Synthesis and properties of 2-amino-5-(5-nitro-2-furyl) thiazole derivatives

The hydrochlorides of the corresponding 2-aminothiazoles, which were converted to the free bases, were obtained by hydrolysis of 2-acylamino-5-(5-nitro-2-furyl) thiazoles. Reactions that take place at the amino group of 2-amino-5-(5-nitro-2-furyl)thiazoles are described.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1038–1041, August, 1985.     

Regioselective functionalization of the thiazole scaffold using TMPMgCl·LiCl and TMP2Zn·2MgCl2·2LiCl

A general method for the synthesis of 2,4,5-trisubstituted thiazoles has been developed. Starting from commercially available 2-bromothiazole, successive metalations using TMPMgCl·LiCl or TMP(2)Zn·2MgCl(2)·2LiCl lead to the corresponding magnesated or zincated thiazoles which readily react with various electrophiles providing highly functionalized thiazoles.     

Synthesis of thiazoles from the reaction of phenyliodonium ylids of cyclic β-dicarbonyl compounds with thioureas

Phenyliodonium ylids of cyclic β-dicarbonyl compounds react with substituted thioureas to form the corresponding thiouronium ylids. The latter, when they have one free amino group, are converted upon heating to fused thiazoles. The reaction can be considered as a modification of the Hantzsch synthesis.     

Palladium(II)-N-heterocyclic carbene-catalyzed direct C2- or C5-arylation of thiazoles with aryl bromides

Herein we report, a series of new benzimidazolium chlorides as N-heterocyclic carbene (NHC) ligand and their corresponding palladium(II)-NHC complexes with the general formula [PdCl₂(NHC)₂] were synthesized. All new compounds were characterized by ¹H NMR, ¹³C NMR, IR spectroscopy and elemental analysis techniques. The catalytic activity of palladium(II)-NHC complexes was investigated in the direct C2- or C5-arylation of thiazoles with aryl bromides in presence of palladium(II)-NHC at 150?°C for 1?h. These complexes exhibited the good catalytic performance for the direct arylation of thiazoles. The arylation of thiazoles regioselectively produced C2- or C5-arylated thiazoles in moderate to high yields.     

A convenient synthesis of 2-acyl benzothiazoles/thiazoles from benzothiazole/thiazole and N,N'-carbonyldiimidazole activated carboxylic acids

A convenient and efficient strategy for the synthesis of 2-acyl benzothiazoles/thiazoles has been developed. The treatment of benzothiazole/thiazole with allylic Grignard reagents readily generates the corresponding 2-Grignard reagents, which is followed by a reaction with N,N'-carbonyldiimidazole activated carboxylic acids to afford various 2-acyl benzothiazoles/thiazoles products. The synthetic method is applicable to a wide array of carboxylic acids and allows easy access to 2-acyl benzothiazoles/thiazoles with considerable yields under mild reaction conditions.     

Mechanisms of antioxidant action: The photo-antioxidant mechanisms of the 4-alkyl-2-mercapto thiazolines in polypropylene

An explanation is given for the favourable effect of oxidative processing on the behaviour of the 4-alkyl-2-mercapto thiazoles (RMTs) as photo-antioxidants in polypropylene (PP). The thiols are shown to be oxidised to the corresponding disulphides, followed by further oxidation through radical intermediates to products which have undergone sulphur loss. The chemistry of the oxidative transformations is believed to involve radical species during the early stages of photo-oxidation.     

Reactions of N-thiobenzoyl-α-amino-acids and related N-substituted thiobenzamides with trifluoroacetic anhydride

5-(2'-Benzamidoacyloxy)thiazoles are formed by the reaction of N-thiobenzoyl-α-amino-acids with trifluoroacetic anhydride. Corresponding esters on similar treatment undergo isosteric S-O exchange, giving N-benzoyl-α-amino-acid esters. While these are further examples of the differences shown in the reactions of N-(2-carboxyalkyl)thiobenzamides compared with their benzamide analogues, N^α-thiobenzoyl-α-amino-acid amides are found to undergo cyclisation in trifluoroacetic anhydride to give 5-trifluoroacetamido-thiazoles, following the same reaction path as their N-benzoyl analogues. Terminal N-thiobenzoyl dipeptides give 5-(N-2-carboxyalkyl) trifluoroacetamido-thiazoles on treatment with trifluoroacetic anhydride, and it is established that trifluoroacetic anhydride fails to cleave the amide group of terminal N-thioacyl dipeptides, and is therefore not a suitable reagent for Edman-type sequence analysis of polypeptides.The present work completes a project establishing routes from α-amino-acids to thiazoles carrying a heteroatom (O, N or S) at the 5-position.     

