Bromination of 4-(2-thienyl)thiazoles and 2-(2-thienyl)quinoline

Depending on the substituent, the bromination of 4-(2-thienyl)thiazoles and 2-(2-thienyl)quinoline takes place in the 5 position of the thiophene or thiazole ring. When an amino group is present in the 2 position of the thiazole ring, bromination takes place in the 5 position of the thiazole ring. When excess brominating agent is present, a second bromine atom enters the 5 position of the free ring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 35–38, January, 1982.     

Synthesis of Some 2-(3-Alkyl/aryl-5-trifluoromethylpyrazol-1-yl)-4-(coumarin-3-yl)thiazoles as Novel Antibacterial Agents

Abstract

Herein, we describe a one-pot synthesis of some novel 2-(3-alkyl/aryl-5-trifluoromethylpyrazol-1-yl)-4-(coumarin-3-yl)thiazoles (6) involving the reaction of 3-alkyl/aryl-5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazole-1-thiocarboxamides (3) with 3-bromoacetylcoumarins (5) in the presence of sodium carbonate in ethanol. Reaction of 3 with 5 in the absence of sodium carbonate, however, resulted in the formation of 2-(3-alkyl/aryl-5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-yl)-4-(coumarin-3-yl)thiazoles, which were subsequently dehydrated to 6 by refluxing in ethanol in the presence of sodium carbonate. The structure of the synthesized compounds (6) was confirmed by infrared (IR), mass, ¹H NMR, and ¹³C NMR spectra and elemental analysis data. Newly synthesized compounds (6) showed moderate to good activity against Gram-positive bacteria.     

The bromination of 2-amino- and 2-acetylamino-4-(2-furyl)-thiazoles

The bromination of 2-amino-and 2-acetylamino-4-(2-furyl)thiazoles has been studied, and it has been shown that bromination takes place first in the furan ring and then, with an excess of bromine, also in the thiazole ring in position 5.     

Chemo- and regioselective cyclohydrocarbonylation of alpha-keto alkynes catalyzed by a zwitterionic rhodium complex and triphenyl phosphite

alpha-Keto alkynes react with CO and H(2) in the presence of catalytic quantities of the zwitterionic rhodium complex (eta(6)-C(6)H(5)BPh(3))(-)Rh(+)(1,5-COD) and triphenyl phosphite affording either the 2-, 2(3H)-, or 2(5H)-furanones in 61-93% yields. The cyclohydrocarbonylation is readily accomplished using substrates containing alkyl, aryl, vinyl, and alkoxy groups at the acetylenic terminal, as well as a variety of primary, secondary, and tertiary alkyl, aryl, and heteroaryl groups connected to the ketone functionality. Structural and electronic properties present in the starting materials mediate the chemo- and regioselectivity of the reaction.     

Nitration of 2- and 4-[2-(2-furyl)vinyl]thiazole derivatives

Nitration of 4-methyl-2-[2-(nitro-2-furyl)vinyl]thiazole with a mixture of concentrated nitric and sulfuric acids leads to 4-methyl-5-nitro-2-[2-(3,5-dinitro-2-furyl)vinyl]thiazole. Under the same conditions 2-methyl- and 2-acetamido-4-[1-R-2-(5-nitro-2-furyl)vinyl]thiazoles (R=CH₃, Cl) are nitrated in the 3 position of the furan ring, 2-amino-4-[1-chloro-2-(5-nitro-2-furyl)vinyl]thiazole is nitrated in the 5 position of the thiazole ring and 2-acetamido-5-nitro-4-[2-(2-furyl)vinyl]thiazole undergoes profound changes. Under the influence of a mixture of of nitric acid and acetic anhydride the latter compound is converted quantitatively to the 5-nitro derivative (with respect to the furan ring), whereas 4-[2-(5-nitro-2-furyl)vinyl]thiazole derivatives do not undergo reaction.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 314–317, March, 1977.     

Formation of 3-[amino(aryl)-methylidene]-1,3-dihydro-2H-indol-2-ones involving ring transformation of 2-aryl-5-(2-aminophenyl)-4-hydroxy-1,3-thiazoles

The reaction of 3-bromooxindole with substituted (hetero)aromatic thioamides in acetonitrile was studied. At room temperature the reaction preferably gives products of ring transformation i.e. 2-aryl-5-(2-aminophenyl)-4-hydroxy-1,3-thiazoles (3b-f,h) whereas at elevated temperature products of an Eschenmoser coupling reaction, i.e. 3-[amino(aryl)-methylidene]-1,3-dihydro-2H-indol-2-ones (2b-f), are formed exclusively. There exist only two exceptions (4-methoxy and 2-pyridinthioamide) in which the Eschenmoser coupling reaction always takes place giving 2a and 2g. Also N-methylation of the starting 3-bromooxindole completely prevents formation of thiazoles. The prepared thiazoles 3b-f are unstable in solution and they undergo slow ring transformation to 2b-f. The rate limiting step of this rearrangement involves cleavage of an intermediary thiirane ring, which is slowed down by electron-withdrawing substituents on the thioamide (ρ = ?1.15).     

