bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and anticonvulsant activity of 3‐[3‐[(dimethylamino)‐methyl]‐5‐methyl‐4H‐1,2,4‐triazol‐4‐yl]‐4‐(o‐chlorobenzoyl)pyridine
Authors: Arora Vinod K. , Knaus Edward E.
Published: March 2009

Wolff‐Kishner reduction of 3‐amino‐4‐(o‐chlorobenzoyl)pyridine (3) afforded 3‐amino‐4‐(o‐chlorobenzyl)pyridine (5), which on subsequent reaction with triethyl orthoformate and then acetyl hydrazide yielded 1‐acetyl‐2‐[N‐[4‐(o‐chlorobenzyl)pyridin‐3‐yl]formimidoyl]hydrazone (7). Cyclization of hydrazone 7 gave 3‐(3‐methyl‐4H‐1,2,4‐triazol‐4‐yl)‐4‐(o‐chlorobenzyl)pyridine (8), which on Jones oxidation yielded 3‐(3‐methyl‐4H‐1,2,4‐triazol‐4‐yl)‐4‐(o‐chlorobenzyl)pyridine (9). The Mannick reaction of 3‐(3‐methyl‐4H‐l,2,4‐triazol‐4‐yl)‐4‐(o‐chlorobenzyl)pyridine (9) with aqueous formalin and dimethylamine hydrochloride afforded 3‐[3‐[(dimethylamino)methyl]‐5‐methyl‐4H‐1,2,4‐triazol‐4‐yl]‐4‐(o‐chlorobenzoyl)‐pyridine (10). 3‐[3‐[(Dimethylamino)methyl]‐5‐methyl‐4H‐1,2,4‐triazol‐4‐yl]‐4‐(o‐chlorobenzoyl)pyridine (10) exhibited good anticonvulsant activity in the subcutaneous pentylenetetrazole anticonvulsant screen indi cating that an appropriately substituted‐pyridine ring moiety can serve as a bioisostere of a chlorobenzene ring with respect to anticonvulsant activity.
Methanetricarboxylates as key reagents for the simple preparation of heteroarylcarboxamides with potential biological activity. Part 2. Reaction of methanetricarboxylates with 2‐aminopyridine, 2‐aminopyrimidine, 2‐aminothiazole and 2‐aminobenzothiazole
Authors: Kutyrev Alexander , Kappe Thomas
Published: March 2009

The reaction of methanetricarboxylates 1a,b with 2‐aminopyridine, 2‐aminopyrimidine, 2‐aminothiazole as well as 2‐aminobenzothiazole yields corresponding heteroarylcarboxylic acid esters 2a,b, 5, 8, 11a,b. These heterocyclic esters were used as a starting material by the reaction with primary amines to obtaining a number of heteroarylcarboxylic amides 4a‐j, 6, 10a,b, 13a‐g bearing various substituents on the carboxamide group.
Novel cyclization reactions of mono‐ and dichloroazodienes. A new synthesis of substituted pyridazines
Authors: South Michael S.
Published: March 2009

Cyclization of the in—situ generated chloroazodienes with a variety of enamines was found to give chloro‐substituted tetrahydropyridazines which could be aromatized to pyridazines by base treatment. This sequence appears to be a formal 4 + 2 hetero Diels‐Alder reaction with a high degree of regio and stereo control and constitutes a new synthesis of substituted pyridazines. However, cyclization of the corresponding dichloroazodienes with acyclic enamines gave not only the expected pyridazine product, but also gave an N‐aminopyrrole product. Combination of the dichloroazodiene with cyclic enamines gave bicyclic dihy‐dropyridazines, bicyclic pyridazines, and acyclic enamines which could be forced to close to the bicyclic dihydropyridazines upon further heating. These results would indicate a stepwise mechanism. The scope and mechanistic speculations on these reactions will be presented.

While exploring the novel cyclization reactions of 4‐chloroazodienes with electron rich olefins we developed a new and general synthesis of substituted 3‐phenypyridazines. A number of these analogs were found to exhibit bleaching herbicidal activity (phytoene desaturase inhibition). Further methodology development coupled with analog synthesis led to the preparation of 3‐heteroaryloxy and 3‐aryloxypyridazines with increased unit activity and selectivity as well as good environmental properties. These compounds were found to be more active than current commercial standards on a number of important weed species with selectivity in corn in the US and small grains in Europe. Greenhouse activity of the most active analogs ranged from 17–140 g/hectare on important narrow‐leaf species.
Synthesis of novel pyrano fused quinolones, coumarins, and pyridones
Authors: Toche R. B. , Jachak M. N. , Sabnis R. W. , Kappe T.
Published: March 2009

Dedicated to Professor Dr. Hans Junek, Graz, on the occasion of his 70th birthday A novel efficient synthesis of pyrano fused heterocycles namely, pyrano[3,2‐c]quinoline‐2,5(6H)‐diones 3a‐e, 7b‐d, pyrano[3,2‐c]benzopyran‐2,5(6H)‐dione (7f), and pyrano[3,2‐c]pyridine‐2,5(6H)‐diones 10, 11 was achieved by the condensation of 4‐hydroxy‐2‐(1H)‐quinolones 1a‐e, 4‐hydroxycoumarin (1f), or 4‐hydroxy‐2(1H)‐pyridone (9) with α‐acetyl‐γ‐butyrolactone (2) or the sodium salt of α‐formyl‐γ‐butyrol‐actone (6), respectively, in the presence of ammonium acetate.
A new domino reaction based on [4+2]‐cycloadditions of pyrido[1,2‐a]pyrazines with azadienophiles
Authors: Billert Thomas , Beckert Rainer , Brandenburg Jörg , Fehling Peer , Döring Manfred , Görls Helmar , Langer Peter
Published: March 2009

The reaction of pyrido[1,2‐a]pyrazines 1 with nitroso compounds 2 provides pyridyl substituted 1,2,4‐triazinones 4 via a domino reaction which involves a cycloaddition and a ring transformation reaction. The intermediate and regioselective formed oxadiazines 4′ were trapped by complexation yielding the (CO)4Mo‐complex 5. Derivatives of diazene such as N‐phenyltriazolindione 6a, phthalazinedione 6b or esters of azodicarboxylic acid 6c‐6f reacted with 1 to give different derivatives of 1,2,4‐triazine 7a‐f. The use of oxygen gave oxadiazinones 8.
Reaction of 4,5‐diamino‐3‐methyl‐1‐phenylpyrazole with 3‐dimethylaminopropiophenones. Synthesis of new 4‐aryl‐6‐methyl‐8‐phenyl‐2,3‐dihydropyrazolo[3,4‐b]diazepines and 4‐aryl‐8‐methyl‐6‐phenyl‐2,3‐dihydropyrazolo[4,3‐b]diazepines
Authors: Insuasty O Braulio , Insuasty I Henry , Quiroga P Jairo , Saitz Claudio , Jullian Carolina
Published: March 2009

