bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxidation of 3‐hydroxykynurenine. A reexamination
Authors: Bolognese A. , Liberatore R. , Riente G. , Scherillo G.
Published: April 2009

The oxidation mixture of 3‐hydroxykynurenine (1), treated with aqueous acetic anhydride and, subsequently, with acidic methanol, yields the 1‐hydroxy‐3‐carbomethoxy‐5‐methoxy‐11‐(β‐aspartoyl‐N‐acetyl‐methyl ester)pyrido[3,2‐a]phenoxazine (5), the 1‐hydroxy‐11‐(β‐aspartoyl‐N‐acetyl‐methyl ester)‐5.H‐pyrido[3,2‐a]‐phenoxazin‐5‐one (6), the 1‐methoxy‐11‐(β‐aspartoyl‐N‐acetyl‐methyl ester)‐5H‐pyrido[3,2‐a]phenoxazin‐5‐one (6a), the l,5‐dimethoxy‐11‐(β‐aspartoyl‐N‐acetyl‐methyl ester)pyrido[3,2‐a]phenoxazine (7) and the 1‐methyl‐1(1′‐[11‐(β‐aspartoyl‐methyl esterimino)]ethenyl)ketal‐1H,5H‐pyrido[3,2‐a]phenoxazin‐5‐one (8). A probable scheme, for the compound formation, is reported.
Synthesis of substituted benzo[b]thiophenes by acid‐catalyzed cyclization of thiophenylacetals and ketones
Authors: Pié Patrick A. , Marnett Lawrence J.
Published: April 2009

Benzo[b]thiophenes substituted at the 3 position with methyl or carboxymethyl and at the 5 position with methyl, methoxy, chloro, bromo and nitro were prepared by cyclization of thiophenyl‐acetals and ketones using a suspension of polyphosphoric acid in refluxing chlorobenzene. The overall efficiency of this method is superior to literature procedures because of the lower temperature and the limited amount of PPA used.
Synthesis of 3‐bromo and 3‐methoxy‐5‐isoxazolylglycine derivatives. Hypothetic precursors of ibotenic acid
Authors: Chiarino Dario , Napoletano Mauro , Sala Alberto
Published: April 2009

A simple synthesis of 3‐bromo and 3‐methoxy analogues of ibotenic acid is reported starting from the corresponding 2‐(3‐substituted‐5‐isoxazolyl)‐2‐oxoacetic acid esters.
Color and constitution. Part 8. Some novel dyestuffs containing indoxyl residues
Authors: Katritzky Alan R. , Li Qiao‐Ling , Fan Wei‐Qiang
Published: April 2009

Novel dyes containing C‐likned indoxyl residues are prepared by two routes: (a) by the reaction of C‐electrophiles with N‐acetylindoxyl and (b) by the reaction of active methylene compounds with 2‐chloroindole‐3‐one. The visible absorption spectra are recorded and discussed.
A novel regioselective t‐butylation as applied to the synthesis of 5‐cyano‐1‐(1,1‐dimethylethyl)‐N‐methyl‐1H‐pyrazole‐4‐carboxamide
Authors: Tao E. V. P. , Aikins J. , Rizzo J. , Beck J. R. , Lynch M. P.
Published: April 2009

The title compound was synthesized in a regiocontrolled way from 5‐cyano‐1H‐pyrazole‐4‐carboxylic acid, ethyl ester (5) with isobutylene, p‐toluenesulfonic acid and methylamine.
Crystal structure, dissociation and zwitterion formation in 2,6‐diaryl‐1(3)‐oxo‐3(1)‐hydroxy‐5(7)‐imino‐7(5)‐amino‐1 H,5H‐(3‐H,7H)‐pyrazolo[1,2‐a]pyrazoles
Authors: Zvilichovsky Gury
Published: April 2009

Single crystal X‐ray analysis and quaternization of 2,6‐diphenyl‐1(3)‐oxo‐3(1)‐hydroxy‐5(7)‐imino‐7(5)‐1H,‐5H[3H,7H)‐pyrazolo[1,2‐a]pyrazole is described. The dissociation constants are determined and compared with those of 4‐phenyl‐1,2‐dimethyl‐3(5)‐oxo‐5(3)‐hydroxypyrazole and 4‐phenyl‐3,5‐diaminopyrazole. The quaternization of the latter compound is also described. The influence of electron donating substituents at the cationic moiety on the electronic spectra of such paraionic systems is discussed. The title products exist in the solid state as zwitterions and probably as covalent species in solution.
Acidity and alkylation of 4‐phenyl‐3,5‐dihydroxypyrazole and its derivatives. C versus O and N alkylation
Authors: Zvilichovsky Gury , David Mordechai
Published: April 2009