Synthesis of 2-guanyl-4-(3-substituted-phenyl)thiazoles with potent histamine H2-antagonism activity

The syntheses of novel 2-guanyl-4-(3-substituted-phenyl)thiazoles showing potent histamine H ₂-antagonism activity is reported. The most potent compound is 17 where the substitution at the 3-position of the phenyl ring is an N-methylamidino function.     

New Approach to Synthesize Symmetrical and Unsymmetrical 6-(N-Alkyl(Aryl)Amino)- and 6-(N,N-Dialkyl(Aryl)Amino)-2,4-Bis(Alkyl(Aryl)Thio)Pyrimidines as anti-Platelet Agents

Abstract

A new and straightforward procedure has been developed for the preparation of symmetrical and unsymmetrical 6-(N-alkyl(aryl)amino)- and 6-(N,N-bisalkyl(aryl)amino)-2,4-bis(alkyl(aryl)thio)pyrimidines. The two identical or different alkylthio groups were successfully introduced into the pyrimidine ring of 4-amino-6-hydroxy-2- mercaptopyrimidine via S-alkylation with alkyl halides, and via a nucleophilic displacement with sodium alkylmercaptides, affording the key intermediate symmetrical and unsymmetrical 2,4-bis(alkyl(aryl)thio)-6-aminopyrimidines. Subsequently, N-alkylation of the 2,4-bis(alkyl(aryl)thio)-6-aminopyrimidines with alkyl halides conveniently gave the desired products. The human anti-platelet activities of all the synthesized new compounds were also evaluated.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

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.     

Spin crossover in a series of iron(II) complexes of 2-(2-Alkyl-2H-tetrazol-5-yl)-1,10-phenanthroline: effects of alkyl side chain, solvent, and anion

2-(2H-Tetrazol-5-yl)-1,10-phenanthroline (HL0), its alkyl-substituted derivatives (Ln, where n = 1-8, 10, 12, 14, and 16, denoting the carbon atom number of the alkyl chain) at the 2H position of the tetrazole ring, and their iron(II) complexes (a for [Fe(L0)2], na for [Fe(Ln)2](ClO4)2, and nb for [Fe(Ln)2](BF4)2) were synthesized and characterized. The crystal structures of a, a.CH3OH, 1a.CH3OH, 1b.CH3OH.CH3CN, 2a.H2O, 2b.H2O, 4b.CH3OH, 5a.H2O, 5b.H2O, 6a, 6b, 7a, 7b, and 16a are described, along with thermal analyses. a undergoes an abrupt spin crossover (SCO) at 255 K with a hysteresis loop of 6 K. a.CH3OH, 2a.H2O, and 2b.H2O exhibit irreversible SCO behaviors due to the loss of solvent molecules upon heating. 3a, 3b, 4a, and 5a.H2O show simple spin transitions above 350 K. The desolvated samples of 4b.CH3OH and 5b.H2O undergo two-step spin transitions. 16a exhibits a two-step SCO behavior between 100 and 300 K, corresponding to sequential phase transitions from the low-spin (LS) phase to the intermediate phase and then to the high-spin phase, respectively, proved by crystal structure analysis and 57Fe M?ssbauer spectroscopy. 1a.CH3OH, 10a, 10b, 12a, 12b, 14a, 14b, and 16b show gradual and incomplete SCO behaviors after cooling down from 400 K. 1b.CH3OH.CH3CN, 6a, 6b, 7a, 7b, 8a, and 8b remain in the LS state even at 400 K. This proves that the alkyl side chains, together with the solvent molecules and anions, play a crucial role in the complicated SCO behaviors in this system.     

Mannich bases and methiodides of 6-(2-furyl)imidazo[2,1-b]thiazole and its substituted derivatives

The Mannich reaction in a number of 6-(2-furyl)-substituted imidazo[2,1-b]thiazoles is realized initially in the 5 position of the imidazothiazole system, whereas it is also realized in the 5 position of the furan ring in the presence of excess reagents if the latter position is not substituted. Iodomethylation occurs at the N₇ atom of imidazothiazole. The Mannich bases of 6-(5-nitro-2-furyl)imidazo[2,1-b]thiazole are iodomethylated only at the aminomethyl group. The pK_a values of the series of compounds were measured.     