New 4‐Aryl‐6‐methyl‐8‐phenyl‐2,3‐dihydropyrazolo[3,4‐b]diazepines and 4‐aryl‐8‐methyl‐6‐phenyl‐2,3‐dihydropyrazolo[4,3‐b]diazepines were obtained from the reaction of 4,5‐diamino‐3‐methyl‐1‐phenylpyrazole 1 with one equivalent of the 3‐dimethylaminopropiophenones 2 in absolute ethanol. The structures of 4‐aryl‐6‐methyl‐8‐phenyl‐2,3‐dihydropyrazolo[3,4‐b]diazepines 3 and 4‐aryl‐8‐methyl‐6‐phenyl‐2,3‐dihydropyrazolo[4,3‐b]diazepines 4 were determined by detailed nmr measurements.
Catalytic hydrogenation of 3‐benzyloxycarbonylaminoazino[1,2‐x]‐azin‐4‐ones. A facile access to 3‐amino‐6,7,8,9‐tetrahydro‐4H‐pyrido[1,2‐a]pyridin‐4‐ones and 3‐Amino‐6,7,8,9‐tetrahydro‐4H‐azino[1,2‐x]pyrimidin‐4‐ones
Authors: Rečnik Simon , Toplak Renata , Svete Jurij , Pizzioli Lucija , Stanovnik Branko
Published: March 2009

By catalytic hydrogenation of 3‐(benzyloxycarbonyl)amino‐4H‐pyrido[1,2‐a]pyridin‐4‐ones 28 and 29, and azino[1,2‐x]pyrimidin‐4‐ones 32–35, 41, and 42, partial saturation of the heterocyclic systems and removal of the benzyloxycarbonyl moiety was observed to give 3‐amino‐6,7,8,9‐tetrahydro‐4H‐pyrido[1,2 a]pyridin‐4‐ones 30 and 31, and 3‐amino‐6,7,8,9‐tetrahydro‐4H‐azino[1,2‐x]pyrimidin‐4‐ones 36–39, 43, and 44 in high yields. The methods represent a simple two step synthesis, starting from heterocyclic α‐amino compounds and methyl (Z)‐2‐(benzyloxycarbonyl)amino‐3‐dimethylaminopropenoate followed by catalytic hydrogenation.
Ring transformations of heterocyclic compounds. XX Benzo‐fused spiro[cyclohexadiene‐dihydroindoles] by ring transformation of pyrylium salts with anhydrobases of benzo[e]‐ and benzo[g]indolium salts
Authors: Zimmermann Thomas
Published: March 2009

The diastereoselective synthesis of 6‐aroyl‐3,5‐diarylspiro[cyclohexa‐2,4‐diene‐1,2′2′,3′‐dihydro‐1′H‐benzo[e]indoles] 6 and ‐benzo[g]indoles] 7 from 2,4,6‐triarylpyrylium perchlorates 1 and in situ generated 2‐methylene‐2,3‐dihydro‐1H‐benzo[e]indoles 3 or ‐benzo[g]indoles 5 (anhydrobases of the corresponding 2‐methyl‐1H‐benzo[e]indolium perchlorates 2 and 2‐methyl‐3H‐benzo[g]indolium perchlorates 4, respectively) in the presence of triethylamine/acetic acid in ethanol by a 2,5‐[C4+C2] pyrylium ring transformation is reported. Spectroscopic data of the transformation products and their mode of formation are discussed.
Inverse electron demand diels‐alder reactions of psoralens. Synthesis and mass spectra of novel pyridazinocoumarins
Authors: González José Carlos , Dedola Teresa , Santana Lourdes , Uriarte Eugenio , Begala Michela , Copez Debora , Podda G.
Published: March 2009

Diels‐Alder reactions between the furan double bond of 8‐methoxypsoralen and 1,2,4,5‐tetrazine or 3,6‐bistrifluoromethyl‐1,2,4,5‐tetrazine were accompanied by the release of diatomic nitrogen and the opening of the furan ring to leave a 6‐pyridazinocoumarin. When 3,6‐bis(methoxycarbonyl)‐1,2,4,5‐tetrazine was used as diene with 8‐methoxy‐, 5‐methoxy‐ or 8‐hydroxypsoralen as substrate a previously unknown heterocyclic framework was created. Formation of the fourth ring was accompanied by conversion of the furan ring to a pyrone, presumably by intramolecular transestenfication with release of methanol. The characterization of the products of these reactions by exhaustive mass spectrometric analysis is discussed.
An efficient route for synthesis of 5,6‐diphenylimidazo‐[2,1‐b]thiazoles as antibacterial agents
Authors: Hozien Zeinab A. , Abd El‐Wareth A. O. Sarhan , El‐Sherief Hassan A. H. , Mahmoud Abdalla M.
Published: March 2009

The reaction of 4,5‐diphenylimidazol‐2‐thione (1) with aromatic ketones 2a‐i using the acidified acetic acid method afforded the 4,5‐diphenyl(2‐imidazolylthio)acetophenones 3a‐h in good yields. While, the cyclized product 4i was obtained directly upon reaction of 1 with α‐acetyl naphthalene. Compounds 3a‐h were cyclized directly to the corresponding 3‐aryl‐5,6‐diphenylimidazo[2,1‐b]thiazoles (4a‐c) and (4e‐h). In the same manner the reaction of 1 with aliphatic and/or alicyclic ketones gave the 3‐(4,5‐diphenyl‐2‐imidazolylthio)acetone derivatives 5a‐d, 2‐(4,5‐diphenylimidazolylthio)cycloalkanones 8a,d and the tricyclic compounds 9b‐c respectively. The cyclized compounds 6a‐d and 9a,d were obtained by cyclization of 5a‐d and 8a,b respectively. Oxidation of 1 gives the corresponding bis(4,5‐diphenyl‐2‐imidazolyl)‐disulfide (10) in 90% yield. Some of the synthesized compounds were tested for antifungal and antibacterial activity.
Convenient synthesis of 1,2,3,4‐tetrahydro‐pyrimidin‐5‐ylbenzoxazoles
Authors: Jung Myung Hee , Choi Sung‐Won , Cho Kui‐Woong
Published: March 2009

2‐Pyrimidin‐5‐ylbenzoxazoles 7 have been synthesized by condensation of 5‐pyrimidinecarboxaldehyde 4 with substituted aminophenols 5 followed by oxidative cyclization of the resulting Schiff's bases 6 with iodobenzene diacetate. Subsequent formation of methylpyrimidinium salts 8 and reduction thereafter afforded tetrahydropyrimidinylbenzoxazoles 10. This method has been utilized in the synthesis of M1 muscarinic agonist candidates.
Reactions of 6‐aminopyrimidines with 2‐dimethylaminomethylenetetralone. Regiospecific Synthesis Of 5,6‐Dihydrobenzo [h]pyrimido [4,5‐b] quinolines
Authors: Quiroga Jairo , Insuasty Braulio , Insuasty Henry , Abonia Rodrigo , Ortíz Antonio , Sánchez Adolfo , Nogueras Manuel
Published: March 2009

Benzo[h]pyrimido[4,5‐b]quinolines (3) have been synthesized via a regiospecific cyclocondensation reaction between 6‐aminopyrimidines (1) and 2‐dimethylaminomethylentetralone hydrochloride (2). The linear structure of the final compounds were determined by nmr measurements, especially by 1H,1H, 1H,13C COSY and DEPT experiments.
Synthesis of chiral fused heterocyclic compounds containing 1,2,4‐triazole ring
Authors: Shi Haoxin , Wang Zhongyi , Shi Haijian
Published: March 2009

