bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of 2‐amino‐4‐imino‐4,5‐dihydrothiazoles from N‐sulfonyl‐α‐chloroamidines and thiourea
Authors: Abdelaal Salma M. , Bauer Ludwig
Published: April 2009

A number of new and interesting 2‐amino‐4‐(N‐substituted)imino‐4,5‐dihydrothiazoles were synthesized by reacting thiourea (or thiourea hydrochloride) with N‐alkyl‐ or N,N‐dialkyl‐N′‐p‐toluenesulfonyl‐α‐chloroacetamidines, where the N,N‐alkyl groups were ethyl, cyclohexyl, benzyl, β‐phenethyl, (3,5‐dimethyl‐1‐adamantyl)‐methyl, as well as N,N‐dimethyl‐ and N,N‐pentamethylene. Reactions of N‐alkyl‐N‐p‐toluenesulfonyl‐2‐chloroacetamidines (substituents being N‐ethyl, N‐benzyl and N,N‐dimethyl) with thiourea hydrochloride in hot 2‐propanol furnished 2‐amino‐4‐(p‐toluenesulfonyl)imino‐4,5‐dihydrothiazole (in 51, 60 and 65% yields, respectively) and the corresponding amine hydrochloride. In hot acetone or butanone, the reactions of these N‐sulfonyl‐2‐chloroacetamidines with excess thiourea provided 2‐amino‐4‐N‐(alkyl or N,N‐dialkyl)imminium‐4,5‐dihydrothiazole chlorides in 25–80% yield. The by‐product from these reactions was p‐toluenesulfonamide. The structures of the products were established by chemical transformations and spectral methods (nmr and mass spectra).
Syntheses of some hexacarboxylic acid derivatives of hexaazatriphenylene
Authors: Kanakarajan K. , Czarnik Anthony W.
Published: April 2009

Synthetic methods and product characterizations for the conversions of 1,4,5,8,9,12‐hexaazatriphenylene‐hexacarboxylic acid to the corresponding triester triacid, triamic acid, triimide, triester triacid chloride, trimethyl triethyl hexaester, trimethyl ester tri(N,N‐dimethyrjamide, hexaamide, tri(N,N,‐dimethyr)amide triacid, tri(N,N‐dimethyl)amide triacid chloride, and trisphthalhydrazide derivatives are described.
A new synthesis of some indolecarboxylic acids
Authors: Baiocchi Leandro , Giannangeli Marilena
Published: April 2009

1‐Substituted isatins are transformed into indole derivatives by means of ethyl chloroacetate. In fact, under the conditions of the Darzens reaction they give two glycidic ester isomers 4 and 5 which, by hydrolysis in alkaline medium, undergo a transposition to indole‐2,3‐dicarboxylic acids 2 together with minor amounts of indole‐3‐carboxylic acids 3. From isatin itself, 2,3‐dicarboxyindole‐1‐acetic acid (6) was obtained.
2,3,8,9‐Dibenzo‐5,6‐(substituted)benzo‐1,4‐dithio‐7‐azacyclonona‐2,5,8‐trienes. Synthesis and mechanistic study
Authors: Kim Kyongtae , Kim Man Nyoung
Published: April 2009

5‐(2‐Acetamidoaryl)thianthreniumyl perchlorates reacted with potassium hydroxide in methanol at reflux giving 2,3,8,9‐dibenzo‐5,6‐(substituted)benzo‐1,4‐dithio‐7‐azacyclonona‐2,5,8‐trienes 4 in 43 to 75% yields, whereas the reactions of the same compounds with sodium hydride in the absence or in the presence of dimethyl sulfate in refluxing tetrahydrofuran gave N‐acetylated and N‐methylated 4 in 68 to 96% and 27 to 56% yields, respectively. The mechanism of the formation of the products might be explained by a nucleophilic attack of amide ions 10, 12, and 14 at the ipso‐position of the thianthrene ring. A sulfuranyl radical mechanism might be involved in these reactions.
Synthesis of phenylpyrrolylpyrroles. Part III
Authors: Dumoulin H. , Rault S. , Robba M.
Published: April 2009

Several ethyl 3‐[(3‐aryl‐4‐methyl)‐2(1H)‐pyrrolyl]‐4‐methyl‐1H‐pyrrole‐2‐carboxylates have been synthesized using two successive ethyl isocyanide addition‐cyclizations to the appropriate nitropropene derivatives.
The synthesis and transformations of some 3‐thiocarbamoylthiazolidines
Authors: Malešič Mateja , Krbavčíč Ales , Golobič Amalija , Golič Ljubo , Stanovnik Branko
Published: April 2009

In connection with our studies on potential bioactive compounds some new polysubstituted 3‐thiocarbamoylthiazolidines 5, 6, 7, 9 and 10 were prepared in the reaction between 2‐(2‐methoxy‐phenyl)iminothiazolidine (2) and sulfamoylphenyl isothiocyanates 3 and 4a‐c. The structures for compounds 2 and 5 were established by X‐ray analyses, showing that the reaction is taking place at the endo‐cyclic nitrogen atom of thiazolidine ring.
Transformations of methyl L‐(—)‐thiazolidine‐4‐carboxylate, 2‐amino‐2‐thiazoline and 2‐aminothiazole into thiazoloazines and azolothiazoles
Authors: Malešíč Mateja , Krbačič Aleš , Stanovnik Branko
Published: April 2009

In the search for potential immunomodulators methyl L‐(—)‐thiazolidine‐4‐carboxylate (2), 2‐amino‐2‐thiazoline (12), and 2‐aminothiazole (19) were transformed into derivatives of various bicyclic systems. Thus, from compound 2 derivatives of perhydrothiazolo[3,4‐a]pyrazine 4 and 5, perhydrothiazolo[4,3‐c]‐[1,4]oxazine 7, and perhydroimidazo[1,5‐c]thiazole 9a,b, from compound 12 derivatives of 2,3‐dihydro‐thiazolo[2,3‐b]pyrimidine 13a,b, and from compound 19 derivatives of imidazo[2,1‐b]thiazole 21, 22, 24, and 25 were prepared. 6‐(p‐Sulfamoylphenyl)‐7‐oxoperhydroimidazo[1,5‐c]thiazole‐5‐thione (9a) was found to exhibit immunorestoration activity.
A new synthetic route to 7H‐imidazo[1,2‐b][1,2,4]triazoles
Authors: Lee Kee‐Jung , Song Dong‐Hyuk , Kim Dong‐Jin , Park Sang‐Woo
Published: April 2009

The reaction of benzil 1‐ureidoethylidene hydrazones 8 with a mixture of triphenylphosphine, carbon tetrachloride, and triethylamine provides a general route to 7H‐imidazo[1,2‐b][1,2,4]triazoles 18 via the thermal reaction of the expected keto azine carbodiimide intermediates 13, and the structure of 18 was confirmed by X‐ray crystallographic analysis.
AM1 computational study of cycloaddition reaction of vinyl sulfene generated from thiete 1,1‐dioxide
Authors: Jursic Branko S.
Published: April 2009

Theoretical studies of the cycloaddition reaction between vinyl sulfene, norbornene and related systems are presented. Since the parameterized AMI semiempirical method was used, the generated data are only of qualitative value. The vinyl sulfene reactivity was assessed by using frontier molecular orbital (FMO) energy gaps, bond orders, and the charge distribution of the reactants. To obtain more information, as far as the reaction outcome and its feasibility, the transition state structures and activation barriers for competitive pathways are computed.
Manganese(III)‐mediated intermolecular cyclization reactions of alkenes and active methylene compounds
Authors: Ouyang Jie , Nishino Hiroshi , Kurosawa Kazu
Published: April 2009

