Solid solutions photodimerization

Some quinolizinium derivatives such as MPB-07 60 have importance as chloride channel activators. This compound has been shown to be photolabile in aqueous solution when exposed to daylight, being transformed into the phenolic derivative 62 with the deprotonated form 61 as an intermediate, as shown in Scheme 1 <2002JPS324>. A highly regioselective solid-state photodimerization of naphthoquinolizinium salts has also been described <2002EJO2624>. 

An asymmetric photosynthesis may be performed inside a crystal of -cinnamide grown in the presence of E-cinnamic acid and considered in terms of the analysis presented before on the reduction of crystal symmetry (Section IV-J). We envisage the reaction as follows The amide molecules are interlinked by NH O hydrogen bonds along the b axis to form a ribbon motif. Ribbons that are related to one another across a center of inversion are enantiomeric and are labeled / and d (or / and d ) (Figure 39). Molecules of -cinnamic acid will be occluded into the d ribbon preferentially from the +b side of the crystal and into the / ribbon from the — b side. It is well documented that E-cinnamide photodimerizes in the solid state to yield the centrosymmetric dimer tnixillamide. Such a reaction takes place between close-packed amide molecules of two enantiomeric ribbons, d and lord and / (95). It has also been established that solid solutions yield the mixed dimers (Ila) and (lib) (Figure 39) (96). Therefore, we expect preferential formation of the chiral dimer 11a at the + b end of the crystal and of the enantiomeric dimer lib at the —b end of the crystal. Preliminary experimental results are in accordance with this model (97). 

Marubayashi et al. <1997J(P2)1309> have also shown that solid-state dimerization is possible and propose that there is a buffer zone in the crystal structure of 1,4-dihydropyridines that governs the solid-state photodimerization process. This is exemplified by the fact that dimethyl l,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicar-boxylate 83 cannot undergo solid-state photodimerization (Equation 21), whereas the structurally related (4/ 3, l / 3 )-methyl-l-phenyl-2-piperidinoethyl-l,4-dihydro-2,6-dimethyl-4-(2-thienyl)pyridine-3,5-dicarboxylate 84 affords a single product 5 (Scheme 2). Interestingly, when the photodimerization conditions are applied to the corresponding solution-phase reaction, the sole product is that of aromatization giving product 85. 

The stereochemistry of photodimerization in the solid state and solution has been reported for several halogenated derivatives of t-1 (Table 2) (59-62). Solid state photodimerization of stilbenes, like other alkenes, is subject to topochem-ical control viz, the two reactive double bonds must be parallel and separated by < 4.2 A (63). The photostability of t-1 in the solid state (39b,59) is consistent with its reported crystal packing (64). The halogenated stilbenes 15-20 serve to illustrate the variety of stereochemical outcomes observed for solution and solid state dimerization (eq. 11). 

Excimer emission (460 nm) is observed from crystalline 16 at -186°C, but not at room temperature or in a methylcyclohexane glass (60). Photodimerization in the solid state results in a decrease in excimer fluorescence intensity and the appearance of monomer emission. Evidently, solid state photodimerization results in the isolation of monomer molecules among the dimers, as has been observed with anthracenes (65). The absorption spectrum of polycrystalline 16 is broader than the solution spectrum but the long-wavelength maximum (300 nm) is unchanged. 

It is well established, in a qualitative sense, that chemical reactions occurring in crystals are subject to restrictive forces, not found in solution, which limit the allowable range of atomic and molecular motions along the reaction coordinate. This often leads to differences, either in the product structures or the product ratios, in going from solution to the solid state. This was first demonstrated in a systematic way by Cohen and Schmidt in 1964 in their studies on the solid state photodimerization of cinnamic acid and its derivatives (1 ). This work led to the formulation of the famous topochemical principle which states, in... 

