1,3,4‐Thiadiazole, 1,3,4‐thiadiazine, 1,3,6‐thiadiazepane and quinoxaline derivatives from symmetrical hydrazine‐1,2‐dicarbothioamide as well as N,N″‐ethane‐1,2‐diylbis(thiourea) derivatives

Reactions of N,N′‐disubstituted hydrazine‐1,2‐carbothioamides 8a‐c and substituted N,N″‐ethane‐1,2‐diylbis(thioureas) 9a‐c with 2,3,5,6‐tetrachloro‐1,4‐benzoquinone (chloranil, 10a ) and 2,3,5,6‐tetrabromo‐1,4‐benzoquinone (bromanil, 10b ) to form N,N′‐disubstituted 1,3,4‐thiadiazole‐2,5‐diamines 11a‐c , substituted 3‐amino‐6,7‐dichloro‐2,3‐dihydro‐1H‐4,2,1‐benzothiadiazine‐5,8‐diones 12a‐c , 2,3,7,8‐tetrahalothianthrene‐1,4,6,9‐tetrones 13a,b , substituted 5,6,8‐trihalo‐7‐oxo‐3,7‐dihydroquinoxaline‐2H‐carbothioamides 14a‐c, 15a‐c and 7‐substituted imino‐1,3,6‐thiadiazepane‐2‐thiones 16a‐c are reported.     

Design and synthesis of novel quinoline derivatives bearing oxadiazole,isoxazoline, triazolothiadiazole,triazolothiadiazine, and piperazine moieties

A new series of 2,3-disubstituted quinoline derivatives were synthesized from 2-chloroquinoline-3-carbaldehyde. In the reaction sequence, acetanilide was cyclized to give 2-chloroquinoline-3-carbaldehyde 1 , which was transformed to 2-(4-phenylpiperazin-1-yl)quinolin-3-carbaldehyde 2 by reaction with 4-phenylpiperazine in DMF-containing anhydrous K₂CO₃; then, compound 2 was oxidized by iodine in methanol, and methyl 2-(4-phenylpiperazin-1-yl)quinoline-3-carboxylate 3 was synthesized. The key intermediate 4 , 4-amino-5-[2-(4-phenylpiperazin-1-yl)quinolin-3-yl]-4H-1,2,4-triazole-3-thiol, was prepared using the ester 3 by a series of step. Reaction of 5 with various aromatic carboxylic acids or phenacyl bromides yielded 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles 5a-c and 1,2,4-triazolo[3,4-b][1,3,4]thiadiazines 6a-c , respectively. Moreover, compound 2 condensed with o-phenylenediamine to give 2-[2-(4-phenylpiperazin-1-yl)quinolin-3-yl]-1H-benzimidazole 7 . Interaction of 7 and 2-chloromethyl-5-aryl-1,3,4-oxadiazoles in the presence of K₂CO₃ led to the title compounds 8a-c . Furthermore, 4,5-dihydroisoxazoline derivatives 9a-c were obtained by the reaction of readily accessible starting materials including 2-(4-phenylpiperazin-1-yl)quinolin-3-carbaldehyde 2 , 1-phenyl-2-(triphenylphosphoranylidene)ethanone and hydroximoyl chlorides under mild conditions in the presence of Et₃N. The hydrazone intermediates 10a-c were obtained by the condensation of 2 with aroylhydrazides in ethanol, then, refluxing in acetic anhydride yielded 3-acetyl-5-aryl-2-[2-(4-phenylpiperazin-1-yl)quinolin-3-yl]-2,3-dihydro-1,3,4-oxadiazoles 11a-c . Structures of these compounds were established by their elemental analysis, IR, ¹H NMR, and mass spectral data.     

