On the 3-Aminophenothiazine Synthesis

Abstract

Investigation of the key step of 3-aminophenothiazine (5) synthesis, that is thiation of N-(4-phenylaminophenyl)-phthalimid (3) was carried out. The best results were achieved using microwave irradiation, when 55% of the pure thiation product 3-phalimidophenothiazine (4) were isolated in 10–20 min reaction time.     

SYNTHESIS OF SALICYLTHIOAMIDES AND 4 H-1, 3, 2 BENZOXAZAPHOSPHORIN-DERIVATIVES

Abstract

Recent studies have shown that the dimer of p-methoxyphenylthionophosphinesulfide, 1, is a very superior thiation reagent, as ketones, amides, and esters are in most cases quantitatively converted to their thio-analogues.     

Deoxydative thiation of 3-substituted pyridine N-oxides with 4-methoxytoluene-α-thiol: A divergent route to pyridinethiols

Synthesis of 3-substituted 2-pyridinethiols was achieved by thiation of pyridine N-oxides with 4-methoxytoluene-α-thiol in the presence of diethylcarbamoyl chloride followed by cleavage of the resulting sulfides. The ease of substitution was shown to be affected by nucleophilicity of the N-oxide oxygen. Addition of zinc bromide to the reaction, a need for triethylamine, decreased most of the yield for thiation products but the formation of 3-methoxy-2-methoxybenzylthiopyridine was only improved. A plausible mechanism of the substitution, particularly β-thiation to the N-oxide function, is discussed compared with the regiochemistry observed in the reaction with diethoxyphosphoryl chloride instead of diethylcarbamoyl chloride. The debenzylation to pyridinethiol was also found to be dependent on the electron-density in the pyridine ring.     

2,4-Bis(4-methylpheylthio)-1,3,2λ5,4λ5-dithiadiphosphetan-2,4-dithion: Ein neues Reagens zur Schwefelung von N,N-disubstituierten Amiden

2,4-Bis(4-methylphenylthio)-1,3,2λ⁵,4λ⁵-dithiadiphosphetane-2,4-dithione: A New Reagent for Thiation of N,N-Disubstituted Amides As a new reagent for the thiation of amides, the easily accessible 2,4-bis(4-methylphenylthio)-1,3,2λ⁵,4λ⁵-dithiadiphosphetane-2,4-dithione ( 9 ) shows a remarkable selectivity. This selectivity – the preferred thiation of N,N-disubstituted amides – is complementary to the one of the well known Lawesson reagent. Thiation of diamides of type 2 with 9 leads via cyclization of the corresponding dithiodiamides to 1,3-thiazole-5(4H)-thiones 1 (Scheme 3).     

Sulfur Isotopic Exchange Between Two Thiophosphoryl Compounds

Abstract

Thiophosphoryl compounds are useful sulfur donors in thionation reactions (1,2) leading to P=S –> P=O exchange in thiation reagents. Although the reverse conversions P=O –> P=S are also known, mechanisms of both these types of reactions are not thoroughly studied. The analogy of chemical and isotopic exchange reactions in thiophosphoryl moiety push us to investigate the kinetics of isotopic exchange between two thiophosphoryl compounds.     

Quinazolincs. X. Direct formation of aminoquinazolines from hydroxyquinazolines and phenyl phosphorodiamidate

Treatment of several types of liydroxyquinazoline ring systems with phenyl phosphorodiamidate resulted in direct formation of the corresponding aminoquinazolines. The reaction can be conducted either by fusion in the absence of solvent or with diphenyl ether added as a diluent. The main advantage of the method is that it obviates the usual requirement for chlori-nation or thiation prior to animation.     

MICROWAVE INDUCED DRY-MEDIA SYNTHESIS OF SPIRO[INDOLE-THIAZOLIDINONES/ THIAZINONES] AS POTENTIAL ANTIFUNGAL AND ANTITUBERCULAR AGENTS AND STUDY OF THEIR REACTIONS

A series of new spiro[3H-indole-3,2′-thiazolidine]-2,4′(1H)-diones (IV) and spiro[3H-indole-3,2′-tetrahydro-1,3-thiazine]-2,4′(1H)-diones (V) have been synthesized in 85–93% yield by the one-pot environmentally benign microwave induced technique involving the cyclocondensation of 3-arylimino-2H-indol-2-ones (III) with thioacids viz. mercapto aceticacid (a)/3-mercapto propionicacid (b) using montmorillonite KSF as inorganic solid support. Intermediates (III) were synthesized in situ by the reaction of indole-2,3-diones (I) and substituted anilines (II). The spiro compounds have been further subjected to solvent-free acetylation, aminoalkylation and thiation under microwave irradiation using solid supports. The synthesized compounds have been screened in vitro for antifungal activity against Rhizoctonia solani, Fusarium oxysporum, and Collectotrichum capsici, and antitubercular acivity against Mycobacterium tuberculosis.     

