Carboxamide and nitrile

The chroman ring system is stable to organometallic reagents, for example in the formation of the tertiary alcohol (690) in high yield (63HCA650), and to the usual interconversion of carboxylic acid, acyl chloride, carboxamide and nitrile. 

The absorption data of many chromone-2-carboxylic acids and esters have been recorded [24, 27,28, 32,36,40, 55,63,77,88, 123,133], but the majority of these were determined in one solvent, usually methanol or ethanol. A recent spectral study [ 134] of several simple chromones, including chromone-2-carboxylic acid, its ethyl ester, the corresponding carboxamide and nitrile, in cyclohexane, methanol and water led to assignment of some of the absorption bands. As the polarity of the solvent decreased, fine structure appeared in some of the bands, as shown in Figure 2.7. Table 2.2 lists the absorption maxima and absorptivities of a number of compounds related to chromone-2-carboxylic acid. One notable feature is a shift to longer wavelength of the 311 nm band of the parent ester when an amino or hydroxyl... 

A carboxyl or carboxylate group at C-2 of chromones exhibits most of the usual reactions of this function but there are differences in reactivity between it and, for example, a similar group at C-6. In this section, the reactions of the carboxyl group and the properties of the compounds thereby obtained are surveyed carboxylic esters, acyl halides, carboxamides and nitriles are the main classes discussed. 

This reaction can be applied to different reagent combinations. The reagents most often used are carboxamides and formaldehyde or nitriles and formaldehyde (67FRP1478076 71ITP886285, 71S92 93T3907). The cycloalkane[e]oxazines 173 prepared by this method are listed in Table II. 

The suffixes -oic acid, -al, -amide and -nitrile are used to name acyclic compounds having one or two characteristic groups. Locants are not necessary, as these groups must be at the end of a chain. The suffixes -carboxylic acid, -carbaldehyde, -carboxamide and -carbonitrile are used when more than two groups are attached to chains or one or more groups are attached to cycles. 

Oxo-4//-pyrido[ 1,2-a]pyrimidines unsubstituted at position 3 were prepared from the 3-carboxamides, 3-nitriles,268 and 3-acetyl derivatives.168... 

Table 3.3 Electrochemical ligand parameters of the five species which may be involved in nitrile hydrolysis (substrates, products, intermediates). Whereas nitriles are not tightly bound, hydroxide binds to either metal center more strongly than both carboxamide and the corresponding base, acylamidate. Here, however, relative Brpnsted acidities of water and carboxamides must be taken into account. Water can only be transferred to a nitiile before being deprotonated at Zn(II) but not at Co(II) which means that this is not the actual mechanism of biochemical nitiile hydrolysis. Negative values of -log are given in brackets because they correspond to unstable complexes which hardly persist in water...

Adducts (6) and (7) from amides and chlorophosphoric acid aiyl esters or dichlorophosphoric acid aryl esters respectively are well known. - The adducts are formed in a 1 1 ratio. They have been applied to the synthesis of mixed anhydrides from diarylphosphoric acids and carboxylic acids, as well as mixed substituted esters of pyrophosphoric acid. The adduct formation between primary or secondary carboxamides and dichlorophosphates has been used to prepare nitriles and isonitriles respectively. The adduct from DMF and phenyldichlorophosphate is a useful reagent for the preparation of carboxylic acid esters from the corresponding acids and alcohols, 3-lactams from imines and carboxylic acids," carboxylic acid anhydrides, carboxylic acid esters and thiol esters. Adducts of amides with ester amides or diamides of chlorophosphoric acid have been studied. ... 

It has been shown that new types of supported Au, Cu, Sn-Pt, Sn-Ru, Re-Pt, catalysts have been prepared and used for selective hydrogenation of different organic carbonyl compounds (unsaturated aldehydes, esters, carboxylic acids, carboxamides, etc.) and nitriles. Supported Sn-Pt and Au catalysts were also... 

Two reactions of sulfonyl azides show promise in the preparation of u-triazole amino carboxamides (Eq. 18) and nitriles (Eq. 19). ... 

A number of reactions relevant to fine chemicals manufacture can be catalyzed by superacids, for example, dehydration of carboxamides to nitriles, Friedel-Crafts alkylation and acylation, Fisher indole synthesis of coumarins, isomerization of limonene, condensation of hydroquinone with aniline, and esterification in general (Hino and Arata, 1980, 1985 Joshi and Rajadhyaksha, 1980 Rajadhyak-sha and Chaudhari, 1987 Kumbhar and Yadav, 1989 Rajadhyaksha and Joshi, 1991 Kumbhar et al., 1994). Two particularly important reactions are described here. 

An article entitled Facile Conversion of Carboxamides to Nitriles [1053] describes the ready conversion of alkyl, benzylic, aryl, and heteroaryl carboxamides bearing various functionalities to the corresponding nitriles in good yields of 76-96% using liquid diphosgene (trichloromethyl chloroformate) as the dehydrating agent. In many cases, the procedure does not require an extraction step, and hence offers a very simple work-up. 

Synthesis of Nitriles from Amides. Aryl carboxamides and other electron-rich amides could be converted to the corresponding nitriles in good yields by treatment with Ag20 and EtI in benzene at reflux (eq 23). This technique is typically compatible with acid-labile moieties or protecting groups (TBDPS, isopropy-lidene). Although this technique was found to be very efficient for the transformation of electron-rich carboxamides, simple aliphatic amides are rarely suitable for this purpose. 

The Michael addition, i.e the fusion of an enolate with an a,P-unsaturated aldehyde, ketone, ester, carboxamide, or nitrile, belongs to the most prominent organic reactions/ " The literature abounds with impressive examples as is the manufacture of chrysanthemic acid from two isoprene building blocks, namely, ethyl P,P-dimethylacrylate and 4-chlorophenyl prenyl (3-methyl-2-butenyl) sulfone. ... 

Table 3 gives the corresponding physical properties of some commercially important substituted pyridines having halogen, carboxyHc acid, ester, carboxamide, nitrile, carbiaol, aminomethyl, amino, thiol, and hydroxyl substituents. 

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