Synthesis and antimicrobial activity of new 1,2,4-triazole, 1,3,4-oxadiazole, 1,3,4-thiadiazole,thiopyrane, thiazolidinone,and azepine derivatives

4-oxo-4-phenylbutanehydrazide 3 was reacted with aryl or alkyl isothiocyanates to give the corresponding N-substituted-2-(4-oxo-4-phenylbutanoyl) hydrazine-1-carbothioamide 4a-c . Cyclization of thiosemicarbazides 4a-c with sodium hydroxide led to the formation of 3-(4-sub-5-thioxo-1,2,4-triazol-3-yl)-propanone 5a-c . Desulfurization of thiosemicarbazides 4a-c by mercuric oxide afforded 3-(5-(sub-amino)-1,3,4-oxadiazol-2-yl)-propanone 6a-c . The reaction of 4a-c with phosphorus oxychloride gave 3-(5-(sub-amino)-1,3,4-thiadiazol-2-yl)-propanone 7a-c . Treatment of 4a-c with ethyl-bromoacetate or α-bromopropionic acid gave N′-(3-sub-thiazolidin-2-ylidene)-butanehydrazide 8a-c and (N′-(3-sub-oxothiazolidin-2-ylidene)-butanehydrazide 9a-c . Chlorination of oxothiazolidine-hydrazide 9a-c by phosphorus oxychloride afforded N-(3-sub-4-oxothiazolidine)-butane-hydrazonoyl-chloride 10a-c . The reaction of 10a-c with mercaptoacetyl-chloride yielded 2-((4-benzoyl-thiopyrane) hydrazono)-3-sub-thiazolidinone 11a-c . Also, reacted of 10a-c with hydrazine hydrate afforded N″-(3-sub-oxothiazolidine)-butane-hydrazon-hydrazide 12a-c . The 3-sub-2-((pyridazine) hydrazono) thiazolidinone 13a-c was obtained by cyclization of 12a-c via refluxing in DMF. The reaction and cyclized of 9a-c with chloroacetyl-chloride in ethanolic KOH afforded 1-((3-sub-4-oxothiazolidine) amino)-azepine-dione 14a-c . The chemical structures of the new compounds have been confirmed by diverse spectroscopy analyses such as IR, NMR, MS, and elemental analysis. The synthesized compounds were tested for their antimicrobial activity and these compounds were considered (Pyridazin-hydrazono-thiazolidinone 13a-c , oxothiazolidin-azepinedione 14a-c , N-thiazolidin-hydrazon-hydrazide 12a-c , and thiopyran-hydrazono-thiazolidinone 11a-c ) the most effective as antimicrobial activity.     

3,3-Dimethyl-2,3,5,6-tetrahydroimidazo[2,1-b][1,3,4]thiazasilole and Its Derivatives with Five-Coordinate Silicon Atom

Previously unknown 3,3-dimethyl-2,3,5,6-tetrahydroimidazo[2,1-b][1,3,4]thiazasilole and its zwitterionic derivatives containing five-coordinate silicon atom, namely 7-substituted 3,3-dimethyl-2,3,5,6-tetrahydroimidazo[2,1-b][1,3,4]thiazasilol-4-ium chlorides, have been synthesized by reaction of 1,3-bis(trimethylsilyl)tetrahydroimidazole-2-thione with chloro(chloromethyl)dimethylsilane and subsequent transformations of the products.     

Synthesis and antimicrobial activity of some novel 5-alkyl-6-substituted uracils and related derivatives

6-chloro-5-ethyl-, n-propyl- and isopropyluracils 5a-c were efficiently prepared from the corresponding 5-alkybarbituric acids 3a-c via treatment with phosphorus oxychloride and N,N-dimethylaniline to yield the corresponding 5-alkyl-2,4,6-trichloro-pyrimidines 4a-c, which were selectively hydrolyzed by heating in 10% aqueous sodium hydroxide for 30 minutes. The reaction of compounds 5a-c with 1-substituted piperazines yielded the corresponding 5-alkyl-6-(4-substituted-1-piperazinyl)uracils 6a-j. The target 8-alkyltetrazolo[1,5-f]pyrimidine-5,7(3H,6H)-diones 7a-c were prepared via the reaction of 5a-c with sodium azide. Compounds 6a-j and 7a-c were tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Compound 6h displayed potent broad-spectrum antibacterial activity, while compound 6b showed moderate activity against the Gram-positive bacteria. All the tested compounds were practically inactive against Candida albicans.     

Efficient asymmetric synthesis of [7]helicene bisquinones

The efficient one-pot six-step domino process which occurs when (SS)-2-(p-tolylsulfinyl)-1,4-benzoquinone (1) reacts with 3,6-divinyl-1,2,7,8-tetrahydrophenanthrenes 2a-c allowed enantioselective access to [7]helicene bisquinones 3a-c with excellent optical purities (96 to > 99% ee).     