The reactions of 1,1‐diphenylethene, 1,1‐bis(4‐chlorophenyl)ethene, 1,1‐bis(4‐methylphenyl)ethene, and 1,1‐bis(4‐methoxyphenyl)ethene with 3,5‐diacetyl‐2,6‐heptanedione in the presence of manganese(III) acetate in acetic acid at 80° yielded 4,6‐diacetyl‐8,8‐diaryl‐1,3‐dimethyl‐2,9‐dioxabicyclo[4.3.0]non‐3‐enes (41‐48%), 5‐acetyl‐2,2‐diaryl‐6‐methyl‐2,3‐dihydrobenzo[b]furans (20–21%), 3‐acetyl‐5,5‐diaryl‐2‐methyl‐4,5‐dihydrofurans (5–10%), and benzophenones (3–7%). Similarly, the reactions of 1,1‐diarylethenes with dimethyl 2,4‐diacetyl‐1,5‐pentanedioate or diethyl 2,4‐diacetyl‐1,5‐pentanedioate gave the corresponding 4,6‐bis(alkoxycarbonyl)‐8,8‐diaryl‐1,3‐dimethyl‐2,9‐dioxabicyclo[4.3.0]non‐3‐enes in moderate yields.
Synthesis of pyrroloazepines. Facile synthesis of 2‐substituted pyrrole derivatives by the phosgene method
Authors: Cho Hidetsura , Matsuki Shinsuke , Mizuno Akira , Annoura Hirokazu , Tatsuoka Toshio
Published: April 2009

A highly convenient method for the synthesis of 2‐substituted pyrrole derivatives 7a‐c from pyrrole using phosgene was developed. Successively, 7‐methyl‐6,7‐dihydro‐1H,5H‐pyrrolo[2,3‐c]azepine‐4,8‐dione 1a and 6,7‐dihydro‐1H,5H‐pyrrolo[2,3‐c]azepine‐4,8‐dione 1b (aldisin) were synthesized by phosphorus pentoxide/methanesulfonate and polyphosphoric acid cyclization.
Reactions of benzotriazoles with diethyl ethoxymethylenemalonate; ethylation and michael addition. Comparison with other esters and N‐heterocycles
Authors: Sanna Paolo , Carta Antonio , Paglietti Giuseppe , Bacchi Alessia , Pelizzi Giancarlo
Published: April 2009

Benzotriazole and its 5‐methyl‐and 5‐nitro derivatives react with diethyl ethoxymethylenemalonate by ethylation at each of the ring N‐atoms and through Michael addition, to give the isomeric esters ethyl (E/Z) 3‐[5(6)‐R‐benzotriazol‐1‐yl]propenoates. Benzotriazole and its 5‐nitro derivative react similarly with ethyl acetoacetate but N‐ethyl derivatives are obtained in lower yields. Other 1,2,3‐triazoles derivatives and indole were ineffective in this reaction while benzimidazole produced similar results but accompanied with a small amount of a benzimidazoline addition product, whose structure has been determined by crystallo‐graphic analysis.
Synthesis of 1,3‐diamino‐7,8,9,10‐tetrahydropyrido[3,2‐f]‐quinazolines. Inhibitors of Candida albicans dihydrofolate reductase as potential antifungal agents
Authors: Chan Joseph H. , Baccanari David P. , Tansik Robert L. , Boytos Christine M. , Rudolph Sharon K. , Brown Andrew D. , Hong Jean S. , Kuyper Lee F. , Jones Michael L.
Published: April 2009

A series of novel 1,3‐diamino‐7,8,9,10‐tetrahydropyrido[3,2‐f]quinazolines were synthesized starting from 6‐amino‐5‐cyanoquinoline (4). These compounds inhibited Candida albicans dihydrofolate reductase with Ki values of ≤0.60 aM. One analogue exhibited moderate in vivo efficacy in a C. albicans‐infected mouse model.
Synthesis of 2‐substituted 4‐quinazolone‐5‐carboxylic acids as inhibitors of DNA‐gyrase
Authors: Sui Zhihua , Nguyen Van N. , Fernandez Jeff , Barrett John F. , Ohemeng Kwasi A.
Published: April 2009

A series of 4‐quinazolone‐5‐carboxylic acids were designed as bacterial DNA gyrase inhibitors. The syntheses of the target compounds were accomplished by reacting 3‐aminophthalimide with aroyl chlorides followed by rearrangement of the resulting 3‐acylaminophthalimides under basic conditions. The designed compounds showed moderate DNA gyrase inhibitory activity.
The chemical properties of 1‐substituted 4‐oxopyrimidinium cations
Authors: Vedernikova Irina V. , Claeys Magda , Haemers Achiel , Peten Carl , Van Alsenoy Christian , Ryabukhin Yuryi I.
Published: April 2009

Some theoretical aspects of electrophilic properties of 4‐pyrimidinium cations are discussed. The reactivity towards a series of C‐, H‐, N‐ and O‐nucleophiles is studied.
2‐Benzoyl‐2‐ethoxycarbonylvinyl‐1 and 2‐benzoylamino‐2‐methoxy‐carbonylvinyl‐1 as N‐protecting groups in peptide synthesis. Their application in the synthesis of dehydropeptide derivatives containing N‐terminal 3‐heteroarylamino‐2,3‐dehydroalanine
Authors: Svete Jurij , Aljaž‐Rožič Mateja , Stanovnik Branko
Published: April 2009

Ethyl 2‐benzoyl‐3‐dimethylaminopropenoate (6) and methyl 2‐benzoylamino‐3‐dimethylaminopropenoate (46) were used as reagents for the protection of the amino group with 2‐benzoyl‐2‐ethoxycarbonylvinyl‐1 and 2‐benzoylamino‐2‐methoxycarbonylvinyl groups in the peptide synthesis. Reactions of ethyl 2‐benzoyl‐3‐dimethylaminopropenoate (6) with α‐amino acids gave N‐(2‐benzoyl‐2‐ethoxycarbonylvinyl‐1)‐α‐amino acids 13–19. These were coupled with various amino acid esters to form N‐(2‐benzoyl‐2‐ethoxycar‐bonylvinyl‐1)‐protected dipeptide esters 20–31. The removal of 2‐benzoyl‐2‐ethoxycarbonylvinyl‐1 group, which was achieved by hydrazine monohydrochloride or hydroxylamine hydrochloride, afforded hydrochlo‐rides of dipeptide esters 32–41 in high yields. Similarly, the substitution of the dimethylamino group in methyl 2‐benzoylamino‐3‐dimethylaminopropenoate (46) by glycine gave N‐(2‐benzoylamino‐2‐methoxycar‐bonylvinyl‐1)glycine (47), which was coupled with glycine ethyl ester to give N‐[N‐(2‐benzoylamino‐2‐methoxycarbonylvinyl‐1)glycyl]glycine ethyl ester (48). Treatment of 48 with 2‐arnino‐4,6‐dirnethylpyrimi‐dine afforded N‐[glycyl]glycine ethyl ester hydrochloride (34) in high yield. Amino acid esters and dipeptide esters were employed in the preparation of tri‐ 58‐70, tetra‐ 71–82, and pentapeptide esters 83–85 containing N‐terminal 3‐heteroarylamino‐2,3‐dehydroalanine. 2‐Chloro‐4,6‐dimethoxy‐1,3,5‐triazine was employed as a coupling reagent for the preparation of peptides 58–85.
Nonlinear optical properties of benzofurobenzofurans
Authors: Millefiori Salvatore , Alparone Andrea , Millefiori Arcangelo
Published: April 2009