4‐Phenyl‐3,5‐dihydroxypyrazole is a relatively strong acid, with a pKa of 3.70. The effect of substitution, both in the phenyl ring and on the heterocyclic ring, on the acidity was studied. Electron attracting groups on the phenyl group enhance the acidity. Selective replacement by an alkyl group of one or two of the heterocyclic hydrogens lowers the acidity. Meerwein reagent, as well as methyl iodide bring about alkylation on carbon, whereas diazomethane and diethyl sulfate do not. Michael addition proceeds through both carbon and nitrogen.
Bridged cyanine dyes. Part 3. Zwitterionic bis‐4‐pyridyl and cationic bis‐dimethylanilino derivatives
Authors: Katritzky Alan R. , Fan Wei‐Qiang , Jiao Xue‐Shun , Li Qiao‐Ling
Published: April 2009

The preparation is described of two novel classes of bridged cyanines: zwitterionic bis‐4‐pyridyl and cationic bis‐dimethylanilino and bis‐methylcarbazolyl derivatives 5 and 11. In these compounds an uneven number of carbon atoms of the methine chain forms part of a five‐ or six‐membered ring. The visible absorption is discussed.
Synthesis and biodistribution of p‐iodophenyl analogues of a naturally occurring imidazole ribonucleoside
Authors: Suggs Jennifer A. , Srivastava Prem C.
Published: April 2009

A model iodophenyl imidazole ribonucleoside has been synthesized to study biodistribution properties in laboratory animals. The key intermediate 5‐amino‐1‐(2,3,5‐tri‐O‐acetyl‐β‐D‐ribofuranosyl)imidazole‐4‐[N‐(p‐iodophenyl)carboxamide] (5) was synthesized by coupling N‐succinimidyl‐5‐amino‐1‐(2,3,5‐tri‐O‐acetyl‐β‐D‐ribofuranosyl)imidazole‐4‐carboxylate (4) and p‐iodoaniline. Deacetylation of the intermediate compound gave 5‐amino‐1‐β‐D‐ribofuranosylimidazole‐4‐[N‐(p‐iodophenyl)]carboxamide (6). Ring annulation via diazotization of 5 gave 7‐(2,3,5‐tri‐O‐acetyl‐β‐D‐ribofuranosyl)imidazo[4,5‐d]‐v‐triazin‐[3‐N‐(p‐iodophenyl)]‐4‐one (7). Subsequent deacetylation of 7 afforded 7‐β‐D‐ribofuranosylimidazo[4,5‐d]‐v‐triazin‐[3‐N‐(p‐iodophenyl)]‐4‐one (8). The radiolabeled compounds, [125I]5 and [125I]6 were prepared in a manner similar to the corresponding unlabeled compounds except that p‐[125I]iodoaniline was used for coupling with 4. Biodistribution studies of iodine‐125‐labeled 5 and 6 were performed in female Fischer rats and tumor bearing nude mice. Compound 6 showed uptake in the brain and proliferating tissues such as tumor and bone‐marrow.
Ring‐opening reaction of 1,3,4‐oxadiazolone and 1,3,4‐oxadiazolinethione: Reaction of 2‐phenyl‐1,3,4‐oxadiazolin‐5‐one and 2‐phenyl‐1,3,4‐oxadiazoline‐5‐thione with amines
Authors: Saegusa Yasuo , Harada Shigeo , Nakamura Shigeo
Published: April 2009

The ring‐opening abilities of amines toward 1,3,4‐oxadiazolines, 2‐phenyl‐1,3,4‐oxadiazolin‐5‐one (1a) and 2‐phenyl‐1,3,4‐oxadiazoline‐5‐thione (1b), were investigated with relation to their basicities or pKb values. Oxadiazolines 1a and 1b were easily reacted with amines such as benzylamine and aniline, but not with p‐nitroaniline, to form the corresponding ring‐opening adducts. The reactions of both 1a and 1b with o‐phenylenediamine produced benzodiazoles with the liberation of benzoylhydrazide, whereas the reactions with o‐aminobenzamide furnished quinazolines with the liberation of ammonia. o‐Aminophenol and o‐aminothiophenol were also reacted with 1a and 1b both of them giving 1,5‐dibenzoylcarbohydrazide from 1a and 1,2‐dibenzoylhydrazine from 1b. From the conditions affording the corresponding ring‐opening adducts or reaction products, the ring‐opening abilities of the amines toward 1a and 1b are in good correlation with the strength of their basicities or pKb values. The ring‐opening of oxadiazolines were proved to occur with anilines. Therefore, the other reactions are also supposed to proceed via the ring‐opening steps.
The study of atropoisomers of meso‐tetrakis[2.2]paracyclophanylporphyrin
Authors: Czuchajowski Leszek , Goszczynski Stefan , Wisor Antoni K.
Published: April 2009

Theoretical considerations of atropoisomers of the title compound have revealed the existence of a large number of stable isomeric species. Syntheses, carried out according to two procedures at widely separated temperatures, resulted in the formation of mixtures of atropoisomers in good yield. Two isomeric fractions have been separated and characterized. Some analytical methods have been worked out and have proved useful in separational techniques.
Synthesis of new [[(3‐substituted‐5‐isoxazolyl)‐alkyliden]iminooxy]aminopropanol derivatives
Authors: Chiarino D. , Ferrario F. , Napoletano M. , Sala A.
Published: April 2009