Synthesis of benzoquinone derivatives containing benzotriazole fragments

2,3,5,6-Tetrakis(1H-benzotriazol-1-yl)-1,4-benzoquinone was synthesized in 85% yield by reaction of 2,3,5,6-tetrachloro-1,4-benzoquinone with 1H-benzotriazole in pyridine at room temperature. Treatment of 2,3,5,6-tetrakis(1H-benzotriazol-1-yl)-1,4-benzoquinone with piperidine, ω-amino acids, and aromatic amines gave the corresponding 2,5-diamino-3,6-bis(1H-benzotriazol-1-yl)-1,4-benzoquinones.     

Thermal decomposition of 2-amino-3-aziridino-1,4-naphthoquinones

The course of the thermal decomposition of various 2-amino-3-substituted aziridino-1,4-naphthoquinones (Ia-g) was investigated. In all the cases, the thermal decomposition gave variable amounts of 2,3-diamino-1,4-naphthoquinone (II) and of substituted 1,2,3,4,5,10-hexahydrobenzo[g]quinoxaline-5,10-diones (IIIa-g) with complete stereospecificity. The decomposition of the aziridines Ib,f also gave significative amounts of 2-amino-3-allylamino-1,4-naphthoquinones (IVb,f). In the case of 2-amino-3-(2′-phenyl-3′-ethylaziridino)-1,4-naphthoquinone (Ig), the formation of trans-1-phenyl-1-butene (V), 2-(1-phenylpropyl)-1H-naphtho-imidazole-4,9-dione (VI), 2-phenyl-3-ethyl-3,4,5,10-tetrahydrobenzo[g]quinoxaline-5,10-dione (VII), 2-phenyl-3-ethyl-5,10-dihydrobenzo[g]quinoxaline-5,10-dione (VIII), and a mixture of cis- and trans-4H-2,3,5,6-tetra-hydro-2-phenyl-3-ethyl-5-iminonaphtho[1,2-b]oxazin-6-one (IX) also occurred. Hypotheses concerning the mechanism and the steric course of this reaction are given. The reaction is a general method for the stereospecific synthesis of 2,3-disubstituted 1,2,3,4,5,10-hexahydrobenzo[g]quinoxalines.     

Heterocyclization of thiocarbonohydrazides: Facile synthesis of 5-unsubstituted-1,3,4-thiadiazoles

2-(Hydrazinecarbothioyl)-N-substituted hydrazinecarbothioamides react with 2,3,5,6-tetrachloro-1,4-benzoquinone in high yields in a novel fast and facile method to give 5-unsubstituted-1,3,4-thiadiazole-2-amine derivatives. The synthesized compounds were characterized by spectroscopic methods and confirmed by using X-ray crystallography. A rationale for the formation of the products is presented.     

Rh(II) and Rh(I) two-legged piano-stool complexes: structure,reactivity, and electronic properties

