Ethoxycarbonyl fragmentation

Thiophene, 2-amino-3-cyano-5-phenyl-synthesis, 4, 888-889 Thiophene, 3-amino-4,5-dihydro-cycloaddition reactions, 4, 848 Thiophene, 2-amino-3-ethoxycarbonyl-ring opening, 4, 73 Thiophene, 2-amino-5-methyl-synthesis, 4, 73 Thiophene, 2-anilino-synthesis, 4, 923-924 Thiophene, aryl-synthesis, 4, 836, 914-916 Thiophene, 2-(arylamino)-3-nitro-synthesis, 4, 892 Thiophene, azido-nitrenes, 4, 818-820 reactions, 4, 818-820 thermal fragmentation, 4, 819-820 Thiophene, 3-azido-4-formyl-reactions... 

In another copper-mediated carbene transfer reaction, diazoester 222 has been decomposed in the presence of bis(triethylsilyl- or -germyl)mercury (equation 72) it was assumed that the obtained ketenes 223 result from the insertion of ethoxycarbonyl(trimethylsilyl)carbene into a Hg-element bond followed by a cyclic fragmentation process110. 

A highly exo-selective asymmetric hetero Diels-Alder reaction was the key step in D.A. Evans total synthesis of (-)-epibatidine. The bicyclic cycloadduct was then subjected to a fluoride-promoted fragmentation that afforded a (f-keto ester, which was isolated exclusively as its enol tautomer. The removal of the ethoxycarbonyl functionality was achieved using the Krapcho decarboxylation. Interestingly, the presence of a metal salt was not necessary in this transformation. Simply heating the substrate in wet DMSO gave rise to the decarboxylated product in quantitative yield. 

The scope of the reaction was probed by extending the reaction to the synthesis of six-membered cyclic sulphamides. The reaction of 367 with acetamidine gave 1,2,4,6-thiatriazinone-1,1-dioxides 371 (equation 121) in yields of 20%. Fragmentation of the intermediates prior to cyclization is considered to account for the low yields. Modest yields of the pyridothiatriazinone 372 were obtained by condensation of aminopyridine with 367 (equation 122). Aminotriazoles when reacted with 367 yielded the triazolothiatriazinones 373 (equation 123). The reaction of 2-amino-3-ethoxycarbonyl 4,5,6,7-tetrahydro-l-benzothiophen (374) with isopropyl sulphamoyl chloride gives the iV-(isopropyl)-iV -(3-ethoxycarbonyl-4,5,6,7-tetrahydro-l-benzothiophene)sulphamide (375)369. Cyclization of 375 with 5% sodium hydroxide leads to the formation of the cyclic sulphamide 3-isopropyl-4-oxo-3,4,5,6,7,8-hexahydro-1H [ 1 ] -benzothieno [2,3-d] -2,1,3-thiadiazin-2,2-dioxide (376) in 42% yield. Decarboxylation of 375 also occurs in the reaction with the formation of iV-(isopropyl)-iV -(4,5,6,7-tetrahydro-l-benzothiophene)sulphamide 377... 

These systems uniformly have at least one pyrimidine ring, and they are readily formed from aminodiazines, incorporating the amidine moiety, with bifunctional electrophiles serving as three-carbon fragments. In this way, most frequently, 0x0 derivatives are obtained. Alkoxymethyl-enemalonates and 2-benzoylamino-3-dimethylaminopropenoate convert the amines into 4-oxo isomers via, sometimes isolable, intermediates 2-oxo and/or 4-oxo isomers may be formed with acetylenecarboxylic or acrylic acid derivatives or with ethyl acetoacetate. The decisive factors for the regiochemistry have not yet been fully explored. The base-induced rearrangement of ethyl 2-diazanyl-5-oxo-2,5-dihydroisoxazole-4-carboxylates is also a powerful approach to the bicyclic systems. It gives 3-ethoxycarbonyl-2-hydroxy-4-oxo derivatives which present a versatile substitution pattern for further functionalization. A further important aspect of the synthetic methods discussed above is their wide applicability for preparation of the benzo-fused derivatives. 

An alternative method for the simultaneous derivatization of both carboxylic and amino fragments in amino acids known since the 1990s implies the interaction of these analytes with chloroformates. It leads to the esterification of carboxy groups together with the formation of iV-ethoxycarbonyl derivatives (Fig. 

Modifications of the 3-carboxyl group appear to be worth only in those cases where these derivatives are considered as precursors of the corresponding carboxylic acids [61], however precursors not always exhibit activity in vivo. Replacement of the 3-carboxyl group with acyl, ethoxycarbonyl, methoxycarbonyl and other acidic fragments (hydroxamic, acetic, phosphonic, sulphinic or sulpho) results in complete loss or diminishes dramatically antibacterial activity of these compounds. 

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