bluuebunny/crossref_metadata_2025 huggingface dataset:
Acetylene chemistry. Part 27. Palladium catalysed CC bond formation between quinoline and mono‐substituted alkynes: Synthesis of 4‐alkynyl‐2‐bromoquinolines
Authors: Reisch Johannes , Gunaherath G. M. Kamal B.
Published: March 2009

Six new 4‐alkynyl‐2‐bromoquinolines have been synthesised via palladium catalysed CC bond formation between 2,4‐dibromoquinoline and mono‐substituted alkynes. Position of the alkyne substituent was confirmed to be at C‐4 by an nOe experiment on some methoxy derivatives prepared by nucleophilic displacement of bromo substituent.
On the syntheses and some reactions of bis‐ and tris(methylthio)thiophenes
Authors: Gronowitz Salo , Temciuc Marcel , Hörnfeldt Anna‐Britta
Published: March 2009

Reaction between various thienyllithium derivatives and dimethyl disulfide has been used for the preparation of 2,5‐, 2,3‐, and 3,4‐bis(methylthio)thiophenes, as well as 2,3,4‐ and 2,3,5‐tris(methylthio)thiophenes. Bromination of (methylthio)thiophenes with N‐bromosuccinimide was found to be most convenient for the preparation of brominated (methylthio)thiophenes such as 3‐bromo‐2,5‐bis(methylthio)‐ and 5‐bromo‐2,3‐bis(methylthio)thiophene, 3,4‐dibromo‐2,5‐bis(methylthio)‐, 2,5‐dibromo‐3,4‐bis(methylthio)‐ and 2,3‐dibromo‐4,5‐bis(methylthio)thiophene as well as 3‐bromo‐2,4,5‐tris(methylthio)thiophene. The reaction of methylthio substituted thienyllithium derivatives with methyl chloroformate was used for the syntheses of methyl methylthio substituted thiophenecarboxylates and using 1/3 of an equivalent for the direct preparation of methylthio substituted 3‐thienylcarbinols as tris[2,4,5‐tris(methylthio)‐3‐thienyl]carbinol.
Manganese(III) acetate oxidation of 1‐acetylindole derivatives
Authors: Izumi Taeko , Kohei Kunihiro , Murakami Satoshi
Published: March 2009

In the presence of malonic acid, the reaction of 1‐acetylindole (2) with manganese(III) acetate resulted in the formation of 4‐acetyl‐3,3a,4,8b‐tetrahydro‐2H‐furo[3,2‐b]indol‐2‐one (5). The same reaction of 1‐acetyl‐2,3‐dimethylindole yielded a mixture of 2‐acetoxymethyl‐1‐acetyl‐3‐methylindole and 4‐acetyl‐3a,8b‐dimethyl‐3,3a,4,8b‐tetrahydro‐2H‐furo[3,2‐b]indol‐2‐one, furthermore, the oxidation of 1‐acetylindoline proceeded to the formation of 2, 5 and 1‐acetylindoline‐5‐carboxylic acid.
Haloacetylated enol ethers. 2. Synthesis of 5‐trifluoromethylpyrazoles
Authors: Braibante Mara E. F. , Clar Gunter , Martins Marcos A. P.
Published: March 2009

1‐Methyl‐5‐(trifluoromethyl)‐1H‐pyrazoles 2, 3 and 4,5‐dihydro‐1‐phenyl‐5‐(trifluoromethyl)‐1H‐pyrazol‐5‐ol 4 were prepared by reaction of 4‐alkoxy‐1,1,1‐trifluoro‐3‐alken‐2‐ones 1 and hydrazine, methylhydrazine, and phenylhydrazine, respectively, in good yields. Compound 1 proved to be a versatile building block for the regiospecific construction of pyrazole rings having an 5‐trifluoromethyl substituent.
Natural product chemistry. Part 160. Synthesis of 8‐, 9‐, 10‐ and 11‐methylacronycines to improve the cytostatic activity of acronycine
Authors: Reisch Johannes , Dziemba Peter , Adam Thomas
Published: March 2009

With the help of drug design, 8‐, 9‐, 10‐ and 11‐methylacronycines 24, 25, 26 and 27 have been selected and synthesised to improve the cytostatic potency of acronycine (31). The condensation of phloroglucinol with 6‐methylanthranilic acid gave 7‐hydroxy‐1,9‐dimethyldibenzo[b,j][1,7]phenanthroline‐8,14(5H,13H)‐dione (32) as the main product.
Synthesis of [1,5]benzothiazepine derivatives
Authors: Letois Bertrand , Lancelot Jean‐Charles , Saturnino Carmela , Robba Max , De Caprariis Paolo
Published: March 2009

Various derivatives of 2,3‐dihydro[1,5]benzothiazepin‐4(5H)‐ones were synthesized. Alternative route for the synthesis of 5‐dimethylaminoethyl‐2,3‐dihydro[1,5]benzothiazepin‐4(5H)‐ones and 4‐dimethylaminopro‐poxy‐(2H,5H)‐[1,5]benzothiazepines are described.
Synthesis of 4‐(2‐chloroethyl)‐2,3‐dihydro[1,4]oxazino[2,3‐b]quinoline and 4‐(2‐chloroethyl)2,3‐dihydropyrido[2,3‐b][1,4]oxazine
Authors: Anderson Wayne K. , Dalvie Deepak K.
Published: March 2009

The title compounds were synthesized from 3‐[bis(2‐hydroxyethyl)amino]quinolin‐2(1H)‐one 11a and 3‐[bis(2‐hydroxyethyl)amino]pyridin‐2(1H)‐one 18 respectively. The preparation involved a tandem chlorination/cyclization reaction.
Regio‐ and stereoselective formation of tri‐ and tetrasubstituted tetrahydrofuranylidenes from hydroxy ketosulfones
Authors: Alzérreca Arnaldo , Martínez Judith , Velázquez Loyda , Prieto José A. , Arias LuÍS
Published: March 2009

Four tri‐ and tetrasubstituted E‐1‐(benzenesulfonyl)‐1‐tetrahydrofuranylidenes 7‐10 were synthesized from their corresponding α′‐benzenesulfonyl‐γ‐hydroxyketones 1 in good yields. The examination of the regio‐and steroselectivity of these thermally induced reactions shows preference for both, the exocyclic nature of the double bond and the E‐geometry in all tetrahydrofuranylidenes described. Structural assignments are based on infrared, 1H nmr, 13C nmr, 2D 1H‐1H and 13C‐1H correlation spectra. In contrast to tetrahydrofuranylidenes 7‐10, hemiketal 6 shows no tendency towards dehydration under the thermal reaction conditions used. This paper discusses the extent and limitations of this method as a tool of synthetic utility for the regio‐and stereoselective preparation of the target compounds.
λ‐radiolysis of mitomycin c derivatives
Authors: Kuroda Tokuyuki , Hisamura Koji , Nakamizo Nobuhiro , Otsuji Yoshio
Published: March 2009

The λ‐Radiolysis reactions of mitomycin C (1) and its derivatives were studied in the hope of developing a radiation‐induced drug (RID). The λ‐radiolysis reactions were carried out in aqueous solutions under the condition where hydrated electron (e−aq) was generated as a principal reactive species. The competitive λ‐radiolysis studies revealed that the rate constants for the reactions of 1 with e−aq at room temperature was 3.6 × 1010 dm3 mol−1s−1. Among mitomycin C derivatives, the 5H‐6‐alkoxyimino derivatives 11 and 12, and compound 13 in which ring A of 1 has the 4‐hydroxy‐6‐hydroxyimino structure cleaved to give 1. The mechanic aspect of these λ‐radiolysis reactions is discussed.
New process for the synthesis of imidazo[4,5‐b]pyridine derivatives as potent orally active thromboxane a2 receptor antagonists
Authors: Nicolaï E. , Claude S. , Teulon J. M.
Published: March 2009