The ligand 1,4-bis[4-(diphenylphosphino)butyl]-2,3,5,6-tetramethylbenzene, 3, was used to synthesize a mononuclear Rh(II) complex [(eta(1):eta(6):eta(1)-1,4-bis[4-(diphenylphosphino)butyl]-2,3,5,6-tetramethylbenzene)Rh][PF(6)](2), 6+, in a two-legged piano-stool geometry. The structural and electronic properties of this novel complex including a single-crystal EPR analysis are reported. The complex can be cleanly interconverted with its Rh(I) form, allowing for a comparison of the structural properties and reactivity of both oxidation states. The Rh(I) form 6 reacts with CO, tert-butyl isocyanide, and acetonitrile to form a series of 15-membered mononuclear cyclophanes [(eta(1):eta(1)-1,4-bis[4-(diphenylphosphino)butyl]-2,3,5,6-tetramethylbenzene)Rh(CO)(3)][PF(6)] (8), [(eta(1):eta(1)-1,4-bis[4-(diphenylphosphino)butyl]-2,3,5,6-tetramethylbenzene)Rh(CNC(CH(3))(3))(2)][PF(6)] (10), and [(eta(1):eta(1)-1,4-bis[4-(diphenylphosphino)butyl]-2,3,5,6-tetramethylbenzene)Rh(CO)(CH(3)CN)][PF(6)] (11). The Rh(II) complex 6+ reacts with the same small molecules, but over shorter periods of time, to form the same Rh(I) products. In addition, a model two-legged piano-stool complex [(eta(1):eta(6):eta(1)-1,4-bis[3-(diphenylphosphino)propoxy]-2,3,5,6-tetramethylbenzene)Rh][B(C(6)F(5))(4)], 5, has been synthesized and characterized for comparison purposes. The solid-state structures of complexes 5, 6, 6+, and 11 are reported. Structure data for 5: triclinic; P(-)1; a = 10.1587(7) A; b = 11.5228(8) A; c = 17.2381(12) A; alpha = 96.4379(13) degrees; beta = 91.1870(12) degrees; gamma = 106.1470(13) degrees; Z = 2. 6: triclinic; P(-)1; a = 11.1934(5) A; b = 12.4807(6) A; c = 16.1771(7) A; alpha = 81.935(7) degrees; beta = 89.943(1) degrees; gamma = 78.292(1) degrees; Z = 2. 6+: monoclinic; P2(1)/n; a = 11.9371(18) A; b = 32.401(5) A; c = 12.782(2) A; beta = 102.890(3) degrees; Z = 4. 11: triclinic; P(-)1; a = 13.5476(7) A; b = 13.8306(7) A; c = 14.9948(8) A; alpha = 74.551(1) degrees; beta = 73.895(1) degrees; gamma = 66.046(1) degrees; Z = 2.     

Synthesis and reactions of lithio derivatives of 1-allenylbenzotriazole

1-(2-Chloropropen-2-yl)benzotriazole ( 6 ) is converted by heating with sodium hydroxide or by lithium diisopropylamide at -78° into 1-allenylbenzotriazole ( 1 ) in high yield. Allene 1 undergoes in situ lithiation at the α-carbon and subsequent reactions with iodomethane or carbonyl compounds to produce 1-(1-substituted allenyl)benzotriazoles 9 and 2a-c , respectively. Three equivalents of lithium diisopropylamide dilithiated 1 and afforded symmetrical 1-(1,3-disubstituted allenyl)benzotriazoles 11a,b upon reaction with ketones. The unsymmetrical 1-(1,3-disubstituted allenyl)benzotriazole 5 was obtained via a stepwise addition of benzophenone to the lithio derivative of 1 followed by a second lithiation and quenching with acetone. Monosubstituted allenes 2a and 8 were cyclized into the benzotriazolyl substituted dihydrofuran 3 and dihydropyrrole 4 respectively.     

A convenient synthesis of 2-amino-4H-1,3,4-oxadiazino[5,6-b]-quinoxaline derivatives

The reaction of 6-chloro-2-(1-methylhydrazino)quinoxaline 4-oxide 5 with a 2-fold molar amount of ethyl chloroglyoxalate gave ethyl 8-chloro-4-methyl-4H-1,3,4-oxadiazino[5,6-b]quinoxaline-2-carboxylate 6 , whose reaction with hydrazine hydrate afforded the C₂-hydrazinocarbonyl derivative 7 . The reaction of compound 7 with nitrous acid provided the C₂-acylazide derivative 8 , which was converted into the C₂-amino 9 , C₂-carbamate 11a-c, 12a,b , and C₂-ureido 13a-c, 14 derivatives. The mass spectral fragmentation patterns were examined for compounds 10–14 , wherein the molecular ion peak did not appear in the mass spectra of compounds 10c, 11a-c, 12a,b, 13c , and 14.     

