Isothiazole irradiation

It has been recently found that upon irradiation isothiazoles can be converted to thiazole and isothiazole isomers among other products (Scheme 153). 

Alkyl- and arylthiazoles rearrange undernltraviolel irradiation in different solvents to yield the corresponding isothiazoles or isomeric thiazoles. With alkylthiazoles the overall yields are very low, and it is not possible to use this method preparatively. For arylthiazoles it is possible 2-arylthiazoles. for instance, can be used to prepare 3-arylisothiazoles that are otherwise very difficult to obtain. 

TABLE III-39. RELATIVE PERCENTAGE OF ISOMERS BY IRRADIATION OF PHENYLTHIAZOLES AND ISOTHIAZOLES (217)... 

Irradiation of isothiazole gives thiazole in low yield. In phenyl-substituted derivatives an equilibrium is set up between the isothiazole (59) and the thiazole (61) via intermediate (60) (72AHC(14)l). 

Chioro-4-methylisothiazole is formed by chlorination of 4-methyl-isothiazole under the influence of irradiation, together with an equal quantity of 4-chloromethylisothiazole. Side-chain halogenation of 3-methylisothiazoles has also been carried out with iV-bromosuccin-imide to give bromomethyl and dibromomethyl derivatives. See also reference 17b. 

The irradiation of thiazole did not give any interesting products [69JCS(CC) 1018]. However, 2-, 4-, and 5-methylthiazole gave the corresponding isothiazoles in low yields when irradiated in trifluoroacetic acid (Scheme 31) (93JOC3407). 

The irradiation of isothiazole with a low-pressure mercury arc leads to the formation of thiazole [69JCA(CC)1018], The photochemical behavior of alkyliso-thiazoles has been studied. 3-Methylisothiazole gave 2-methylthiazole in a low yield. 4-Methylisothiazole was converted into 4-methylthiazole, and 5-methyliso-thiazole gave a mixture of 5-methylthiazole (55%) and 4-methylisothiazole (Scheme 38) (72T3141 93JOC3407). Either a ZI (72T3141) or an ICI mechanism was invoked to justify these reactions (93JOC3407). 

Syntheses and reactions of lithiated isothiazoles and thiazoles were reviewed. [95H533] Phenylisothiazoles and phenylthiazoles are known to undergo a variety of phototranspositions upon irradiation in benzene solvent. These reactions were reinvestigated. [94JA2292]... 

In analogy to the isoxazole-to-oxazole rearrangement, thiazoles can be obtained photochemically from irradiation of the corresponding isothiazoles. In several cases, however, irradiations have been conducted for mechanistic purposes only, and mixtures of photoisomers arising from competing reaction mechanisms are often formed [4, 6]. 

Isothiazole gave a low yield of thiazole on irradiation in propylamine, but the reverse reaction was not observed.149 Phenyl- and diphenyl-isothiazoles gave thiazoles on irradiation,150 and the reverse reactions have also been reported.84,151 It appears likely that isothiazole-thiazole photorearrangements proceed through a common intermediate, possibly a tricyclic species in which the negative charge is stabilized by resonance with the phenyl group (Scheme 42).80,150... 

Irradiation of bromothiazoles in various organic solvents (methanol, ether, cyclohexane) produces thiazole (and the isomeric isothiazole) as the main reaction product386. The reactivity decreases in the order 2-bromothiazole > 5-bromothiazole 4-bromoth-iazole, and is probably related to the C—Br bond strengths. The mechanism is considered to involve homolytic cleavage of the C—Br bond, followed by abstraction of a hydrogen atom from the solvent. Oxygen does not exhibit any noticeable effect upon the reaction, but the debromination is accelerated by triethylamine. 

