Cinnamic acid, orientation

Fig. 6 Results from Rietveld refinement of the disordered crystal structure of the P polymorph of p-formyl-tranj--cinnamic acid. The disorder concerns two orientations of the formyl group as shown in (a). The crystal structure in (b) shows only the disorder component of higher occupancy. The results from Rietveld refinement shown at the bottom are for (c) an ordered model comprising only the major orientation of the formyl group, and (d) the final disordered model (right side). Apart from the description of the order/disorder of the formyl group, all other aspects of these refinement calculations were the same. A slight improvement in the quality of the Rietveld fit for the disordered model is evident...

A great number of olefinic compounds are known to photodimerize in the crystalline state (1,2). Formation of a-truxillic and / -truxinic acids from two types of cinnamic acid crystals was interpreted by Bernstein and Quimby in 1943 to be a crystal lattice controlled reaction (5). In 1964 their hypothesis on cinnamic acid crystals was visualized by Schmidt and co-workers, who correlated the crystal structure of several olefin derivatives with photoreactivity and configuration of the products (4). In these olefinic crystals the potentially reactive double bonds are oriented in parallel to each other and are separated by approximately 4 A, favorable for [2+2] cycloaddition with minimal atomic and molecular motion. In general, the environment of olefinic double bonds in these crystals conforms to one of three principal types (a) the -type crystal, in which the double bonds of neighboring molecules make contact at a distance of -3.7 A across a center of symmetry to give a centrosymmetric dimer (1-dimer) (b) the / -type crystal, characterized by a lattice having one axial length of... 

The L-B films offer some advantages over aqueous-hydrocarbon interfaces of micelles and the related assemblies discussed above in terms of the magnitude of their orienting ability and the ease of interpretation of selectivity in photoreactions conducted in them. Molecules in the films have very little freedom of motion (stiff reaction cavities), their interfaces are very well defined, and therefore the alignment of reactant molecules can be readily expressed in the products. Photodimerization of stilbazole derivatives 62, N-octadecyl-l-(4-pyridyl)-4-(phenyl)-l,3-butadiene, (63), surfactant styrene derivatives 64 and 65, and cinnamic acids have been carried out in L-B films [18, 196-200], In all cases, single isomeric head-head dimers are obtained. Geometric isomerization of olefins has not been observed in competition with photodimerization. Independent of the location of the chromophore (i.e.,... 

FIGURE 18.1. Solid-state reactions that occur on irradiation of cinnamic acids. The reaction products are truxillic or truxinic acids, depending on the relative orientations of the molecules in the crystal. The distance between C=C bonds in the solid state must lie in the range 3.6-4.1 A. 

Electrolyses of substrates of the cinnamic acid ester family (Table 4) in anhydrous MeCN were shown to result in formation of 7-60% of the CHD [Eq. (3)], corresponding exclusively to the ( ) coupling as determined from the stereochemistry of the cyclopenta-none formed by hydrolytic decarboxylation [61]. The stereochemistry was later verified by x-ray crystallography [65]. The stereoselectivity in the coupling step was originally rationalized in terms of orientation of the substrate molecules at the electrode surface [61]. However, later kinetic studies have shown that dimerization of the radical anions is fairly slow (Table 3), and takes place in the diffusion layer at a distance from the electrode. 

Baizer and coworkers established the most brilliant industrial electroorganic synthesis of the hydrodimerization of acrylonitrile to adiponitrile. They extended this hydrodimerization to a variety of activated olefins and in some cases [41 3] paid attention to the stereochemistry of products. However, their stereochemical data were not enough to discuss the stereochemical course of the reaction. Afterward, an attempt was made to provide a working hypothesis in the hydrodimerization of cinnamates by considering an orientated adsorption of radical anion intermediates on a cathode surface, but this was not persuasive because of a lack of experimental data on the stereochemistry of both the starting olefins and products. Recently Utley and coworkers [44-46] have reported stereochemical data of hydrodimers derived from a variety of cinnamic acid esters with chiral alcohol components. 

It is interesting that when the functional groups are not directly attached to the aromatic ring, orientation cannot be predicted from a consideration of the point of highest electron density. Cinnamic acid (XII),7 w-nitrostyrene (XIII),8 and 2-phenylethenesulfonyl chloride (XIV),9 all orient predominantly ortho-para, although we should expect these positions to be electronically deficient. 

Photochemical [2+2] cycloaddition of alkenes in the crystalline state is synthetically very useful because it usually produces only one stereoisomer predicted ftom the crystal structure. On the other hand, this stereospeciflcity of the reaction can be a disadvantage because of inaccessibility to other stereoisomers. In order to circumvent such a problem, we explored compelled orientational control of the photodimerization of particular compounds like ranj-cinnamic acids and anthracenecarboxylic acids [74-78]. During our study, photochemistry of fluoro- and chloro-substituted ranj-stilbene-4-carboxylic acids and their methyl esters and alkaline and alkaline earth salts in the crystalline phase was likewise studied in order to synthesize specific stereoisomers selectively (Scheme 41) [79]. Most of these stilbene compounds dimerized to give exclusively or mainly syn head-to-head cyclobutane dimers. Some were photochemicaUy inert. 

When considering reactions in the solid state, it is important to draw distinctions between reactions in crystals and reactions in amorphous solids, since the controlling factors are quite different in these two situations. Reactions in the crystalline state are controlled primarily by topological factors, such as the distances and the relative orientation of potentially reactive groups. Trans-cinnamic acid undergoes photochemical dimerization when the distance between adjacent double bonds in the crystal is shorter than 4 A (Table 2.5 ). Irradiation of 2,5-distyrylpyrazine (DSP) which has two double bonds per molecule leads to a linear high... 

Schock et have engineered a water-soluble plant cyt P450 for improved properties with respect to purification and solubility. Proton NMR relaxation was used to characterize the orientation of the substrate (cinnamic acid) with respect to the heme to better understand the reason for selective hydroxylation of the substrate. 

Other elegant examples on the use of homosynthons have been reported by Wheeler and co-workers, using flexible chiral sulphonamide cinnamic acids, which form dimers via self-complementary hydrogen bonds and via formation of carbojgrlic acids homosynthons. These compounds are reminiscent of the /-shaped dicarbojgrlic acid reported by Feldman and Campbell, which form similar dimers via the same homosynthons (Scheme 7). In such assemblies, the double bonds are oriented in a parallel fashion at suitable distances for the photo-dimerisation upon UV irradiation. 

Unusual modes of dimerization of cinnamic acids have been found in the solid state photodimerization of the octadecyl esters of these acids. Bolt and co-workers have crystallized this ester of cinnamic acid in three different forms, one of which cyclized to an a-truxilic acid type of dimer, one of which was photo-inert, and one of which gave the 6-truxinic acid dimer. Two crystal forms of the ester of trans-p-chloro-cinnamic acid were isolated, one of which cyclized to an a-truxillic acid, the other being photo-inert. The long-chain ester group presumably modifies the crystal structure, and use of orienting groups of this type may allow the formation of other dimers not usually obtained in solid state dimerizations. 

SIA (4-Hydroxy-3,5-Dimethoxy-Cinnamic Acid) (Fig. 63.2) is a phenylpropanoid compound found in various herbal materials and high-bran cereals. It has been reported that sinapic acid has antioxidant efficacy as a metal chelator due to the orientation of functional groups. Administration of sinapic acid exhibited significant reversal of arsenic-induced toxicity in hepatic tissue [68]. 

---