Synthesis of novel 2-aminothieno[3,2-d]thiazoles and selenolo[3,2-d]thiazoles

In this work, we described the synthesis of 3-isothiocyanatoselenophenes starting from 3-aminoselenophenes (using thiophosgene). Those compounds were then converted to the corresponding thioureas in the presence of ammonium hydroxide. Cyclization in 2-aminoselenolo[3,2-d]thiazoles was achieved using DDQ. 2-Aminothieno[3,2-d]thiazoles were obtained from 3-isothiocyanatothiophenes using the same pathway.     

Oxidation of Oxazolines and Thiazolines to Oxazoles and Thiazoles. Application of the Kharasch-Sosnovsky Reaction

Using a modification of the Kharasch-Sosnovsky reaction, the oxidation of oxazolines and thiazolines bearing a variety of 2-alkyl substituents (chiral and achiral) were smoothly oxidized to their corresponding oxazoles and thiazoles, respectively. The key feature involved in the successful implementation of this important oxidation was the use of a mixture of Cu(I) and Cu(II) salts to enhance the oxidation of the intermediate captodative radical, 24. The main limitation of this method was shown when the oxidation failed with oxazolines/thiazolines lacking the carboalkoxy group at C-4.     

A comparison of nucleophilicity and lability of thiazoles and pyridines in substitution reactions at platinum(II) complexes

The second order rate constants, k2, for the displacement of chloride by nitrogen donors L (L = thiazoles, pyridines, amines) from [Pt(S-S)Cl2] [S-S = 1, 2-bis-(phenylsulfanyl) ethane] and [Pt(SNS)Cl]+ [SNS=2, 6-bis- (methylsulfanylmethyl)pyridine] are linearly related to their proton basicity according to a free-energy relationship of the type logk2 = (pKa) + . In the reverse reactions, i.e. the displacement by chloride of the coordinated nitrogen donors, the lability depends not only upon ligand basicity but also upon the nature of the group to be displaced in the order thiazoles < pyridines. This behaviour, attributed to different interactions in the ground state, is confirmed in the solvolytic displacement of the organic bases from complexes of the type trans-[Pt(dmso)(L)Cl2]. Steric retardation, owing to the presence of a methyl group ortho to the nitrogen in the aromatic rings, is considerably less for entering thiazoles as compared to pyridines.     

2‐Bromo‐1‐(1H‐pyrazol‐4‐yl)ethanone: Versatile Precursor for Novel Mono‐ and Bis[pyrazolylthiazoles]

The synthesis of novel bis(thiazoles) 20a , 20b , 20c and 23a , 23b , 23c is reported. Thus, reaction of 2‐bromo‐1‐(5‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl)ethanone ( 6 ) with the corresponding thioamide derivatives 7a , 7b , in refluxing EtOH in the presence of triethylamine, afforded 4‐pyrazolylthiazoles 8a , 8b in good yields. On the other hand, the novel bis(thiazoles) 20a , 20b , 20c and 23a , 23b , 23c were obtained from the reaction of 6 with the corresponding benzaldehyde thiosemicarbazones 19a , 19b , 19c , 22a , 22b , 22c in refluxing EtOH. Compounds 19a , 19b , 19c and 22a , 22b , 22c were obtained by condensation of the corresponding bis(aldehydes) 18a , 18b , 18c and 21a , 21b , 21c with thiosemicarbazide.     

Synthesis and photosynthetic inhibition activity of substituted 5-(bis-trifluoromethyl)methyl)-2-aminothiazoles

The reaction of 5,5,5-trifluoro-4-trifluoromethyl-pent-3-en-2-one with aminothiocarbonyls yielded aminothiourea precursors which readily cyclised to the corresponding thiazole derivatives, 5-(bis-trifluoromethyl)methyl)-2-aminothiazoles. The inhibitory potency of photosystem II activity of these thiazoles was evaluated using fluorescence measurement techniques. Two of the compounds showed a good activity in comparison with the reference compound DCMU, 3-(3,4-dichlorophenol)-1,1-dimethylurea. Calculation of lipophilicity according to Rekker and Frey, and a corresponding experimental determination are reported.     