Synthese von 4,4-disubstituierten 1,3-Thiazol-5(4H)-thionen

Synthesis of 4,4-Disubstituted 1,3-Thiazol-5(4H)-thiones An easy synthesis for the 1,3-thiazol-5(4H)-thiones 5 , a class of heterocycles which have hitherto only been available with difficulty, is described. Reaction of 3-amino-2H-azirines 25 with thiocarboxylic acids at 0° yields monothiodiamides of type 20 (Scheme 6) which, on treatment with Lawesson reagent at 100°, undergo thiation and cyclization to give 5 in good yield.     

Synthesis and exchange reactions of 5-alkyl-2-oxo-6-thioxo-1,2,3,6-hexahydropyrimidine-4-carboxylic acids

An improved preparation of 2-oxo-6-thioxo-1,2,3,6-hexahydropyrimidine-4-carboxylic acid 3, a potent inhibitor of dihydroorotase is presented. Trans-5-alkyl-2-oxo-6-thioxohexahydropyrimidine-4-carboxylic acids 12a-c were synthesised via the thiation of the p-methoxybenzyl esters of 5-alkyldihydroorotic acids with Lawesson's reagent followed by subsequent de-protection. The corresponding cisisomers were prepared by reduction of 5-alkyl-6-thioxoorotic acids with zinc in acetic acid. The stability and exchange reactions of 12a-c under physiological conditions were investigated by ultra-violet and ¹H nmr spectroscopy. The attempted synthesis of 16 , a fused cyclopentyl derivative of 3 is also presented.     

Synthesis and biological screening of some chromonyl-substituted heterocycles derived from 2(3H)-furanone derivative

A 2(3H)-furanone bearing chromonyl moiety at position-3 was synthesized and utilized for the construction of N-heterocycles such as pyrrolone, N-aminoquinolone, and pyridazinone derivatives. The reactivity of the chromonylfuranone toward some nitrogen nucleophiles such as ammonia, benzylamine, hydrazine, and phenylhydrazine was studied. On the other hand, thiation of the starting chromonylfuranone interestingly provides mono- and di-thiated products. The chemoselectivity of these reactions is discussed. The structures of all products obtained were elucidated from their analytical and spectral data. The antimicrobial activities of selected examples of the synthesized compounds were examined against two strains of bacteria and two fungus strains. Some of them showed promising antimicrobial activities.     

Reactivity of pyridazin‐3(2H) thiones

4,6‐Disubstituted pyridazin‐3(2H) thiones 3a–f were prepared by thiation of 4,6‐disubstituted pyridazin‐3(2H)‐one 1a–f either with thiourea or phosphorus pentasulphide. The reactivity of 3a‐f towards nucleophilic and electrophilic species under different conditions was studied successively. The structure of the products was confirmed by NMR and mass spectral data. Mechanisms for their formation are also proposed. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:334–341, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10157     

VIBRATIONAL SPECTRA AND STRUCTURE OF ALKOXY AND CHLOROALKOXY DERIVATIVES OF ANTIMONY(V)

Abstract

Vibrational spectra of (CH₃O) _n SbCl_5–n . n = 1: 1; n = 2: 2: n = 3: 3: n = 4: 4; n = 5: 5; have been recorded. According to ir and Raman data 1–5 are centrosymmetrical bridged dimers. The Raman spectra of 3–5 exhibit v(Sb–O) doublets of terminal CH₃O at 530–541 and 550–570 cm^?1; vibrations of the 4-membered Sb₂O₂ ring, observed in the 500–517 cm^?1 region of the ir spectra of 1–5, are absent. The v(C–O) bands of bridged and terminal CH₃O are shifted to higher wave numbers (60 and 31 cm^?1, respectively) in the series 1 → 5. The stability of the dimers increases in the series 1 < 2 < 3 < 4 ? 5. At 100–120°C and in CH₃CN solutions dimers of 1–3 dissociate to monomers (v(Sb–O) 537–540 cm^?1, ir data). The monochloride, 4, is partially dissociated in CH₃CN. On solution of the tetrachloride, 1, in benzene a dimer-monomer equilibrium has been observed, with the dimeric form being predominant.     

