Frans-Cinnamic acid

Figure A8.12 Enzymatic conversion of frans-cinnamic acid to L-phenylalanine.

Conversion of frans-cinnamic acids into the c/s-isomers (Table 8.12)... 

Condensation of 2-pyrone with dimethyl acetylenedicarboxylate and diethylacetylene proceeds in the expected manner. There is, however, no reaction between di-t-butylacetylene and 2-pyrone, even after solutions of the reactants in bromobenzene have been heated in a sealed tube at 210°C for 5 days. Instead, frans-cinnamic acid is obtained in low yield. 

To understand why solution experiments sometimes fail to produce cocrystal products, and why solvent-drop grinding experiments can work when performed on the same system, the 1 1 cocrystal formed by nicotinamide and frans-cinnamic acid (frans-(2E)-3-phenylacrylic acid) has been studied [56]. In this work ternary isothermal phase diagrams of the cocrystal system was used to understand the crystallization phenomena, and to deduce methodologies and for the experimental design of cocrystal preparation. Cocrystals are most likely to form from solutions in which the two reactants have similar degrees of solubility, and the success of solvent-drop grinding was explained in that crystallization took place in the region of low solvent mole fractions where the cocrystal would be more stable relative to the separated reactants. 

Further support for the intermolecular route is provided by the isolation of the substituted frans-cinnamic acid, the normal Perkin product. This arises through elimination of carboxylic acid from the fully acylated species (393) rather than cyclization. For example, a considerable amount of 2-acetoxy-3-methoxycinnamic acid is formed from 3-methoxysalicylaldehyde, perhaps as a result of steric interference with cyclization so allowing the intermolecular process to predominate (39JPR(152)23). It should be noted that trans- 2-hydroxycinnamic acids do not cyclize under normal Perkin conditions, though the cis isomer does so quite readily. Isomerization of the trans acid has been effected by treatment with a trace of iodine in acetic anhydride or by UV irradiation. 

In addition to the identification of crystal moditications, SSNMR has been used to monitor reactivity and phase changes in different polymorphic forms. For instance, Harris and Thomas (1991) followed the photochemical conversion of formyl-fran -cinnamic acid with SSNMR (see also Section 6.4). Variable temperature techniques have been used to study the interconversion of four polymorphic modifications of sulphanilamide (/ -amino-benzenesulphonamide), including interpretation of at least some of the molecular motions during the course of the transformation (Frydman et al. 1990). A similar combination was augmented with colourimetric techniques to study the coexistence of two phases in the course of a phase transition (Schmidt et al. 1999). Of course, differences between unsolvated and solvated or hydrated crystal moditications may also be readily characterized by the SSNMR technique, as was done with the anhydrous and monohydrate of oxyphenbutazone (Stoltz et al. 1991). Due to the availability of the crystal structures for both modifications the SSNMR results could be interpreted directly in terms of the different atomic environments, especially for the differences in hydrogen bonding in the presence... 

In contrast to solutions, solid drugs have a fixed conformation resulting in topochemical reactions. The majority of photoreactions in the solid state, described in the literature, deal with lattice-controlled examples and photodimerizations. A precondition for these reactions is the parallel position of the double bond of two adjacent molecules in the crystal lattice as shown by the example of the trimorphic, frans-cinnamic acid. Irradiation of the a- and the 5-modifications causes the formation of a-truxillic acid and (i-truxinic acid, respectively, whereas the y-modification is photostable due to the distance of the double bonds fixed by the lattice (Fig. 8) (10). 

The development of the principles of solid-state reactions of substituted cinnamic acids was pioneered by Gerhard M. J. Schmidt. The trans-SLcid was found to be polymorphic, and three different crystal forms (designated a, and 7) were identified by him. The finding that the nature of the cyclobutane derivatives formed by the solid-state photochemical reaction on crystals of frans-cinnamic acid depend on which polymorph is irradiated was of great interest. The products of the photo-... 

This work focused on frans-cinnamic acid and some of its ring substituted derivatives. In homogeneous solution, the distribution of the photoproducts is dependent on the steric and electronic effects of the reagents. Irradiation of a melt or solution of frans-cinnamic acid does not cause dimerization, only isomerization (9,10). Dimers of frans-cinnamic acid can form in the solid state with retention of crystal symmetry because the monomers are held rigidly within the lattice in a uniform and repeating manner forcing an association between monomers. 

Scheme 3 MIO-dependent conversion of phenylalanine into frans-cinnamic acid by phenylalanine ammonia-lyase.

General Considerations. Cinnamic acid solid state photodimerizations are the prototype for the topochemical postulate and reasoning [7], The a-modification of frans-cinnamic acid a-4 gives a-truxillic acid 5 (head-to-tail), while the /i-modification (/J-4) gives /i-truxinic acid 6 predominantly... 

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