Chlorocoumarins

Halogenation. Coumarin reacts with bromine under moderate conditions to give 3,4-dibromocoumarin [42974-18-5] (24). The 3-bromocoumarin [939-18-4] and 3,6-dibromocoumarin [58309-97-0] are formed under more drastic conditions (25). 3-Chlorocoumarin [92-45-5] is formed by reaction with chlorine in dichloroethane (26) or without solvent (27). 

Chlorocoumarin-3-carbonitrile can undergo reaction with aminothiazoles, aminopyrazoles, and aminotriazoles under basic conditions to give the fused azolopyrimidines 173 (Equation 43) <2002HC0129>. Similar ring systems can also be obtained by the reaction of an aminopyrazole with the bis-chromone 174 (Equation 44) <2003HC0615>. 

Halocoumarins also undergo the Perkin rearrangement under various conditions. Thus, heating 3-chlorocoumarins (356), substituted or unsubstituted, with sodium methoxide in methanol gives the corresponding methyl ester of carboxybenzofurans (358, R = H).786,787... 

Chlorocoumarins also give the Perkin rearrangement, but the results vary according to conditions. Thus, 4-chlorocoumarin gives... 

Figure 26. Packing arrangement of 7-chlorocoumarin in the crystalline state. Note the presence of two pairs of reactive 7-chlorocoumarin. In one pair the molecules are related by a centrosymmetry and in the other by a mirror symmetry. On this diagram mirror symmetric molecules appear one on top of another. Centrosymmetric molecules appear to be displaced with respect to the other.

The preparation of chromone-2-carbonyl chlorides from the acid and thionyl chloride often leads to the trichloride (498) as a byproduct (61JGU523) but this is suppressed when a few drops of DMF are added (72JMC865) or phosphorus pentachloride and cyclohexane are used (73BSF2392). When the trichloride is treated with water, an amine or acid, it rearranges to 4-chlorocoumarin (499) (63JGU1806). 

In addition to the examples of coumarin syntheses given in the reviews mentioned above and in the treatise on heterocyclic compounds (B-51MI22400), more recent studies have made use of the Perkin synthesis. These include the use of substituted phenoxyacetic acids to prepare 3-phenoxycoumarins (78CI(L)628> and the synthesis of chlorocoumarins from chlorosalicylaldehydes (81T2613). The use of DBU in place of sodium acetate was necessary to effect the ring closure of a number of o-hydroxyketones (78BCJ1907). 

The reaction of chromone-2-carboxylic acid with thionyl chloride or phosphorus halides gives the trihalide (400). This compound readily loses one of its geminal chlorine atoms and with water, for example, affords 4-chlorocoumarin through the simultaneous loss of carbon monoxide (Scheme 131) (63JGU1806). 

The important points that emerge from the studies on the five chlorocoumarins in the solid state are the following, (a) All chloro substituted coumarins (7-chloro, 6-chloro, 4-chloro, 4-methyl 7-chloro and 4-methyl 6-chloro coumarins) undergo dimerization in the solid state. While four of these give syn head-head dimer as the photoproduct, 4-chlorocoumarin gives a mixture of anti-head-tail and syn head-tail in poor yields ( 25%). (b) Two of them namely 4-... 

Figure 2. Packing Arrangement of (a) 7-Chlorocoumarin and (b) 4-Methyl 7-chlorocoumarin.

Figure 4 Duration of irradiation versus yield-irradiation time given in hours for 7-methoxycoumarin and 7-chlorocoumarin (topochemical reaction) irradiation in days for 4-methyl-6-chlorocoumarin (defect-initiated reaction)...

The situation with respect to the photobehavior of 7-chlorocoumarin is interesting (Fig. 11). There are two reaction pathways in this crystal one that favors the formation of the vyn-IIII isomer arising from reaction between the transla-tionally related molecules with a center-to-center distance of 4.54 A and another that would yield the anti-HT dimer, corresponding to the reaction between the centrosymmetrically related molecules, the center-to-center distance being 4.12 A. Experiment clearly shows that only the yy -HH dimer is obtained—not the one that would correspond to the path of least motion. This is supported by the results of the lattice energy calculations. The implication is that the shape of the free volume is anisotropic, with the larger volume or extension in the direction of the translational periodicity of 4.54 A. 

Figure 15 Packing arrangement of 7-chlorocoumarin molecules in crystals. Note that in principle dimerization can occur between centrosymmetric or mirror symmetric pairs of molecules. Both are within the stipulated topochemical distance.

Salicylaldehydes and some o-hydroxyaryl ketones react with Meldrum s acid to give coumarin-3-carboxylic acids <03TL1755>. 3-Cyanocoumarins, and thus the 3-carboxylic acids, are available in high yield from a Knoevenagel reaction between salicylaldehydes and malononitrile in water <0382331>. 3-Chlorocoumarins result from the cathodic reduction of trichloroacetyl esters of o-hydroxyacetophenones <03T9161>. 

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