A new synthetic route to prepare the 4‐[3‐(4‐chlorophenyl)methyl‐6‐chloroimidazo[4,5‐b]pyridin‐2‐yl]‐3,3‐dimethylbutanoic acid (UP 116‐77) is described. UP 116‐77 is a potent orally active TXA2/PGH2 receptor antagonist currently under pharmacological investigation. Its development needed a suitable synthesis for industrial processing. The cyclization of 3‐amino‐5‐chloro‐2‐(4‐chlorophenyl)methylaminopyridine 4 with 3,3‐dimethylglutaric anhydride in refluxing acetic acid affords a new efficient and simple way to UP 116‐77 and subsequently to various 2‐substituted imidazo[4,5‐b]pyridine derivatives.
Synthesis and structural determination of 5H‐benzocyclohepten‐5,8‐imines
Authors: Dicesare John C. , Burgess Jason P. , Mascarella S. Wayne , Carroll F. Ivy , Rothman Richard B.
Published: March 2009

Treatment of 4‐hydroxy‐N‐methylisoquinolinium iodide with triethylamine in tetrahydrofuran or acetonitrile forms 2‐methyl‐4‐oxidoisoquinolinium (2)in situ.Once formed,2can be trapped with dipolarophiles possessing varying degrees of activation to form the 5H‐benzocyclohepten‐5,8‐imine ring system. Various 2‐D nmr experiments were used in the identification of the stereochemical and regiochemical assignments for the ring system.
Action of benzyl chloride on 2‐(N,N‐dimethylamino)pyridine and 2‐benzoylaminopyridine
Authors: Kowalski Piotr
Published: March 2009

The results of the reaction of 2‐(N,N‐dimethylamino)pyridine (1) and 2‐benzoylaminopyridine (2) with benzyl chloride (3) proved that 3 did not undergo direct reaction with the pyridine ring to form a C‐benzyl product.
Reaction of enaminonitriles with isocyanates. Synthesis of new 2‐oxo‐ and 6‐oxopyrimidines
Authors: Cocco Maria Teresa , Congiu Cenzo , Maccioni Antonio , Onnis Valentina
Published: March 2009

The reaction of enaminonitriles 1 with aryl or benzyl isocyanates afforded C‐ 3–5 or N‐adducts 6–8 or a mixture of both depending on the substitution pattern of the considered enaminonitrile. The one‐step synthesis of 6‐oxopyrimidines 9–11 and 2‐oxopyrimidines 12–14 by cyclization of compounds 3–5 and 6–8 respectively is also described.
On the formation of homo‐azasteroidal esters of N,N‐bis(2‐chloroethyl)aminobenzoic acid isomers and their antitumor activity
Authors: Anastasiou A. , Catsoulacos P. , Papageorgiou A. , Margariti E.
Published: March 2009

The N, N‐bis(2‐chloroethyl)aminobenzoate isomers and the 4‐methyl‐3‐N, N‐bis(2‐chloro‐ethyl)aminobenzoate of 3β‐hydroxy‐13α‐amino‐13,17‐seco‐5α‐androstan‐17‐oic‐13,17‐lactam, 3α‐hydroxy‐13α‐amino‐13,17‐seco‐5α‐androstan‐17‐oic‐13,17‐lactam, 3α‐hydroxy‐13α‐amino‐13,17‐seco‐5‐androsten‐17‐oic‐13,17‐lactam and 17β‐hydroxy‐3‐aza‐A‐homo‐4α‐androsten‐4‐one, have been prepared and their biological activity evaluated against P388 leukemia in vivo and Ehrlich Ascites tumor (EAT), P388 and L1210 leukemias and Baby Hamster cells (BHK) in vitro. The esters in which the alkylating congener is linked to the lactam alcohol in the axial position are inactive in vivo in P388 leukemia, while compounds 1, 4, 6, 13, 14 and the alkylating congeners 17, 18 and 20 are active. The effect of the homo‐azasteroidal of N, N‐bis(2‐chloroethyl)aminobenzoic acid isomers and of 4‐methyl‐3‐N, N‐bis(2‐chloroethyl)aminobenzoic acid on the incorporation of the radioactive precursor into the DNA of L1210, P388 leukemias, Ehrlich ascites tumor and, baby Hamster kidney cells was investigated. Higher inhibitory effects on the incorporation of the radioactive precursor was obtained with the ortho derivatives, yielding <70% inhibition of thymidine incorporation in all tumor lines tested.
Photochemical reactivity of 9‐vinyladenine with diethyl fumarate
Authors: D'Auria Maurizio , Vantaggi Anna
Published: March 2009

The photochemical reaction between 9‐vinyladenine (2) and diethyl fumarate (4) gave an unusual photoadduct, epimers 4 and 5, probably derived from attack of the vinyl group on N‐3 and reaction of diethyl fumarate on N‐9 and N‐6.
Synthesis of 1,4‐dihydro‐4‐oxopyrrolo[1,2‐b]pyridazine‐3‐carboxylic acids and 1,4‐dihydro‐4‐oxoimidazo[1,5‐b]pyridazine‐3‐carboxylic acids as potential antibacterial agents
Authors: Ruxer J. M. , Lachoux C. , Ousset J. B. , Torregrosa J. L. , Mattioda G.
Published: March 2009

To check the antibacterial potential of two families of aza analogues of the quinolones, 1,4‐dihydro‐4‐oxopyrrolo[1,2‐b]pyridazine‐3‐carboxylic acids and 1,4‐dihydro‐4‐oxoimidazo[1,5‐b]pyridazine‐3‐carboxylic acids, we have prepared a few derivatives in theses families using N‐aminopyrrole and N‐aminoimidazole derivatives as starting building blocks and the classical pathways of the quinolone series. The compounds showed no interesting antibacterial activity.
Synthesis of 4,4‐disubstituted piperidine analogs of (±)‐cis‐N‐[1‐(2‐hydroxy‐2‐phenylethyl)‐3‐methyl‐4‐piperidyl]‐N‐phenylpropanamide
Authors: Brine G. A. , Stark P. A. , Carroll F. I. , Singh P.
Published: March 2009

Condensation of (±)‐1‐benzyl‐3‐methyl‐4‐piperidone (1) with aniline followed by trapping of the intermediate imine with cyanide generated a mixture of isomeric nitriles 2A and 2B, the structures of which were established unambiguously by obtaining an X‐ray crystal structure on nitrile 2B. Subsequent elaboration of the nitrile intermediates provided analogs of (±)‐cis‐N‐[1‐(2‐hydroxy‐2‐phenylethyl)‐3‐methyl‐4‐piperidyl]‐N‐phenylpropanamide having a second substituent (carbomethoxyl, carboethoxyl, methoxymethyl) at the piper‐idine 4‐position. The conversion of the carboxamide intermediates 3A and 3B to the carboalkoxyl intermediates 5A, 5B and 6A was accomplished utilizing a modified esterification procedure. Proton nmr data are presented for both the final products and the key synthetic intermediates.
Synthesis and NMR characterization of 4‐[(2‐tetrahydro‐pyranyloxy)methyl]piperidine and intermediates
Authors: Petric Andrej , Barrio Jorge R.
Published: March 2009

4‐(Hydroxymethyl)piperidine was selectively protected with tetrahydropyranyl group in several steps to give the title compound. Use of 1H and 19F nmr spectra in structure determination is discussed.
The versatile chemistry of thiophenes: The effects of b‐side contra c‐side annelation on reactivity
Authors: Gronowitz Salo
Published: March 2009

The synthesis of the nine dithienopyridines and twenty‐four thienonaphthyridines with angular annelation is described. They are all conveniently obtained by Pd(0)‐catalysed couplings between heterocyclic o‐formylboronic acids or o‐formylstannyl derivatives with heterocyclic o‐amino‐halo derivatives. The effect of the use of silver oxide and cupric oxide as co‐reagent is discussed.