A series of new chiral (S)‐3‐ary1‐6‐pyrrolidin‐2‐yl‐[1,2,4]triazolo[3,4‐b]thiadiazole (II1‐5), (S)‐1‐(3‐aryl‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazol‐6‐yl)‐ethylamine (II6‐8) and (S)‐1,2‐bis(3‐aryl‐[1,2,4]triazolo‐[3,4‐b][1,3,4]thiadiazol‐6‐yl)‐ethylamine (II9‐11) were prepared by the condensation of 3‐aryl‐4‐amino‐5‐mercapto‐1,2,4‐triazoles with different L‐amino acids in the presence of phosphorus oxychloride and evaluated for their antibacterial activity.
Synthesis and potential central nervous system stimulant activity of 5,8‐methanoquinazolines and bornano‐triazines fused with imidazole and pyrimidine
Authors: Nagai Shinichi , Miyachi Takamasa , Nakane Tetsu , Ueda Taisei , Uozumi Yasuhiro
Published: March 2009

Starting from 3‐chloro‐5,8‐methanoquinazoline 1 and 3‐chloro‐bornano[1,2,4]triazine 7, the novel 5,8‐methanoquinazolines 5a‐b and bornano[1,2,4]triazines 10a‐b fused with imidazole and pyrimidine were prepared. None of these compounds showed any satisfactory central nervous system stimulant activities.
New synthesis of oxindole‐1‐carboxamides
Authors: Porcs‐Makkay Marta , Simig Gyula
Published: March 2009

A new synthesis of oxindole‐1‐carboxamides was elaborated by the reaction of oxindole‐1‐phenyl‐carboxylate with various amines. This method also permitted the preparation of N,N‐disubstituted oxindole‐1‐carboxamides.
Intramolecular catalysis of aminolysis of phosphorus heterocycles incorporating an α‐aminoamide moiety. III. Synthesis of 2‐oxo or 2‐thioxo 1,3‐disulfonyl‐1,3,2‐diazaphospholidines and reactions with amines and alcohols
Authors: Dujols Frédéric J. M. , Mulliez Michel E.
Published: March 2009

A series of 2‐oxo or 2‐thioxo 1,3‐disulfonyl‐1,3,2‐diazaphospholidines 4was prepared by condensation of phosphonyl dichlorides 2 with bis‐N,N'‐sulfonylethylenediamines 1 in pyridine. Complete aminolysis or alcoholysis of heterocycles 4 took place with regeneration of sulfonyldiamines 1. These reactions are very sensitive to steric hindrance, and hydrolysis is generally favoured over aminolysis. The results are discussed in terms of mechanisms of phosphorylation.
Preparation and reactions of pyridinyl tellurides
Authors: Shilai Manabu , Uchiyama Masanobu , Kondo Yoshinori , Sakamoto Takao
Published: March 2009

Tellurium‐metal exchange reaction of n‐butyl 2‐pyridinyl telluride derivatives with n‐butyllithium or dilithium dimethylcyanocuprate proceeded smoothly to give the corresponding 2‐pyridinylmetal derivatives, which are important intermediates for functionalization of pyridines.
Studies on uracils: A facile one‐pot synthesis of pyrazolo[3,4‐d]pyrimidines
Authors: Bhuyan P. J. , Borah H. N. , Lekhok K. C. , Sandhu J. S.
Published: March 2009

The reaction of 6‐hydrazino uracils 1 and nitrones 2 result in an efficient one‐pot synthesis of pyrazolo[3,4‐d]pyrimidines 3 in excellent yields. The isolation of the by‐product aniline from the reaction mixture supported the plausible mechanism for the formation of pyrazolo[3,4‐d]pyrimidines.
An improved synthesis of 5,6,7,8‐tetrahydro‐1,7‐naphthyridine ‐ a conformationally‐restricted analog of 2‐(3‐pyridyl)ethylamine
Authors: Dow Robert L. , Schneider Steven R.
Published: March 2009

The 5,6,7,8‐tetrahydro‐1,7‐naphthyridine (7) pharmacophore has the potential to serve as a confor‐mationally‐locked analog of the pharmacologically active 2‐(3‐pyridyl)ethylamine (1) core structure. This paper describes the synthesis of 5,6,7,8‐tetrahydro‐1,7‐naphthyridine (7) via a five‐step sequence, which affords a significant improvement over previously reported syntheses.
Reaction of 3‐substituted and 4‐bromo‐3‐substituted isoquinolin‐1‐(2h)‐ones with propargyl bromide
Authors: Usifoh Cyril Odianose
Published: March 2009

Isoquinolinones were brominated using N‐bromosuccinimide in dimethylformamide at room temperature to give 4‐bromo‐3‐substituted isoquinolin‐1‐(2H)‐ones. The reaction of these isoquinolinones with propargyl bromide in the presence of anhydrous potassium carbonate yielded N and O‐alkylated products.
A convenient synthesis of pyrazolidine and 3‐amino‐6,7‐dihydro‐1H,5H‐pyrazolo[1,2‐a] pyrazol‐1‐one
Authors: Boros Eric E. , Bouvier Frédéric , Randhawa Sab , Rabinowitz Michael H.
Published: March 2009

A convenient four‐step synthesis of the aminobicyclopyrazolone hydrochloride 1·HC1 was achieved starting from di‐tert‐butyl hydrazodiformate (8). The route entails cyclization of 8 with 1,3‐dibromopropane under phase transfer conditions followed by deprotection of 1,2‐di‐tert‐butoxycarbonylpyrazolidine (9) to give pyrazolidine hydrochloride (2·HC1). Cyanoacetylation of the latter and ring closure of the resulting cyanoacetyl pyrazolidine (7) gave 1·HC1. This novel synthesis circumvents distillation of pyrazolidine (2) and flash chromatography to provide the hydrochloride of 1 in 35–46% overall yields compared to 6% yield for the patent procedure.
Preparation of 1H‐pyrazole‐5‐carboxamides from dilithiated C(α), N‐phenylhydrazones and lithiated ethyl oxanilates or lithiated ethyl oxamate
Authors: Downs Jennifer R. , Pastine Stefan J. , Schady Deborah A. , Greer Heather A. , Kelley Wayne , Embree Mildred C. , Townsend Jessica D. , Beam Charles F.
Published: March 2009

Dilithiated C(α), N‐phenylhydrazones were prepared in excess lithium diisopropylamide and condensed with either ethyl oxanilate, ethyl 4′‐chlorooxanilate, or ethyl oxamate to give intermediates that were quenched and acid cyclized to substituted lH‐pyrazole‐5‐carboxamides.
The syntheses of nitrogen‐oxygen donor macrocycles containing pyridine ring
Authors: Zhao Bin , Wang Feng Qin , Tian Lai Jin
Published: March 2009

Five new nitrogen‐oxygen mixed donor macrocycles have been prepared by condensation of 2,6‐bis [(2‐formylphenyl)oxymethyl]pyridine with different diamino compounds in hot methanol, followed by a one‐pot reduction of the intermediate bis‐Schiff base. All the macrocycles were identified by elemental analysis, and ir, uv, and nmr spectroscopy.
Random optimizations for direct heteronuclear correlations
Authors: Hadden Chad E. , Moon Joe B. , Hadden Daneen T. A.
Published: March 2009

