Chromone-2-carboxamides

The spectra of 3-phenyl-5,7,4 -trihydroxychromone-2-carboxylic acid and its ethyl ester have been determined in ethanol and in cyclohexane [135]. It is possible to distinguish between linear and angular benzochromone-carboxy-lic acids by ultraviolet spectroscopy [136]. The effect of various substituents on the colour and spectra of iV-substituted chromone-2-carboxamides has been mentioned earlier (p. 79). 

Amides are usually prepared by adding the acyl chloride in an inert solvent to ammonia [57] or an amine, in the same solvent when desired. Many N-substituted chromone-2-carboxamides have been prepared by this method, including A(-alkyl [11, 36, 158, 170], iV-aryl [11, 125, 128, 139, 158, 170, 172, 173], A -carboxyalkyl [124, 128, 171], A-heteroaromatic [124, 174] and NN-dialkyl [31] amides. Although primary amides may be readily prepared from the esters [57, 150-152] and a few other amides have been similarly obtained... 

V-Alkyl- and -aryl derivatives of chromone-2-carboxamide (which also have analgesic properties [195] (p. 106)) are described as exhibiting notable anticoagulant activity [11] but members of the same team found a low degree of antibacterial action in the chromone-2,3-lactone (110) and its 6-methyl, -bromo and -chloro derivatives [139]. The Clermont-Ferrand team recently reported that chromone-2-carbohydroxamic acid (sodium salt), when injected into the male rat, had no effect on the activities of the enzymes lactate dehydrogenase, transaminases and adenosine 5 -triphosphatase... 

A new cascade reaction of isocyanides, chromone 3-carboxylic acid (311), and nucleophiles (ROH, RNH2, and NaN3), catalysed by Sc(OTf)3 under microwave irradiation, has been developed as a multicomponent method for the preparation of chromone-2-carboxamides and chromone-2-carboxamido-3-esters (313). The sequence apparently commences by the Michael addition of RN=C to generate intermediate (312). ° ... 

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... 

A Russian team [128] studied the relationship between chemical constitution and colour in a series of chromone-2-carboxylic acid amides (37). When R = H, the compound is colourless but as the substituent is varied through methyl, methoxy, hydroxy to diethylamino, the colour changes through greenish yellow to red. Similar substituents in the meta position exert comparatively little effect. When R = SO3H, the anilide is greenish yellow in the solid state but colourless in solution its crystalline sodium salt is colourless. Since A-4-hydroxyphenyl-A-methylchromone-2-carboxamide (38) is colourless [128], it was suggested that the colour of the anilides was related to their ability to enolize. 

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. 

Klutchko S, Brown RE, Von Strandtmann M (1976) Substituted chromone-3-carbonitriles, carboxamides and carboxylic acids usefttl for preventing asthmatic symptoms. US 3937837... 

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