Thiazole dioxides

An example of 1,3-dipolar cycloaddition involving a thiazole dioxide derivative was described (99T(55)201). A-Benzoyl-(R)-thiazolidin-4-carboxylic acid 5,5-dioxide 120 was cyclized to the bicylic mesoionic thiazolo-oxazolium 5,5-dioxide with Ac O and reacted with the imine 121 in DMF... 

The 2-metalated thiazoles react with a variety of electrophilic substrates in a standard way, leading to addition products with aldehydes, ketones, carbon dioxide, epoxides, nitriles, Schiff bases, and to substitution products with alkyl iodides (12, 13, 437, 440). 

It is also possible to use more powerful reagents to nitrate thiazoles for example, 2-methylthiazole has been nitrated using nitronium tetrafluorobo-rate and the complex nitrogen dioxide-boron tn fluoride (240). The overall yield is about 50 to 60%. 

Reactions. Heating an aqueous solution of malonic acid above 70°C results in its decomposition to acetic acid and carbon dioxide. Malonic acid is a useful tool for synthesizing a-unsaturated carboxyUc acids because of its abiUty to undergo decarboxylation and condensation with aldehydes or ketones at the methylene group. Cinnamic acids are formed from the reaction of malonic acid and benzaldehyde derivatives (1). If aUphatic aldehydes are used acryhc acids result (2). Similarly this facile decarboxylation combined with the condensation with an activated double bond yields a-substituted acetic acid derivatives. For example, 4-thiazohdine acetic acids (2) are readily prepared from 2,5-dihydro-l,3-thiazoles (3). A further feature of malonic acid is that it does not form an anhydride when heated with phosphorous pentoxide [1314-56-3] but rather carbon suboxide [504-64-3] [0=C=C=0], a toxic gas that reacts with water to reform malonic acid. 

In contrast to thiazoles, certain isothiazoles and benzisothiazoles have been directly oxidized to sulfoxides and sulfones. 4,5-Diphenyl-l,2,3-thiadiazole is converted by peracid into the trioxide (146). Although 1,2,5-thiadiazole 1,1-dioxides are known, they cannot be prepared in good yield by direct oxidation, which usually gives sulfate ion analogous to the results obtained with 1,2,4- and 1,3,4-thiadiazoles (68AHC 9)107). 

Thiazino[2,3-6]pteridine structure, 3, 284 Thiaziridines dioxides synthesis, 7, 197 Thiaziridinimines existence, 7, 197 Thiazirines synthesis, 7, 196 Thiazirines, 3-phenyl-synthesis, S, 45 Thiazole, 2-acetoxy-4-methyl-synthesis, 6, 254... 

Although thiazole chemistry has been extensively reviewed, 5-oxide and 5,5-dioxide derivatives had not been previously extensively treated. As already cited some aspects appeared regularly in Progress in Heterocyclic Chemistry (Section I). 

Papers dealing with this topic are exhaustively reviewed in Comprehensive Heterocyclic Chemistry I (84CHEC-I(6)235) and II (96CHEC-II(3)373). Nevertheless, little information is available on the 5-oxides. Recently, the heteroaromaticity of thiazole compared with isothiazole and thiadiazole 5,5-dioxide systems was studied (97MI1). Quantum-chemical calculations and X-ray studies were performed on 3,3 -di[l,3-thiazolidin-4-one] derivatives (95JCC(25)589) studied for their potential biological activity (97FA(52)43). 

Other interesting three-component cycloadditions are the following Sulfur dioxide and diazo compounds lead to episulfones (equation 75)436—in a special case to 4,5-dihydrothiepine S,S-dioxides437 sulfur dioxide, ketene, and arylimine lead to thiazole derivatives438 (equation 76) sulfur dioxide, quinone, and alkenes lead to benzoxathiane derivatives439 (equation 77). 

N,N-Diacyl-thiohydroxylamine werden durch Natrium-bis-[2-methoxy-athyl]-dihydrido-aluminat in Benzol mit guten Ausbeuten zu Aldehyden reduziert. Mit Hilfe von 3-Oxo-2,3-dihydro-(benzo-[d]-l,2-thiazol)-l,l-dioxid gelingt es auf diese Weise Car-bonsaure-chloride auf einfache Weise in Aldehyde zu iiberfiihren z. B.2 ... 

Aldehyde allgemeine ArbeitsvorschrifL Zu einer Suspension von 1 Mol 3-Oxo-2-acyl-2,3-dihydro-(ben-zo-[d]-l,2-thiazol)-l,l-dioxid in abs. Benzol wird unter Riihren und unter Stickstoff cine Losung von 0,5 Mol Natrium-bis-[2-methoxy-athoxy]-dihydrido-aluminat in abs. Benzol bei 0-5° innerhalb 5—10 Min. in kleinen Portionen gegeben. Man riihrt 2 Stdn. bei dieser Temp., vcrsetzt mit Wasser, saugt den Niederschlag ab, wascht mit Benzol nach, schiittelt die waBr. Phase mit Benzol aus, und dampft nach Trocknen die Benzol-Losungen ein. Der Riickstand wird destilliert bzw. kristallisiert. 