The geometric structure, dipole moment, μ, linear polarizability, α and first hyperpolarizability, β, of symmetrically substituted amino‐and cyanobenzofurobenzofurans and dihydrobenzofurobenzofurans have been calculated by ab initio coupled perturbed Hartree‐Fock methods. Singlet electronic transition energies and excited state dipole moments have been calculated by the AMI program. The benzofurobenzofuran derivatives are planar, while dihydrobenzofurobenzofuran derivatives have a V‐shaped form, in agreement with experimental X‐ray data. The molecular structure is rather unaffected by substitution. The linear polarizability is weakly sensitive to the substituent and substituent position, while β value changes over about 1 order of magnitude. Although both series of compounds have relatively modest hyperpolarizability, reaching ca. 60% β of para‐nitroaniline, they have good properties for second harmonic generation devices: transparency in the visible spectral region, thermal stability and conformational rigidity.
Alkylation of 4,5‐dichloropyridazin‐6‐one with α,ω‐dibromoalkanes or 4,5‐dichloro‐1‐(ω‐bromoalkyl)pyridazin‐6‐ones
Authors: Kim Sung‐Kyu , Cho Su‐Dong , Kweon Deok‐Heon , Yoon Yong‐Jin , Kim Jung‐Ho , Heo Jung‐Nyoung
Published: April 2009

Alkylations of 4,5‐dichloropyridazin‐6‐one (1) with dibromoalkanes 2 or 3 in the presence of potassium carbonate or tetrabutylammonium bromide/potassium hydroxide were investigated under restricted condition. Reactions of 1 with 2 or 3, except for 2b and 3b, in the presence of potassium carbonate or tetrabutylammonium bromide/potassium hydroxide gave only the N‐alkylation products 3 and/or 4. Alkylation of 1 with 2b or 3b in the presence of potassium carbonate yielded the N‐alkylation products 3b and/or 4b and the O‐alkylation product 5 as the main product, whereas treatment of 1 with 2b or 3b in the presence of tetrabutylammonium bromide/potassium hydroxide afforded selectively the N‐alkylation products 3b and/or 4b.
Palladium(0)‐catalyzed allylation of heterocycles with cyclopentene derivatives
Authors: Arnau N. , Cortés J. , Moreno‐Mañas M. , Pleixats R. , Villarroya M.
Published: April 2009

Palladium(0)‐catalyzed allylation of imidazoles, 6‐methyluracil, 2‐pyrimidinone, and Meldrum's acid with cyclopentadiene monoepoxide and cis‐cyclopentene‐3,5‐diol mono and dicarbonate is described.
2,4,6‐Triphenylpyridine as a neutral leaving group in the palladium(0)‐catalyzed allylation of nucleophiles
Authors: Moreno‐Mañas M. , Mortal L. , Pleixats R.
Published: April 2009

Palladium(0)‐catalyzed allylation of nucleophiles such as morpholine, sodium dimethyl malonate and 2,6‐dimethylaniline can be achieved under very mild conditions using N‐allyl‐2,4,6‐triphenylpyridinium tetrafluoroborates as allylating reagents in reactions in which 2,4,6‐triphenylpyridine acts as the neutral leaving group.
Studies on pyrrolidinones. Synthesis of some bioisosteres of 3,3,5‐trimethylcyclohexyl pyroglutamate
Authors: Rigo Benoǐt , Laruelle Claude
Published: April 2009

The synthesis of new N‐(4‐chlorobenzyl) and N‐(4‐chlorobenzoyl)pyroglutamic esters and amids whose the structure conserves the main structural features of the cholesterol lowering agent crilvastatin is described.
Synthesis of thienothiazocinoisoindolediones and thienothiazinoisoindolones from mercaptothiophenes and chloromethylphthalimide
Authors: Netchitaïlo Pierre , Othman Mohamed , Decroix Bernard
Published: April 2009

2‐Thienylthiomethylphthalimides 3a,b were synthesized by action of Chloromethylphthalimide on 2‐or 3‐mercaptothiophene. Reduction of 3a,b and Wittig reaction using carbethoxycarbonyltriphenyl‐phosphorane gave the corresponding acetic acids 5a,b which cyclized under Friedel and Crafts conditions to lead the thienothiazocinoisoindolediones 6a,b. Thienothiazinoisoindolones 7a,b were obtained from hydroxyisoindolones derivatives 4a,b in acid conditions via an acyliminium ion.
Synthesis of ethyl 2‐aminodihydro‐5‐pyrimidinecar‐boxylate derivatives and 3,7‐diethoxycarbonyl‐4,6‐dihydro‐2,4,6,8‐tetraaryl‐1H‐pyrimido[1,2‐a]pyrimidines
Authors: Milcent René , Malanda Jean‐Claude , Barbier Géo , Vaissermann Jacqueline
Published: April 2009

Reactions of ethyl 3‐aryl‐2‐benzoylpropenoates 1 with guanidine andN‐alkyl(or benzyl)guanidines have been investigated. Ethyl 2‐aminodihydro‐5‐pyrimidinecarboxylate derivatives 3, 4 or 5, and 3,7‐diethoxy‐carbonyl‐4,6‐dihydro‐2,4,6,8‐tetraaryl‐1H‐pyrimido[1,2‐a]pyrimidines6have been synthesized.
An expedient synthesis of (±)‐2‐amino‐3‐(3‐hydroxy‐5‐methylisoxazol‐4‐yl)propionic acid hydrobromide via a 3‐bromoisoxazole intermediate
Authors: Hanson Robert N. , Mohamed Farid A.
Published: April 2009

The excitatory, amino acid ±2‐amino‐3‐(3‐hydroxy‐5‐methylisoxazol‐4‐yl)propionic acid hydrobromide was prepared in gram quantities in an 3.3% overall yield from methylbut 2‐ynoate. The key step was the facile preparation of methyl 3‐bromo‐5‐methylisoxazole‐4‐carboxylate.
Tetracyclic systems: Synthesis of isoindolo[1,2‐b]thieno‐[2,3(3,2 or 3,4)‐e][1,3]thiazocines and Isoindolo[2,1‐a]thieno‐[2,3(3,2 or 3,4)‐f][1,4] and [1,5]diazocines
Authors: Pigeon Pascal , Decroix Bernard
Published: April 2009

Cyclization of thioglycolic acids derivatives 3a‐d gave isoindolo[1,2‐b]thieno[2,3(3,2 or 3,4)‐e][1,3]‐thiazocines 4a‐d. Isoindolo[2,1‐a]thieno[2,3(3,2 or 3,4)‐f][1,4] or [1,5]diazocines 10b or 11a‐c were synthesized from Beckmann or Schmidt rearrangement of the ketones 7a‐c.
Mass spectrometric behaviour of 1‐imino‐substituted pyrazolo[1,2‐a]‐[1,2,4]triazoles under electron and chemical ionization
Authors: Joutsiniemi Karoliina , Vainiotalo Pirjo , Morgenstern Olaf , Klemann Anke
Published: April 2009