Total synthesis of (-)-gambierol

The first total synthesis of (-)-gambierol (1), a marine polycyclic ether toxin, has been achieved. Key features of the successful synthesis include (1) a convergent union of the ABC and EFGH ring fragments (5 and 6, respectively) via our developed B-alkyl Suzuki-Miyaura cross-coupling strategy leading to the octacyclic polyether core 4 and (2) a late-stage introduction of the sensitive triene side chain by use of Pd(PPh(3))(4)/CuCl/LiCl-promoted Stille coupling. The ABC ring fragment 5 was synthesized in a linear manner (B --> AB --> ABC), wherein the A ring was formed by intramolecular hetero-Michael reaction and the C ring was constructed via 6-endo cyclization of hydroxy epoxide 7. An improved synthetic entry to the EFGH ring fragment 6 is also described, in which SmI(2)-induced reductive cyclization methodology was applied to the stereoselective construction of the F and H rings, leading to 6 with remarkable overall efficiency. Stereoselective hydroboration of 5 and subsequent Suzuki-Miyaura coupling with 6 provided endocyclic enol ether 45 in high yield, which was then converted to octacyclic polyether core 4. Careful choice of the global deprotection stage was a key element for the successful total synthesis. Functionalization of the H ring and global desilylation gave (Z)-vinyl bromide 2. Finally, cross-coupling of 2 with (Z)-vinyl stannane 3 under Corey's Pd(PPh(3))(4)/CuCl/LiCl-promoted Stille conditions completed the total synthesis of (-)-gambierol (1).     

Some transformations of acetylenic alcohol epoxides

It is shown that the hydration of acetylenic alcohol epoxides containing an epoxide ring in the position relative to the triple bond in the presence of sulfuric acid leads to the formation of acetylenic triols: 6-methyl-4-heptyne-1,2,6-, 7-methyl-5-octyne-2,3,7-, 2,7-dimethyl-5-octyne-2,3,7-, and 2,3,7-trimethyl-5-octyne-2,3,7-triols. It was established that the hydration process is hampered as the number of alkyl substituents attached to the epoxide ring increases. The triols were subjected to intramolecular cyclization under the influence of mercuric chloride to the corresponding chloromercurated derivatives of furan: 2-(1-chloromercuri-2-methyl-1-propenyl) and 5-methyi-2-(1-chloromercuri-2-methyl-1-propenyl)furans. The IR and PMR spectral data are presented.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1164–1167, September, 1977.     

2-(4-Biphenylyl)-1,3,4-oxadiazoles: synthesis and mesogenic studies

A series of 2-(4-biphenylyl)-1,3,4-oxadiazoles bearing alkyl or alkoxy substituents at the 4? position, and a hydrogen, or alkyl substituent (linear, branched, fluorinated or functionalised) at the 5 position were synthesised and characterised (51 compounds). Their mesogenic properties were evaluated using differential scanning calorimetry and polarising optical microscopy. Results show that substitution of the 1,3,4-oxadiazole ring for a terminal benzene ring in a conventional p-terphenyl enriched the mesogenic properties. Most of the new oxadiazole compounds exhibit either monotropic or enantiotropic smectic A mesophases with widths ranging from 3 to 50°C. A few compounds (short tailed) exhibit nematic phases and some compounds with branched or fluorinated alkyl substituents at the 5 position are also mesogenic.     

Polymesomorphism in a homologous series of 2-(4-alkoxyphenyl)-5-(4-methylphenyl)pyridines

A new series of 2-(4- n -alkoxyphenyl)-5-(4-methylphenyl)pyridines (CH C H C H NC HOC H , n 1-10) (APMPP), which are teraryl compounds containing a pyridine ring in n 2 m 1 the centre position of the rigid core, was synthesized and the phase transitions of the homologues were studied using DSC measurements, polarizing optical microscopy and miscibility tests with terephthalylidene-bis-4- n -pentylaniline (TBPA). Only a nematic phase was found for the shorter alkoxy homologues with n 4. The longer alkoxy homologues with n 4 showed the sequence of enantiotropic phase transitions CrG-SmF-SmC-SmA-N-I, while a monotropic CrH phase was observed for the n 5-10 homologues. Interestingly, the polymesomorphisms appear when n is larger than 4. 3 6 4 5 3 6 4     

Reaction of 2-(4-Arylthiazol-2-yl)-4-chloro-3-oxobutyronitriles with Secondary Aliphatic Amines

We have obtained 2-(4-arylthiazol-2-yl)-4-chloro-3-oxobutyronitriles by acylation of 4-aryl-2-cyanomethylthiazoles with -chloroacetyl chloride. We have studied their reaction with secondary aliphatic amines, leading to formation of 4-dialkylamino-2-(4-arylthiazol-2-yl)-3-oxobutyronitriles, and also intramolecular alkylation with formation of 3-aryl-7-cyano-6(5H)-oxopyrrolo[2,1-b]thiazoles. We have determined some aspects of the tautomerism of the synthesized compounds.     