Differences in electrophilic substitution, metalation and cycloaddition of b‐ and c‐fused isomers is treated. Theoretical calculations at the RHF/3–21G* level are in agreement with the orientation and reactivity in the nitration of dithieno[3,4‐b:3′,4′‐d] pyridine and dithieno[2,3‐b:3′,2′‐d] pyridine observed experimentally. The preparation of N‐oxides of the above‐mentioned ring‐systems and their reactivity will also be discussed.
An efficient synthesis of chlorinated imidazoles throughtert‐butyldimethylsilyloxy derivatives
Authors: Estenne Geneviève , Leclerc Gr̀rard , Dodey Pierre , Renaut Patrice
Published: March 2009

The protection of 2‐substituted imidazole‐5‐methanol derivatives bytert‐BDMS allowed the chlorination of the heterocycle in position 4 with good yield whereas direct chlorination on the imidazole alcohol was unsuccessful.
The oxidation of a selenium‐bridged bisquinoline using m‐chloroperbenzoic acid
Authors: Löwe Werner , Schmidt Robert , Luger Peter
Published: March 2009

The oxidation of compound 1 with m‐chloroperbenzoic acid resulting in selenoxide 2, seleninate 4 and selenite 6 is reported here.
Synthesis of 5,6‐dihydro‐4H‐pyrrolo[1,2‐a][1,4]benzodiazepine and 10,11‐dihydro‐5H,12H‐pyrrolo[2,1‐c][1,4]benzodiazocine derivatives via cyclization of 2‐aminomethylpyrroles
Authors: Korakas D. , Varvounis G.
Published: March 2009

We have synthesized pyrrolo[1,2‐α][1,4]benzodiazepine 6 and pyrrolo[2,1‐c][1,4]benzodiazocines 12 and 13 from the corresponding 1‐arylpyrrole 1d and 1‐benzylpyrroles 7a and 7b by routes involving four and five steps, respectively.
Conversion of N‐arylglycolohydroxamic acids to 1,2,3‐oxathiazolidin‐4‐one 2,2‐dioxides
Authors: Geffken Detlef , Geisel Sabine
Published: March 2009

N‐Arylglycolohydroxamic acids 1A are converted by in situ prepared 2,2′‐dipyridyl sulfite to 1,2,3‐oxathiazolidin‐4‐one 2,2‐dioxides 5, the formation of which can be rationalized via a radical pair mechanism. The alkylating potential of the heterocyclic system 5 is demonstrated by the alkaline ethanolysis giving rise to the open chained 2‐ethoxypropionanilide 6.
Nitrosation of methyl and phenyl styryl ketoximes under oxygen. Formation of 4‐nitro‐1‐hydroxypyrazole 2‐oxides and 3,5‐diphenyl‐4‐nitrato‐4,5‐dihydroisoxazole
Authors: Hansen John F. , Georgiou Paul J.
Published: March 2009

The nitrosation of the oximes of 4‐phenyl‐3‐buten‐2‐one and 1,3‐diphenyl‐2‐propen‐1‐one under oxygen has been reinvestigated. In addition to 4‐oxo‐ and 4‐oximino‐4H‐pyrazole 1,2‐dioxides previously reported, the reactions give 4‐nitro‐1‐hydroxypyrazole 2‐oxides. In the case of 1,3‐diphenyl‐2‐propen‐1‐one oxime the nitrosation reaction also gives 3,5‐diphenyl‐4‐nitrato‐4,5‐dihydroisoxazole. Evidence is presented suggesting that the nitrate ester is formed through the rearrangement of a peroxynitrite intermediate.
Studies on the hydrogenation of 6‐(hydroxymethyl)pyridine‐2‐carboxylates and its application to the synthesis of 6‐(hydroxymethyl)piperidine‐2‐carboxylic acid derivatives
Authors: Bolós Jordi , Gubert Santiago , Anglada Lluís , Pérez Angel , Sacristán Aurelio , Ortiz José A.
Published: March 2009

The synthesis of the novel amino acid 6‐(hydroxymethyl)‐2‐piperidinecarboxylic acid (1a) and its ethyl ester 1b is reported. In the hydrogenation of 6‐(hydroxymethyl)pyridine‐2‐carboxylates, hydrogenolysis of the alcohol group appeared as an unusual side reaction. Optimization of the reaction conditions allowed us to minimize hydrogenolysis and afforded pure 1.
Aminothiazole derivatives. II. A facile synthesis of condensed 4‐aminothiazole derivatives using α‐bromolactams and thioamides
Authors: Uchikawa Osamu , Aono Tetsuya
Published: March 2009

The reaction of an α‐bromolactam with a thioamide was found to give a cyclic 4‐aminothiazole derivative. Novel heterocyclic compounds such as 4,5,6,7‐tetrahydrothiazolo[4,5‐b]pyridines 10, 5,6,7,8‐tetrahydro‐4H‐thiazolo[4,5‐b]azepines 11, 4,5,6,7,8,9‐hexahydrothiazolo[4,5‐b]azocine 12 and 9,10‐dihydro‐4H‐thiazolo[4,5‐b][1]benzazepines 18 were thus prepared and the utility of this method in the construction of 4‐aminothiazole‐containing compounds was suggested.
Synthesis of 3‐[[(2‐benzimidazolyl)thio]methyl]‐1‐methyl‐1,8‐dihydrocycloheptapyrazol‐8‐ones
Authors: Kugishima Hideki , Horie Takahisa , Imafuku Kimiaki
Published: March 2009

3‐(Bromoacetyl)tropolone was reacted with five 2‐mercaptobenzimidazoles to give 3‐[[(2‐benzimidazolyl)thio]acetyl]tropolones. These products were heated with methylhydrazine to afford 3‐[[(2‐benzimidazolyl)thio]methyl]‐1‐methyl‐1,8‐dihydrocycloheptapyrazol‐8‐ones. In these reactions, 1‐methyl‐3‐[(1‐methylhydrazino)methyl]‐1,8‐dihydrocycloheptapyrazol‐8‐one was isolated as a minor product.
Synthesis of N‐octylmonoaza‐15‐crown‐5 having a dodecylphosphoric acid functional group and the binding ability toward alkali metal cations
Authors: Habata Yoichi , Akabori Sadatoshi
Published: March 2009