The spectra of five pharmacologically interesting substituted pyrazolo[1,2‐a][1,2,4]triazole hydroiodides were measured under electron and chemical ionization. In the electron ionization spectra, in addition to the intense molecular ion peak of the free base (M+*), there was also a relatively intense molecular ion peak of the hydroiodide form, which is unusual since the hydroiodides are rarely so stable. The phenylimino and phenylamino substituents of the triazole ring affected the fragmentation behaviour of the compounds very much. The chemical ionization reagent gases used in this work were methane, isobutane, deuterated ammonia and acetone. In all the cases practically only [M+H]+ions were observed, the only exception being acetone which also gave rise to intense [M+C2H3O]+and [M+C3H7O]+adduct ions. None of the reagent gases used was able to cause any fragmentation.
Synthesis of 2‐aminoquinazolines from ortho‐fluorobenzaldehydes
Authors: Hynes John B. , Campbell Johnny P.
Published: April 2009

The reaction of guanidine carbonate with various ortho‐fluorobenzaldehydes in N,N‐diinethylacetamide was investigated as a potential route for preparing 2‐aminoquinazolines. Eleven new 2‐aminoquinazolines were elaborated in this manner in low to moderate yields. In general the best results were obtained with ortho‐fluorobenzaldehydes possessing an electron withdrawing substituent at the other ortho position. Complex mixtures were obtained using 2‐fluorobenzaldehyde, 2,5‐difluorobenzaldehyde and 2‐fluoro‐5‐methoxybenzaldehyde which were not resolved.
Bicyclic [b]‐heteroannulated pyridazine derivatives.4. Cyclization reactions of 4‐aryltetrahydropyridazine‐3,6‐dione 3‐hydrazones with some keto esters
Authors: Lange Jerzy , Pytlewska Elzbieta , Plenkiewicz Jan , Kulinski Tomasz , Karolak‐Wojciechowska Janina , Rump Slawomir
Published: April 2009

Ethoxycarbonylalkylidene derivatives2and6of the title hydrazones were obtained in the reaction with ethyl pyruvate or ethyl aroylformate and ethyl acetoacetate, respectively, in methanol. Both compounds were mixtures of geometric isomers with high predominance of one of them. Nmr spectroscopy revealed an unexpected magnetic non‐equivalence of the CH2protons in the ester ethyl group of the major isomer of6. On heating (˜200°) in an inert medium or on refluxing in ethanolic sodium ethoxide2cyclized to the corresponding pyridazino[6,1‐c]‐triazines4, whereas6formed pyrazolylpyridazines7. The structure of the latter was unambigously established by X‐ray analysis. Alkylation of4awith benzyl bromide in the presence of tetrabutylammonium bromide occurred selectively on the pyridazineNatom.
A new and efficient route to amino derivatives of [1,6]‐ and [2,7]naphthyridones
Authors: Nemazany Alexei , Haider Norbert
Published: April 2009

Reaction of N‐substituted amides of 2‐chloro‐ or 4‐chloronicotinic acid with CH‐acidic nitriles in the presence of a base provides a convenient access to amino derivatives of 1,6‐naphthyrid‐5(6H)‐one, compounds of type 4 and 5, or 2,7‐naphthyrid‐1(2H)‐one 7.
Organic syntheses based on 2‐oxoglutaric acid. V. Syntheses of novel 2H‐1,4‐benzothiazines and a 2,5‐dihydro‐1,5‐benzothiazepine
Authors: Blitzke Torsten , Sicker Dieter , Wilde Horst
Published: April 2009

Syntheses aimed on the incorporation in heterocycles of segments originating in the precursor 2‐oxoglutaric acid are described. Cylocondensation of dimethyl 2‐oxoglutarate 1, dimethyl 3‐bromo‐2‐oxoglutarate 2, and dimethyl (E)‐2‐oxoglutaconate 3 with 2‐aminobenzenethiol gave rise to the novel 2H‐1,4‐benzothiazines 4 and 5, and the 2,5‐dihydro‐1,5‐benzothiazepine 6, respectively, by incorporation of either the segments C‐1/C‐2 or C‐2/C‐3 or C‐3/C‐4/C‐5 of the precursor.
Conformational and stereoelectronic control in ring‐transformations of cis‐4,5‐dialkoxytetrahydropurine‐2,6,8‐triones
Authors: Poje Nevenka , Palković Antun , Poje Mirko
Published: April 2009

Divergent acid‐catalysed ring‐openings of 4,5‐dimethoxytetrahydropurine‐2,6,8‐triones 2 at position 4, yielding 1‐(5‐methoxyhydantoin‐5‐carbonyl)ureas 4 (R7 = Me) or 5‐methoxy‐5‐ureido‐2,4,6‐pyrimidinetriones 5 (R7 = H), can be rationalized by assuming a preference for one of two conformational isomers of the cis‐fused system, associated with the N‐substitution effects. Intramolecular transamidation 5 → 4 presumably occurs via a bicyclic acid aminal type intermediate 3, heretofore misassigned as the reaction product. A curious base‐catalysed rearrangement was encountered with the 5 (R1 = R3 = Me, R7 = H) cases, which afforded 5‐methoxy‐1,5‐bis(methylaminocarbonyl)hydantoins 7. Remarkable stability of the conformationally rigid propellane type 4,5‐ethylenedioxytetrahydropurine‐2,6,8‐triones 9 toward acids, shows that the mode of ring‐opening at position 4 is controlled by powerful Stereoelectronic factors. However, an alternative ring‐opening at the 1,6‐bond has occurred on heating aqueous solutions of 9a (R7 = H); the ensuing decarboxylative rearrangement leads to 1,3‐dimethylallantoin (12) and its precursor, 1‐(2‐hydroxyethoxy)‐2,4‐dimethyl‐3,7‐dioxo‐2,4,6,8‐tetraazabicyclo[3.3.0]octane(11).
Synthesis of 6,7‐dihydrobenzo[4,5]cyclohept‐[1,2‐b]indol‐12(5H)‐one and related compounds
Authors: Joseph B. , Cornec O. , Mérour J.‐Y. , Solans X. , Font‐Bardia M.
Published: April 2009

The synthetic routes of 6,7‐dihydrobenzo[4,5]cyclohept[1,2‐b]indol‐12(5H)‐one 5 from either 1‐methyl or 1‐sulfonylindole‐2‐carboxaldehyde 1 or ethyl 1,2‐dimethylindole‐3‐carboxylate 6 are reported. The structure of the ketone 5a was confirmed by X‐ray crystallography. Several indole derivatives have been prepared with potential antitumor activity.
Ring‐transformation reactions of 5‐hydroxy‐2‐oxabicyclo[3.2.0]‐heptan‐4‐ones and 5‐hydroxy‐2‐oxabicyclo[3.2.0]hept‐6‐en‐4‐ones
Authors: Shimo Tetsuro , Minamishin Hidemi , Somekawa Kenichi
Published: April 2009

Dehydrochlorination of chlorinated 5‐hydroxy‐2‐oxabicyclo[3.2.0]heptan‐4‐ones, 3a‐c, which were obtained from the photo[2+2]cycloadditions between 4‐hydroxy‐3(2H)‐furanone 1 and chloroethylenes, with triethylamine gave 2‐ethenyl‐3(2H)‐furanones 4a,b or 2‐(2‐cyanoethyl)‐3(2H)‐furanone 4c. 2‐Oxa‐bicyclo[3.2.0]hept‐6‐en‐4‐ones 7 being [2+2]cycloadducts between 1 and acetylenes gave 2,3‐dihydro‐3‐oxooxepin derivatives 8 by electrocyclic rearrangement.
Syntheses of polysubstituted pyrroles and of 2,3‐disubstituted quinoxalines and substituted benzo[g]quinoxalines
Authors: Adembri Giorgio , Celli Angela Maria , Sega Alessandro
Published: April 2009

