Synthesis of thiazolines and thiazolidines

Primary -ethynylamines form thiazolines with isothiocyanates, while secondary -ethynylamines give thiazolidines. Data on the IR, PMR, and UV spectra of the compounds obtained are presented.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 471–474, April, 1972.     

Direct preparation of thiazoles, imidazoles, imidazopyridines and thiazolidines from alkenes

A range of heterocycles, namely thiazoles, imidazoles, imidazopyridines, thiazolidines and dimethoxyindoles, have been synthesised directly from alkenes via a two-step ketoidoination/cyclisation protocol. The alkene starting materials are themselves readily accessible using many different and well-established approaches, and allow access to a variety of heterocycles with excellent yields and regioselectivity.     

Photoaddition of ketones to imidazoles,thiazoles, isothiazoles and isoxazoles. Synthesis of their oxetanes

Imidazole itself did not undergo photoaddition reactions with ketones. However, irradiation of 1-acetyl and 1-benzoylimidazole, and 1,1-carbonyldiimidazole with benzophenone yielded oxetanes. On irradiation with carbonyl compounds, 1,2-dimethylimidazole and 1-benzylimidazole did not give oxetanes but a hydroxyaryl or hydroxyalkyl derivative. Thiazole itself did not yield any photoaddition product, but 2,4-dimethylthiazole afforded oxetanes on irradiation with benzophenone and with 3-benzoylpyridine. Irradiation of 2,4-dimethylthiazole with acetophenone led to the formation of a dimeric material. On irradiation with benzophenone, 4-methylisothiazole did not yield an oxetane but rather a hydroxyphenyl derivative. 3,5-Dimethylisoxazole on irradiation with benzophenone and with 3-benzoylpyridine gave oxetanes. Irradiation of 4,5-dimethylisoxazole yielded similarly an oxetane with benzophenone     

Oxidation of 4-carboxylate thiazolines to 4-carboxylate thiazoles by molecular oxygen

A facile and environment-benign oxidation by molecular oxygen was applied for the conversion of 4-carboxylate thiazolines to 4-carboxylate thiazoles. The substituent effect on thiazoline ring was investigated. It was found that electron-poor group on the thiazoline ring could facilitate the oxidation.     

Selective synthesis of 2-substituted 4-carboxy oxazoles, thiazoles and thiazolidines from serine or cysteine amino acids

The synthesis of new 4-carboxy oxazoles, thiazoles and thiazolidines by condensation of serine or cysteine with aldehydes or acids is described. Due to the optimization of a mild and selective procedure, which takes advantage of the positive effect of microwave irradiation on the MnO₂ mediated oxidation step, the 2-substituted-4-carboxy derivatives can be obtained in multi-gram scale. Examples of coordination chemistry to Ni(II) and Co(II) are described.     

Les reactions de transposition photochimique en serie heterocyclique—IV: Photo-isomerisation des phenyl-methyl thiazoles et isothiazoles isomeres

The photochemical behaviour of twelve phenylmethylthiazole isomers is identical to that of non-methylated products. Thus, in order of decreasing reactivity we have: 2-phenylthiazole or 5-phenylisothiazole > 5-phenylthiazole or 3-phenylisothiazole > 4-phenylthiazole or 4-phenylisothiazole. The two latter undergo photoisomerization only to a slight extent.Most of the rearranged compounds (95%) are formed either by a valence bond isomerization mechanism via bicyclic intermediates where the phenyl group is conjugated to the cycle, or by the Kellogg mechanism, through a 180° rotation around the bonds adjacent to the sulphur atom.These results have furthermore allowed us to confirm the selective action of iodine in these isomerization reactions.     

Synthesis of new thiazole analogues of pyochelin, a siderophore of Pseudomonas aeruginosa and Burkholderia cepacia. A new conversion of thiazolines into thiazoles

Three pyochelin analogues and their methyl esters all containing a thiazole ring have been synthesised from the same Weinreb amide key intermediate. One of these analogues called HPTT-COOH, a molecule released in the course of pyochelin and yersiniabactin biosynthesis, was efficiently synthesised using a new base induced conversion of the key compound 2′-(2-hydroxyphenyl)-2′-thiazoline-4′-(N-methoxy,N-methyl) carboxamide into 2′-(2-hydroxyphenyl)-2′-thiazole-4′-(N-methoxy,N-methyl) carboxamide.     

Steroidal oxazoles,oxazolines, and oxazolidines

In recent years the interest of this investigator has been attracted to a series of new compounds in which a cyclopentanoperhydrophenanthrene system is condensed with various heterocyclic rings. As was to be expected, the addition of heterocycles to steroids often leads to a change of their physiological activity and the appearance of new interesting biological properties. Since the numerous data on the synthesis and properties of the steroidal oxazoles, oxazolines, and oxazolidines are scattered, this stimulated us to write the present review, in which the literature published up to the end of 1994 is systematized.     

Syntheses of alpha-fluoro-alpha,beta-unsaturated thioamides and thiazolines from a fluorophosphonodithioacetate

A high-yielding synthesis of methyl fluoro(diethoxyphosphono)dithioacetate starting from its difluorinated analogue is reported. Fluorophosphonothioacetamides and -methylthiazolines, prepared from this new dithioester, have been successfully transformed into highly functionalized fluoroalkenes. Good stereoselectivity in favor of the E isomer was observed from the fluorophosphonomethylthiazolines. The potential of these new fluorinated olefinating reagents for the synthesis of modified peptides and glycosides is also disclosed.     