The oxidation of a thiazolidine derivative to the corresponding thiazole using activated manganese dioxide in dichloromethane at 100 °C is shown in Scheme 6.100. Further manipulation of this molecule led to dimethyl sulfomycinamate, a methano-lysis product of the thiopeptide antibiotic sulfomycin I [203]. 

When dimethyl-2,2-dioxo-5-methyl-177,377-pyrrolo[l,2-r-][l,3]thiazole-6,7-dicarboxylate was heated under flash vacuum pyrolysis at 700°C/10 3mmHg, sulfur dioxide was eliminated and the vinylpyrrole 391 was obtained, which can be explained by allowed suprafacial [1,8]H shifts in the 871 1,7-dipolar system 390. Concerted sigmatropic shifts can only occur when the methyl groups adopt an inward (Z)-conformation (Scheme 57) <2002J(P1)1795, 2004TL3889, 2005JOC6629>. 

Reaction of the thia-amino acid 392 with trifluoroacetic anhydride gave the 2,2,2-trifluoro-l-[7-(trifluoromethyl)-l//-pyrrolo[l,2-c]-[l,3]thiazol-6-yl] ethanone pyrrole 395. The formation of the pyrrole can be rationalized by a sequence involving trifluoroacetylation of the enamine 392 affording dione 393 followed by loss of water and carbon dioxide to give the aromatic product 395. These decarboxylations afford fluorinated derivatives of heterocyclic skeletons known to exhibit interesting biological activity (Scheme 58) <2000T7267>. 

Chemical manganese dioxide (CMD). This form of Mn02 is used for batteries it is available from I. C. Sample office (Cleveland, Ohio, 44101). Shioiri et al. report it is superior to commercial activated Mn02 (Aldrich) and more convenient than freshly prepared activated Mn02 for dehydrogenation of 2-(l-ami-noalkyl)thiazolidine-4-carboxylic acids to the corresponding thiazoles (thiazole amino acids). 

Thiophene-1-oxide and 1 -substituted thiophenium salts present reduced aromaticity.144 A variety of aromaticity criteria were used in order to assess which of the 1,1-dioxide isomers of thiophene, thiazole, isothiazole, and thiadiazole was the most delocalized (Scheme 46).145 The relative aromaticity of those molecules is determined by the proximity of the nitrogen atoms to the sulfur, which actually accounts for its ability to participate in a push-pull system with the oxygen atoms of the sulfone moiety. The relative aromaticity decreases in the series isothiazole-1,1-dioxide (97) > thiazole-1,1 -dioxide (98) > thiophene-1-dioxide (99) then, one has the series 1,2,5 -thiadiazole-1,1 -dioxide (100) > 1, 2,4-thiadiaz-ole-1,1-dioxide (101) > 1,2,3-thiadiazole-1,1 -dioxide (102) > 1,3,4-thiadiazole-l,1-dioxide (103) in the order of decreasing aromaticity. As 1,2,5-thiadiazole-1,1-dioxide (100) was not synthesized, the approximations used extrapolations of data obtained for its 3,4-dimethyl-substituted analogue 104 (Scheme 46). 

In nature, an enzyme requiring two co-factors, thiamine diphosphate 2 and flavin adenine dinucleotide, accomplishes the oxidation of pyruvate to acetyl phosphate. The thiazole ring in thiamine condenses at the 2-position with pyruvat eliminating carbon dioxide to give an activated species that is oxidised by the flavin. An enzymatic oxidation process then reactivates the reduced flavin. The redox... 

Thiazoles also undergo Diels-Alder additions, but have been used less. In the examples shown, 5-ethoxy-4-methylthiazole is converted into the pyridinedicarboxylic acid (738), and into pyridoxine (737) (65FRP1400843). The mechanism must be similar to that proposed for the oxazole additions. In both cases the initial adducts are treated with hydrochloric acid sulfur dioxide is said to be given off in the first case, hydrogen sulfide in the second, the latter providing an analogy with the oxazole mechanism. 

J 4-Hydroxy-2-methyl-1,1-dioxo-1,2-di hydro-116-benzo[e][1,2]thiazine-3-carboxylic acid (5-methyl-thiazol-2-yl)-amide, 4-hydroxy-2-methyl-A/-(5-methyl-2-thiazoyl)-2H-1,2-benzothiazine-3-carboxamide-1,1 -dioxide, C14H13N3O4S2, Mr 351.40, mp 264 °C (decomp.)... 

H,3 H-Oxazolo[4,3-c][ 1,4]thiazine-6-carboxylic acid, 8,8a-dihydro-3,3-dimethyl-methyl ester X-ray diffraction, 6, 647 Oxazolo[2,3-h]thiazol-3(2H) -one 1,1-dioxide synthesis, 6, 1005... 

---