The preparation of new [[(3‐substituted‐5‐isoxazolyl)alkyliden]iminooxy]aminopropanol compounds is reported starting from the corresponding 1‐isoxazolylalkanones. The 1H‐ and 13C‐nmr studies, carried out to establish the Z‐ and E‐configuration of new derivatives, are also described.
Tricyclic heterocyclic systems: Pyrazolo[5′,4′:4,5]‐and pyrazolo‐[3′,4′:4,5]pyrano[2,3‐b]pyridine derivatives
Authors: Melani Fabrizio , Cecchi Lucia , Colotta Vittoria , Palazzino Giovanna , Filacchioni Guido
Published: April 2009

By reacting 2‐chloronicotinoyl chloride with acetyl or benzoyl acetate, ethyl 2‐methyl‐ or 2‐phenyl‐4‐oxopyrano[2,3‐b]pyridine‐3‐carboxylates were prepared. The nucleophilic rearrangement of the latter with hydrazines gave rise to the title compounds.
Derivatives of 2‐oxo‐3(2H)‐benzothiazolineacetonitrile and related compounds. I. Synthesis of N‐hydroxy‐2‐oxo or thioxo‐3(2H)‐benzothiazolineethanimidamide and related products
Authors: D'Amico John J. , Marvel John T. , Bollinger Frederic G.
Published: April 2009

The following methods afforded the titled acetonitriles 1–5 in excellent yields: (1) the reaction of the appropriate 2‐benzothiazolinones with chloroacetonitrile under basic conditions and (2) the dehydration of the appropriate 2‐oxo‐3(2H)‐benzothiazolineacetamides with phosphorus oxychloride or pentoxide. The reaction of the acetonitriles 1–5 and 2‐thioxo‐3(2H)‐benzothiazolmeacetonitrile with hydroxylamine afforded the titled compounds 6–11. Supporting nmr and mass spectral data are discussed.
Some reactions of 1‐alkyl‐1,2,3,4‐tetrahydropyridines with organic azides. Synthesis of 1‐alkylpiperidylidene‐2‐sulfonamides
Authors: Warren Brent K. , Knaus Edward E.
Published: April 2009

The 1,3‐dipolar cycloaddition reaction of 1‐substituted‐1,2,3,4‐tetrahydropyridines4a‐dwith organic azides5afforded the respective 1‐substituted‐piperidylidene‐2‐sulfonamides6. In contrast, the reaction of (E)‐1‐(1‐propenyl)‐1,2,3,4‐tetrahydropyridine (4e) with 4‐chlorobenzenesulfonyl azide yielded6mas well as 1‐(4‐chlorophenyl)sulfonimine‐1,2,3,4‐tetrahydropyridine (7) arising from addition of the azide to the (E)‐1‐(1‐propenyl) substituent of4e.
A new and convenient synthesis of N‐substituted perhydroazepines from adipaldehyde and primary amines with tetracarbonylhydridoferrate, HFe(CO), as a selective reducing agent
Authors: Shim Sang Chul , Doh Chil Hoon , Kim Tae Jeong , Lee Hak Ki , Kim Ki Doo
Published: April 2009

Ethanolic tetracarbonylhydridoferrate combined with adipaldehyde is very efficient for the selective transformation of an amino group into perhydroazepine. A large variety of both aliphatic and aromatic amines react with adipaldehyde in the presence of tetracarbonylhydridoferrate at room temperature and carbon monoxide to give the corresponding N‐alkyl‐ and N‐arylperhydroazepines in good to excellent yields.
Synthesis of cis‐4‐methyl‐3‐phenylpyrrolidines as potential dopaminergic agonists
Authors: Crider A. Michael , Sylvestri Susan C. , Tschappat Kathryn D. , Dick Ronald M. , Leader W. Greg
Published: April 2009

cis‐3‐(3,4‐Dihydroxyprienyl)4‐methyl‐1‐(n‐propyl)pyrrolidine (23) was synthesized and evaluated for dopaminergic activity. The synthesis of 23 involved selective 4‐acylation of the 3‐phenylpyrrolidine‐2,5‐dione 15 and cis‐addition of hydrogen to a 4‐methyl‐3‐phenyl‐3‐pyrroline 4. Pharmacological evaluation of 23 showed that introduction of a cis‐4‐methyl group into the 3‐phenylpyrrolidine nucleus decreases dopaminergic activity.
Chemistry of Peri‐condensed pyrroles. Synthesis of 4H‐naphtho[1,4‐def]carbazole. A new route to nitrotriphenylenes
Authors: Klemm L. H. , Hall Eliot , Sur Sandip K.
Published: April 2009

