furfuryl-mercaptan (the impact component of roasted coffee) results. 2-Hydroxymethyl-4-thiolanone, which may be formed by the same route, was identified for the first... 

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