Tetraacetylethylene (1), and cis‐diacetylethylene (4) reacted under mild conditions with 3‐amino‐2‐butenoic acid methyl ester (6), benzene‐1,2‐diamine and naphthalene‐2,3‐diamine to give polysubstituted pyrroles, 2,3‐disubstituted quinoxalines and 2,3‐disubstituted benzo[g]quinoxalines respectively. Some aspects of the reactions mechanisms are discussed.
Syntheses of substituted pyrrolo[2,3‐d]imidazoles
Authors: Shafiee A. , Hadizadeh F.
Published: April 2009

Starting from the readily available 5‐hydroxymethyl‐2‐mercapto‐1‐methylimidazole (1) substituted pyrrolo[2,3‐d]imidazoles were prepared.
2‐Mono‐ and 2,5‐bis[bis[(4‐dimethylamino)phenyl]hydroxymethyl]‐substituted furans, thiophenes and N‐methylpyrroles: New color‐formers for carbonless imaging
Authors: Katritzky Alan R. , Zhang Zhongxing , Lang Hengyuan , Jubran Nusrallah , Leichter Louis M. , Sweeny Norman
Published: April 2009

2‐Mono‐ and 2,5‐bis[bis[(4‐dimethylamino)phenyl]hydroxymethyl]substituted furan, thiophene and N‐methylpyrrole were synthesized by mono‐ and dilithiation of furan, thiophene and N‐methylpyrrole, respectively, and subsequent reaction with Michler's ketone. The title compounds develop black or dark‐blue colors in acidic media.
Reactions of 1,2,4‐triazin‐5(2H)‐ones with phenols and aromatic amines
Authors: Chupakhin Oleg N. , Rusinov Vladimir L. , Beresnev Dmitri G. , Neunhoeffer H.
Published: April 2009

1,2,4‐Triazin‐5(2H)‐ones 1 react as well with phenols, resorinol and its dimethyl ethers, as with dimethyland diethylaniline, yielding 6‐aryl‐1,6‐didydro‐1,2,4‐triazin‐5(2H)‐ones 2, 4–8, 12–15. Oxidation of the 1,6‐dihydroadducts 2a,b gives the corresponding 3‐aryl‐6‐hydroxyphenyl‐1,2,4‐triazin‐5(2H)‐ones 3a,b. Rection of 1,2,4‐triazinones 1 with 2‐naphthylamine leads to destruction of the 1,2,4‐triazine ring yielding benzo[e]indole‐2,3‐dione 19.
Synthesis of dithia‐ and tetrathiacyclophanes incorporating isoxazole units
Authors: Hatta Taizo , Kawano Muneob , Maeda Hironori , Tsuge Otohiko
Published: April 2009

The reaction of 5‐bromomethyl‐3‐(p‐bromomethylphenyl)isoxazole with o‐, m‐, and p‐bis(mercap‐tomethyl)benzenes gave the corresponding dithia‐ and/or tetrathiaisoxazolophanes, whose relative yields strongly depended upon the nature of the mercaptomethyl compound. The above isoxazole dibromide reacted with the bis(mercaptomethyl)isoxazole to afford a mixture of two isomeric dithiaisoxazolophanes.
Synthesis of Dialkyl 1,4‐Dihydro‐2,6‐dimethyl‐4‐(heteroaryl)‐pyridine‐3,5‐dicarboxylates as Calcium Channel Antagonists
Authors: Anana Raymond D. , Knaus Edward E.
Published: April 2009

The Hantzsch condensation of the heteroarylcarboxaldehydes 3a‐c with alkyl acetoacetates 4a‐c and alkyl 3‐aminocrotonates 5a‐b afforded the respective dialkyl 1,4‐dihydro‐2,6‐dimethyl‐4‐(heteroaryl)‐pyridine‐3,5‐dicarboxylates 6a‐f possessing a C‐4 4‐quinolinyl, 8‐quinolinyl or 1‐oxido‐4‐pyridinyl substituent Calcium channel antagonist structure‐activity relationships acquired indicate that i) the position of the quinolyl nitrogen atom was not a determinant of activity, ii) increasing the size of the C‐3 and C‐S alkyl ester substituents decreases potency and iii) a C‐4 1‐oxido‐4‐pyridinyl substituent abolishes activity. The most active, and equipotent C‐4 4‐quinolinyl 6a and 8‐quinolinyl 6b analogs, were approximately 8‐fold less potent calcium channel antagonists than the reference drug nifedipine.
New anti‐tumor agents. 3. Phenolic benzopyran lactone and amine derivatives
Authors: Jurd Leonard
Published: April 2009

2‐Aminopyridine, sesamol and 4‐hydroxy‐3,5‐dimethoxybenzaldehyde condense to form a Mannicb base 3b which reacts with tetronic acid to yield lactone 4c. Cyclization of 4c yields the benzopyran lactone 1b; this inhibits growth of tumors in NCI in vitro tests. Alkaline hydrolysis of acetylated and methylated intermediate lactones, e.g. 4e, in the presence of acetone leads to the formation of novel lactones, e.g., of type 6, which incorporate the acetone nucleus. Compound 6 is of interest since it inhibits tumor growth in vitro and has been selected by NCI for ongoing in vivo testing with human cancers. Heating 3b with mixtures of propionaldehyde and secondary amines such as morpholine leads to 3‐methylbenzopyrans containing the amine nucleus, e.g. 7b. Unlike 3,4,5‐trimethoxyphenyl compounds, e.g. 7a, phenolic analogs of type 7b do not inhibit growth of tumors in vitro.
Reaction of 5‐amino‐1‐phenylpyrazole‐4‐carbonitriles with dimethyl acetylenedicarboxylate. Synthesis and structural determination of trimethyl 4,8‐dioxo‐1‐phenyl‐4,5,5a,8‐tetrahydro‐1H‐pyrazolo[3,4‐e]indolizine‐5,5a,6‐tricarboxylate derivatives
Authors: Tominaga Yoshinori , Yoshioka Noriko , Castle Raymond N. , Luo Jiann‐Kuan , Hata Tadashi
Published: April 2009

The reaction of 5‐amino‐1‐phenylpyrazole‐4‐carbonitriles 1a‐c with dimethyl acetylenedicarboxylate in the presence of potassium carbonate in dimethyl sulfoxide gave trimethyl 4,5,5a,8‐tetrahydro‐1‐phenyl‐4,8‐dioxo‐1H‐pyrazolo[3,4‐e]indolizine‐5,5a,6‐tricarboxylate derivatives 3a‐c from the basic solution. The products were formed by a double Michael reaction of 1 with dimethyl acetylenedicarboxylate followed by cyclization to the cyano group. The structure of product 3a was established by X‐ray crystallography.
A new efficient route to imidazo[4,5‐c]pyrazol‐5‐ones
Authors: Vicentini Chiara B. , Veronese Augusto C. , Manfrini Maurizio
Published: April 2009

The synthesis of imidazo[4,5‐c]pyrazol‐5‐ones (6) is reported. 5‐Amino‐4‐ethoxycarbonylaminopyra‐zoles 3a‐g when heated at 200° for 2 hours afford 6a‐g. In a similar manner imidazo[4,5‐c]pyrazol‐5‐one (6a) is readily obtained from 4‐amino‐5‐ethoxycarbonylaminopyrazole (5a).
On the relocation of the amino functionality to the ethyl side chain in aminoglutethimide: Synthesis and aromatase‐inhibitory activity of 3‐(2′‐N,N‐diethyl‐amino)ethyl‐3‐phenylpiperidine‐2,6‐dione
Authors: Moniz George A. , Hammond Gerald B.
Published: April 2009