A novel optimization method is described for the acquisition of direct one‐bond heteronuclear correlations. The RDSQC (Randomly optimized Direct correlation Single Quantum Coherence) experiment utilizes an optimization based on the randomly ordered sampling of a range of couplings. The random order of the l/(2*(1JCHmin)) delays removes the signal dependency on a single type of apodization, thus eliminating a significant portion of the F1 artifacts induced in the accordion‐optimized ADSQC experiment. Compared to the statically optimized GHSQC, the randomly optimized data maintains the desired signal intensity in most cases, with a small loss for the weakly coupled proton‐carbon pairs and significant gains for the more strongly coupled pairs. Compared to the accordion‐optimized ADSQC data, the randomly optimized data afforded similar signal‐to‐noise without the F1 modulated artifacts simplifying spectral interpretation.
A simple one pot synthesis of condensed 1,2,4‐triazines by using the tandem aN‐SNipso and SNH‐SNipsa reactions
Authors: Chupakhin Oleg N. , Rusinov Gennady L. , Beresnev Dmitry G. , Charushin Valery N. , Neunhoeffer Hans
Published: March 2009

A new synthetic approach to condensed 1,2,4‐triazines based on using the tandem AN‐SNipso and SNH‐SNipso reactions has been developed. 5‐Methoxy‐3‐penyl‐1,2,4‐triazine and its N1‐methyl quaternary salt were found to react with C,N‐, C,O‐ and N,N'‐bifunctional nucleophiles (m‐phenylenediamine, resor‐cinol, semicarbazide and ureas) into triazacarbazoles, benzofuro[2,3‐e][1,2,4]‐triazines, and 6‐azapurine derivatives. In all cases nucleophiles attack first the unsubstituted C‐6 carbon of the triazine ring, while the final stage is replacement of the methoxy group affording cyclization products.
Pyridazines 93. an unexpected reaction behaviour of 3‐aminopyridazine towards 2‐methylphenylisocyanate
Authors: Heinisch Gottfried , Hetzenauer Alfred , Matuszczak Barbara , Rakowitz Dietmar , Mereiter Kurt
Published: March 2009

Reaction of 3‐aminopyridazine (1) with 2‐mefhylphenylisocyante (4) affords not only the desired urea derivative (5) but also an unexpected side‐product (6), which could be identified as the corresponding biuret derivative by means of elemental and spectroscopic data as well as crystal structure determination.
Studies with enaminones: reactivity of 1,5‐disubstituted‐1,4‐pentadien‐3‐ones toward electrophilic reagents. a novel route to azolylazines, benzofuranals, pyranones
Authors: Al‐Mousawi Saleh , El‐Sherbiny Seham , John Elizabeth , Abdel‐Khalik Mervat Mohammed , Elnagdi Mohammed Hilmy
Published: March 2009

Several new enaminodienones prepared from substituted acetone and dimethylformamide dimethylacetal were used as precursors for synthesis of pyridines, pyranones and benzofurans.
About 1‐triphenylmethyl‐3‐tert‐butylaziridinone and some of its reactions
Authors: Lengyel István , Cesare Victor , Karram Halina , Taldone Tony
Published: March 2009

A high‐yield synthesis of 1‐triphenylmethyl‐3‐tert‐butylaziridinone (4), its physical and spectral properties, the limits of its thermal stability, and reactions with methanol, benzylamine and sodium methoxide in methanol are described.
Synthesis and isolation of nitro‐bT‐carbolines obtained by nitration of commercial β‐carboline alkaloids
Authors: Ponce María A. , Erra‐Balsells Rosa
Published: March 2009

Nitration of commercial full aromatic β‐carboline alkaloids nor‐harmane (1), harmane (2), harmine (3), harmol (4), and the 7‐acetylated derivative of harmol (5) is described. Advantages and disadvantages of different nitration reagents which involve acidic conditions (HNO3/H+) and neutral conditions (Cu(NO3)2; ceric ammonium nitrate) are discussed. A complete 1H and 13C‐nmr characterization including ms and also uv absorption spectra in neutral and acid media is presented. A detailed ei‐ms and ld‐tof‐ms study is enclosed because the nitro‐β‐carbolines constitute a new family of β‐carboline‐like chromophores with potential use as matrix in uv‐maldi‐tof‐ms.
Synthesis and isolation of bromo‐β‐carbolines obtained by bromination of β‐carboline alkaloids
Authors: Ponce María A. , Erra‐Balsells Rosa
Published: March 2009

β‐Carbolines (1–5) undergo electrophilic aromatic substitution with N‐bromosuccinimide under different experimental conditions. Although 6‐bromo‐nor‐harmane (la) obtained by bromination of nor‐harmane (1) was isolated and fully characterized sometime ago, the other bromoderivatives of nor‐harmane (1b‐1e) and harmane (2a‐2e) were partially described as part of the reaction mixtures. The preparation and subsequent isolation, purification and full characterization of 1b, 1c, 1d, 1e, 2a, 2b, 2c, 2d, 2e are reported (mp, Rf, 1H‐nmr, 13C‐nmr and ms) together with the preparation, isolation and charaterization, for the first time, of the bromoderivatives obtained from harmine (3a‐3e), harmol (4a, 4b) and 7‐acetylharmol (5a‐5c). As brominating reagent N‐bromosuccinimide and N‐bromosuccinimide‐silica gel in dichloromethane and in chloroform as well as the β‐carboline ‐ N‐bomosuccinimide solid mixture have been used and their uses have been compared. Semiempirical AMI and PM3 calculations have been performed in order to predict reactivity in terms of the energies of HOMO, HOMO‐LUMO difference and in terms of the charge density of β‐carbolines (1–5) and bromo‐β‐carbolines (1a‐1e, 2a‐2e, 3a‐3e, 4a, 4b, 5a, 5b and 5c) (Scheme 1). Theoretical and experimental results are discussed briefly.
Studies on the chemical transformations of rotenoids. 6 Synthesis and antitumor‐promoting activity of benzofuro[2,3‐d]pyridazines fused with 1,2,4‐triazole, 1,2,4‐triazine and 1,2,4‐triazepine
Authors: Nagai Shin‐Ichi , Takemoto Satoshi , Ueda Taisei , Mizutani Kanako , Uozumi Yasuhiro , Tokuda Harukuni
Published: March 2009

[1]Benzofuro[2,3‐d]pyridazines fused with 1,2,4‐triazole (6 and 7), 1,2,4‐triazine (8–10) and 1,2,4‐tri‐azepine (12) were prepared by the ring closure of 4‐hydrazino‐[1]benzofuro[2,3‐d]pyridazine (5), derived from naturally occurring rotenone. Compounds (la and lb) exhibited significant inhibitory activity against 12‐O‐tetradecanoylphorbol 13‐acetate (TPA)‐induced Epstein‐Barr virus early antigen (EBA‐EA) activation in Raji cells. In contrast, the fused [1]benzofuro[2,3‐d]pyridazines except 6c and 8 were quite inactive.
1,6‐ and 1,7‐naphthyridines III. 13C‐NMR analysis of some hydroxy derivatives
Authors: Blanco M. Mercedes , Buldain Graciela , Schapira Celia B. , Perillo Isabel
Published: March 2009