Reaction of 1‐nitrotriphenylene (7a) with triethylphosphite (Cadogan reaction) produces 4H‐naphtho[1,4‐def]carbazole, a likely component of fossil fuels. Surprisingly 7a and its 2‐isomer are obtained from treatment of triphenylene with sulfuric acid/trifluoroacetic anhydride in nitromethane. Correlation between ultraviolet spectra and substitution reactions in peri‐condensed pyrroles and thiophenes is presented.
A facile route to 4,5,6,7‐tetrahydrothiophenes and benzothiophenes
Authors: Nishio Takehiko , Okuda Norikazu , Kashima Choji
Published: April 2009

2‐Substituted tetrahydro‐ and cyclopentathiophenes 2 were produced in high yields by treatment of the semi‐cyclic trisubstituted 1,4‐diketones 1 such as 2‐phenacylcyclohexan‐1‐one, 2‐acetonylcyclohexan‐1‐one, and 2‐phenacylcyclopentan‐1‐one, with Lawesson's reagent.
Reactions of pyridinium or isoquinolinium ketene dithioacetals with aromatic N‐imines and S‐imines
Authors: Tominaga Yoshinori , Hosomi Akira
Published: April 2009

Reactions of ketene dithioacetals, 1‐[1‐substituted 2,2‐bis(methylthio)ethenyl]pyridinium 1a‐i or ‐isoquinolinium 2a,b iodides with aromatic N‐imines, 1‐aminopyridinium 3a‐1,1‐aminoquinolinium (4), and 2‐amino‐isoquinolinium (5) mesitylene sulfonates gave the corresponding 2‐methylthioimidazo[1,2‐a]pyridines 9a‐k, 2‐methylthiopyrazolo[1,5‐a]pyridines 11a‐q, 2‐methylthioimidazo[2,1‐a]isoquinoline derivatives 10a,b and 2‐methylthiopyrazolo[1,5‐a]quinoline (12). The benzoyl compounds, 1‐[1‐benzoyl‐2,2‐bis(methylthio)ethenyl]‐pyridinium iodides 1g,h,i reacted with N‐imine 3a to give the 3‐benzoyl‐2‐methylthioimidazo[1,2‐a]pyridines 9h‐k. The reaction of pyridinium ketene dithioacetals 1a,f,g (R1 = COOEt, COPh, and CN) with substituted pyridinium N‐imines having an electron‐withdrawing group on the pyridine ring afforded only the corresponding pyrazolo[1,5‐a]pyridine derivatives 11j‐r in good yields. Reactions of ketene dithioacetals with various S‐imines are also described. Possible mechanisms for the formation of 9 and 11 are described.
Total synthesis of γ‐lycorane
Authors: Sugiyama Naokazu , Narimiya Mamoru , Iida Hideo , Kikuchi Toyohiko
Published: April 2009

The homophthalimide derivative was easily converted to the cis‐octahydrophenanthridine derivative in good yield and this to γ‐lycorane 1 (1).
A rare case of three rearrangements during the cycloaddition‐elimination reaction of 4‐methyl‐5‐phenylimino‐Δ2‐1,2,3,4‐thiatriazoline with 2‐pyridyl isothiocyanate
Authors: L'abbé Gerrit , Allewaert Kathy , Toppet Suzanne
Published: April 2009

2‐Pyridyl isothiocyanate (7), with its electrophilic and basic properties, gives a series of ring‐transformation reactions with 4‐methyl‐5‐phenylimino‐1,2,3,4‐thiatriazoline (1) at 60°. Two dithiazolidines, 8 and 10, are formed as major products at an early stage of the reaction, whereas two thiadiazolidines, 9 and 11, predominate at the end. The mechanism (Schemes II and III) has been elucidated by following the reaction course under a variety of conditions and by analyzing the products by 13C nmr spectroscopy.
The reactions of thiosemicarbazides and 5‐halovalerophenones
Authors: Kane John M. , Stewart Kenneth T.
Published: April 2009

5‐Halovalerophenones reacted with substituted thiosemicarbazides affording two different heterocyclic ring systems. Reactions with 4‐substituted thiosemicarbazides gave 3‐aryl‐4,5,6,7‐tetrahydro‐1H‐1,2‐diazepine‐1‐carbothioamides whereas reactions with 2,4‐dimethylthiosemicarbazide gave hexahydro‐1,3‐dimethyl‐8a‐aryl[1,2,4]triazolo[1,5‐a]pyridine‐2(3H)‐thiones.
Synthesis and aldose reductase inhibitory activity of N‐1,N‐4‐disubstituted 3,4‐dihydro‐2(1H)‐quinoxalinone derivatives
Authors: Sarges Reinhard , Lyga John W.
Published: April 2009

Synthetic routes have been developed for the preparation of 4‐acylated, 4‐benzenesulfonylated, and 4‐methylated 3,4‐dihydro‐2(1H)‐quinoxalinone‐1‐acetic acids. One example of the corresponding propionic acid has also been made. These compounds have been evaluated for their ability to inhibit bovine lens aldose reductase in vitro. Some members from this series also show weak activity in vivo, inhibiting sorbitol formation in sciatic nerves of streptozotocin‐diabetic rats.
Syntheses d'aryltetrahydropyrannyl ethers
Authors: Cottet Françoise , Cottier Louis , Descotes Gérard , Srivastava Rajendra Mohan
Published: April 2009