Aminoglutethimide [3‐(4‐aminophenyl)‐3‐ethylpiperidine‐2,6‐dione] has been used clinically in the treatment of metastatic breast carcinoma. Inhibition of tumor growth is due to interference with estrogen biosynthesis. However, its action is not specific and its metabolism gives rise to toxic and non‐inhibitory metabolites. We sought to explore the impact of relocating the amino group in aminoglutethimide to the ethyl side chain. To that end, we now report the synthesis and aromatase‐inhibitory activity of 3‐(2′‐N,N‐diethylamino)ethyl‐3‐phenylpiperidine‐2,6‐dione 5. The introduction of the amino functionality on the ethyl group is accomplished via reductive animation of aldehyde 8, prepared in three steps from benzyl cyanide. The synthetic route presented can be used for the preparation of related derivatives of aminoglutethimide.
A new route to the improved synthesis of 1‐(alkoxymethyl)‐5‐alkyl‐6‐(arylselenenyl)uracils
Authors: Lee Namkyu , Kim Young‐Woo , Kim Key H. , Kim Dae‐Kee
Published: April 2009

A new route to C‐6‐selenenyl analogs of compound 1a from 5‐alkyl‐6‐chlorouracils 6a‐b has been described. A mild and highly efficient synthesis of 1‐(alkoxymethyl)‐5‐alkyl‐6‐(arylselenenyl)uracils 8a‐e has been accomplished from 6a‐b in good yields using a two step procedure. Silylation of 5‐alkyl‐6‐chlorouracils 6a‐b using N,O‐bis(trimethylsilyl)acetamide followed by regioselective alkylation of the silylated intermediate with ethyl or benzyl chloromethyl ether in dichloromethane afforded the desired 1‐(alkoxymethyl)‐5‐alkyl‐6‐chlorouracils 7a‐d in 88–94% yields. Compounds 7a‐d readily underwent addition‐elimination reaction with an appropriate arylselenol in the presence of ethanolic sodium hyroxide to produce the corresponding 1‐(alkoxymethyl)‐5‐alkyl‐6‐(arylselenenyl)uracils 8a‐e in excellent yields (94–99%).
Synthesis of 5‐ethylpyrimidine nucleoside analogs
Authors: Takenaka Keiko , Muraoka Masako , Tsuji Tadakazu
Published: April 2009

This paper describes the synthesis of acyclic, cyclic, and deoxy sugar nucleosides of 5‐ethylpyrimidine, i.e., i) 1‐(2‐hydroxyethoxymethyl), 1‐(2‐methoxyethoxymethyl), and 1‐ethoxyethyl derivatives of 5‐ethyl‐uracil and 5‐ethylcytosine, ii) 5‐ethyl‐1‐(tetrahydro‐2H‐pyran‐2‐yl)‐ and ‐1‐(tetrahydrofuran‐2‐yl)uracils, and iii) 5‐ethyl‐2′‐deoxyuridine.
Nitration in the imidazo[1,2‐a]pyrazine series. Experimental and computational results
Authors: Vitse Olivier , Bonnet Pierre‐Antoine , Bompart Jacques , Viols Henri , Subra Guy , Chapat Jean‐Pierre , Grassy Gérard
Published: April 2009

Nitration was carried out on a series of imidazo[1,2‐a]pyrazine derivatives. The reactivities of diversely substituted derivatives and of all positions of substitution were analysed and experimental results compared with 13‐nmr data and semi empirical calculations (AMI). Although the unsubstituted heterocycle is highly resistant to nitration, electron‐donating groups such as alkoxy or alkylamino on position 8 enhance the reactivity of the imidazo[1,2‐a]pyrazine derivatives towards electrophilic substitution and, more specifically, nitration. The 13‐nmr experiments, electronic distributions and Molecular Electrostatic Potential isodensity surfaces calculated on the neutral forms are in good agreement with experimental results indicating position 3 is the most reactive position towards nitration.
Nucleophilic addition to substituted 1H‐4,5‐dihydroimidazolium salts
Authors: Salerno Alejandra , Ceriani Vanina , Perillo Isabel A.
Published: April 2009

1H‐4,5‐Dihydroimidazolium salts 1 react readily with nucleophilic reagents originating cyclic products which may be stable or become transformed into acyclic compounds maintaining the structural ethylenediamine unit. With methylmagnesium iodide compound 1e affords the expected imidazolidine, but in the case of substituted 1‐aryl‐3‐methyl‐2‐phenyl salts 1b‐d the N‐aryl‐N′‐methylethylenediamines 3b‐d and acetophenone (4) were isolated, the process representing the transfer of the C‐2 unit to a nucleophilic carbon. With alkaline cyanides salts 1 react efficiently affording α,α‐diaminonitriles 5. In these compounds the cyano group may be readily substituted by nucleophiles (hydroxyl anion, species with nucleophilic carbon and reagents that act by hydride ion transfer), in a way similar to the salts but with better yields.
Syntheses of five potential heterocyclic amine food mutagens
Authors: Tanga M. J. , Bupp J. E. , Tochimoto T. K.
Published: April 2009

The syntheses of the potential heterocyclic amine food mutagens, 3,5,7‐trimethyl‐2‐aminoimidazo‐[4,5‐b]pyridine, 1,4,7‐trimethyl‐2‐aminoimidazo[4,5‐c]pyridine, 1,6,7‐trimethyl‐2‐aminoimidazo[4,5‐c]‐pyridine, 3,4,6‐trimethyl‐2‐aminoimidazo[4,5‐c]pyridine, and 1,4,6‐trimethyl‐7‐aminoimidazo[4,5‐c]‐pyridine are described.
Substituted ethyl 2‐acyl‐3‐amino‐6‐methylthieno[2,3‐b]pyridine‐4‐carboxylates as synthons for novel heterocycles
Authors: Coppo Frank T. , Fawzi Maged M.
Published: April 2009

The triethylamine‐catalyzed reaction of 4‐substituted ethyl 2‐acyl‐3‐amino‐6‐methylthieno[2,3‐b]pyridine‐4‐carboxylates IIIa‐h with 2,2,6‐trimethyl‐4H‐1,3‐dioxin‐4‐one IV gave 4‐substituted ethyl 3‐acetyl‐2‐hydroxy‐7‐methylthieno[2,3‐b:4,5‐b′]dipyridine‐9‐carboxylates Va‐h. Some of the thienodipyridines (V) reacted with excess IV to give 5‐substituted ethyl 3‐acetyl‐4,8‐dimethyl‐2‐oxo‐2H‐pyrano[2,3‐b]‐pyrido[3′,2′:4,5]thieno[2,3‐e]pyridine‐10‐carboxylates VI.
Synthesis, structure and reactivity of imidazo[1,2‐a][1,8]naphthyridines
Authors: Gueiffier Alain , Viols Henri , Blache Yves , Chapat Jean Pierre , Chavignon Olivier , Teulade Jean Claude , Fauvelle Florence , Grassy Gérard , Dauphin Gérard
Published: April 2009