A new N‐octylmonoaza‐15‐crown‐5 having an alkylphosphoric acid functional group (3c) was synthesized. It was revealed that 3c selectively transported sodium ion under neutral source phase/acidic receiving phase condition, and selectively transported lithium ion under basic source phase/acidic receiving phase condition. From an ir and 13C nmr spectral study of the lithium hydroxide and sodium thiocyanate complexes of 3c, it is suggested that 3c does not incorporate cations into the three dimensional cavity using the crown ring and the phosphoric acid site, but that the crown and the phosphoric acid sites act on the cations independently; only the crown ether site of 3c significantly coordinates to the cations under neutral source phase condition, and the phosphate anion is mainly employed under basic conditions.
1,2,3‐Triazolodiazepines.I. Preparation and benzodiazepine receptor binding of 1‐benzyl‐ and 1‐phenethyl‐1,2,3‐triazolo‐[4,5‐b][1,4]diazepines
Authors: Biagi Giuliana , Giorgi Irene , Livi Oreste , Scartoni Valerio , Velo Silvia , Lucacchini Antonio , Senatore Generoso , Barili Pier Luigi
Published: March 2009

Several new 1,2,3‐triazolo[4,5‐b][1,4]diazepines were prepared starting from 1‐benzyl‐1 and 1‐phenethyl‐4,5‐diamino‐1,2,3‐triazole2(Scheme 1), by condensation reactions with β‐diketones (Scheme 2), β‐ketoesters (Scheme 3), and diethyl malonates (Scheme 4). In the first case we obtained compounds3and4with basic properties, while the ester function condensations gave cyclic amide derivatives7, 8, 10, 12and13with acid properties. SomeN‐methyl derivatives11, 14and15were obtained from the cyclic amide compounds. Most of compounds were tested for their ability to displace [3H]flunitrazepam from bovine brain membranes but no compound showed benzodiazepine receptor binding affinity.
Steric fixation of bromovinyluracil: Synthesis of furo[2,3‐d]pyrimidine nucleosides
Authors: Eger Kurt , Jalalian Mohammad , Schmidt Mathias
Published: March 2009

A new synthetic procedure for the preparation of 5,6‐dihydrofuro[2,3‐d]pyrimidin‐2(3H)‐one (3) and its deoxyriboside 8 is reported. Compound 3 undergoes nucleophilic reactions with various agents to yield 5‐substituted uracil derivatives. The dehydro derivative of 3, furo[2,3‐d]pyrimidin‐2(3H)‐one (18) was synthesized by cyclization of BVU 15, which made us develop a reproducible and high yield method for the synthesis of BV(D)U. Starting from 18, the α‐deoxyriboside 20 and the β‐riboside 22 were prepared.
Aldol reactions of γ‐ and ϵ‐methylene in 5‐membered heteroaromatic compounds
Authors: Lee Chang Kiu , Gong Jin Soon , Lee In‐Sook Han
Published: March 2009

5‐Methyl‐2‐thiophenecarboxaldehyde (1a) and 3‐methyl‐2‐thiophenecarboxaldehyde (6) underwent intermolecular aldol reactions in which the methyl group behaved as active methylene in the presence of potassium cyanide. 5‐Methylfurfural (1b) gave only 5,5′‐dimethylfuroin in the presence of potassium cyanide. But 1b formed an intermolecular aldol reaction product when sodium hydroxide was used.
Thiazolo[4,5‐d]pyrimidines. Part I. synthesis and anti‐human cytomegalovirus (HCMV) activity in vitro of certain alkyl derivatives
Authors: Lewis Arthur F. , Revankar Ganapathi R. , Fennewald Susan M. , Rando Robert F. , Huffman John H.
Published: March 2009

Alkyl derivatives of the thiazolo[4,5‐d]pyrimidine congeners of guanine and uracil were prepared and assessed for in vitro activity against human cytomegalovirus (HCMV). The finding that the 3‐pentyl 1b and 3‐hexyl 1c derivatives of 5‐aminothiazolo[4,5‐d]pyrimidine‐2,7(3H,6H)‐dione (1e) had potent in vitro anti‐HCMV activity prompted a broader study of alkyl derivatives in this ring system. A series of 3‐alkyl derivatives of 1e, viz. 1f‐w, were prepared by direct alkylation of the sodium salt of 1e and by subsequent modifications, 2a‐d. For comparison with 1c, 5‐amino‐2‐hexylaminothiazolo[4,5‐d]pyrimidin‐7(6H)‐one (4) was prepared and studied. The 3‐(2‐alkenyl) derivatives of 1e were found to be the more active antiviral agents with the Z isomer of 5‐amino‐3‐(2‐penten‐1‐yl)thiazolo[4,5‐d]pyrimidine‐2,7(3H,6H)‐dione (1f) having the better therapeutic index. Analogous 4‐(2‐alkenyl) derivatives of 2‐aminothiazolo[4,5‐d]pyrimidine‐5,7(4H,6H)‐dione 6a and 6b were also prepared but were found to have poor therapeutic indices. Single crystal X‐ray diffraction analysis was used to unequivocally establish the structure of 1f.
Synthesis and reactivities of 10‐S‐3 trithiadiazapentalene derivatives
Authors: Matsumura Noboru , Kusamiya Motoyuki , Inoue Hiroo , Yasui Masanori , Iwasaki Fujiko
Published: March 2009

1,3‐Bis(p‐substituted‐phenylthiocarbamoyl)‐2‐imidazolidinethiones 3a‐f reacted with bromine to give trithiadiazapentalene derivatives 5a‐f, bearing the exocyclic C‐N double bonds, in moderate yields. The molecular structure of 5b was elucidated by the X‐ray crystallographic analysis. The treatment of 5b‐f with hydrochloric acid gave the ring‐opening products, 1,3‐bis(p‐substituted‐phenylthiocarbamoyl)‐2‐imidazo‐lidinones 9b‐f, accompanied by the production of elemental sulfur. Reduction of 5b, 5d, and 5e with sodium borohydride gave the ring‐opening compounds, 1,3‐bis(p‐substituted‐phenylthiocarbamoyl)‐2‐imidazolidines 13b, 13d, and 13e respectively.
A large scale synthesis of 3‐chloro‐5‐methoxypyridazine
Authors: Bryant Robert D. , Kunng Fen‐Ann , South Michael S.
Published: March 2009

A large scale synthesis of 3‐chloro‐5‐methoxypyridazine was developed (18 moles) that relies on the protection of the pyridazinone nitrogen of 4,5‐dichloro‐3(2H)‐pyridazinone as the tetrahydropyranyl derivative 2. The 5‐chloro position of the protected pyridazinone was selectively displaced with methoxide to give 3 followed by catalytic hydrogenation of the 4‐chloro group to give 4. Removal of the protecting group with acid followed by phosphorous oxychloride treatment gave the target compound 6 in good yield. This route is superior to the previously described synthesis of this compound.
Formation of lactones in the heck reaction
Authors: Parker Julie A. , Stanforth Stephen P.
Published: March 2009

The Heck reaction of methyl 2‐bromobenzoate with methyl acrylate gave a mixture of alkene 1 and lactone 9. Acrylonitrile and methyl 2‐bromobenzoate gave lactone 10. Ethyl 2‐bromobenzoate and methyl acrylate or acrylonitrile gave the alkenes 2 and 4 respectively.
Synthesis of 1‐alkoxy‐5‐alkyluracils
Authors: Kim Dae‐Kee , Kim Ganghyeok , Lim Jinsoo , Kim Key H.
Published: March 2009