L'addition de méthoxyphénols1sur le dihydropyranne en milieu acide donne des produitsC‐ et/ouO‐tétrahydropyrannylés3et4dont le pourcentage est fonction du nombre de substituants méthoxy et de la force du catalyseur acide. Les aryl tétrahydropyrannyléthers, orthocarbonylés9sont obtenus selon une réaction de Mitsunobu. Les rendements dependent de la nature des substituants sur les composés aromatiques et hétérocycliques.
On triazoles. XVII. The reaction of 5‐amino‐1,2,4‐triazoles with N‐heterocyclic β‐oxo‐esters
Authors: Reiter József , Rivó Endre
Published: April 2009

Pyrrolo[3,4‐d]‐1,2,4‐triazolo[1,5‐a]pyrimidinone (3d), pyrido[3,4‐d]‐1,2,4‐triazolo[1,5‐a]pyrimidinone (3e) and pyrido[4,3‐e]‐1,2,4‐triazolo[1,5‐a]pyrimidinone (4e) derivatives representing three new ring systems were synthesised. Their structure was proved by comparing their uv and cmr spectra with those of the known benzo‐ and thieno‐1,2,4‐triazolo[1,5‐a]pyrimidinones used as model compounds.
Structural studies of bicyclomycin
Authors: Kohn Harold , Abuzar Syed , Korp James D. , Zektzer Andrew S. , Martin Gary E.
Published: April 2009

The complete 1H and 13C nmr assignments for both bicyclomycin (1) and bicyclomycin‐3′‐ethyl carbamate (2) were achieved through the combined use of a series of nmr techniques. Extensive use of the long range heteronuclear multiple quantum chemical shift correlation experiment (HMBC) permitted the assignments of all the exchangeable protons as well as the 2,5‐piperazinedione carbonyl carbons in both compounds. The X‐ray crystallographic structure of 2 was determined and compared to the reported structure of bicyclomycin. Compound 2 crystallizes in the orthorhombic space group P212121 with four molecules in a unit cell having dimensions a = 7.931(2), b = 10.834(4), and c = 24.468(7) Å. The structure refined to a final R value of 6.2%.
Synthesis and studies of piperidinone, the major metabolite of a new antidepressant drug S 3344
Authors: Berthelot Pascal , Vaccher Claude , Devergnies Monique , Flouquet Nathalie , Debaert Michel
Published: April 2009

The synthesis of 1‐(4‐fluorobenzyl)‐6‐isopropyl‐2‐piperidinone 7a, a major metabolite of a new antidepressant S 3344, is described and then substituted with various substituents. The 1H and 13C nmr provide information on their structure.
Synthesis and in vitro biological activity of some 7‐[hydrazino], ‐[hydrazonyl] and ‐[pyrazolyl]quinolone‐3‐carboxylic acids
Authors: Ziegler Carl B. , Kuck Nydia A. , Harris Sonja M. , Lin Yang‐I
Published: April 2009

1‐Ethyl‐6‐fluoro‐7‐hydrazino‐1,4‐dihydro‐4‐oxoquinoline‐3‐carboxylic acid (8) has been prepared and served as a versatile intermediate from which a number of hydrazone, pyrazole and dihydropyridazine derivatives were synthesized. The in vitro biological activity of some of these derivatives is reported.
Synthesis of 8,9‐difluoro‐2‐methyl‐6‐oxo‐1,2‐dihydropyrrolo[3,2,1‐ij]quinoline‐5‐carboxylic acid
Authors: Parikh Vinod D. , Fray Andrew H. , Kleinman Edward F.
Published: April 2009

A new and efficient seven‐step synthesis of 8,9‐difluoro‐2‐methyl‐6‐oxo‐1,2‐dihydropyrrolo[3,2,1‐ij]‐quinoline‐5‐carboxylic acid (9), an important intermediate used in the synthesis of quinolone antibacterials, has been developed beginning with commercially available 2,3,4‐trifluoronitrobenzene. Selective displacement of the 2‐fluorine of the starting material with the anion of ethyl acetoacetate and subsequent hydrolysis and decarboxylation affords the arylacetone derivative 11. Reduction of the ketone and nitro groups of 11 followed by condensation with diethyl ethoxymethylenemalonate gives 14, which is cyclized to the indole derivative 15 by the Mitsunobu procedure. Friedel‐Crafts cyclization of 15 and acid hydrolysis gives the title compound 9.
Asymmetric reaction. XV. Structure and relative configuration of a reductive dimerization product of ethyl phenylglyoxylate, diethyl diphenyltartrate
Authors: Ohgo Yoshiaki , Kimura Michio , Takeuchi Seiji
Published: April 2009

