Selenazoles, condensed

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). 

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

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

In the reaction of 4-substituted 2-aminoselenazoles with ethyl propiolate and dimethylacetylene dicarboxylate. the major products obtained from such a condensation are substituted 7H-selenazolo[3,2-a]pyrimidin-7-ones (5) and not the alternative isomeric substituted 5H-selenazoles[3,2-a]pyrimidin-5-ones (6). Distinction between the alternative structures was based on infrared, ultraviolet, and NMR data (Scheme... 

Comparative studies have been undertaken between different heterocyclic series, especially the azoles, thiazoles. oxazoles. imidazoles, and selenazoles. In a large number of these studies, the heterocycles are condensed w ith aromatic nuclei. 

The difficulties encountered in the synthesis of 2-alkyl- and 2-aryl-substituted selenazoles lie principally in the preparation of the corresponding selenoamides. In this respect, a method is worthy of note in which the use of selenoamides is dispensed with. For this, a nitrile, a hydrogen selenide, and an a-halogenoketone are reacted together in the presence of a condensation catalyst. Phosphorus oxychloride, alone or mixed with zinc chloride or phosphorus trichloride, is specially suitable. The yields of the corresponding 2-alkylseIenazoles are up to a maximum of 25%,... 

A variation of the general method for the synthesis of 2-amino-selenazoles is to avoid the use of the free a-halogenocarbonyl compound and in its place react the corresponding ketone and iodine with selenourea.This procedure is also taken from thiazole chemistry. By contrast with thiourea, the reaction with selenourea needs a longer reaction time and the work up of the reaction mixture is somewhat more difficult. Usually an excess of the ketone is used. In the preparation of 2-amino-4-( n-nitrophenyl)selenazole, a very high yield, calculated on the amount of iodine used, was obtained. To explain this peculiar result, the oxidative action of the nitro group was invoked. This liberates free iodine from some of the hydrogen iodide eliminated in the condensation reaction, and the free iodine then re-enters into the reaction. 

The free selenazole hydrazines are solids, sometimes well crystallized compounds. They show the typical properties of hydrazines. Thus they reduce Fehling s solution on warming and liberate silver, even in the cold, from ammoniacal silver nitrate solution. Further, they react with carbonyl compounds for example, benzylidene hydrazones are formed with benzaldehyde. These are identical with the hydrazones formed by direct condensation from benzaldehyde selenosemicarbazone and the corresponding a-halogenocarbonyl compound. 2-Hydrazino-4-phenylselenazole has also been reacted with acetophenone. The 2-a-methylbenzylidenehydrazone of 4-phenyl-selenazole (2, K = CJl, R" = H, R" = NH—N CMe-aH ) forms golden yellow plates mp 171°C. ... 

The preparation of the selenazolyl-pyrazolones was then effected by a second method, in which first the pyrazolone ring and afterward the selenazole ring was formed. For this purpose -ketoester seleno-semicarbazones were first converted to the corresponding 1-seleno-carbamoyl-3-aIkylpyrazol-5-one. These, by condensation with a-halo-genocarbonyl compounds according to the Hantzsch synthesis, formed the selenazole ring as a second step (17). 

For 2-amino-4-(m-nitrophenyi) selenazole, the yield is particularly high. This has been explained by the oxidizing effect of the nitro group, which liberates iodine from the hydrogen iodide eliminated in the condensation reaction. 

Amino-4-(2-thienyI)selenazole ( n.p. 132°C. yield = 82%) also has been prepared by condensation of selenourea on 2 bromoacetylthiophene (Scheme 26). In a first step the bromhydrate is obtained (105). 

Selenourea condenses with halogenated ketones to yield selenazoles according to the equation... 

The quaternary salts of selenium-nitrogen heterocycles are labile to nucleophiles and can be converted to other heterocyclic systems by ring expansion [82, 103], An example is conversion of 1,2,4-selenadiazolium trifluoromethane sulfonate (67) into 1,3,5-selenadiazine (68) (Scheme 17) [104], 2,3-Dimethyl-1-benzo-l, 3-selenazolium tetrafluoroborate is readily condensed with aromatic aldehydes to 2-styrylselenazole [105] or treated with sodium hydride to give 3-methyl-2-methylene-2,3 -dihydro-1 -benzo-1,3 -selenazole [106],... 

Condensation of selenocarboxamides with a-chloro- or a-bromocarbonyl compounds gives access to a wide variety of substituted 1,3-selenazoles by choosing suitable reaction partners and, in most cases, they are produced in good to excellent yields [3, 14, 174], For example, the phenacetyl bromide (100) and selenobenza-mide (101) gave 2,4-diphenyl-l,3-selenazole (102) (Scheme 30) [174],... 

Hydrogen selenide reacts with a mixture of a nitrile and an a-halo ketone or 2-halo aldehyde acetal in the presence of a condensation catalyst to give selenazoles (Scheme 20) (48YZ191, 79S66). 

Aryl-4-chloromethylselenazoles (72) are hydrolyzed to alcohols (73). Manganese dioxide oxidation of (73) affords 4-formyl derivatives (74) which by condensation with ethyl azidoacetate give azidocrylates (75). Thermal cyclization of compounds (75) give pyrrolo[3,2-d]selenazoles (76 Scheme 27) (79JHC1563). 

Selenazoles have been prepared by reactions using hypervalent iodine reagents. Condensation of a-tosyloxy-ketones with primary selenoamides affords 1,3-selenazoles in a one-pot process (Equation 7) <200081219, 2004CJI63>. Reactions of alkynyl(phenyl)iodonium salts with primary selenoamides give 1,3-selenazoles (Equation 8) <2001JHC503>. 

Condensation of selenourea [H2NC(=Se)NH2] with a-haloketones affords 2-amino-l,3-selenazoles (Equation 9). 2-Amino-l,3-selenazole-5-carboxylates are available from the A acyl-selenoureas by reactions with bromoacetic acid (Equation 10) <1999JHC901, 1999PS169, 1996JCM530, 1995JHC177>. 

Condensation of selenazadienes (l.Oequiv) with a-haloketones (l.Oequiv) gives 5-acyl-2-amino-l,3-selenazoles 9 under reflux conditions (Equation 14). Reactions of selenazadienes (2.0equiv) with l,3-dichloro-2-propanone in the presence of triethylamine (3.6equiv) gave the corresponding bis(2-amino-5-selenazolyl) ketones 74 at 50 °C (Equation 15) <2006831, 1998T2545>. 

Selenazofurin (72), a promising antitumor agent, has been synthesized from methyl 2,5-anhydroalloni-midate (68), as illustrated in Scheme 20. The key step of the synthesis is the fonnation of the selenazole (71) by the condensation of the selenoester (69) with ethyl 2-amino-2-cyanoacetate (70). ... 

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