The 13C‐NMR spectra of some 1,6‐naphthyridines 2 and 1,7‐naphthyridines 3, as well as those of N‐methyl derivatives 4 and 5, were recorded and analyzed. Results in dimethyl‐d6 sulfoxide and deuteriochlo‐roform provide useful data on intra and intermolecular hydrogen bonds.
Syntheses of substituted pyrrolo[2,3‐d]imidazole‐5‐carboxylates and substitued pyrrolo[3,2‐d]imidazole‐5‐carboxylates
Authors: Shafiee A. , Mojarrad J. Shahbazi , Jalili M. A. , Adhami H. R. , Hadizadeh F.
Published: March 2009

Starting from readily available p‐substituted‐benzylamines a series of ethyl 2‐alkylthio‐1‐substituted‐ben‐zylpyrrolo[2,3‐d]imidazole‐5‐carboxylates was prepared. In addition, starting from 2‐alkyl‐4(or 5)‐formylimidazoles and methyl 4′‐bromomethylbiphenyl‐2‐carboxylate a series of methyl substituted‐pyrrolo[2,3‐d]imidazole‐5‐carboxylates and methyl substituted‐pyrrolo[3,2‐d]imidazole‐5‐carboxylates was prepared.
Identification of degradants of a complex alkaloid using NMR cryoprobe technology and ACD/structure elucidator
Authors: Martin Gary E. , Hadden Chad E. , Russell David J. , Kaluzny Brian D. , Guido Jane E. , Duholke Wayne K. , Stiemsma Bruce A. , Thamann Thomas J. , Crouch Ronald C. , Blinov Kirill , Elyashberg Mikhail , Martirosian Eduard R. , Molodtsov Sergey G. , Williams Antony J. , Schiff Paul L.
Published: March 2009

Identification of degradants of pharmaceuticals is a necessary challenge of the drug development process following the subjection of candidate molecules to a variety of physico‐chemical stresses. It would be desirable to be able to conduct such studies on a minimal amount of material. As a prototypical study, the isolation and identification of degradants of a sample of the complex indoloquinoline alkaloid, cryptospirolepine, was undertaken after prolonged storage in DMSO solution using a combination of cryogenic NMR probe technology and CASE (Computer‐Assisted Structure Elucidation) programs. None of the starting alkaloid remained after storage; a chromatogram of the DMSO solution demonstrated the presence of >25 components in the mixture. The two most abundant degradation products were identified as the known alkaloid cryptolepinone (∼35%) and an unprecedented rearrangement product, DP‐2, (∼16%).
Seco‐isopowellaminone: A new heterocycle from nornarwedine
Authors: Hirnschall Manfred , Froehlich Johannes , Jordis Ulrich , Mereiter Kurt
Published: March 2009

It is known that Nornarwedine‐type molecules can be converted into crinine‐type compounds by a reverse Michael‐ / Michael addition. Narwedine and bromonarwedine yield, as confirmed by X‐ray structure determination, the known seco‐powellaminone as well as the novel seco‐isopowellaminone.
Novel fluorescent 2‐(2‐aminofluorophenyl)benzoxazoles: Syntheses and photophysical properties
Authors: Tanaka Kiyoshi , Komiya Tomohiro
Published: March 2009

2‐(2‐Amino‐3,4,5,6‐tetrafluorophenyl)benzoxazole (2) absorbs in long wavelength band (λabsmax = 346 nm in methanol) and in the normal wavelength band (λabsmax = 285.5 nm), and emits blue fluorescence. The emission intensity is highly affected by the solvent polarity and is large in a polar solvent such as methanol. 2‐(2‐Pentafluorobenzamido‐3,4,5,6‐ tetrafluorophenyl)benzoxazole (5) emits green fluorescence along with the short wavelength emission around 380 nm and their relative intensity depends on the solvent polarity. Green fluorescence is enhanced in nonpolar solvents such as chloroform and toluene, resulting in the considerably large Stokes shift.
Synthesis of 4‐alkyl‐1,2‐diphenyl‐3,5‐dioxopyrazolidines possessing aryl methylsulfonyl and sulfonamide pharmacophores for evaluation as selective cyclooxygenase‐2 (COX‐2) inhibitors
Authors: Rahim M. Abdur , Rao P. N. Praveen , Knaus Edward E.
Published: March 2009

A group of 1,2‐diphenyl‐3,5‐dioxopyrazolidines possessing a methylsulfonyl (11) or sulfonamide (15) substituent at the para position of the N1‐phenyl ring, in conjunction with a hydrogen, methyl or fluoro sub‐stituent at the para position of the N2‐phenyl ring, and a C‐4 n‐butyl, methyl or spiro‐cyclopropyl substituent were synthesized for evaluation as potential cyclooxygenase‐2 (COX‐2) selective inhibitor antiinflammatory agents. The title compounds 11 and 15 were synthesized using a four‐step and a three‐step reaction sequence, respectively. Thus, the acetic acid promoted condensation of a nitrosobenzene 5 with an aniline derivative (6, 12) gave the corresponding azobenzene product (8, 13) which was reduced with zinc dust in the presence of ammonium chloride to yield the corresponding hydrazobenzene (9, 14). Base‐catalyzed condensation of 9 and 14 with a malonyl dichloride (10) afforded the target 3,5‐dioxopyrazolidine product (11,15). 4‐n‐Butyl‐1‐(4‐methylsulfonylphenyl)‐2‐phenyl‐3,5‐dioxopyrazolidine (11a) was a selective COX‐1 inhibitor (COX‐1 IC50 = 8.48 μM). In contrast, 4‐n‐butyl‐1‐(4‐methylsulfonylphenyl)‐2‐(4‐tolyl)‐3,5‐dioxopyrazolidine (11b, COX‐2 IC50 = 11.45 μM) and 4‐n‐butyl‐1‐(4‐methylsulfonylphenyl)‐2‐(4‐fluorophenyl)‐3,5‐dioxopyrazoli‐dine (11c, COX‐2 IC50 = 9.86 μM) were about 46‐fold and 20‐fold less selective COX‐2 inhibitors respectively, relative to the reference drug celecoxib.
Synthesis of indeno[2,1‐a]pyrrolo[3,4‐c]carbazole lactam regioisomers using ethyl cis‐β‐cyanoacrylate as a dienophile and lactam precursor
Authors: Hudkins Robert L. , Ho Park Chung
Published: March 2009

Reported here is the synthesis and characterization of the indenopyrrolocarbazole ring system utilizing a Diels‐Alder reaction with 2‐indenylindole and maleimide. Clemmensen reduction of imide 10 furnished the 5‐oxo (16) and 7‐oxo (17) lactam regioisomers. A new regiospecific route to 5‐oxo 16 was developed using ethyl cis‐β‐cyanoacrylate as the dienophile. The regio and stereochemical characterization of the cycloadducts was confirmed by X‐ray crystallography.
Syntheses and properties of benzodipyrrinones
Authors: Boiadjiev Stefan E. , Lightner David A.
Published: March 2009