The hydrogenation of ethyl phenylglyoxylate catalyzed by bis(dimethylglyoximato)cobalt(II)‐quinine gave a novel reductive dimerization product, diethyl diphenyltartrate, with a slight optical activity. The crystals obtained from its benzene‐hexane solution were investigated by X‐ray diffraction method. The crystal is triclinic, space group p1, a = 10.078(3), b = 10.283(2), c = 9.781(3) Å, α = 109.80(2), β = 102.35(3), γ = 78.50(2)°, Z = 2, V = 922.7 Å3, Dc = 1.29 g cm−3,μ = 7.46 cm−1 for Cu Kα. The structure was solved by the direct method, and refined by a block‐diagonal least‐squares procedure: R = 0.059 for 2568 reflections with | Fo | >3σ(| Fo | ). The relative configuration around the two chiral carbons indicated that the molecule is in the threo‐form, and the Newman projection showed that the molecule has the staggered conformation. There were two relatively strong intramolecular hydrogen bonds between the two hydroxyl groups and the two carbonyl oxygen atoms of ethoxycarbonyl groups.
Total assignment of the proton NMR spectrum of dinaphtho[1,2‐B:2′,3′‐d]thiophene
Authors: Johnston Milton D. , Martin Gary E. , Castle Raymond N.
Published: April 2009

Recently, there has been some question regarding the 1H‐nmr spectrum of dinaphtho[1,2‐b‐2′,3′‐d]‐thiophene. A recent study has reported differences in some of the proton resonance positions from results of earlier work. We report the total assignment of the 1H‐nmr spectrum of the title compound using a combination of 1H‐COSY and one dimensional NOE‐difference spectroscopy (NOEDS).
Synthesis of a pyrrolo annulated pyrido[2,3‐D]pyrimidine as a potential nonclassical antifolate
Authors: Gangjee Aleem , Patel Jasmin , Lin Fu‐Tyan
Published: April 2009

Cyclocondensation of 2,4,6‐triaminopyrimidine (4) with ethyl N‐benzyl‐4‐oxo‐3‐pyrrolidine carboxylate (5) in diphenyl ether regiospecifically afforded a new tricyclic, angular 1,3,8‐trisubstituted pyrrolo[3′,4′:4,5]‐pyrido[2,3‐d]pyrimidine‐6‐one 1 in excellent yield. The ketoester 5 was prepared by a literature method. Compound 1 in addition to being a new heterocyclic system is an important key precursor to a variety of classical and nonclassical tricyclic, 5‐deaza analogues of the folate cofactor 5,10‐methylenetetrahydrofolate 3.
Steroidal imidazopyridines and lactam imidazopyridines
Authors: Nikolaropoulos Sotirios , Catsoulacos Panayotis
Published: April 2009

Condensation of 17β‐acetoxy‐2α‐bromo‐5α‐androstan‐3‐one with unsubstituted and substituted amino‐pyridines, gives the corresponding 17β‐acetoxy‐5α‐androstanimidazo[1,2‐a]pyridines. Treatment of 16α‐bromo‐3‐aza‐A‐homo‐4α‐androsten‐4,17‐dione with 2‐aminopyridine or methyl‐2‐aminopyridine produces the corresponding 3‐aza‐A‐homo‐4α‐androsten[16,17:2′,3′]imidazo[1,2‐a]pyridines. Similarly, from 2α‐bromo‐17β‐acetamido‐5α‐androstan‐3‐one and methylaminopyridine the 17β‐acetamido‐5α‐androstan[2,3:2′,3′]imidazo[1,2‐a]methylpyridine has been obtained.

The structure of the compounds was apparent from their chemical properties and spectral data (ir, uv and nmr).
Imidazolyl derivatives of the thiochroman ring
Authors: Cozzi Paolo , Pillan Antonio
Published: April 2009

The synthesis of 2‐(1H‐imidazol‐1‐yl)‐4H‐1‐benzothiopyran‐4‐ones 3 from 3‐bromo‐4H‐1‐benzothiopyran‐4‐ones 1 and imidazole is described. The reaction of 1 with secondary amines gives the corresponding 3‐amino‐thiochromones 11. Compounds 3 can be oxidized to the sulfones 4 from which the thiochromanols 5 and thiochromene 7 can be easily obtained. 3‐Bromo‐2,3‐dihydro‐6‐methyl‐4H‐1‐benzothiopyran‐4‐one 12 and imidazole led by dehydrohalogenation to thiochromone, while the ketal 13 rearranged to benzo[b]thiophene 16.
Investigation of the reactions of 2‐hydrazino‐benzimidazoles with β‐diketones: Synthesis of 2‐(3,5‐disubstituted‐ 1H‐pyrazol‐1‐yl)benzimidazoles
Authors: Joshi Krishna C. , Jain Renuka , Dandia Anshu , Sharma Kanti
Published: April 2009