The synthesis and reactivity of imidazo[1,2‐a][1,8]naphthyridines are reported. Electrophilic substitution reactions were studied and the site of the reaction was established with the aid of high‐field 1H and 13C nmr spectra. The experimental C‐1 position reaction was correlated with a CNDO/2 calculations.
Heterocycles structurally influenced by a side chain. X. Effect of temperature and side chain on the imine‐enamine tautomerism in the quinoxalinone and pyridopyrazinone systems
Authors: Seki Taketsugu , Iwanami Yasuo , Kuwatani Yoshiyuki , Iyoda Masahiko
Published: April 2009

3‐(1‐Benzoyl)ethyl‐1H‐pyrido[2,3‐b]pyrazin‐2‐one (7), 3‐(1‐ethoxycarbonyl)ethyl‐1H‐pyrido[2,3‐b]‐pyrazin‐2‐one (8), and 3‐(1‐benzoyl)ethyl‐1H‐quinoxalin‐2‐one (9) exist only in the imine form due to the steric effect of the methyl substituent. As regards the imine‐enamine tautomerism, 3‐(β‐carbonylmethylene) derivatives of 1,2‐dihydro‐4H‐pyrido[2,3‐b]pyrazin‐3‐one such as 12 and 15–18 gradually change from the enamine form to the imine form with elevated temperatures; however, 3‐(carbonylmethylene) derivatives of 3,4‐dihydro‐1H‐pyrido[2,3‐b]pyrazin‐2‐one such as 10, 19 and 20 show little temperature effect. 2‐Phenacylidene‐1,2‐dihydro‐4H‐pyrido[3,4‐b]pyrazin‐3‐one (21) and 3‐phenacylidene‐3,4‐dihydro‐1H‐pyrido[3,4‐b]pyrazin‐2‐one (22), which exist in the enamine form, show no temperature effect.
Benzimidazo[1,2‐c]quinazoline dimers as potential antitumor agents
Authors: Braña Miguel F. , de Vega María Jesús Pérez , Perron Denise , Conlon Donna , Bousquet Peter F. , Robinson Simon P.
Published: April 2009

The 6‐substituted benzimidazo[1,2‐c]quinazoline 1 is a lead structure from our DNA intercalator program and is cytotoxic to the human colon cancer tumor line HT‐29 with an inhibitory concentration 50, IC50 of 4.00 μM. In order to try and improve the limited cytotoxicity of this class of compound we prepared a series consisting of two benzimidazo[1,2‐c]quinazoline moieties linked by a polyalkylamino bridge, of different length and substitution. The compound with the ‐NH‐(CH2)3‐N(CH3)‐(CH2)3‐NH‐bridge had an inhibitory concentration 50, IC50 of 0.5 μM. When tested in vivo, however, no clear anti‐tumor activity was produced in the human breast cancer tumor line MX‐1 or the human melanoma tumor line LOX, human tumor xenografts models.
Studies on the chemistry of O,N‐ and S,N‐containing heterocycles. 16. Investigations on the synthesis of new tricyclic β‐lactams via [2+2]cycloaddition reaction
Authors: Pippich Susanne , Bartsch Herbert , Erker Thomas
Published: April 2009

Starting from methylthioimidates 1–8 a series of corresponding tricyclic β‐lactams was synthesized via [2+2]cycloaddition with ketenes generated in situ from substituted acetyl chlorides. Dependent on the bicyclic starting material and on the substituent of the corresponding acetyl chloride N‐acetyl derivatives were obtained as by‐ or sole products.
The synthesis of azahomotryptophane derivatives. The transformation of N‐trifluoroacetyl‐5‐bromo‐4‐oxonorvaline methyl ester into 4‐(imidazo[1,2‐a]azinyl‐3)‐4‐oxohomoalanine derivatives
Authors: Škof Marko , Svete Jurij , Stanovnik Branko
Published: April 2009

Azatryptophane homologues, 4‐(imidazo[1,2‐a]pyridinyl‐3)‐ 9a‐9f and 4‐(imidazo[1,2‐a]pyrimidinyl‐3)‐4‐oxohomoalanine derivatives 9g‐91, were prepared from N,N‐dimethyl‐N′‐(pyridinyl‐2)‐ 6a‐6f and N,N‐dimethyl‐N‐(pyriniidinyl‐2)formamidines 6g‐6i, and (S)‐N‐trifluoroacetyl‐5‐bromo‐4‐oxonorvaline methyl ester (2) and its (R,S)‐isomer.
Synthesis of novel heterocycles from 2‐amino‐3‐cyanomethyl‐sulfonyl‐4,5‐dimethylfuran
Authors: Stephens Chad E. , Sowell J. Walter
Published: April 2009

The synthesis and selected reactions of the versatile heterocycle 2‐amino‐3‐cyanomethylsulfonyl‐4,5‐dimethylfuran is reported. In particular, cyclization reaction of the aminofuran yielded a number of novel furo[3,2‐b]thiazine 1,1‐dioxides. Additionally, a novel tetracyclic system, namely a pyrrolo[2′,3′:5,6]‐[1,4]thiazino[3,2‐b]quinoline 4,4‐dioxide, is prepared via an intramolecular triple‐cyclization in which the furan ring is opened and reclosed as a pyrrole.
Synthesis of nitrogen‐containing heterocycles. 8. Preparation and ring‐opening of spiro[cycloalkane‐[1′,2′,4′]triazolo[1′,5′‐c]pyrimidine] derivatives
Authors: Miyamoto Yoshiko , Yamazaki Chiji
Published: April 2009

Diaminomethylene‐ and aminomethylthiomethylenehydrazones [2] of cyclic ketones 1–8 readily reacted with ethoxymethylenemalononitrile to give spiro[cycloalkane‐1,2′‐[1,2′,4′]triazolo[1,5′‐c]pyrimidine‐8′‐carbonitrile] derivatives 12–19 through the electrocyclic reaction of the initially formed condensation products 26 in moderate to high yields. The spiro[cyclopentanetriazolopyrimidine] derivatives underwent ring‐opening at the cycloalkane moiety upon heating in solution to give 2‐alkyl‐5‐substituted‐[1,2,4]triazolo[1,5‐c]pyrimidine‐8′‐carbonitriles 20–23. When an alkyl substituent was introduced into the cyclopentane ring, cleavage of the spiro compounds occurred preferentially at the cyclopentane moiety between the spiro carbon and the more branched one. In contrast, the cyclohexane ring, especially of spiro‐5‐amino‐triazolopyrimidines 17 and 18 strongly resisted to ring‐opening under similar conditions, but those of 5‐methylthiotriazolopyrimidines 14 gave up to 17 percent of cleavage after prolonged heating in hot ethanol. 2‐t‐Butyl‐5‐methylthio‐2,3‐dihydro[1,2,4]triazolo[1,5‐c]pyrimidine‐8‐carbonitrile 25 [R3 = C(CH3)3] was highly susceptible to the cleavage even at room temperature and produced the corresponding 2‐unsubstituted triazolopyrimidine 24 with loss of the t‐butyl group.
On the synthesis and isolation of chlorocarbazoles obtained by chlorination of carbazoles
Authors: Bonesi Sergio M. , Erra‐Balsells Rosa
Published: April 2009