Steroidal isoxazoles,isoxazolines and isoxazolidines

The present review considers new useful heterocyclosteroids which contain five-membered heterocyclic systems, namely, isoxazoles, isoxazolines and isoxazolidines, condensed to the cyclopentanoperhy-drophenanthrene skeleton, in different positions of the molecule, with changes in their physiological activity and the appearance of new interesting biological properties. Literature coverage for the review includes publications up to the end of 1996.     

1, 3-azaphospholo[5, 1-b]thiazolines and benzothiazoles

The title compounds 3 and 7 are novel heterocyclic systems incorporating two-coordinate phosphorus. They are obtained in reasonable to good yields from the condensation of suitable 2-ethyl-3-alkylthiazolinium and -benzothiazolium bromides 2 and 6 with phosphorus trichloride in the presence of triethylamine in an aprotic solvent. Intermediate dichlorophosphino-substituted N-ylides can be observed or isolated in some cases. From a 2-methyl-3-alkylthiazolinium bromide ( 2a ), a 1-(dichlorophosphino) substituted 1, 3-azaphospholo[5,1-b]thiazoline ( 4 ) was obtained. The chemical shift of the two-coordinate phosphorus in 1,3-azaphosphole derivatives clearly reflects the influence of the heterocyclic system annulated to its 1,5-bond and of the substituents in its 2-and 4-positions.     

Palladium-catalyzed reaction of bromine- and iodine-containing isothiazoles with olefins

3-Bromo-4-alkenylisothiazoles were synthesized by the reaction of 3-bromo-4-iodoisothiazole with olefins in the presence of palladium acetate Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 534–536, March, 1998.     

A rapid, four-component synthesis of functionalized thiazoles

An efficient synthesis of 2-(dialkylamino)-4-phenyl)-1,3-thiazol-5-yl)(phenyl)methanone using acid chlorides, secondary amines, 2-bromoacethophenone and ammonium thiocyanate is described.     

Novel structural motifs consisting of chiral thiazolines: synthesis, molecular recognition, and anticancer activity

The facile synthesis of linear and cyclic chiral oligo(4-alpha/beta-methyl)thiazolines is described. Linear oligothiazolines have been efficiently synthesized by the iterative formation of thiazoline rings and two-directional block condensation. The construction of 24- to 36-membered cyclic oligothiazolines was achieved through the head-to-tail cyclo-oligomerization of doubly deprotected linear fragments. Studies of the interactions of both the linear and cyclic oligomers with chiral compounds revealed that cyclic oligomers displayed a strong binding affinity towards mandelic acid, whereas linear oligomers showed a poor affinity. Linear oligomers have been proven to inhibit the cell growth of the cancer cell lines HPAC, PC-3, and HCT-116. Studies of the structure-activity relationships showed that the IC50 values are clearly dependent on both the length and the terminal functionalities of the linear oligomers. Longer derivatives showed more potent activity (e.g., hexi- and octithiazolines exhibit IC50<1 microM) against all three cancer cell lines. In sharp contrast, cyclic oligomers were inactive to all three cell lines.     

A synthesis of isothiazoles and pyrimidines via a vilsmeier-haack reaction

A new synthesis of isothiazoles is reported which involves the reaction of Vilsmeier salts of N,N-dimethylamides with enamino nitriles, and treatment of the intermediates successively with sodium hydrosulfide and iodine. 4-Isothiazolecarbonitriles prepared were: 3-phenyl; 3,5-dimethyl; 3,5-diphenyl; 3-methyl-5-phenyl; and 3-phenyl-5-methyl. The 5-phenylisothiazoles were obtained in low yields due to a side reaction involving the formation of pyrimidines. Pyrimidines encountered were 6-chloro-2,4-diphenyl and 6-chloro-4-methyl-2-phenylpyrimidines.     

Perhalogenated thiazoles. Their synthesis,reactions and mass spectra

The synthesis of six new mixed perhalogenaled thiazoles ane reported. Three of these contain a 2-fluoro substituent one of which includes the novel 5-bromo-4-chloro-2-fluorothiazole. The mass spectral fragmentation pattern of the perhalogenated thiazoles was used to elucidate the orientation of the halogen suhstituents. A novel halogen migration from carbon to nitrogen in the mass spectrum was observed for several of the perhalogenated thiazoles. Nucleophilie displacement of fluoride ion in 4,5-diehloro-2-flurothiazile ( 7 ) by cyano, hydroxyl and methoxyl unions and by diclhyl amine produced the respective 2-substituted dichlorothiazoles. The ease of electrophilic substitution on carbon in the polyhalogenated thiazoles was observed to be 2 > > 5 > 4. Sulfur tetrafluoride fluorinalion of 2-earboxy-4,5-dichlorothiazole, formed by lilhiation and eurbonation of tricblorolhiazole, yielded 4,5-dicbloro-2-trifluoromethylthiazole.     

Microwave-assisted novel and efficient one-pot synthesis of fused steroidal and non-steroidal isothiazoles

An efficient microwave promoted one-pot synthesis of steroidal and non-steroidal isothiazole derivatives from corresponding β-bromo-α,β-unsaturated aldehydes has been described using a sodium thiocyanate-urea system. The β-bromo-α,β-unsaturated aldehydes derivatives are efficiently synthesized from corresponding cyclic ketones using Vilsmeir formylation reaction. The synthetic protocol is also applied for the synthesis of antifungal brassilexin.