The whole truth, however, is not nearly as simple as this. The experimental evidence has not been collected systematically, and it is not known, in most cases, whether singlet or triplet states are involved. In the last ten years, at least sixty papers have been published in which reasonably reliable structures have been assigned to the cyclobutane dimers produced by irradiation of a great variety of unsymmetrical olefins in solution. (The stereo- and regioselectivity in solid-state photodimerization reactions have also received a lot of attention, but they are determined by the alignment of the monomers in the crystal lattice, not by frontier orbital effects.) For irradiation in solution, head-to-head dimers are described as major or sole products in forty of these papers, and head-to-tail dimers are described in twenty of them. In addition, almost all photodimerizations of 9-substituted anthracenes (479) give the head-to-head dimer (480),385 whereas the... 

They reported even the effect of added impurities coumarin, which is photoinert in the solid state, photodimerized when admixed (by cooling the melt) with various foreign substances such as antipyrine (Scheme 60) [97]. Compounds which are photoreactive in solution may frequently be photoinert in the solid state owing to the rigid crystalline environment. Addition of external substances disrupts the crystal lattice and the compounds recover their photoreactivity. This is very commonly observed. 

A ditopic hydrogen-bond-donor template (257) in the form of resorcinol facilitated [2-1-2] cross-photodimerization of 4-Cl-stilbazole and 4-Me-stilbazole in a rare coctystal solid solution. However, the photocycloaddition did not occur in the absence of a template. Intramolecular head-to-head photocyclodimer (260) vras obtained via... 

As mentioned above, an example where lattice control over the course of an organic solid state reaction is explicit is provided by the solid state photodimerization of trans-cinnamic acid and many of its derivatives.When irradiated in the melt or in solution, cinnamic acid derivatives do not dimerize — the presumed singlet photoexcited state being too short-lived for reaction in such mobile phases. The only consequence of irradiation is trans cis isomerization. Irradiation of crystalline solids, however, was found to result in one of three distinct events — and that which occurs found to depend upon the solvent of crystallization— see Scheme 6.1. The contribution of Schmidt, Cohen, and co-workers at the Weizmarm Institute in Israel was first to appreciate the importance of polymorphism and then to establish a direct correlation between the molecular packing within a particular polymorphic phase and the nature of the photodimer which results. ... 

By examining any correlation between excimer formation (as evidenced by characteristic excimer fluorescence) and dimerization quantum yield, one could perhaps determine whether dimerization is dependent upon prior excimer formation. Excimer fluorescence from anthracene solutions at room temperature is negligible although it has been observed in the solid state at low temperature.<75) Unfortunately, the data for substituted anthracenes allow no firm conclusions to be drawn. Some derivatives dimerize but do not exhibit excimer fluorescence. Others both dimerize and show excimer fluorescence. Still others show excimer fluorescence but do not dimerize and finally, some neither dimerize nor show excimer fluorescence. Hopefully, further work will determine what role excimer formation plays in this photodimerization. 

Irradiation of cycloocta-2,4-dien-l-one (55) in pentane gives a racemic photodimer, anti-tricyclofSAO.O Jhexadeca- , 11 -diene-3,16-dione (60) in 10% yield along with polymeric materials 34). Efficient and enantioselective photodimerization of 58 was achieved by irradiation of the 2 1 inclusion complex 59 formed between 2 a and 5813). When a solution of 2a and an equimolar amount of 58 in ether-hexane (1 1) was kept at room temperature for 12 h, 59 was obtained as colorless needles of mp 105 to 108 °C. Irradiation of 59 in the solid state for 48 h gave (—)-60 of 78 % ee in 55 % yield. 

The second example is an intermolecular crystal-state reaction. Cross-conjugated 1,5-disubstituted 1,4-dien-3-ones in solution undergo both cis-trans photoisomerization and photodimerization, yielding complex mixtures of products, including die all-trans-substituted cyclobutane 2 in the case of 1,5-diphenyl-1,4-pentadien-3-one. In contrast, dienones such as 3a in whose crystals adjacent molecules lie parallel and strongly overlapped react in the solid to give 3b as the sole photoproduct. This isomerically pure tricyclic diketone results, formally, from an eight-center dimerization. It is not formed in the reaction in solution, and could be prepared by other methods only with considerable difficulty (4). 