New access to pyrazole,oxa(thia)diazole and oxadiazine derivatives

1,4‐Disubstituted thiosemicarbazides 1b–f reacted with ethenetetracarbonitrile ( 5 ) in di‐ methylformamide with formation of 2‐substituted 5‐phenyl‐1,3,4‐thiadiazoles 2a–f and 2‐substituted 5‐phenyl‐1,3,4‐oxadiazoles 4a–f . Upon addition of 5 to 1c–e in chlorobenzene, 3‐amino‐2‐benzoyl‐4,5,5‐tri‐ cyano‐2,5‐dihydro‐1H‐pyrazole‐1‐[N‐(4‐tricyanovi‐nyl)phenyl]carbothioamide ( 12 ), 5‐benzylamino‐, and 5‐allylamino‐4‐benzoyl‐2,3‐dihydro‐[1,3,4]thiadiazol‐ 2,2‐dicarbonitrile ( 13a,b ) and 5‐amino‐1‐benzoylpyrazole‐3,4‐dicarbonitrile ( 14 ) as well as 2‐phenyl‐ 4H‐[1,3,4]‐oxadiazine‐5,6‐dicarbonitrile ( 15 ) were formed. Rationales for the role of the solvent and the conversions observed are presented. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:12–19, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20071     

A new method for the synthesis of 6H,11H-indolo[3,2-c]-isoquinolin-5-ones/thiones and their reactions

The synthesis of 8-substituted and unsubstituted 6H,11H-indolo[3,2-c]isoquinolin-5-ones/thiones 3a-c and 4a-c and their derivatives viz, ethyl (8-substituted-6H,11H-indolo[3,2-c]isoquinolin-5-on-6-yl)acetates 5a-c , (8-substituted-6H,11H-indolo[3,2-c]isoquinolin-5-on-6-yl)acetyl hydrazides 6a-c , 3,5-disubstituted-pyrazoles 7a-c and 8a-c , 3-substituted-pyrazol-5-ones 9a-c and 5-(8-substituted-6H,11H-indolo[3,2-c]isoquinolin-5-on-6-yl)methyl-1,3,4-oxadiazole-2-thiones 10a-c , also ethyl (8-substituted-11H-indolo[3,2-c]isoquinolin-5-ylthio)ace-tates 11a-c , (8-substituted-11Hindolo[3,2-c]isoquinolin-5-ylthio)acetyl hydrazides 12a-c , 3,5-disubstituted-pyrazoles 13a-c and 14a-c , 3-substituted-pyrazol-5-ones 15a-c and 5-(8-substituted-11H-indolo[3,2-c]isoquin-olin-5-yl)thiomethyl-1,3,4-oxadiazole-2-thiones 16a-c is described.     

Synthesis,photochemical synthesis and antitumor evaluation of novel derivatives of thieno[3',2':4,5]thieno[2,3-c]quinolones

The novel derivatives of thieno[3',2':4,5]thieno[2,3-c]quinolones 6a, 6b, 7, 10a and 10b were synthesized in multistep synthesis starting from thiophene-3-carboxaldehyde and malonic acid reacting in aldol condensation or from 3-bromothiophenes or methyl 4-bromothiophene-2-carboxylate reacting in Heck reaction. They resulted in corresponding substituted thienylacrylic acids 3a-c, which were cyclized into thieno[2,3-c]thiophene-2-carbonyl chlorides 4a-c and converted into thieno[2,3-c]thiophene-2-carboxamides 5a-d. Prepared carboxamides were photochemically dehydrohalogenated into corresponding substituted thieno[3',2':4,5]thieno[2,3-c]quinolones 6a-d. Compound 7 was prepared from 6d by alkylation with N-[3-(dimethylamino)propyl]chloride hydrochloride in the presence of NaH. Compounds 10a and 10b were prepared from 6c in the multistep synthesis over acid 8 and acid chloride 9. Compounds 6a, 6b, 7, 10a and 10b were found to exert cytostatic activities against malignant cell lines: pancreatic carcinoma (MiaPaCa2), breast carcinoma (MCF7), cervical carcinoma (HeLa), laryngeal carcinoma (Hep2), colon carcinoma (CaCo-2), melanoma (HBL), and human fibroblast cell lines (WI-38). The compound 6b, which bears the 3-dimethylaminopropyl substituent on quinolone nitrogen and methoxycarbonyl substituent on position 9, exhibited marked antitumor activity. On the contrary, compound 7, which also bears the 3-dimethylaminopropyl substituent on the quinolone nitrogen but anilido substituent on position 9, exhibited less antitumor activity than the others.     