2,3‐Benzannelated dipyrrinone analogs (1 and 2) of xanthobilirubic acid (3) are prepared by base‐catalyzed condensation of isoindolinone (5) and indolin‐2‐one (6) respectively, with methyl 3‐(2‐formyl‐3,5‐dimethyl‐1H‐pyrrol‐4‐yl)propanoate (4). Nuclear Overhauser effect H‐nmr studies indicate that both 1 and 2 adopt preferentially a syn‐Z configuration. The former forms a hydrogen‐bonded homodimer in nonpolar solvents; the latter is intramolecularly hydrogen bonded.
New reactions of N‐T‐butyl‐N‐benzoylhydrazine with triphosgene
Authors: Qing‐Min Wang , Jun‐Ran Cheng , Run‐Qiu Huang
Published: March 2009

N‐tert‐Butyl‐N‐benzoylhydrazine was prepared in a new and convenient procedure with good yield. Triphosgene underwent reaction with three equivalents of N‐t‐butyl‐N‐benzoylhydrazine using six equivalents of triethylamine as a base to yield the cyclic tetramer of N‐t‐butyl‐N‐isocyanatobenzoylamide. Treatment of triphosgene with three equivalents of N‐t‐butyl‐N‐benzoylhydrazine either in the presence of three equivalents of triethylamine or in the absence of triethylamine afforded the cyclic pentamer of iso‐cyanate, from which tert‐butyl is eliminated.
Oxidative cyclization of n‐methyl‐ and n‐benzoylpyridylthioureas. Preparation of new thiazolo[4,5‐b] and [5,4‐b] pyridine derivatives
Authors: Jouve Karine , Bergman Jan
Published: March 2009

Cyclization of N‐methyl‐ and N‐benzoylpyridylthioureas, prepared from the corresponding aminopy‐ridines, has been realized using various conditions. With bromine in acetic acid or potassium ferricyanide, the cyclization occurred on the nitrogen of the pyridine ring and pyridinium salts or 1,2,4‐fhiadiazolo[2,3‐a]pyridylidene systems were obtained. On the other hand, treatment of the thioureas with sodium methoxide in N‐methylpyrrolidinone (NMP) led to formation of fhiazolo[4,5‐b] and [5,4‐b]pyridines, which are interesting targets for biological evaluation.
Synthesis and unusual stability of pyridine and n‐methyl pyridinium 1,3‐dioxolanes
Authors: Hobson Stephen T. , Boecker Joseph D. , Gifford James H. , Nohe Tara L. , Wierks Carl H.
Published: March 2009

Differentially substituted bridged pyridinium oximes are necessary in research on antidotes for organophosphate poisoning. A solid‐phase synthesis would improve the yield and ease of purification of these compounds. To predict the lability of the linker in the final step of our proposed synthesis, we synthesized a series of pyridine and N‐methyl pyridinium acetals. These compounds proved to be resistant to acid catalyzed hydrolysis. This stability may be useful for synthetic manipulation of pyridine aldehydes.
Synthesis of homochiral 2‐C‐trifluoromethyl D‐and L‐ribose via trifluoromethylation of pentopyranosid‐2‐uloses
Authors: Eilitz Uwe , Böttcher Christoph , Hennig Lothar , Burger Klaus , Haas Alois , Gockel Simone , Sieler Joachim
Published: March 2009

Efficient syntheses of 2‐C‐trifluoromethyl D‐ and L‐ribose and some O‐glycosides via trifluoromethylation of D‐ and L‐3,4‐O‐isopropylidene‐β‐erythro‐pentopyranosid‐2‐ulose with Ruppert's reagent are described.
Synthesis of novel 2‐amino‐1,3‐thiazole‐5‐carboxylates utilising ultrasonic and thermally mediated aminolysis
Authors: Baker Luke A. , Williams Craig M.
Published: March 2009

Novel 2‐amino‐1,3‐thiazole‐5‐carboxylates have been synthesised in high yield by unprecedented ultrasonic and thermally mediated nucleophilic displacement of bromide from ethyl 2‐bromo‐1,3‐thiazole‐5‐car‐boxylate by primary, secondary and aryl amines.
An anomalous course of the reduction of 2‐(3‐oxo‐3,4‐dihydro‐quinoxalin‐2‐yl)benzene diazonium salt. Synthesis of a new quinoxalino[1,2‐c][1,2,3]benzotriazine system
Authors: Wiedermannová Iveta , Slouka Jan , Humpa Otakar , Lemr Karel
Published: March 2009

By diazotization of 3‐(2‐aminophenyl)quinoxaline‐2(lH)‐one la and 3‐(2‐aminophenyl)‐6,7‐dimethylquinoxaline‐2(lH)‐one 1b followed by the reaction with sodium sulphite new quinoxalino[1,2‐c]‐[1,2,3]benzotriazins 4a and 4b were prepared, respectively.
Structural characterization of a degradation product of tin ethyl etiopurpurin (SnET2): Comparison of the long‐range heteronuclear correlations detected using conventional GHMBC and IMPEACH‐MBC in conjunction with submicro NMR probe technology
Authors: Hadden Chad E. , Duholke Wayne K. , Kaluzny Brian D. , Sanders Phillip E. , Thamann Thomas J. , Martin Gary E. , Rosenqvist Kenneth , Robinson Byron C. , Masuno Mako N.
Published: March 2009

During the terminal heat sterilization of the lipid emulsion final dose formulation of the photodynamic therapeutic (PDT) agent tin ethyl etiopurpurin (SnET2), a new degradant was observed at very low levels. The degradant, which was prone to photo‐instability, was isolated by preparative chromatography and subsequently characterized by mass spectrometry and NMR methods. Reproducible parent ion clusters were only observable via negative ion APCI methods. Because of the limited isolate sample, NMR characterization was done using 1.7 mm SMIDG (SubMicro Inverse‐Detection Gradient) NMR probe technology in conjunction with the accordion‐optimized IMPEACH‐MBC long‐range heteronuclear shift correlation experiment. The “static” 8 Hz optimization of the GHMBC experiment failed to allow the observation of a number of long‐range correlations that were of critical importance to the determination of the structure of the impurity. In contrast, all of the correlations required to assemble the structure were obtained from an IMPEACH‐MBC experiment optimized for long‐range heteronuclear couplings in the range from 2–10 Hz.
Syntheses of [1,2,3]selenadiazolo[4,5‐e]benzofuran or benzothiophene, [1,2,3]thiadiazolo[4,5‐e]benzofuran or benzothiophene, and 2‐benzofuranyl‐1,3,4‐oxodiazole derivatives
Authors: Shekarchi M. , Ellahiyan F. , Akbarzadeh T. , Shafiee A.
Published: March 2009

