Carboxamide groups

Chlorosulfonyl isocyanate has been used to introduce 3-carboxamide groups. The initial product, an A -chlorosulfonylcarboxamide, is treated with tri-n-butylstannanc to form the primary carboxamide[15], 3-Cyano groups can also be introduced using chlorosulfonyl isocyanate. The intermediate N-chlorosulfonylindole-3-carboxamide is converted to 3-cyanoindole on reaction with triethylamine[16] or DMF[17],... 

Acrylamide, C H NO, is an interesting difiinctional monomer containing a reactive electron-deficient double bond and an amide group, and it undergoes reactions typical of those two functionalities. It exhibits both weak acidic and basic properties. The electron withdrawing carboxamide group activates the double bond, which consequendy reacts readily with nucleophilic reagents, eg, by addition. 

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. 

A side chain carboxyl group in perhydropyrido[l,2-a]pyrazines was obtained from an ester group by acidic or alkalic hydrolysis. A side chain carboxyl group was converted into a carboxamide group by the treatment with an amine in the presence of 1-hydroxybenzotriazole (OOJAP(K)OO/ 86659). 

Fluorenone derived linker 17 prepared in two steps was coupled to aminomethyl-PS via DIPCDI [21]. Due to the presence of an electron-withdrawing carboxamide group, the release of carboxylic acids from this support requires strong acids, such as trifluoromethanesulfonic acid (TFMSA) (Scheme 1). Insertion of an oxygen adjacent to the biphenyl rings to the fluorenone scaffold provides xanthene 18 handle [22]. The oxygen is strategically located to decrease the acid concentration required... 

The number of X-ray structures published since the publication of CHEC-II(1996) has increased, underlining the importance of this technique in structure elucidation. The structure of a number of 1,2,4-thiadiazoles and 1,2,4-thiadiazolidines has been determined by X-ray techniques and they are listed in Table 1. The first preparation of an A7-oxide derivative of a 1,2,4-thiadiazole 2 has been reported. The X-ray structure of compound 2 shows that it has a nearly planar ring this conformation is stabilized by hydrogen bonding with the carboxamide group <1999J(P1)2243>. 

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

In the HMBC spectrum this NH proton exhibited 3/(CH) correlation to the C3" (5174.15) and 2/(CH) interaction to the C13 (5165.48) carbonyl, the latter in turn showing 2/(CH) interaction with H12(56.05). Thus it became clear that a carboxamide group linked the conjugated triene and the cyclopentenone unit. A 2/(CH) coupling of the triene terminus H7 to C4 (5jj/5c 5.86/71.20) established the point of attachment of the triene unit to C4. An observed NOE interaction between the H7 and H5 lent further support to this attachment and was suggestive of proximal orientation of the trans-A1 bond to the epoxy unit in the most preferred conformation. The absolute configuration at C4 was not established. 

Figure 8.2 Polyacrylamide gel formation and hydrolysis of acrylamide to acrylate. (A) Acrylamide and A,A-methylenebisacrylamide (bis) are copolymerized in a reaction catalyzed by ammonium persulfate [(NH4)2S208] and TEMED. (B) A very short stretch of cross-linked polyacrylamide is represented. Cross-linking between similar structures leads to the formation of ropelike bundles of polyacrylamide that are themselves cross-linked together forming the gel matrix. In the lower portion of (B) is shown how pendant, neutral carboxamide groups can become hydrolyzed to charged carboxyls.

It took more than 20 years for manufacturers to devise production and distribution networks for delivering consistently high-quality gels to customers. The problems that the companies faced stem from the limited shelf life of polyacrylamide gels. Because polyacrylamide gels hydrolyze over time as shown in Figure 8.2, they are inherently unstable. At basic pH, the pendant, neutral carboxamide groups (-CO-NH of the acrylamide monomers hydrolyze to ionized carboxyl... 

About the same time, and independently of this study, a group at Sandoz reported [3] the synthesis of 3-indolyltropine esters such as ICS 205-930 (8) with a pharmacological profile similar to that of MDL 72222. In this case the strategy [55] had been to select 5-HT, metoclopramide and 5-carboxami-dotryptamine (9) [56] as the starting points and carry out a systematic modification of the carboxamide group and the side-chain at C-3 on the indole nucleus. 

The preferential formation of ( )-alkene on Wittig reaction of phenyl 3-pyridyl ketones (bearing an oxazole carboxamide group at the / -position of the phenyl ring) with Ph3P=CH(CH2)4C02 K+ has been attributed to interaction between the amide (rather than oxazole) moiety and the carboxyl terminus during oxaphosphetane formation. ... 

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