1‐Alkoxy‐5‐alkyluracils 2a‐f have been prepared by the reaction of 2‐alkyl‐3‐methoxyacryloyl isocyanates 8a‐b with alkoxyamines 9a‐c followed by cyclization of the resulting N‐alkoxy‐N'‐(2‐alkyl‐3‐methoxyacryloyl)ureas 10a‐f. The isocyanates 8a‐b were prepared from ethyl 2‐alkylacrylates 3a‐b in 5 steps.
Convenient synthesis of mesitylene‐bridged hexaazamacrobicyclic compounds
Authors: Krakowiak Krzysztof E. , Bradshaw Jerald S.
Published: March 2009

Two mesitylene‐bridged hexaazamacrobicyclic ligands 1 and 2 were prepared by a three‐step process from available 2,4,6‐tris(bromomethyl)mesitylene (9) and N, N'‐di‐p‐tosylethylenediamine and N, N'‐di‐p‐tosyl‐1,3‐diaminopropane. First, mono‐BOC‐protected ditosylamines 5 and 6 were prepared by treating the two diamines with BOC‐O‐BOC. These mono‐BOC‐protected diamines were treated with the tris(bromomethyl)‐mesitylene followed by deprotection to give 2,4,6‐tris(2,5‐ditosyl‐2,5‐diazapentyl)mesitylene (3) and its 2,6‐diazahexyl analog 4. These latter intermediates were treated with tris(bromomethyl)mesitylene to give the mesitylene‐bridged hexaazamacrobicycles. This three‐step synthesis replaces the reported nine‐step process.
A convenient route to heteronaphthacenes
Authors: Markgraf J. Hodge , Patterson Daniel E.
Published: March 2009

Heteronaphthacenes 1 were prepared in two steps from 1,3‐dihydrobenzo[c]thiophene 2,2‐dioxide (4) and dienophiles 2 via convenient high‐temperature Diels‐Alder reactions.
Design of antineoplastic agents on the basis of the “2‐phenyl‐naphthalene‐type” structural pattern. 3. synthesis and biological activity evaluation of 5H‐benzo[b]naphtho‐[2,3‐d]pyrrole‐6,11‐dione derivatives
Authors: Luo Yi‐Lin , Chou Ting‐Chao , Cheng C. C.
Published: March 2009

A number of 5H‐Benzo[b]naphtho[2,3‐d]pyrrole‐6,11‐dione derivatives were synthesized. Their biological activity was compared with that of the corresponding benzoxazolo‐ and benzthiazolo‐analogues.
Synthesis and reactions of 9,10‐diazatetracyclo‐[6.3.0.0.4,110.5,9]undecanes
Authors: Gribble Gordon W. , Hirth Bradford H.
Published: March 2009

The tandem 1,3‐dipolar cycloaddition between sydnones and 1,5‐cyclooctadiene provides 9,10‐diazatetracyclo[6.3.0.0.4,110.5,9]undecanes (the Weintraub reaction) in modest to good yields.
The isolation and structure determination of cryptomisrine, a novel indolo[3,2‐b]quinoline dimeric alkaloid from cryptolepis sanguinolenta
Authors: Sharaf Maged H. M. , Schiff Paul L. , Tackie Albert N. , Phoebe Charles H. , Johnson Robert L. , Minick Doug , Crouch Ronald C. , Martin Gary E. , Andrews C. Webster
Published: March 2009

The isolation and structure determination of cryptomisrine, a novel indolo[3,2‐b]quinoline dimeric alkaloid obtained from extracts of the roots of the Ghanaian medicinal plant Cryptolepis sanguinolenta is reported. The structure determination was made via a consideration of the spectral data, including uv, ir, nmr, and mass spectra. In particular, one‐dimensional proton/carbon nmr, one‐dimensional nOe difference nmr, and a series of homonuclear (COSY) and inverse‐detected heteronuclear two‐dimensional (HMQC, HMBC) experiments were utilized, as well as high resolution FABMS. Cryptomisrine is most unusual in that its two monomeric parts apparently exist in such a C2 symmetric environment that only one set of proton and carbon nmr resonances are observed. Cryptomisrine is the first example of a dimeric indolo‐[3,2‐b]quinoline alkaloid to have been isolated from nature.
One‐pot synthesis of some 2H‐Pyran‐2‐one derivatives
Authors: Kepe Vladimir , Kočevar Marijan , Polanc Slovenko
Published: March 2009

A one‐pot synthesis of various 2H‐pyran‐2‐one derivatives 5–19 starting from methyl ketones 1, N,N‐dimethylformamide dimethyl acetal and N‐acylglycines 3 in acetic anhydride is described.
Generation and reactivity of N,N‐dimethylaminobenzotriazolylcarbene a new nucleophilic carbene
Authors: Katritzky Alan R. , Cheng Dai , Leeming Peter , Ghiviriga Ion , Hartshorn Chris M. , Steel Peter J.
Published: March 2009

N,N‐Dimethylaminobenzotriazolylcarbene (5) reacted with phenyl isocyanate in a [1+2+2] cycloaddition and then with nucleophiles to generate various hydantoins 10 in a one‐pot procedure. It was also found that this novel carbene reacted with trans‐dibenzoylethylene (11) in a [1+4] cycloaddition, generating 2‐dimethylamino‐3‐benzoyl‐5‐phenylfuran (13) and 2‐phenyl‐3‐[benzotriazol‐1‐yl]‐4‐benzoylfuran (14) whose structures were confirmed by 1H‐13C long range correlations as well as the structure of furan 14 being confirmed by X‐ray crystallography.
The synthesis and structure of a new type of aromatic heterocyclic macrocycle. IV. Synthesis of a 1,3,4‐oxadiazole‐containing azomacrocycle
Authors: Zheng Shengping , Wang Shu , Hua Wenting
Published: March 2009

A novel azomacrocycle containing the 1,3,4‐oxadiazole ring has been prepared from 2,5‐bis[3‐(4‐hydroxyphenylazo)phenyl]‐1,3,4‐oxadiazole 5 and 2,5‐bis(2‐chloromethlylphenyl)‐1,3,4‐oxadiazole 8. The coupling reaction between the diazonium salt 4 and bisphenol A has been reported.
Conversion of 3‐hydroxy‐1,2,3,4‐tetrahydroquinoline‐2,4‐diones to 2,3a,4,5‐tetrahydrofuro[2,3‐c]quinoline‐2,4‐diones via an intramolecular wittig reaction
Authors: Klásek Antonín , Kafka Stanislav
Published: March 2009

The preparation of 2,3a,4,5‐tetrahydrofuro[2,3‐c]quinoline‐2,4‐diones starting from 3‐hydroxy‐1,2,3,4‐tetrahydroquinoline‐2,4‐diones and using the reaction path via bromoacetylderivatives and triphenylphosphonioacetyl derivatives of the initial substances is described. The nmr spectra of the products are discussed.
1,3‐cycloaddition reactions of 2‐oxo‐2H‐[1]benzopyran‐4‐carbonitrile N‐oxide. Synthesis of several new 4‐substituted coumarins
Authors: Nicolaides Demetrios N. , Fylaktakidou Konstantina C. , Litinas Konstantinos E. , Papageorgiou George K. , Hadjipavlou‐Litina Dimitra J.
Published: March 2009

