Truxillic and truxinic acids

It is well established that cinnamic acid and some substituted cinnamic acids (including frans-p-coumaric acid but not ferulic acid) can be dimerized in vitro by sunlight to truxillic and truxinic acids and their derivatives... 

It has been tempting for researchers to assume that the crosslinking takes place when an excited double bond adds to one of its neighbors to form cyclobutane-type structures. Parallels from the poly(vinyl cinnamate) system have been drawn to the well-known dimerization of cinnamic acid to truxillic and truxinic acids. A study of a number of substituted cinnamic acids revealed that in order for efficient dimerization to take place the double bonds of two neighboring cinnamate structures must lie within 3.6—4.1 A of each other 25>. The regularity of structure in the crystalline state is not preserved in solution or in the polymeric medium. It has been difficult, therefore, to conclude that cyclobutane-type structures are formed predominantly during the photocrosslinking of poly (vinyl cinnamate). 

Studies [126] of electronic structures in photo-isomerization and photo-dimerization of cinnamic acid showed that phosphorescence of cinnamic groups occurs at about 20,000/cm. Also, it was demonstrated when photo sensitizers are present, the critical distance between donor, sensitizer, and acceptor molecules (cinnamic acid) is about 10 A [126]. Although all the details of incipient photocross-linking of poly(vinyl cinnamate) have to date stUl not been fully worked out, most accept that all three mechanisms take place. These are dimerizations to truxillic and truxinic acid type structures and polymerizations through the double bonds. The excited states of the molecules can be produced by direct irradiation and also through intersystem crossing from an appropriate photosensitizer [126]. 

Much earlier, well before Minsk, in 1895, Berham and Kursten recognized that solid cinnamic acid undergoes a chemical change when exposed to light. Following this. Ruber established that the change is a dimerization of the acid to form a cyclobutane derivative. This dimerization results in formation of truxillic and truxinic acids ... 

Stdrmer, H. and Laage, E. (1921). Truxillic acids. (III). Natural and artihcial truxihic and truxinic acids. Berichte, 54B, 77-84. [234]... 

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... 

Scheme 3 Photodimerisation of trans-cinnamic acid (9) and three of the possible diastereomers, the a-truxillic acid (10), the p-truxinic acid (11) and the 5-truxinic acid (12)...

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). 

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... 

Scheme 6.2 Photodimerization of cinnamic acid to produce a-truxillic acid (II) and (3-truxinic acid (III).

Damen and Neckers (111) were more successful in this respect. They also used cyclobutane derivatives and copolymerized the bis(vinylbenzyl)ester of a-truxillic acid, 3 truxinic acid, and 6-truxinic acid. After removing the template, trans-cinnamic acid was bound to each pair of benzyl alcohols in a cavity. Irradiation of the polymers yielded dimerization of the trans-cinnamic acid. Table VIII shows the composition of the products from hydrolysis of the polymers. 

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. 

A head-to-tail (HT) centro-symmetric relation was found between the monomers in the a-type polymorph that yields truxilic acid dimer. Whereas the P-type polymorph crystallizes with mirror symmetry, a head-to-head (HH) relation between the monomer molecules and on irradiation yields truxinic acid dimer. On the other hand, in the third y-form the repeat distance >4.2 A was found to be photostable. Schmidt postulated that the olefins should be aligned parallel with a distance <4.2 A between the olefinic bond pairs and the reaction should take place with minimum atomic movement. The maximum distance criterion proposed in Schmidt s postulate may be related to maximum distance for interaction between the orbital clouds that can be slightly larger than the sum of van der Waal s radii. ... 

Rennert, J. and Grossman, D., Photochemical scission of cinnamic acid dimers, a-truxillic and 5-truxinic acids, /. Photochem., 3, 163,1974. 

Topochemical control of solid state dimerizations is well illustrated by the example of the frows-cinnamic acids.(112) The a form of ftmv-cinnamic acid is known to have a molecular separation of 3.6 A between double bonds and the molecules are arranged in a head-to-tail fashion. -Cinnamic acid has approximately the same intermolecular distance in the crystal but the molecules are arranged in a parallel head-to-head manner. a-Truxillic (101) and /3-truxinic (102) acids are the products expected and observed ... 

C18H16O4, Mr 296.32. These acids are formed as pho-todimerization products of cinnamic acid. The a- and e-truxillic acids as well as the /S-, S-, and neo-truxinic... 

A photochemical template effect (footprinting) was demonstrated by Damen and Neckers" through the use of polystyrene networks that were prepared in the presence of monomers appended with truxinic or truxillic acids. Treatment of the hydrolyzed polymers with cinnamoyl chloride, followed by irradiation and hydrolysis, yielded dimers whose composition was biased in favor of the photoproduct with which the polymer had been molded. 

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