ELECTROCHEMICAL ISOMERIZATION OF SULFINE

Abstract

Electrochemical isomerization of 1-phenyl-2, 2-dimethylpropane-1-thione S-oxide (phenyl-t-butylsulfine, E and Z form, 1a and 1b) was studied. Anodic isomerization of 1a gave the two isomers of the sulfine only, but cathodic reductive isomerization of 1a gave pivalophenone and 1-cyano-2-phenyl-3, 3-dimethyl-1-butene in addition to the E and Z isomers. This is the first example of an electrochemical reaction of a sulfine.     

STRUCTURES OF PYRIDINE CARBOXYLATE COMPLEXES OF COBALT(II) AND COPPER(II)

Abstract

The syntheses and crystal structures of [Co(nic)₂(H₂O)₄] (1). [Co(iso)₂(H₂O)₄] (2). [Cu(nic)₂(H₂O)₄] (3), and [Cu(iso)₂(H₂O)₄] (4) (nic = nicotinate; iso = isonicotinate) are reported. Complex 1 crystallizes in monoclinic, space group C2/m with cell parameters a =14.150(4). b = 6.883(2)., c = 8.497(2) Å, β= 118.28(2)° and Z = 2. The other crystals. 2. 3. and 4. are all triclinic, Pī; a = 9.777(3), b = 6.348(4), c = 6.888(3)Å, a= 113.10(6)., β= 110.55(3). γ = 97.61(5)°, and Z=l for 2; a = 7.0281(4), b = 7.7176(6), c = 8.6978(7)Å, a = 68.103(7), β = 68.526(5), γ = 62.550(6)°, and Z=1 for 3; a = 9.1807(4), b = 6.3334(3), c = 6.8871(3)Å, a= 108.213(4), β = 99.433(4), γ= 105.190(4)°, and Z= 1 for 4. The arrangements around the metal ions are trans-octahedra with two pyridyl nitrogens and two aqua oxygens in the equatorial positions and two aqua oxygens in the axial positions, although the Cu(II) complexes show a larger Jahn-Teller distortion.     

SYNTHESIS AND REACTIONS OF HALO DERIVATIVES OF 4-ISOPROPYL-2H-1,4-THIAZIN-3-ONE

Abstract

Reaction of 4-isopropyl-2H-1,4-thiazin-3-one 1 (R [dbnd] i-Pr) with N-chloro- and N-bromosuccinimide occurred exclusively at the 6-position to give 6-chloro and 6-bromo derivatives of 1 (R [dbnd] i-Pr), respectively, in high yield, in sharp contrast to the 2-aroyloxylation by benzoyl peroxide or m-chloroperbenzoic acid reported earlier.² Reaction of 1 (R [dbnd] i-Pr) with methanesulfonyl chloride in the presence of aluminum chloride afforded an addition compound, 4-isopropyl-5,6-dichloro-1,4-tetrahydrothiazin-3-one. The 2-chloro derivative 6 of 1 (R [dbnd] i-Pr) was successfully prepared by hydrolysis of the 2-m-chloroben-zoyloxy derivative of 1 (R [dbnd] i-Pr) followed by treatment with thionyl chloride. Derivative 6 reacted readily under mild conditions with water, alcohols, thiols, ammonia and amines to give various 2-substituted compounds of 1 (R [dbnd] i-Pr). With phenol as a nucleophile, 1 (R [dbnd] i-Pr) reacted exclusively at the para position. Reaction at carbon atoms also occurred with N,N-dimethylaniline and 2,6-xylidine.     