Synthesis of 3,4-Biheterylthieno[2,3-b]-thiophenes. Part I: Synthesis of 3,4-Bi(1′,3′,4′-thiadiazolyl-, s-triazolyl-,1′,3′,4′-thiadiazinyl-, 1′,3′,4′-triazinyl-, thiazolyl-, 1′,3′-thiazinyl- and primidinyl)-thieno[2,3-b]thiophenes

3,4-Diamino-2,5-dicarbethoxythieno[2,3-b]thiophene ( 1 ) was allowed to react with NaNO 2 and active methylenes to afford the corresponding azo compounds 2a-c . Hydrazonyl chloride 2a was treated with carbon disulfide, phenyl isothiocyanate, benzonitrile, benzyl cyanide, malononitrile, benzalaniline, ethyl mercaptoacetate, and ethyl glycinate to give 1,3,4-thiadiazolyl-, s-triazolyl-, 1,3,4-thiadiazinyl-, 1,3,4-triazinylthieno[2,3-b]thiophenes 3-6 respectively. The reaction of 2b,c with urea, thiourea, and guanidine afforded pyrimidinyl- and thiazinylazothieno [2,3-b]thiophenes 7-10 respectively. Bithiazolylthieno[2,3-b]thiophenes 11 and 13 were synthesized by treating compound 1 with CS 2 along with halo compounds. The addition of S,S-, N,S-, and N,O-acetals to the Schiff base 14 afforded compounds 15-17 respectively.     

Reaction of Sulfene wild Heterocyclic N,N-Disubstituted α-Aminomethylene Ketones IV. Synthesis of 3,4-Dihydro-5H-[1]benzothiopyratio [3,4-e]-1,2-oxathiin and 2,3,6,7-Tetrahydro-5H-thiopyrano[3,4-e]-1,2-oxathiin Derivatives

The reaction of sulfene with N,N-disubstituted 3-aminomethylene-2,3-dihydro-4-thiochromanones and-2,3,5,6-tetrahydro-4-thiopyranones gave 1,4-cycloadducts which are derivatives of new heterocyclic systems, namely 3,4-dihydro-5H-[1]benzothiopyrano[3,4-e]-1,2-oxathiin and 3,4,7,8-tetrahydro-5H-thiopyrano[3,4-e]-1,2-oxathiin, respectively. Furthermore, some pyrazole derivatives VII and VIII were prepared from 3-hydroxymethylene-2,3-dihydro-4-thiochromanone or 2,3,5,6-tetrahydro-4-thiopyranone and hydrazines.     

4-(对取代苯基)-2-[2-(取代苯基)呋喃-4-甲酰胺]-1',3',4'-均三唑[1,2-d]-1,3,4-噻二唑类衍生物的合成和生物活性

以1-氨基-5-巯基-2-(对取代苯基)-1,3,4-均三唑和5-取代苯基-2-呋喃甲酰异硫氰酸酯为原料, 合成了10个未见文献报道的含苯环连呋喃的均三唑并噻二唑类衍生物, 通过元素分析, ¹H NMR, IR和MS确定化合物的结构, 初步生物活性测试表明标题化合物具有一定的除草活性.     

Reaction of N-acyl-and N-[N-arylsulfonylbenz(acet)imidoyl]-1,4-benzoquinone monoimines with hydrazoic acid

N-Aroyl-3,5-dimethyl-and N-[N-arylsulfonylbenz(acet)imidoyl]-3,5-dimethyl-1,4-benzoquinone monoimines react with hydrazoic acid according to the 1,4-addition pattern. N-Acyl-2,3,5,6-tetrachloro-1,4-benzoquinone monoimines take up hydrazoic acid at the double C=N bond (1,2-addition).     

Synthesis of 2,5-Disubstituted 1,3,4-Oxadiazine and 1,3,4-Thiadiazine from Substituted Acetophenones and Acid Hydrazides Using [Hydroxyl(tosyloxy)iodo]benzene

A novel and direct method for the efficient synthesis of 2,5-disubstituted 1,3,4-oxadiazines from the reactions of [hydroxy(tosyloxy)iodo]benzene with substituted acetophenones, followed by the treatment with acid hydrazide and K₂CO₃, is reported. The methodology is also extended to the synthesis of 5-aryl-6H-1,3,4-thiadiazin-2-amine by using thiosemicarbazide under similar experimental conditions.