1,3‐Cycloaddition reactions of new 2‐oxo‐2H‐[1]benzopyran‐4‐carbonitrile N‐oxide 2 with dipolarophiles, o‐aminophenols and o‐phenylenediamine resulted in 4‐heterocyclic substituted coumarin derivatives. These derivatives are screened for antiinflammatory activity in vitro through their antiproteolytic activity, the interaction with 1,1‐diphenyl‐2‐picrylhydrazyl and the ability to affect superoxide anion and to inhibit β‐glucuronidase and soybean lipoxygenase.
A facile synthesis of 3‐substituted 2‐cyanoquinazolin‐4(3H)‐ones and 3‐alkyl‐2‐cyanothieno[3,2‐d]pyrimidin‐4(3H)‐ones via 1,2,3‐dithiazoles
Authors: Lee Hyi‐Seung , Chang Yong‐Goo , Kim Kyongtae
Published: March 2009

The reaction of methyl anthranilate with 4,5‐dichloro‐1,2,3‐dithiazolium chloride (Appel's salt) in the presence of pyridine (2 equivalents) in dichloromethane at room temperature gave methyl N‐(4‐chloro‐5H‐1,2,3‐dithiazol‐5‐ylidene)anthranilate (3a) (50% yield), which reacted with sterically less hindered primary alkylamines to give directly 3‐alkyl‐2‐cyanoquinazolin‐4(3H)‐ones 5 in moderate to good yields. With tert‐butylamine, N‐(2‐methoxycarbonylphenyl)iminocyanomethyl N‐(tert‐butyl) disulfide 7 and methyl 2‐(N‐cyanothioformamido)anthranilate (8) were isolated in 33% and 59% yields, respectively. The cyano group of quinazoline 5a (R = CH3) is readily displaced by various nucleophiles to give 2‐substituted quinazolinones 11–19, which indicates that compounds 5 can be utilized as starting materials for the synthesis of new 2‐substituted quinazolines. Similarly 3‐alkyl‐2‐cyanomieno[3,2,‐d]pyrimidin‐4(3H)‐ones 22 were prepared from methyl 3‐[N‐(4‐chloro‐5H‐1,2,3‐dimiazol‐5‐ylidene)]‐2‐thiophencarboxylate (21) in moderate to good yields.
Novel heterocycles. Synthesis of 2,3‐dihydro‐6‐methyl‐2‐phenyl‐4H,6H‐pyrano[3,2‐c][2,1]benzothiazin‐4‐one 5,5‐dioxide and related compounds
Authors: Coppo Frank T. , Fawzi Maged M.
Published: March 2009

The reaction of 2‐chloro‐4‐(methylsulfonyl)benzoyl chloride (5) with 1‐methyl‐1H‐2,1‐benzothiazin‐4‐(3H)‐one 2,2‐dioxide (4) gave the O‐benzoyl compound, 1‐methyl‐2,2‐dioxido‐1H‐2,1‐benzothiazin‐4‐yl 2‐chloro‐4‐(methylsulfonyl)benzoate (6), which rearranged to give the C‐benzoyl isomer, [2‐chloro‐4‐(methylsulfonyl)phenyl] (4‐hydroxy‐1‐mefhyl‐2,2‐dioxido‐1H‐2,1‐benzothiazin‐3‐yl)methanone (7). The O‐cinnamoyl compound 13 that resulted from the addition of 2,4‐dichlorocinnamoyl chloride (11) to compound 4 rearranged to give the C‐cinnamoyl compound, 3‐(2,4‐dichlorophenyl)‐1‐(4‐hydroxy‐1‐methyl‐2,2‐dioxido‐1H‐2,1‐benzothiazin‐3yl)‐2‐propen‐1‐one (15). On the other hand, 1‐methyl‐2,2‐dioxido‐1H‐2,1‐benzothiazin‐4‐yl 3‐phenyl‐2‐propenoate (19) (from cinnamoyl chloride (17) and compound 4) rearranged to give 2,3‐dihydro‐6‐methyl‐2‐phenyl‐4H,6H‐pyrano[3,2‐c][2,1]benzothiazin‐4‐one 5,5‐dioxide (21), an example of a hitherto unknown ring system. Additional examples of this novel heterocycle were prepared from 1‐methyl‐7‐(trifluoromethyl)‐1H‐pyrido[2,3‐c][1,2]thiazin‐4(3H)‐one 2,2‐dioxide (23) and 1‐methyl‐1H‐thieno[3,2‐c][1,2]thiazin‐4(3H)‐one 2,2‐dioxide (8).
Cyclocondensation of 6‐acetyl‐4,7‐dihydro‐5‐methyl‐7‐phenyl[1,2,4]triazolo[1,5‐a]pyrimidine with hydroxylamine and hydrazine
Authors: Desenko Sergey M. , Komykhov Sergey A. , Orlov Valery D. , Meier Herbert
Published: March 2009

The cyclocondensation of 6‐acetyl‐4,7‐dihydro‐5‐methyl‐7‐phenyl[1,2,4]triazolo[1,5‐a]pyrimidine (3) with hydroxylamine or hydrazine leads to 3a,4,9,9a‐tetrahydro‐3,9a‐dimethyl‐4‐phenylisoxazolo‐[5,4‐d][1,2,4]triazolo[1,5‐a]pyrimidine (4a) and 3a,4,9,9a‐tetrahydro‐3,9a‐dimethyl‐4‐phenyl‐1H‐pyrazolo[3,4‐d][1,2,4]triazolo[1,5‐a]pyrimidine (4b), respectively. In the presence of methanolic hydrogen chloride, 4b undergoes a cleavage of the pyrimidine ring to yield (5‐amino‐1,2,4‐triazol‐1‐yl)(3,5‐dimethylpyrazol‐4‐yl)phenylmethane (5). The structure determination of the compounds obtained is based on 1H and 13C nmr spectra including NOE measurements.
Preparation of 1,2‐disubstituted‐3‐hydroxy‐4(1H)‐quinolinones and the influence of substitution on the course of cyclization
Authors: Hradil Pavel , Hlaváč Jan , Lemr Karel
Published: March 2009

Synthesis of 1,2‐disubstituted‐3‐hydroxy‐4(1H)‐quinolinones by the cyclization of N‐substituted phenacyl or acetonyl anthranilates is described. Two methods were employed for cyclization of anthranilates. Heating in polyphosphoric acid has a wide scope of applicability. The thermal cyclization in boiling N‐methylpyrrolidone is limited by steric effect.
A simple one step synthesis of new 3,5‐disubstituted‐4‐amino‐1,2,4‐triazoles
Authors: Bentiss Fouad , Lagrenée Michel , Traisnel Michel , Mernari Bouchaib , Elattari Hassan
Published: March 2009

A number of symmetrically 3,5‐disubstituted 4‐amino‐1,2,4‐triazoles have been prepared by the reaction of aromatic nitriles with hydrazine dihydrochloride or sulfate with an excess of hydrazine hydrate in ethyl ene or diethylene glycol under a nitrogen atmosphere. The structures of the new triazoles derivatives were confirmed by analytical and spectral data.
Fused 1,2‐dithioles. IV. Synthesis and reactions of 1,2‐dithiole s‐oxides
Authors: Schachtner Josef Emmeram , Zoukas Thomas , Stachel Hans‐Dietrich , Polborn Kurt , Nöth Heinrich
Published: March 2009