Synthesis and Crystal Structure of 5-[（1H-1,2,4-Triazol-1- yl）methyl]-4-（2,3-dimethoxybenzylideneamino）-2- 2H-1,2,4-triazole-3（4H）-thione Monohydrate

1 INTRODUCTION Heterocyclic compounds bearing the 1,2,4-tri- azole moiety have attracted considerable attention over the past few decades since they exhibit some fungicidal activities against Puccinia recondite and applications in the field of root-growth regu- lation[1~3]. Meanwhile, 4-amino-5-mercapto-1,2, 4-triazole moiety has great versatility in fusing tovarious ring systems and possesses a broad spec- trum of biological activities[4, 5]. In our con- tinuous work directed towards the…     

Reaction of 5-(3,4-dimethoxyphenyl)pyrazine-2,3-dicarbonitrile with alkyl radicals

The reaction of 5-(3,4-dimethoxyphenyl)pyrazine-2,3-dicarbonitrile (Ib) with alkyl radicals gives addition products at the C(6)-position of the pyrazine ring as the intermediates which collapse into substitution products, 6-alkyl-5-(3,4-dimethoxyphenylpyrazine-2,3-dicarbonitrile (II), under oxidative conditions. Under non-oxidative conditions the intermediate is converted into dihydropyrazine derivatives, 6-alkyl-(3,4-dimethoxy-phenyl)-5,6-dihydropyrazine-2,3-dicarbonitrile (III), and 3,6-disubstituted pyrazine derivatives, 3,6-dialkyl-5-(3,4-dimethoxyphenyl)pyrazine-2-carbonitrile (IV) and 3-acyl-6-alkyl-5-(3,4-dimethoxyphenyl)pyrazine-2-carbonitrile (V).     

(-)-(R)- and (+)-(S)-Carvone in the Synthesis of Optically Active Acetylenic Alcohols,Ethers, and Dichlorosilyl Derivatives

Reaction of butyllithium with acetylene and 1-hexyne gave the corresponding lithium acetylides which reacted with (-)-(R)- and (+)-(S-carvone in a stereospecific fashion to give lithium (1-ethynyl- or 1-hexynyl)-5-isopropenyl-2-methyl-2-cyclohexenolates. Hydrolysis of the latter gave individual optically active tertiary terpene alcohols having both acetylenic and p-menthene fragment. Their treatment with methyl iodide in the presence of hexamethylphosphoric triamide afforded the corresponding methyl ethers. The reaction of 3-ethynyl-5-isopropenyl-3-methoxy-2-methylcyclohexene with butyllithium and trichloro(vinyl)silane yielded optically active dichlorosilyl-containing acetylenic compounds.     

Ligand-induced haptotropic rearrangements in bis(indenyl)zirconium sandwich complexes

Addition of principally sigma-donating ligands such as THF, chelating diethers, or 1,2-bis(dimethyl)phosphinoethane to eta(9),eta(5)-bis(indenyl)zirconium sandwich complexes, (eta(9)-C(9)H(5)-1,3-R(2))(eta(5)-C(9)H(5)-1,3-R(2))Zr (R = alkyl or silyl), induces haptotropic rearrangement to afford (eta(6)-C(9)H(5)-1,3-R(2))(eta(5)-C(9)H(5)-1,3-R(2))ZrL adducts. Examples where L = THF and DME have been characterized by X-ray diffraction and revealed significant buckling of the eta(6) benzo ring, consistent with reduction of the arene, and highlight the importance of the zirconium(IV) canonical form. For the THF-induced haptotropic rearrangements, the thermodynamic driving force for ring migration has been measured as a function of indenyl substituent and demonstrates silylated sandwiches favor THF coordination and the eta(6),eta(5) bonding motif over their alkylated counterparts. In the case of chelating diethers, measurement of the corresponding equilibrium constants establish more stable eta(6),eta(5) adducts with five- over four-membered chelates and with smaller oxygen and carbon backbone substituents. Kinetic studies on both THF and DME addition to (eta(9)-C(9)H(5)-1,3-(SiMe(3))(2))(eta(5)-C(9)H(5)-1,3-(SiMe(3))(2))Zr established a first-order dependence on the incoming ligand, consistent with a mechanism involving direct attack of the incoming nucleophile on the eta(9),eta(5) sandwich. These results further highlight the ability of the indenyl ligand to smoothly adjust hapticity to meet the electronic requirements of the metal center.