Reaction of 2‐hydrazinobenzimidazoles with β‐diketones in neutral and acidic media revealed that 2‐(3,5‐disubstituted‐1H‐pyrazol‐1‐yi)benzimidazoles are formed in the former case, whereas hydrazones are obtained in acidic medium. Further the alkylation of > NH of the title compound was investigated. Characterisation of these products have been done by elemental analysis, ir, pmr, 19F nmr, 13C nmr and mass spectral studies.
Antimykotische wirkstoffe. XXI. Aliphatisch und alicyclisch substituierte chlor‐diallylamino‐1l,3,5‐triazine
Authors: Kreutzberger Alfred , Schläfer Irmtraut
Published: April 2009

Aus der nucleophilen Substitution eines Chloratoms in 2,4‐Dichlor‐6‐(diallylamino)‐1,3,5‐triazin (1) durch Amine (2a‐g) gehen die Alkylamino‐ und Cycloalkylamino‐chlor‐(diallylamino)‐1,3,5‐triazine (3a‐g) hervor. Von den zur Untermauerung des Strukturtyps 3 herangezogenen spektroskopischen Daten sind besonders charakteristisch die durch das 1,3,5‐Triazinringsystem hervorgerufene IR‐Bande bei 800 cm−1, die den Allylgruppen zuzuordnenden vier 1H‐NMR‐Signale zwischen 4,1–6,1 ppm und das beim massenspektroskopischen Abbau auftretende Rumpfkation m/e 158. Auffallend ausgeprägt sind in Verbindungsklasse 3 antimykotische, trichomonazide und herbizide Wirksamkeit.
Mannich reactions of heterocycles with dimethyl(methylene) ammonium chloride: A high yield, one‐step conversion of estazolam to adinazolam
Authors: Gall Martin , Kamdar Bharat V. , Lipton Michael F. , Chidester Connie G. , Duchamp David J.
Published: April 2009

The readily prepared ammonium salt, (CH3)2N+ = CH2Cl−, 4, functionalized heterocycles differently, but in a predictable fashion, under neutral, basic or acidic conditions. Triazolo‐ and imidazobenzophenones 1b′ and 5, which primarily underwent intramolecular isomerization to indolols 2a′ and 6a rather than intermolecular electrophilic substitution under conditions of the normal aqueous Mannich reaction, were converted with 4 to the desired benzophenone derivatives, 1c′ and 7, respectively, in moderate yields. The 1‐unsubstituted triazolo‐ or imidazobenzodiazepines, 10a (estazolam) and 10b, were transformed to the corresponding 1‐(dimethylamino)methyl derivatives, 11a (adinazolam) and 11b, in good to moderate yields (61% and 32%, respectively.) Under acidic reaction conditions, 1‐methyl triazolobenzodiazepine, 10d (alprazolam), afforded 12e, the product of attack at C‐4 of the triazolo[4,3‐a][1,4]benzodiazepine ring system. Under strongly basic conditions in which the anion of 10d was generated prior to reaction with 4, both 12e and its isomer, 15, were formed. These results complement the report that 4 may be used to functionalize the 1‐methyl position of triazolobenzodiazepines, and further demonstrate the versatility of reagent 4 in heterocyclic synthesis.
Synthesis of 2‐hetaryl‐6H‐pyrazolo[3,4‐d]‐1,2,3‐triazoles
Authors: Rangnekar D. W. , Dhamnaskar S. V.
Published: April 2009

A novel efficient synthesis of 2‐hetaryl‐4‐methyl‐6‐phenyl‐6H‐pyrazolo[3,4‐d]‐1,2,3‐triazoles was achieved by the reaction of 5‐amino‐3‐methyl‐4‐nitroso‐1‐phenyl‐1H‐pyrazole with heterocyclic amines followed by air oxidation in the presence of cupric acetate.
1,3‐Dipolar cycloadditions of azomethine ylides with dipolarophiles. II. Synthesis of pyrrolizidines
Authors: Orsini F. , Pelizzoni F. , Forte M. , Sisti M. , Merati F. , Gariboldi P.
Published: April 2009

Substituted pyrrolizidines have been synthesized by 1,3‐dipolar cycloaddition of various dipolarophiles with the azomethine ylide generated by treatment of proline with benzaldehyde in dimethylsulfoxide. The regio‐ and stereochemical outcome of the reaction as well as the stability of the isomers obtained are discussed.
2‐(methylpyridyl)‐X‐azolo[4,5‐b]pyridines: Bases, salts and polymethine dyes
Authors: Savarino Piero , Carpignano Rosarina , Viscardi Guido , Barni Ermanno , Di Modica Gaetano
Published: April 2009

A series of heterocyclic bases containing 2‐(methyl‐3‐pyridyl)‐X‐azolo[4,5‐b]pyridine was synthesized and the obtained bases were then quaternized. The structures of the salts were assessed by nmr and uv spectroscopy. From quaternary salts, styryl dyes were prepared and similarly characterized. The physical and spectroscopic data of the compounds were compared with those of other isomers, previously described, and of the corresponding benzo‐X‐azole derivatives.
4‐Diazomethylcoumarins and related stable heteroaryldiazomethanes. Thermal conversion into condensed pyrazoles
Authors: Ito Keiichi , Maruyama Junko
Published: April 2009