Dehydrogenation of ethyl 3‐methyl‐4‐oxo‐4,5,6,7‐tetrahydrobenzofuran‐2‐carboxylate 1 with 2,2′‐azobi‐sisobutyronitrile and N‐bromosuccinimide gave ethyl 4‐hydroxy‐3‐methylbenzofuran‐2‐carboxylate 3. Reaction of compounds 3–4 with hydrazine hydrate afforded the corresponding hydrazides 5a‐b. The reaction of 5a‐b with aldehydes yielded substituted hydrazones 6a‐l. Compounds 7a‐d were prepared from compounds 6a‐d and bromine in acetic acid. Lead tetraacetate oxidation of compounds 6e‐l afforded substituted oxadiazoles 8e‐l. Selenium dioxide oxidation of 4‐oxo‐4,5,6,7‐tetrahydrobenzofuran semicarbazones 9, 14a and 4‐oxo‐4,5,6,7‐tetrahydrobenzothiophene 14b gave the tricyclic 1,2,3‐selenadiazoles 10, 15a and 15b respectively. Reaction of semicarbazones 9, 14a and 14b with thionyl chloride afforded the corresponding 1,2,3‐thiadiazoles 12, 16a and 16b respectively.
3‐(phenylhydrazono)‐indan‐1‐one and 2‐dimethylaminomethylene‐3‐(phenylhydrazono)‐indan‐1‐one as useful synthons for the construction of new heterocyclic systems
Authors: Abu Elmaati Tarek M. , Said Samy B. , Abu Elenein Nahla S. , Khodeir Nabiel M. , Sofan Mamdouh M.
Published: March 2009

The hydrazone 1 reacts with DMFDMA to give 2‐dimethylaminomethylene‐3‐(phenylhydrazono)‐indan‐1‐one (2) which reacts with hydrazine hydrate and the pyrazole derivative 4 to afford the indenopyrazole derivatives 3 and the indenofluorene 5 respectively. The reaction of 2 with the active methylene compounds, mainly malononitrile, cyanoacetamide and malononitrile dimer was investigated and found to proceed successfully to yield the indenopyran 7, indenpyridine 8b and trinitrile 9 respectively. Compound 2 reacted with lH‐benzimidazole‐2‐acetonitrile 10 to give to the diazaindenofluorene derivative 11. Also, 2 reacted with ω‐cyano compounds 12a,b to afford the indenopyran 14. On the other hand the hydrazone 1 was allowed to react with the enaminones 15, 18 and 21 affording the diazabenzoazulene derivatives 17, 20 and the indeno[1,2‐b]pyridin 23, respectively.
Unusual fragmentation of fulvene endoperoxides with phenyliodosyl bis(trifluoroacetate) (PIFA)
Authors: Özer Galip , Saraçoǧlu Nurullah , Balci Metin
Published: March 2009

Reaction of unsaturated fulvene endoperoxides with dimethyl 1,2,4,5‐tetrazine‐3,6‐dicarboxylate gave saturated fulvene endoperoxides containing the 1,2‐dihydropyridazine ring. Treatment of dihydropyridazine endoperoxides with water followed by phenyliodosyl bis(trifluoroacetate) oxidation provided acrylic acid derivatives and dimethyl pyridazine‐3,6‐dicarboxylate.
Synthesis of chlorophyll‐a skeleton homologs using grignard reaction with methyl pyropheophorbide‐a
Authors: Wang Jin‐Jun , Shim Young Key , Jiang Gui‐Ji , Imafuku Kimiaki
Published: March 2009

From methyl pyropheophorbide‐a (MPPa) (1), methyl 2‐formylmethyl‐2‐devinyl‐9‐ethylenedioxy‐9‐deoxopyropheophorbide‐a (2) and methyl 3‐acetyl‐9‐ethylenedioxy‐2‐devinyl‐9‐deoxopyropheophorbide‐a (3) were prepared. The Grignard reactions of 2 and 3 were performed using cycloalkyl magnesium bromides to afford cycloalkyl‐substituted sec‐alcohol 4 and tert‐alcohols 9a‐c, respectively. By the deprotection of the ethylenedioxy group, these alcohols were respectively converted to exocyclic ketones 5 and 10a‐c, which were dehydrated to give chlorins 6 and 11a‐c having an alkenyl function at the 2‐position. On the other hand, the oxidation and deprotection of the alcohol 4 gave a diketo chlorin 8.
Synthesis and biological activities of 2‐alkylthio‐5‐furylmethylidene‐4H‐imidazolin‐4‐ones
Authors: Yang Feng‐Ling , Liu Zhao‐Jie , Huang Xiao‐Bo , Ding Ming‐Wu
Published: March 2009

Novel 2‐alkylthio‐5‐furylmethylidene‐4H‐imidazolin‐4‐ones 4 have been synthesized via tandem aza‐ Wittig reaction. The structures were determined by ir, nmr, mass spectroscopy, and elemental analysis. They were screened for fungicidal activities against Fusarium oxysporium, Botryosphaeria berengeriana and Rhizoctonia solani, and growth inhibition of Barnyard grass and Cole root and stalk. A few of them possess significant biological activities.
A convenient synthesis of novel pyrido(1′,2′:1,2)imidazo[5,4‐d]‐1,2,3‐triazinones from imidazo[1,2‐a]pyridines
Authors: Zamora Héctor Salgado , Rizo Benito , Campos Elena , Jiménez Rogelio , Reyes Alicia
Published: March 2009

The imidazo[1,2‐a]pyridine system was investigated as a synthon for the building of very attractive fused triazines, a planar, angular tri‐heterocycle with potential biological activity. Thus ethyl 3‐nitroimidazo[1,2‐a]pyridine‐2‐carboxylate was treated with ammonia or with an excess of primary amines to generate the corresponding substituted nitro carboxamidoimidazopyridines. The nitro substituent in the latter products, was reduced to yield 3‐amino‐2‐carboxamidoimidazo[1,2‐a]pyridine derivatives, which in turn were treated with nitrous acid to furnish 1‐oxo‐2‐substituted pyrido(1′,2′:1,2)imidazo[5,4‐d]‐1,2,3‐triazines.
Synthesis of new 2,3‐dihydrofuran‐3‐one derivative and its reactions with some primary amines
Authors: Üngören Ş. H. , Saçmaci M. , Akçamur Y. , Arici C. , Ülkü D.
Published: March 2009

The Wittig reaction of 2,3‐dihydro‐4‐(4‐methoxybenzoyl)‐5‐(4‐methoxyphenyl)‐furan‐2,3‐dione (1) with methyl (triphenylphosphoranylidene)acetate (2) stereo‐ and regioselectively afforded methyl (Z)‐[2,3‐dihydro‐4‐(4‐methoxybenzoyl)‐5‐(4‐methoxyphenyl)‐3‐oxofuran‐2‐ylidene]acetate (3) in good yield. The reactions of 3 with primary amines (4a‐k) gave corresponding 1‐substituted 2,3‐dihydro‐1Hpyrrol‐3‐ones (5a‐k).
Studies with enaminones: The reaction of enaminones with aminoheterocycles. A route to azolopyrimidines, azolopyridines and quinolines
Authors: Almazroa Sarah , Elnagdi Mohamed H. , El‐Din Abdellatif M. Salah
Published: March 2009