Synthesis of 2,4-Diamino-5-Cinnamoylthiazoles and Their Attempted Cyclization

Synthesis of 4-amino-2-aryl(or alkyl)amino-5-cinnamoylthiazoles by a [(C ─ N ─ C ─ S) + C] ring construction route is reported. Unlike the analogous 2′-aminochalcones, neither do these thiazoles cyclize to bicyclic pyridones, nor could these be prepared from the corresponding 5-acetylthiazoles and benzaldehyde.     

Iodine-promoted direct sulfenylation of 2,3-dihydroimidazo[2,1-b]thiazoles with disulfides

A novel and facile method for the direct sulfenylation of 2,3-dihydroimidazo[2,1-b]thiazoles with disulfides has been developed. The transformation is promoted by iodine under metal-free conditions, providing the corresponding products in moderate to good yields.     

Synthesis of 2-Substituted-4-carbethoxythiazoles

In the presence of boron trifluoride etherate, aryl and alkylthioamides react with ethyl diazopyruvate to give high yields of corresponding thiazoles.     

Addition of heteroaromatics to alkylidenecyclopropanes catalyzed by palladium

The reaction of heteroaromatics, such as furans, thiophenes, thiazoles, and pyrroles, with alkylidenecyclopropanes proceeded smoothly in the presence of palladium catalysts, producing the corresponding alpha-allylated products in good to high yields. For example, the reaction of 3-butylpentylidenecyclopropane (1a) with 2-methylfuran (2a), ethyl 2-thiophenecarboxylate (4a), 2-isobutylthiazole (6a), and 1-methylpyrrole (11b) gave the alpha-allylated products in 70%, 66%, 77%, and 30% yield, respectively. The reaction proceeded predominantly through distal bond cleavage. The order of reactivity of heteroaromatics toward 1a is as follows: furan > thiophene approximately thiazole (5-position) > thiazole (2-position) approximately pyrrole. This methodology provides a means for introducing an allylic group to various kinds of heteroaromatics under mild conditions.     

Study of the diazoimine/triazole equilibria for substituted thiazoles and thiadiazoles

Several diazomethyl and diazoester substituted thiazoles and thiadiazoles were prepared and their ring/chain equilibria studied by nmr spectroscopy. The diazomethyl derivatives 17a,b,d and 19a exist predominantly or exclusively in the triazole form. Ring-opening is promoted by introducing an ester group at the diazo function (17c,e, 19b, 21) or by changing thiazoles for thiadiazoles in the following order: thiazole < 1,3,4-thiadiazole < 1,2,4-thiadiazole. The diazoimine/triazole equilibria are also shifted towards the diazo form by raising the temperature and by using less polar solvents in the order: dimethyl sulfoxide < acetonitrile < chloroform < benzene. The ir spectra (potassium bromide discs) of the compounds indicate that they all, except 21 , exist in the crystalline state in the triazole form.     

Polymethine dye derivatives of pyrazolo[4, 5-d]thiazole

Quino(2)monomethine-, carbo-, mero-, dimero-, and rhodacyanines, as well as styryl dyes containing 4-methyl-6-phenyl- and 4, 6-diphenlpyrazolo[4, 5-d]thiazoles groupings are prepared. Study of the colors of the synthesized dyes, showed that dyes containing a pyrazolo[4, 5-d]moiety to be considerably more deeply colored, than the corresponding benzothiazole derivatives.     

Synthesis of novel bis- and poly(aryldiazenylthiazoles)

A novel series of bis- and poly(arydiazenyl)thiazoles were prepared in good yields by the reaction of the appropriate α-keto-hydrazonoyl chlorides with the corresponding bis- and poly(hydrazinecarbothioamide) in refluxing EtOH/DMF in the presence of few drops of TEA. Based on elemental analyses as well as spectral data, the structures of the new compounds were confirmed.     

Cyclocondensation of β-(aryl/heteroaryl)methylaminoenones with thionyl chloride: a facile general approach for the synthesis of 2,4-bis(het)aryl-5(het)aroylthiazoles

An efficient, regioselective route to 2,4-bis(het)aryl-5(het)aroylthiazoles has been developed by cyclocondensation of thionyl chloride with novel β-(het)arylmethylaminoenones which are readily accessible by the reaction of (het)arylmethylamines with 1,3-bis(het)arylmonothio-1,3-diketones. The method allows entry to 2,4,5-trisubstituted thiazoles, with full control for the introduction of either a (het)aryl group at 2,4 positions or a (het)aroyl group at 5 position of the thiazole ring.