SYNTHESIS OF BRANCHED-CHAIN HEXULOSE DERIVATIVES AS MODEL FOR THE SYNTHESIS OF TALAROMYCINS

The synthesis of 3,5-dideoxy-1,2-O-isopropylidene-5-C-hydroxymethyl-β-D-erythro- (1) and α-L-threo-hexulopyranose (2) from 3-deoxy-1,2-O-isopropylidene-β-D-erythro-hexulopyranose (5) from D-fructose is described, as well as their respective transformation into 3,5-dideoxy-1,2-O-isopropylidene-5-C-hydroxymethyl-β-D-threo-(3) and -α-L-erythro-hexulopyranose (4) by inversion of configuration at C-4.     

THE SYNTHESIS OF SOME C-4 AND C-9 SUBSTITUTED DERIVATIVES OF KDN2EN METHYL ESTER

The synthesis of a number of C-4 and C-9 substituted derivatives of KDN2en methyl ester 2 is reported. 9-Deoxy-9-iodo, 9-azido-9-deoxy and 9-O-methyl derivatives of 2(compounds 5, 7and 9) were prepared from the corresponding 9-O-tosylate, methyl 2,6-anhydro-3-deoxy-9-O-p-toluenesulfonyl-D-glycero-D-galacto-non-2-enonate (3). These compounds have been fully characterised as the peracetates 6, 8 and 10. Treatment of 3 with KSAc gave the 9-thioacetyl derivative which was isolated as the peracetate 11. 4-C-Ethenyl-4-deoxy (14), 4-C-phenyl-4-deoxy (15) and 4-C-[1-(methoxycarbonyl)ethenyl]-4-deoxy (16) derivatives of 2were prepared via the palladium-catalysed coupling of the 4-epi-chloride, methyl 5,7,8,9-tetra-O-acetyl-2,6-anhydro-4-chloro-3,4-dideoxy-D-glycero-D-talo-non-2-enonate (12) with the appropriate organostannanes.     

BIS-DESULFOGLUCOSINOLATES: A NEW CLASS OF BOLAFORMS

ABSTRACT

Bis-desulfoglucosinolates 14–18 bearing d-gluco, lacto, malto and cellobio saccharidic moieties were synthesized in two steps from the corresponding protected 1-thio-β-d-glycopyranoses 5, 8, 10 and 12 and bis-hydroximoyl chlorides 3a and 4a derived from 1,8-octanedial (1) and 1,12-dodecanedial (2). Fully deprotections of the intermediate O-acetylated derivatives 6, 7, 9, 11 and 13 were realized either using Zemplén method or methanol/triethylamine/water mixture, the choice of the conditions being dependent on the solubility in methanol of the fully and partially acetylated derivatives.     

PREPARATION OF NEW DERIVATIVES OF THIAZOLE,THIAZOLIDINE, AND THIAZOL-2-YLPYRAZOLO[3,4-D]PYRIMIDINE SULFONAMIDO CONJUGATES

Several new thiazoles ( 3–7 ), thiazolylpyrazole carbonitrile ( 10 , 11 ), and Thiazolidine sulfonamido conjugate derivatives ( 19–26 ) were prepared starting with p-Piperidinesulfonylacetophenones ( 1 , 2 ). The structure of these compounds was elucidated on the bases of elemental analysis, IR, PMR, and mass spectra. The antimicrobial activities of some selected compounds are also reported.     

ON THE REARRANGEMENT OF N-ARYL SULFIMIDES

Abstract

N-Aryl-S,S-dialkylsulfimides, 1, with R¹ = alkyl other than CH₃, have been rearranged by heating in ethanol yielding o-alkylthiomethyl-anilines, 2, as main products. Isomeric o-methylthioalkyl-anilines, 14, are formed in minor amounts only. Reactions of sulfimides, 1, with R¹ = CH₃, with certain alkylating or acylating agents yielded o-methylthiomethylated, N-alkylated or -acylated products 9. Mechanistic considerations are discussed. The rearrangement of sulfimides 1 has been assumed to occur via [2,3]-sigmatropic reactions of intermediate azasulfonium ylids 3. Attempts to resolve (+)-camphor-10-sulfonates of N-aryl sulfimides failed, but optically active N-aryl sulfimides could be obtained by reaction of anilines with optically active sulfoxides and P₄O₁₀. Optically active 2,6-disubstituted sulfimides, 1, could be rearranged in ethanolic KOH to yield optically active cyclohexadienimines 12, indicating a transfer of asymmetry from sulfur to carbon and supporting the assumption of a sigmatropic rearrangement.