The enaminones 1b,d,f react with 4‐phenyl‐3‐methyl‐5‐pyrazoleamine 3a to yield the pyrazole derivatives 4a‐c that cyclised readily on reflux in pyridine solution in presence of hydrochloric acid to yield the pyrazolo[1,5‐a]pyrimidines 5a‐c. Similarly 3(5)‐amino‐1H‐triazole (3b) reacted with 1b,d,f to yield the triazolo[1,5‐a]pyrimidines 5d‐f. In contrast attempted condensation of the 5‐tetrazoloamine (3c) with 1a,d,e resulted in its trimerisation and only triaroylbenzene 8a,d,e was isolated. The reaction of 1a,b,d with anthranilonitrile 9a and the reaction of 1a‐c with the 2‐aminocyclohexene thiophene‐3‐nitrile 10a afforded the cis enaminones 11a‐c and 12a‐c. Similarly, reaction of 1a‐c with the methylanthranilate 9b and reaction of 1b,e with ethyl 2‐aminocyclohexene thiophene‐3‐carboxylate 10b afforded the cis enaminones 11d‐f and 12d,e respectively. Attempted cyclization of 11a‐c into quinoline failed. Successful cyclization of 11d into the quinolinone 13 could be affected, on heating for five minutes in a domestic microwave oven at full power. The reaction of 1a‐c,f with piperidine afforded the trans enaminones 14a‐d. Similarly, trans 14e was formed from the reaction of 1b with morpholine. The coupling reaction of 1b with excess of benzene diazonium chloride afforded the formazane 16. The enaminone 2 reacted with heterocyclic amines to yield the pyridones 17,18.
Study of the structure of 1‐hydroxymethylindazole and 1‐hydroxymethylbenzotriazole by X‐ray crystallography, multinuclear NMR in solution and DFT calculations
Authors: Alkorta Ibon , Elguero José , Jagerovic Nadine , Fruchier Alain , Yap Glenn P. A.
Published: March 2009

1‐Hydroxymethylindazole and 1‐hydroxymethylbenzotriazole have been studied in solution by 1H, 13C and 15N NMR spectroscopy and the X‐ray structure of the second compound determined. DFT and GIAO calculations have been used to discuss geometries, energies (comparatively with 2‐substituted isomers) and NMR chemical shifts.
Pyrrolocarbazole analogs of aromatic skeleton of indolocarbazole natural products
Authors: Fousteris Manolis A. , Koutsourea Anna I. , Arsenou Evaggelia S. , Nikolaropoulos Sotiris S. , Stamos Ioannis K. , Leondiadis L.
Published: March 2009

The synthesis of seven pyrrolo[2,3‐a]carbazoles derivatives using Fischer indole cyclization conditions is described. Polyphosphoric acid trimethylsilyl ester was used as a mild catalyst for the cyclization step of intermediate arylhydrazones which were prepared from ethyl 7‐oxo‐4,5,6,7‐tetrahydroindole‐2‐carboxylate and used as such without further purification. In all cases a mixture of two products was obtained, the dihydro and the corresponding dehydrogenated one. The completion of the dehydrogenation was achieved by treatment of this resultant mixture with dichlorodicyanoquinone.
Synthesis, NMR spectra and X‐ray data of chloro and dichloro derivatives of 3‐hydroxy‐2‐phenylquinolin‐4(1H)‐ones and their cytostatic activity
Authors: Hradil Pavel , Krejčí Petr , Hlaváč Jan , Wiedermannová Iveta , Lyčka Antonín , Bertolasi Valerio
Published: March 2009

As known, some derivatives of quinolin‐4(1H)‐one possess interesting biological properties. The biological and cytostactic activity of 2‐substituted 3‐hydroxyquinolin‐4(1H)‐ones has not been reported yet. In this paper the synthesis of a series of chloro and dichloro 2‐phenyl‐3‐hydroxyquinolin‐4(1H)‐ones and their characterization by NMR spectra and X‐ray data is described. Their cytostatic properties have been evaluated and the results are reported.
Facile synthesis, spectral characterization and antimicrobial activity of 6‐substituted‐2,4,8,10‐tetra‐t‐butyl dibenzo[d,g][1,3,6,2]dioxathiaphosphocin 6‐oxides
Authors: Kasthuraiah M. , Kumar K. Ananda , Reddy C. Suresh
Published: March 2009

Several novel 2,4,8,10‐tetra‐t‐butyl‐6‐substituted dibenzo[d,g][1,3,6,2]dioxathiaphosphocin 6‐oxides were synthesized in high yield by cyclocondensation of 2,2′‐thiobis(2,4‐di‐t‐butylphenol) with phosphorus oxychloride in the presence of triethylamine and a catalytic amount of dimethylaminopyridine (DMAP) in dry toluene followed by in situ reaction with different bulky phenols/thiophenols under the same reaction conditions. The structures of the synthesized compounds were confirmed by analytical, IR, multinuclear NMR studies. Their antibacterial and antifungal activities were evaluated against Staphylococcus aureus, Escherichia coli, Aspergillus niger and Fusarium oxysporium, respectively. Some of them showed moderate activity against these microorganisms.
Generation and reactivity of 3‐carbethoxy‐5‐phenyl‐5H,7H‐thiazolo[3,4‐c]oxazol‐4‐ium‐1‐olate
Authors: Pinho e Melo Teresa M. V. D. , Gomes Clara S. B. , Soares Maria I. L. , Gonsalves Antóanio M. d'A Rocha , Paixão José A. , Beja Ana M. , Silva Manuela Ramos
Published: March 2009

3‐Carbethoxy‐5‐phenyl‐5H,7H‐thiazolo[3,4‐c]oxazol‐4‐ium‐1‐olate was generated from (2R,4R)‐N‐ethoxyoxalyl‐2‐phenylthiazolidine‐4‐carboxylic acid and its reactivity studied. This münchnone showed low reactivity as dipole although from the reaction with dimethyl acetylenedicarboxylate the corresponding (3R)‐3‐phenyl‐17H,3H‐pyrrolo[1,2‐c]thiazole‐5,6,7‐tricarboxylate could be isolated. The thermolysis of (2R,4R)‐N‐ethoxyoxalyl‐2‐phenylthiazolidine‐4‐carboxylic acid in refluxing acetic anhydride led to the synthesis of N‐(1‐ethoxycarbonyl‐2‐phenylvinyl)‐2‐phenyl‐4‐thioxo‐1,3‐thiazolidine. The structure of methyl (2R,4R)‐N‐ethoxyoxalyl‐2‐phenylthiazoliddine‐4‐carboxylate was determined by X‐ray crystallography.
One‐step synthesis of aminopyrimidines from 5‐Oxo‐4H‐benzopyrans
Authors: Salfrán Esperanza , Seoaneb Carlos , Suárez Margarita , Verdecia Yamila , Alvarez Amaury , Ochoa Estael , Martínez‐Alvarez Roberto , Martín Nazario
Published: March 2009

Novel 4‐amino‐6‐aryl‐2‐phenylpyrimidine‐5‐carbonitriles have been prepared in one step procedure from the readily available 4‐aryl‐2‐amino‐3‐cyano‐5,6,7,8‐tetrahydro‐7,7‐dimethyl‐5‐oxo‐4H‐benzopyrans. The mass spectroscopy study under EI conditions shows molecular peaks with high intensity corresponding to the loss of benzonitrile from the C2 position of the pyrimidine ring. Semiempirical (AMI and PM3) and ab initio HF/6–31G* calculations reveal a favored distorted geometry where the three rings are not in the same plane.