A more significant difference between 1 -methylpyrazole and isothiazole photochemistry, however, appears to be the minor role of the N-2-C-3 interchange pathway in isothiazole chemistry. Thus, although N2-C3 interchange is a major transposition pathway in pyrazole chemistry, it is only a minor pathway upon irradiation of phenylisothiazoles in benzene solution. In fact, 4-phenylisothiazole (55), the compound most expected to react via the N-2-C-3 interchange pathway, was the only isomer that did not yield a transposition product upon irradiation in benzene solution (Scheme 27). This is not due to the photostability of the compound. Indeed, 55 is the most reactive of the six isomers. Nevertheless, even after consumption of 85% of 55, no phototransposition product could be detected. 

Irradiation of isothiazole gives thiazole in low yield. Irradiation of 3-, 4-, or 5-phenyl-substituted isothiazoles generates an equilibrium mixture of phenylthiazoles with the starting phenylisothiazole <2000JOC3626>. A mechanism for 2-phenylthiazole/3-phenylisothiazole/4-phenylthiazole photoisomerization is shown in Scheme 12 <2002T8037>. 

Irradiation of 2-phenylbenzoxazole forms a head-to-tail dimer, 1,3-diazetidine 436, whereas benzoxazole itself, in the presence of oxygen, gives the dimeric product, 437. Isothiazoles yield lactams 438 on reaction with diphenylketene. Benzotriazole and its 2-alkyl derivatives undergo photochemical ( > 290 nm) [2 + 2] cycloaddition to maleinimides to give adducts 439 <20020L1487>. 

Nitrile sulfides are well suited for the synthesis of isothiazoles incorporating the C=N-S unit via their 1,3-dipolar cycloaddition reactions with double or triple-bonded dipolarophiles. Benzonitrile sulfide 210 is readily prepared from decarboxylation of oxathiazolone 209 using microwave irradiation <05SC807>. Subsequent cycloadditions to dimethyl acetylene-dicarboxylate (DMAD) and dimethyl fumarate afford 211 and 212, respectively. In the case of ethyl propiolate, a 1 1 regioisomeric mixture of phenylisothiazoles 213 and 214 is obtained. 

The phototransposition chemistry of iV-substituted pyrazoles and of isothiazoles has been of considerable interest [1] since the first reports that W-methylpyrazole 1 undergoes photoconversion to W-methylimidazole 2 [2] and that irradiation of isothiazole 3 leads to the formation of thiazole 4 [3]. 

Convincing evidence for the involvement of an isocyanide in the P4 isothiazole -> thiazole phototransposition was obtained by studying the photochemistry of 4-benzylisothiazole 55. In this case, irradiation in methanol containing ammonia led to the formation of the nitrile photocleavage product 56, which was trapped by reaction with benzylbromide to yield benzylthioether 57,... 

Photolysis of 3-phenyl-5(4H)-isoxazolone yields 2,5-diphenylpyrazine in 67% yield. Singlet excited isoxazol-5-one (224) undergoes both decarbonylation and decarboxylation to carbene intermediates, both of which are captured by alcohol or amine solvents. With triplet sensitisers an oxaziridine intermediate reacts with the solvent. N-Acylisoxazol-5-ones decarboxylate to yield singlet carbenes (225) which cyclise at the acyl oxygen to yield the isoxazoles (227), and the isothiazoles (228) are obtained via thioacyl carbenes (226) from N-thioacylisazol-5-ones. " The isolation of (229) as the main product from irradiation of benzophenone/N,N-dimethylaniline in the presence of the non-polymerising... 

Reactions of Isothiazoles.—Photolytic. Whilst photoisomerization of isothiazoles to thiazoles is well documented, examples of this reaction occurring with isothiazol-3(2H)-ones have not previously been reported. Irradiation of (10 R = alkyl or Ph) gave the corresponding thiazolone (11). The isomerization probably involves homolysis to a biradical, which cyclizes to an a-lactam and subsequently undergoes ring-expansion. Support for the homolytic step comes from the isolation of a small amount of (12) from the photolysis of (10 R = Ph). 

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