Toda et al. reported that the topotactic and enantioselective photodimerization of coumarin and thiocoumarin takes place in single crystals without significant molecular rearrangements [49]. Molecular motion needs to be called upon to explain the photochemically activated cycloaddition reaction of 2-benzyl-5-benzylidenecyclopentanone. The dimer molecules, once formed, move smoothly in the reactant crystal to form the product crystal [50]. Harris et al. investigated the reactivity of 10-hydroxy-10,9-boroxophenanthrene in the solid state and the mechanism of the solid-state reaction was characterized by both X-ray diffraction and thermal analysis [51]. It was demonstrated that the solution chemistry of 10-hydroxy-10,9-boroxophenanthrene is different from that in the solid state, where it undergoes dimerization and dehydration to form a monohydride derivative. 

Ultraviolet irradiation of the methiodide or hydrochloride of 2-styryl-pyridine (XCIII) in the solid state results in transformation of the trans-isomers to the corresponding dimers (XCVa, b) on the other hand irradiation in benzene solution gives both isomerization and dimerization.309 Dimer (XCVa) was produced in low yield on irradiation of XCIII in the powdered form in the presence of air.308 This is in contrast to the reported stability of XCIII toward photodimerization.109 Similar dimerizations have been reported in the case of 2,4-dichloro-3-cyano-6-styrylpyridine,164 2-styrylquinaldine (XCV) and frans-4,4 -diguanyl-stilbene bis(2-hydroxyethane sulfonate) (stilbamidine) (XCIV).82,83... 

Photodimerization of stilbazole salts in solution and solid state has been reported by Williams (58) and by Quina and Whitten (66a,b). 

The j5-chlorobenzenesulfonate salt of N-octadecyl-trans-4-stil-bazole (27) fails to dimerize in solution or when incorporated into CTAB micelles (66a,b). However, irradiation in the solid state or in monolayer assemblies yields the syn head-to-head dimer 23 accompanied by long-wavelength fluorescence attributed to the excimer. Evidently, aggregation of the hydrophobic hydrocarbon tails is more important than like-charge repulsion in determining the stereochemistry of photodimerization in the case of 27. Whitten and co-workers (66c) recently reported the observation of strong red-shifted fluorescence attributed to... 

In a systematic study of the 2ir + 2tt photodimerization of cinnamic acids it was shown that reactions in crystals occur with molecularity, selectivity, and efficiencies that are quite different from those observed in solution. Cinnamic acids and their derivatives were shown to crystallize in three distinct packing arrangements known as a-, (3-, and 7-forms. The packing arrangement of a given crystal form determines whether or not a 2tt + 2tt photodimerization may occur in the solid state and which of the possible products will form (Scheme 1). Al-... 

The (Z) isomer (189) of 4-benzylidene-2-phenyl-5(4//)-oxazolone rearranges to the (E) form on irradiation. The photodimerization of compound (190) in solution results in the centrosymmetric cyclobutane derivative (191). A different kind of photodimerization occurs when the oxazolone (192) is irradiated in the solid state, compound (193) being formed (79TL2461, 79TL3139). 

Photodimerization of dibenzoazaazulene 10 gave only syn dimers 61 and 62, with 61 favored in solid-phase dimerization and 62 predominating in solution. Eximers have been proposed to be responsible for the formation of syn isomers (84JOC2978). 

As a second example of intersystem crossing mechanism in biochromophores we include here the case of the DNA pyrimidine nucleobases, starting by the uracil molecule [91]. In previous sections we presented a model for the rapid internal conversion of the singlet excited rationalizes the ultrafast decay component observed in these systems, both in the gas phase and in solution. Despite the short lifetimes associated to this state, which is the main contributor to the photophysics of the system, formation of photodimers PyroPyr has been observed for the monomers in solution, as well as in solid state, for oligonucleotides, and DNA [92], Since the sixties, the determination of the mechanism of the photoinduced formation of cyclobutane dimers has been the subject of numerous studies [92, 93-97], One of the most classic models that has been proposed for the photodimerization of Pyr nucleobases in solution invokes photoexcitation of a molecule to a singlet state followed by population of a triplet state by an intersystem crossing mechanism... 

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). 

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