1,2‐Dithiolopyrrolones and their heterologues of type 1 are resonance stabilized systems displaying a high dipole moment. Upon oxidation with organic peracids compounds 2, 5, 15a, 16a, 20a and 25a gave the corresponding S(2)‐oxides and, depending on substituents, in some cases the S(2)‐ and S(1)‐dioxides. The S(2)‐monoxides showed a proclivity to disproportionation and were easily reduced to dithioles with symme trical dimethylhydrazine. From S(2)‐oxides and several primary amines bicyclic isothiazole‐S‐oxides were obtained (S/N‐exchange reaction). From the N‐unsubstituted isothiazole S‐oxide 10e the N‐hydroxyisothiazole 9d was synthesized by an aza‐Pummerer‐type rearrangement. The assumption is made that S(2)‐oxides may be biologically important as active metabolites of pyrrothines and analogues of type 1 in their action as antibacterials and antimycobacterials.
9,9′‐Thiobis‐(1,2,3,4,7,8‐hexahydro‐7‐methyl‐6H‐pyrimido[1,6‐a]pyrimidine‐6,8‐dione)
Authors: Šimo Ondrej , Rybár Alfonz , Alföldi Juraj , Pätoprstý Vladimír
Published: March 2009

The 6‐(3‐hydroxypropylamino)‐3‐methylpyrimidine‐2,4‐dione (1) did not afford the expected 6‐(3‐chloro‐propylamino)‐ derivative on reaction with thionyl chloride, but, instead, the pyrimidine rings were joined via a sulfur bridge to give 9,9′‐thiobis(1,2,3,4,7,8‐hexahydro‐7‐melnyl‐6H‐pyrimido[1,6‐a]pyrirnidine‐6,8‐dione) (3). An identical 9,9′‐thiobis‐ derivative 3 was obtained when reacting thionyl chloride with 1,2,3,4,7,8‐hexahydro‐7‐methyl‐6H‐pyrimido[1,6‐a]pyrimidine‐6,8‐dione (4). We suppose the sulfoxide‐ derivative 2 to be the intermediate of both routes: it underwent reduction to the final sulfide 3 in excess thionyl chloride.
The solid‐state michael addition of indole to 4‐arylidene‐3‐methyl‐5‐pyrazolone
Authors: Li Xiao‐Liu , Wang Yong‐Mei , Matsuura Teruo , Meng Ji‐Ben
Published: March 2009

The Michael addition reactions of indole to 4‐arylidene‐3‐methyl‐1‐phenyl‐5‐pyrazolone 1 were investigated in the solid state, by which a series of new compounds, 1‐aryl‐1‐(3‐indolyl)‐1‐(3′‐methyl‐1′‐phenyl‐5′‐pyrazolon‐4′‐yl)methanes 2, were easily obtained. This provides a feasible method of preparing novel compounds containing two heterocyclic groups at the same carbon.
A new approach to the synthesis of benzofuro[3,2‐b]quinolines, benzothieno[3,2‐b]quinolines and indolo[3,2‐b]quinolines
Authors: Rádl Stanislav , Konvička Petr , Váchal Petr
Published: March 2009

Treatment of 2‐hydroxy‐, 2‐mercapto‐, and 2‐ethoxycarbonylamino‐benzonitriles 12 with 2‐fluoro‐ or 2‐nitrophenacylbromides 13 under alkaline conditions provided the corresponding benzofuran, benzothiophene, and indole intermediates 10, respectivelly. Nucleophilic cyclization of these compounds led to the corresponding tetracyclic quinolinones 7a, 7b, and 3. Denitrocyclization reaction of compounds 10 (R = NO2) was found especially useful. Compounds 7a, 7b, and 3 were converted to their chloro derivatives 14a‐c, which were reduced with hydrogen and a catalyst to the corresponding compounds 8a, 8b, and 2. The presented pathway represents a new method of preparation of quindoline 2 and its O and S analogs 8. Chloro derivatives 14 are reactive enough to provide the corresponding methoxy derivatives 15 and dimethylamino derivatives 16. Methylation of compounds 7a and 7b with iodomethane providing mixtures of major N‐methyl derivatives 17 and minor O‐methyl derivatives 15 were also studied.
Synthesis of benzo[b]thieno‐ and benzo[b]furano‐[2,3‐a]pyrrolo[3,4‐c]carbazole‐5‐, ‐7‐ and ‐5,7‐dione
Authors: Hudkins Robert L. , Johnson Neil W.
Published: March 2009

Benzo[b]thieno[2,3‐a]pyrrolo[3,4‐c]carbazoles and benzo[b]furano[2,3‐a]pyrrolo[3,4‐c]carbazoles were prepared from 2‐(2‐benzo[b]thieno)‐ (8) and 2‐(2‐benzo[b]furano)‐3‐[3‐(2,5‐dioxo‐lH‐pyrrolidinyl)]indole (9) by a palladium(II)acetate/tetrachloro‐1,4‐benzoquinone oxidative A‐E ring closure.
Synthesis of 3‐Carboxylic derivatives of 1,5‐benzodiazepines
Authors: Mansour O. , Szymonski B. , Morand J. M. , Cussac M. , Thomasson F.
Published: March 2009

A series of 3‐carboxylic derivatives of disubstituted 1,5‐benzodiazepines(5–9)was synthesized by hetero‐cyclisation from 1,2‐diaminobenzene(1)with dibenzoylmethane(2)followed by bromination on position 3 and by introduction of the carboxylic group or introduction of the malonic moiety. Reduction of the hetero‐cycle gave the perhydro derivative diethyl (2,4‐diphenyl‐1,2,4,5‐tetrahydro‐3H‐1,5‐benzodiazepin‐3‐yl)malonate(9).
Synthesis and characterization of new heterocyclic derivatives by oxidation of 1‐amino‐2‐methylindoline
Authors: Peyrot L. , Elkhatib M. , Vignalou J. R. , Metz R. , Elomar F. , Delalu H.
Published: March 2009

1‐Amino‐2‐methylindoline is a precursor used in the synthesis of antihypertension drugs. It reacts with monochloramine to lead to the formation of 1‐amino‐2‐methylindole and azo(2‐methyl)indoline. These new products have been isolated and characterized by microanalysis, uv, gc/ms, ir, and 1H/13C nmr. The reaction leads to the transient formation of an indolic aminonitrene. 1‐Amino‐2‐methylindole formation proceeds in strongly alkaline medium by rearrangement of a diaziridine intermediate. In neutral or slightly alkaline medium, one obtains a precipitate of tetrazene type (‐N‐N=N‐N‐), the azo(2‐methyl)indoline. The study of the thermochemical properties shows that tetrazene decomposes towards 150 °C to give the 1,1′‐bi(2‐methyl)indoline. The stability of the starting reagents and products was the subject of a systematic investigation. A reaction mechanism is proposed.
Synthesis of new 5‐substitutedbenzo[b]thiophene derivatives
Authors: Pérez‐Silanes S. , Martínez‐Esparza J. , Oficialdegui A. M. , Villanueva H. , Orúas L. , Monge A.
Published: March 2009

Previous works of our group have dealt with the synthesis of 1‐(aryl)‐3‐[4‐(aryl)piperazin‐1‐yl]propane derivatives in the search for new and efficient antidepressants with a dual mode of action: serotonin reuptake inhibition and 5‐HT1A receptor afinity [1‐4]. From these studies we concluded that the 3‐[4‐(aryl)piperazin‐1‐yl]‐1‐(benzo[b]thiophen‐3‐yl)propane derivatives led to the best results. The continuation of this research project required the preparation of some new 3‐acyl‐5‐substituted benzo[b]thiophenes with a wide variety of substituents at the 5 position, ranging from nitro to hydroxyl derivatives. To obtain these derivatives we acylated the corresponding 5‐substituted benzo[b]thiophenes when it was possible.
Easy access to medium rings by entropy/strain reduction, Part 3. Competition between dihydroazepine and enamine formation in reaction of tetrahalosubstituted dibromides with primary amines
Authors: Walsh James G. , Gilheany Declan G.
Published: March 2009

