1.2- Selenazoles

Selenazoles.—2,4-Disubstituted selenazotes (83) can be prepared in moderate to good yields by an extension of the Hantzsch reaction, the reaction of a halogenoketone with, in this case, a selenoamide. Appropriate manipulation of 

6 Isothiazoles, Isoselenazoles, and Isotellurazoles Synthesis.—Several new methods for the synthesis of isothiazoles and benziso-thiazoles have been reported. Nitrile sulphides are probable intermediates in one such synthesis they are produced by the thermolysis of l,3,4-oxathiazol-2-ones 

The nitrile sulphide can also be generated from a fluorinated benzylamine derivative 

The thiochromanones (95 R = Me or Ph) react with hydroxylamine 0-mesitylenesulphonate to yield sulphilimines (96) these, with base, rearrange to 1,2-benzisothiazoles (97). A remarkable preparation of a 1,2-benzisothiazole (99 X = S) and of a 1,2-benzisoselenazole (99 X = Se), by the reaction of 2,l,3-benzothia-(or selena-)diazole (98 X = S or Se) with benzyne, has been reported. Another interesting synthesis, this time of a 2,1-benzisothiazole (102), is by the reaction of the fluorosilylated amine derivative (100) with bis(tri-methylsilyl)sulphur di-imide (101).  

Reactions.—2-Substituted isothiazolin-3-ones (103) isomerize to 3-substituted thiazolin-2-ones (104) in high yield when irradiated in benzene. The isomerization probably involves homolysis to a biradical, which then re-cyclizes to an cr-lactam. Ring-expansion to the thiazolone follows. This Reporter notes that this reaction is almost the exact converse of the thermolysis of yff-lactam disulphides that was mentioned earlier. Thermolysis of isothiazoles (105 R R = H or Me) in the gas phase at 590 °C yields thioketens (RCH=C=S), and kinetic experiments showed that this decomposition is not a radical process.  

A number of selenazoles have been prepared by an extension of the Hantzsch synthesis. i8-2i7 jjj Hantzsch synthesis (see p. 357), intermediate A -selenazolines have been isolated. The first meso-ionic selenium compound has been prepared through conversion of A-phenylbenzimidoyl chloride, PhCCl=NPh, into selenobenzanilide, which, on condensation with a-bromo-phenylacetic acid followed by cyclization of the product, gives anhydro-2,3,5-triphenyl-4-hydroxyselenazolium hydroxide (120).  

spectra of compounds (121) have been compared with those of the corresponding thiazoles.  

Various reactions of ethyl 2-aminoselenazole-4-carboxyIate have been reported. Mononitration of the parent 2-heteroaryl-selenazoles (122 X = S or Se, = R2 = H) with a mixture of concentrated nitric and sulphuric acids initially gives the mononitro-compounds (122 = NOg, R = H) and then 

2-Iminoselenazolidin-4-ones react with isothiocyanates at the ring N-atom to give thioureas (125), but with isocyanates they react with the exocyclic N-atom to give ureas (126). New merocyanine dyes containing selenazolidine rings 

The meso-ionic selenazole (120) is an extremely reluctant dipolarophile, but when heated under reflux for one week with dimethyl acetylenedicarboxylate in benzene it gives a pyridone, presumably by loss of selenium from the intermediate (127).  

The 2-hydrazino-selenazoles (88 X = Se), and also the corresponding thiazoles (88 X = S), are obtained from the reaction between phenacyl bromides and seleno- or thio-semicarbazide under alkaline conditions. Selenazolidine-2-carboxylic acid has been obtained by the reduction of selenocysteamine followed by treatment with Na02CCH0.  

Reference has already been made to recent reviews on selenazoles. Relatively little new work has appeared during the past two years. The Hantzsch synthesis has been adapted to the production of 2-thienyl (and furyl)selenazoles from the appropriate selenamides. -  

Selenazolidines have become accessible by an adaptation of the well-known thiazolidine synthesis from aziridines. The interaction of aziridines (286) with aldehydes or ketones in conjunction with hydrogen selenide produces the appropriate selenazolidines (287) in satisfactory yields. More highly substituted examples arise analogously from (290). The compounds yield stable N-acyl derivatives (288) however, benzoylation of 2-monosubstituted or 2-unsubstituted selenazolidines results in ring-opening and formation of N,Se-dibenzoylselenocysteamine (289 R = H).  

Other ring-scissions, e.g. under the influence of Raney nickel, and the oxidation of the resulting linear products to diselenides were also described. The spectral properties of representative compounds were discussed in detail. 

Representatives of the selenazolo[3,2-b]-l,2,4-triazine system (296) are accessible from 6-substituted 2,3 4,5-tetrahydro-a5-triazin-5-one-3-selenones (295) by successive condensation with bromoacetic ester and ring-closure of the primary substitution products with acetic anhydride.  

This chapter deals with benzothiazole, followed by all other fused structures incorporating thiazole, in their order of increasing ring-complexity. The pattern of the previous Reports is closely followed, in the hope of providing a measure of continuity, and with the aim of presenting the material in an increasingly condensed form. 

No quantitative data are available for the nitration of selenazole, though it is said to be more reactive than thiazole 4-methylselenazole is nitrated at the expected 5-position (48YZ195J97). 

