Carboxamide group, dehydration

Pyridazinecarboxamides are prepared from the corresponding esters or acid chlorides with ammonia or amines or by partial hydrolysis of cyanopyridazines. Pyridazinecarboxamides with a variety of substituents are easily dehydrated to nitriles with phosphorus oxychloride and are converted into the corresponding acids by acid or alkaline hydrolysis. They undergo Hofmann degradation to give the corresponding amines, while in the case of two ortho carboxamide groups pyrimidopyridazines are formed. 

DEHYDRATION OF CARBOXAMIDE GROUPS TO CYANO GROUPS DURING ACTIVATION... 

The 3-carboxamides were dehydrated to the 3-nitriles.711,255,284 The 3-nitrile group of 4-oxo-4//-pyrido[l,2-a]pyrimidines was transformed with sodium azide to a tetrazolyl group.155 The 3-carbazoyl group was acylated at N-2,138 and in the 6,7,8,9-tetrahydro series, it was transformed to a —CONHN=CH—NMe2 group284 or condensed with aldehydes.266... 

The carboxamide groups of asparagine and glutamine derivatives 26 are susceptible to dehydration during carbodiimide-mediated esterification at the a-carboxy groups (Scheme 4).[64] reaction probably involves formation of aspartyl- or glutamylisoimide 28 by attack... 

Scheme 4 Side Reaction of Cyano Formation by Dehydration of Carboxamide Groups of Asparagine and...

Reactions are carried out at room temperature in dichloromethane which is an excellent swelling agent for polystyrene supports. Dimethylformamide can be added to increase the solubility of some amino acid derivatives e.g. Boc-Arg(N02), Boc-Arg(Tos), Boc-His(Tos), Boc-Trp, and Boc-Asn(Xan), but it increases the rate of undesirable rearrangement of O-acylisourea to A-acylurea which is not reactive.P The principal limitations in using car-bodiimides are racemization, rearrangement of O-acylisourea to A-acylurea 5, and dehydration of Asn and Gin side-chain carboxamide groups. Fortunately this dehydration problem is completely avoided by the use of additives such as A-hydroxysuccinimide (HOSu) and 1,2,3-benzotriazol-l-ol (HOBt). Additives also reduce racemization and A-acyl-urea formation. Other carbodiimides have also been used in SPPS such as or N-tert-... 

Interaction between a carboxamide group attached to one ring and a lactam carbonyl of another ring under dehydrating conditions leads to the formation of a pyrimidin-4-one. 

In a series of syntheses of potential antisecretory antidiarrheals, the thiazohne moiety in 1383 was constructed by condensation of 2-aminoethanethiol 1382 with the cyano group in 1381, which was generated from the carboxamide group in 1380 by dehydration with phosgene in 88% yield [1049]. 

Chlorination and Dehydration of Substituted Carboxamide Groups. Secondary amides and A, N,Af-trisubstituted ureas possessing an N-H bond are converted to imidoyl chlorides - and... 

Aliphatic and aromatic carboxamides, with the exception of p-nitrobenzamide, are dehydrated in this way in high yield. Acid-labile protective groups such as tetra-hydropyranyl and tert-butyldimethylsilyl ether and base-sensitive compounds are not attacked. A,A -Sulfinyldi-1,2,4-triazole, easily prepared from thionylchloride and triazole [THF, (C2H5)3N, 0 °C, 1 h] in 85-95% yield, was used without further purification. 

The action of gaseous ammonia on diethyl chromone-2,6-dicarboxylate (478) is a good example of the different reactivity between identical substituents in the same molecule. The 2-carboxylate function is more reactive even than an ester group in a side chain such as —0CH2C02Et, which is unaffected by ammonia. This is consistent with the low electron density of C-2.2-Carboxamides, such as (479), need drastic conditions for their dehydration... 

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