The reaction of Z,Z‐2,3,4,5‐tetrahalo‐2,4‐dien‐1,6‐dibromides (3, R1 ‐ R4 = Cl, Br) with primary amines in the presence of potassium carbonate leads to both the dihydroazepines 4 and secondary enamines 5. The formation of enamine is suppressed with toluene sulfonamide as nitrogen source. (2Z,4Z)‐2,3,4,5‐Tetrabromo‐hexa‐2,4‐diene‐1,6‐diol (2, R1 ‐ R4 = Br) is atropisomeric in solution.
Synthesis of 2‐(2‐, 3‐, and 4‐pyridyl)benzoxazoles by the reaction of phenolic schiff bases with thianthrene cation radical
Authors: Park Myeong Soon , Ha Park Koon , Jun Kun , Shin Seung Rim , Oh Sea Wha
Published: March 2009

2‐(2‐, 3‐, and 4‐Pyridyl)benzoxazole derivatives were prepared in excellent yields by the oxidative cyclization of phenolic Schiff bases with thianthrene cation radical perchlorate in the presence of 2,6‐di‐tert‐butyl‐4‐methylpyridine.
Facile one‐pot syntheses of new polyfunctional pyrazolyl substituted and pyrazolofused pyridines
Authors: El Latif Fawi M. Abd , El Rady Eman A. , Döupp Dietrich
Published: March 2009

Ethyl 2‐cyano‐3‐(5‐chloro‐1,3‐diphenylpyrazol‐4‐yl)acrylate (1) undergoes both conjugate addition of a number of methylene‐active ethanenitriles and direct addition of other active methylene donors to the cyano carbon atom. These additions are the starting events of cascades of subsequent reactions eventually forming (i) novel polyfunctional pyrazolyl‐substituted monocyclic pyridines (4a,band6), (ii) 1,3‐benzothiazole and benzimidazole‐fused pyridines (11, 13) and (iii) pyrazolo[5,4‐b]pyridines (19b, 20) in one‐pot reactions in ethanolic solution containing catalytic amounts of piperidine.
Regioselective synthesis of ethyl pyrazolecarboxylates from ethyl 3‐[(dimethylamino)methylidene]pyruvate and diethyl 3‐[(dimethylamino)methylidene]‐2‐oxosuccinate. Isolation of ethyl 4,5‐dihydro‐1‐heteroaryl‐5‐hydroxy‐1H‐pyrazole‐5‐carboxylates as stable intermediates in the pyrazole ring formation
Authors: Hanzlowsky Andrej , Jelenčič Blanka , Rečnik Simon , Svete Jurij , Golobič Amalija , Stanovnik Branko
Published: March 2009

Reactions of ethyl 3‐[(E)‐(dimethylamino)methylidene]pyruvate (3) and 3‐[(dimethylamino)methyl‐idene]‐2‐oxosuccinate (4) with hydrazine monohydrochloride (5a) and (hetero)arylhydrazines (5b‐i) afforded, regioselectively, 1‐substituted ethyl 1H‐pyrazole‐5‐carboxylates 9a‐f and diethyl 1H‐pyrazole‐3,4‐dicarboxylates, 11a‐i, respectively. Upon treatment of 3 with pyridazinylhydrazines 5d‐f, the stable intermediates, 1‐substituted ethyl 4,5‐dihydro‐5‐hydroxy‐1H‐pyrazole‐5‐carboxylates 8d‐f, were isolated. Treatment of compounds 8d‐f in acetic acid under reflux furnished the pyrazoles 9d‐f. On the other hand, reaction of 3 with N,N′‐dimethylhydrazine (51) gave ethyl 1‐methyl‐1H‐pyrazole‐3‐carboxylate (14). The structures of compounds 3, 4, 14 were determined by nmr (noesy and hmbc techniques), while the structures of compounds 8f, 9f, and 11e, f were determined by X‐ray diffraction.
Cyanomethylation of anthranilic acid
Authors: Mitchell Miguel O. , Hurley Ashley R.
Published: March 2009

Anthranilic acid reacts with chloroacetonitrile and N,N‐diisopropylethylamine in DMF to yield 3‐imino‐2,3‐dihydro‐4,1‐benzoxazepin‐5(1H)‐one (1) as the only reaction product. Also known as Ashley's fluorescer, compound 1 is fluorescent and binds to calcium carbonate, including the calcium carbonate‐rich antennae of Daphnia pulex, the water flea.
2,4‐Dinitroimidazole: Microwave assisted synthesis and use in synthesis of 2,3‐dihydro‐6‐nitroimidazo[2,1‐b]oxazole analogues with antimycobacterial activity
Authors: Bhaumik Kankan , Akamanchi K. G.
Published: March 2009

2,4‐Dinitroimidazole (2,4‐DNI), an important starting material for nitroimidazooxazole and nitroimidazooxazine types of antitubercular agents was synthesized by rearrangement of 1,4‐dinitroimidazole (1,4‐DNI) under microwave irradiation. Various new nitroimidazooxazoles analogues were prepared using 2,4‐DNI and were tested preliminarily against Mycobacterium tuberculosis, H37Rv strain. Some were found to be active.
Simple, efficient, high yield syntheses of substituted and unsubstituted 5‐benzoylbarbituric acids, and their corresponding schiff base phenylhydrazones
Authors: Jursic Branko S. , Neumann Donna M. , Bowdy Katharine L. , Stevens Edwin D.
Published: March 2009

Preparation procedures for biologically important benzoylbarbiturates are presented. Several procedures are optimized to cover the preparations of a wide variety of substituted 5‐benzoylbarbiturates. To further explore the biological importance of these compounds, multi‐ gram preparation procedures for nitrophenyl‐hydrazones of benzoylbarbiturates and their corresponding salts with organic amines are discussed. It is demonstrated that these compounds can exist in several tautomeric forms and that the equilibrium in solution can be changed by temperature as well as by the pH of the solution. X‐ray structural analysis performed on one of the nitrophenylhydrazones of benzoylbarbiturates fully agrees with the presented spectroscopic studies. AMI semi‐empirical studies show that the enol form is preferred in the gas phase of benzoylbarbiturates over the keto form, which was also confirmed by NMR spectroscopic studies with chloroform as the solvent. Furthermore, AMI computed structural and electronic properties of the dinitrophenylhydrazone of 4‐hydroxybenzoylbarbiturate compared favorably with the X‐ray determined structure.
Alkylation of 2‐pyridinones: Synthesis of novel acyclonucleosides
Authors: El‐Essawy Farag A. , Khattab Ahmed F.
Published: March 2009

This paper presents the synthesis of some novel acyclonucleosides containing 2‐pyridinones and 2‐hydroxyethoxymethyl, 2,3‐dihydroxy‐propyl side chain. The tosylate of these nucleosides analogues could be modified to azido derivatives. Also, acyclonucleosides with 1‐ethoxymethyl, 1‐benzyloxymethyl, 1‐methylthiomethy 1 and 2‐hydroxyethyl side chains have been investigated. The O‐alkylated pyridine derivatives were obtained during most reactions.