Nitration of isoxazoles with mixed acids gives only a 3.5% yield of the 4-derivative (59ZOB535), though with nitronium tetrafluoroborate substantially higher yields can be obtained (81USP4288445). Nitration of 5,5 -diisoxazolyl (7.46) occurs at the 4- and 4 -positions, whereas the 3,3 - 

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In the first chapter, devoted to thiazole itself, specific emphasis has been given to the structure and mechanistic aspects of the reactivity of the molecule most of the theoretical methods and physical techniques available to date have been applied in the study of thiazole and its derivatives, and the results are discussed in detail The chapter devoted to methods of synthesis is especially detailed and traces the way for the preparation of any monocyclic thiazole derivative. Three chapters concern the non-tautomeric functional derivatives, and two are devoted to amino-, hydroxy- and mercaptothiazoles these chapters constitute the core of the book. All discussion of chemical properties is complemented by tables in which all the known derivatives are inventoried and characterized by their usual physical properties. This information should be of particular value to organic chemists in identifying natural or Synthetic thiazoles. Two brief chapters concern mesoionic thiazoles and selenazoles. Finally, an important chapter is devoted to cyanine dyes derived from thiazolium salts, completing some classical reviews on the subject and discussing recent developments in the studies of the reaction mechanisms involved in their synthesis. 

Hofmann (1), of the Zurich School, was the first to have tried unsuccessfully to prepare the unsubstituted parent compound, selenazole much later, in 1955, Metzger and Bailly (2) were equally unsuccessful in trying to prepare selenazole from 2-aminoselenazole by reduction of the diazo compound,... 

This chapter is an attempt to present the important results of studies of the synthesis, reactivity, and physicochemical properties of this series of compounds. The subject was surveyed by Bulka (3) in 1963 and by Klayman and Gunther (4) in 1973. Unlike the oxazoles and thiazoles. there are few convenient preparative routes to the selenazoles. Furthermore, the selenium intermediates are difficult to synthesize and are often extremely toxic selenoamides tend to decompose rapidly depositing metallic selenium. This inconvenience can be alleviated by choice of suitable reaction conditions. Finally, the use of selenium compounds in preparative reactions is often complicated by the fragility of the cycle and the deposition of metallic selenium. 

Selenazoles and their derivatives, that is. selenazolines and selenazo-lidines. aremainh used in cyanine-type dyes and photographic sensitizers as well as in pharmacology and chemotheraphs. 

The different functional categories of the selenazoles have been classed in according to the functional priority or to the quantity of prepared compounds. 

The maximum yield of 2-alkylseIenazole is 25%. In this way. 4-methylselenazole (7) was obtained starting from hydrogen cyanide, hydrogen selenide and chloroacetone. It is the only known selenazole not substituted in the 2-position. The yield relative to chloroacetone is very low (2.5%) (Scheme 2). 

In thiazole series the application of Tchemiac s method (S). which consists of cyclizing the intermediary iminoketothioether, obtained by reaction of a thiocyanoketone upon a labile hydrogen compound, is suitable and occurs with an average yield of 50%. In selenazole series this cydization does not happen from selenocyanoketones and by using different acidic media (9). 

Alkyl and aryl selenazoles are weakly basic, and their quaternary salts are easily hydrolvzed in aqueous solution. 

It can be noted that the thiazoles are generally more volatile than the corresponding pyridines. while the boiling points of the selenazoles are much higher than others ... 

The condensation of a-haloketones with monosubstituted alkyl or aryl-selenoureas (25) leads to 2-alkylamino- (26. 27) or 2-arylaminOselana-zoles (28) while disubstituted selenoureas give 2-(dialkylamino) selenazoles (26. 27) (Table X-3a). 

Amino-4-aryl-5-acetic acid selenazoles were used by Knott (2l i as intermediates in the preparation of T.2, 4.6-naphthoselenazoles (21. 30, 31). 

From the point of view of reactivity, there is little difference betvv een 2-amino-selenazoles and aryl- Or alkyl-2-aminoselenazoles, except that the A"-arvl derivatives are generallv less basic and that their salts are more easily hydrolyzed. 

The salts of derivatives possessing phenyl substitutents on the selenazole ring are easily hydrolyzed in aqueous solution. 

Condensation of 2-hydrazinoseIenazoles with /3-keto esters (R,-CO-CHn-COOR) yields l- selenazol-2-yl)-3-alkylpyrazol-5-ones (Scheme 20) (34). 

The preparation of substituted selenazole thioethers (Scheme 22) has already been described (35. 36). These compounds are obtained by the action of a haloketothioether on. for example, selenoacetamide. selenobenzamide, and A -ethylselenourea. These selenazoles have not been characterized, but they have been used as intermediates in the preparation of cyanine dyes. 

PyrryH-selenazoles (Scheme 23). obtained by condensation of 2-chloroacetylpyrrole with selenoamides, are also used in dye chemistry (371. 

The general formula of the 2-(2- or 4-furyl. thienyl, or selenienyljselenazoles is shown in Scheme 24 (40, 105. 106). (Selenienyl-2), (furyl-2), (thienyl-2), and (chloromethyi-4)selenazoles may be prepared by Hantzsch s reaction from selenoamides as described in Scheme 25. Hydrolysis give hydroxymethyl derivatives. 

The 2-[2-thienyl]selenazole is formylated in the 5-position by action of n-butyllithium. dimethyl formamide. and hydrolysis (106). 

The nitration of 2-[2-thienyl] and [2-selenienyl] selenazoles is achieved accordine to Scheme 29 (106). 

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