Carbazole (1) undergoes electrophilic aromatic substitution with various chlorinating reagents. Although 3‐chlorocarbazole (1b), 3,6‐dichlorocarbazole (1d) and 1,3,6,8‐tetrachlorocarbazole (1f) obtained by chlorination of carbazole were isolated and characterized sometime ago, 1‐chlorocarbazole (1a), 1,6‐dichlorocarbazole (1c) and 1,3,6‐trichlorocarbazole (1e) had never been isolated from the reaction mixtures. The preparation and subsequent isolation and characterization of 1a, 1b, 1c, 1d, 1e and 1f are reported (mp, tR, Rf, 1H‐ and 13C‐nmr, ms). Physical and spectroscopic properties of 1c are compared with those of 1b and 1d in order to show that the former is the major product obtained in several chlorinating processes. As chlorinating reagents, chlorine in glacial acetic acid, sulfuryl chloride, N‐chlorosuccinimide, N‐chlorosuccinimide‐silica gel, N‐chlorobenzotriazole, and N‐chlorobenzotriazole‐silica gel in dichloromethane and in chloroform have been used and their uses have been compared. The chlorination reaction of different carbazole derivatives such as 2‐hydroxycarbazole (2), 2‐acetoxycarbazole (3), 3‐bromocarbazole (4) and 3‐nitrocarbazole (5) was also studied and the corresponding chloro derivatives 2a, 2b, 2c, 2d, 3a, 3b, 3c, 3d, 3e, 3f, 4a, 4b, 4c, 4d, 5a and 5b are described for the first time. Semiempirical PM3 calculations have been performed in order to predict reactivity of carbazole (1), substituted carbazoles 2–5 and chlorocarbazoles (Scheme 1). Theoretical and experimental results are discussed briefly.
Furopyridines. XXIII. Synthesis and reactions of chloropyridine derivatives of furo[2,3‐b]‐, ‐[2,3‐c]‐ and ‐[3,2‐c]pyridine
Authors: Shiotani Shunsaku , Taniguchi Katsunori
Published: April 2009

Chlorination of the N‐oxides of furo[2,3‐b]‐ 1a, ‐[2,3‐c]‐ 1b and ‐[3,2‐c]pyridine 1c with phosphorus oxychloride afforded compounds substituted normally at the α‐ or λ‐position to the ring nitrogen, 2a, 2′a, 2b, 2c, 2′c and 2′c, and in addition, in the case of 1b, compounds substituted on the furan ring, 2′b and 2″b. The structures of these compounds were confirmed from their ir, nmr and mass spectra. The major chlorinated products 2a, 2b and 2c were converted to methoxy‐ 5a, 5b and 5c, N‐pyrrolidyl‐ 7a, 7b and 7c, and phenylthiofuropyridines 8a, 8b, and 8c.
Synthesis and structural characterization of substituted thieno[2,3‐b]pyridines from o‐chloroformyl‐1,4‐dihydropyridines
Authors: Suárez Margarita , Ochoa Estael , Pita Beatriz , Espinosa Remberto , González Leandro , Martín Nazario , Quinteiro Margarita , Seoane Carlos , Soto Jose L.
Published: April 2009

Novel 4,7‐dihydrothieno[2,3‐b]pyridines 10a‐d have been prepared in a one step procedure from the readily available o‐chloroformyl substituted 1,4‐dihydropyridines 9a‐d and ethyl mercaptoacetate in good yields. Semiempirical calculations reveal a favoured geometry with a boat conformation in the dihydropyridine system and a planar thieno ring. The calculated charge density values for the olefmic carbons (C5 and C6) are in agreement with the experimental push‐pull effect observed in the 13C nmr.
Synthesis and spectral properties of 2,3‐dihydro‐4‐(paramethylphenyl)‐7‐[(o, m‐, and p‐substituted)phenoxy]‐1H‐1,5‐benzodiazepine‐2‐thiones
Authors: Cortés Eduardo Corés , Torres Mario Martínez
Published: April 2009

A series of twelve new 2,3‐dihydro‐4‐(para‐methylphenyl)‐7‐[(o‐, m‐, and p‐substituted)phenoxy]‐1H‐1,5‐benzodiazepine‐2‐thiones. which have potentially useful pharmacological properties, has been synthesized by condensing the 3,3‐dimercapto‐1‐(p‐methylphenyl)‐2‐propen‐1‐one with 3,4‐diaminophenyl‐R‐phenyl ethers. The structure of all products was corroborated by ir; 1H‐nmr; 13C‐nmr and ms.
ω‐Dialkylaminoalkyl ethers of phenyl‐(5‐substituted 1‐phenyl‐1H‐pyrazol‐4‐yl)methanols with analgesic and anti‐inflammatory activity
Authors: Menozzi Giulia , Mosti Luisa , Fossa Paola , Mattioli Francesca , Ghia Marco
Published: April 2009

A series of carbinols 3a‐f was prepared starting from methanols 1a‐f via oxidation with pyridinium chlorochromate to aldehydes 2a‐f, followed by a Grignard reaction of the latter. Reaction of 3a‐f with ω‐chloroalkyldialkylamine hydrochlorides afforded a series of aminoether derivatives 4g‐t. Compounds 4i,m‐p,s showed a good analgesic activity in the acetic acid writhing test in mice. Moreover, compounds 4h,1,s exhibited a moderate anti‐inflammatory activity in the carrageenan‐induced edema assay in rats.
Methanetricarboxylates as key reagents for the simple preparation of heteroarylcarboxamides with potential biological activity. Part 1 reaction of methanetricarboxylates with indoline and 1,2,3,4‐tetrahydroquinoline
Authors: Kutyrev Alexander , Kappe Thomas
Published: April 2009

The reaction of methanetricarboxylates 2a,b with indoline as well as 1,2,3,4‐tetrahydroquinoline yields tricyclic 4‐hydroxy‐2(1H)‐quinolones with an ester group in position 3 (3, 8a,b). These heterocyclic esters condense with primary aliphatic, aromatic, and heteroaromatic amines to give the corresponding amides 5a‐e and 10a‐t.
A built‐in route leading to a self‐inclusion complex of 6A,6B‐(bis‐O‐p‐allyloxyphenyl)hexakis(2,3‐di‐O‐methyl)‐α‐cyclodextrin
Authors: Chen Zhen , Bradshaw Jerald S. , Habata Yoichi , Lee Milton L.
Published: April 2009

Hexakis(2,3‐di‐O‐methyl)‐α‐cyclodextrin was treated with 2,4‐dimethoxybenzene‐1,5‐disulfonyl chloride to give 6A,6B‐di‐O‐sulfonated product 5 in only a 3.0% yield. When treated with sodium p‐allyloxyphenoxide, 5 gave 6A,6B‐(bis‐O‐p‐allyloxyphenyl)hexakis(2,3‐di‐O‐methyl)‐α‐cyclodextrin (6) in a 57% yield. A careful 1H nmr analysis of 6 shows that one of the allyloxphenyl groups is in the α‐cyclodextrin cavity. This is the first intramolecular complex formed from a modified α‐cyclodextrin. Molecular modeling was used to explain the experimental facts. A novel built‐in route leading to a self‐inclusion α‐cyclodextrin complex is proposed for this reaction.
Thermal reactions of 2‐(2‐oxo‐3‐nitro‐4‐quinolinyl)malonates
Authors: Täubl A. Elisabeth , Stadlbauer Wolfgang
Published: April 2009

Depending on the ester substituent, diethyl 2‐(3‐nitro‐2‐oxo‐4‐quinolinyl)malonates 2 give upon thermolysis ethyl 2‐(3‐nitro‐2‐oxo‐4‐quinolinyl)acetates 4, whereas dimethyl 2‐(3‐nitro‐2‐oxo‐4‐quinolinyl)‐malonates 3 cyclize to give 1‐methoxycarbonylisoxazolo[3,4‐c]quinolin‐4(5H)‐ones 5. The necessary reaction conditions can be obtained easily with the help of differential scanning calorimetry.