4‐Diazomethyl‐substituted coumarins, 1‐methyl‐2(1H)‐quinolinones,1‐thiocoumarin and their tricyclic analogs were found to be easily cyclized into the corresponding pyrazole isomers condensed with heteroaromatics. Thermodependent feature of these conversions and the remarkably accelerating effect of the alkyl substituent peri to the diazomethyl group were realized. Some other diazomethyl compounds connected with 2‐pyridinone, 3‐pyrazolone, chromone and 1‐thiochromone were prepared, and their stability and thermal properties were compared.
6‐(substituted phenyl)‐5‐methyl‐4,5‐dihydro‐pyridazin‐3(2H)‐ones of medicinal interest. The synthesis of SK&F 94836 and SK&F 95654
Authors: Burpitt B. E. , Crawford L. P. , Davies B. J. , Mistry J. , Mitchell M. B. , Pancholi K. D. , Coates W. J.
Published: April 2009

Two synthetic routes to the dihydropyridazinone‐cyanoguanidine 4 (SK&F 94836) are described, both proceeding via the anilino compound 6. An efficient synthesis of the dihydropyridazinone‐pyridone 5 (SK&F 95654) is reported. This synthesis proceeds via the fluoro‐keto‐acid 24, with subsequent displacement of the fluoro substituent by 4‐pyridone. The surprising effectiveness of water as a solvent in this reaction has been highlighted.
Amidomethylation of phenanthridines: Synthesis and structure determination by 1H NMR
Authors: Freter K. R. , Grözinger K. G. , Kriwacki R. W.
Published: April 2009

Phenanthridine reacts with N‐(hydroxymethyl)phthalimide to give, in two steps, three monosubstituted aminomethylphenanthridines. The three isomers were separated by chromatography on silica gel. The position of substitution was determined using one‐ and two‐dimensional 1H nmr methods.
Preparation and characterization of nickel(II), copper(II) and palladium(II) complexes with 5,14‐dihydro‐7,16‐diethyl‐dipyrazo[b,i][1,4,8,11]tetraazacyclotetradecine
Authors: Hashimoto Mamoru , Izuchi Nobuko , Sakata Kazunori
Published: April 2009

A novel macrocycle, 5,14‐dihydro‐7,16‐diethyldipyrazo[b,i][1,4,8,11]tetraazacyclotetradecine, has been synthesized from 1,2‐diaminopyrazine and 2‐ethyl‐3‐ethoxyacrolein. The absorption bands appearing in the energy range greater than 20000 cm−1 were attributable to the π → π transitions. The bands in the range of the 20100–23300 cm−1 show more bathochromic shift and greater intensity than those observed for corresponding 5,14‐dihydro‐7,16‐diethyldibenzo[b,i][1,4,8,11]tetraazacyclotetradecine and/or 5,14‐dihydro‐7,16‐diethyl‐(Z)‐dipyrido[b,i][1,4,8,11]tetraazacyclotetradecine. The nickel(II), copper(II) and palladium(II) complexes of 5,14‐dihydro‐7,16‐diethyldipyrazo[b,i][1,4,8,11]tetraazacyclotetradecine have been synthesized using a metal template reaction. In 1H and 13C nmr spectra, the signals of annulene skeleton for metal‐free ligand and its complexes were found to observe in the lower field than those of the dibenzoanalogue.
Pyridazines with heteroatom substituents in position 3 and 5. 2. Regioselective introduction of mercapto groups in pyridazines
Authors: Olesen Preben H. , Kappe Thomas , Becher Jan
Published: April 2009

The nucleophilic substitution of halogen in 3,5‐dichloro‐6‐phenylpyridazine 1, 5‐chloro‐2‐methyl‐6‐phenylpyridazin‐3(2H)‐one 13 as well as in 3‐chloro‐2‐methyl‐6‐phenylpyridazin‐5(2H)‐one 14 with methoxy, ethoxy and the 2‐methyl‐2‐propanethiolate anion is described. In the last type of compounds the t‐butylthio groups can be eliminated regioselectively with Lewis acids, resulting in the formation of monomercapto and mono‐thiopyridazines.
Benzimidazole condensed ring systems. 2. New synthesis of substituted 1‐oxo‐1H,5H‐pyrido[1,2‐a]benzimidazole‐4‐carbonitriles and related derivatives
Authors: Rida Samia M. , Soliman Farid S. G. , Badawey El‐Sayed A. M. , Kappe Thomas
Published: April 2009

The synthesis of some 3‐substituted and 2,3‐disubstituted‐1‐oxo‐1H,5H‐pyrido[1,2‐a]benzimidazole‐4‐carbo‐nitriles 5,6 by fusing 1H‐benzimidazole‐2‐acetonitrile 1 with some β‐keto esters 2,4 in the presence of ammonium acetate or with ethyl β‐aminocrotonate 3 is described. The tricyclic compounds were converted to their N‐5 methyl of N‐5 ethyl derivatives 8,9. Vilsmeir‐Haack formylation of 3‐methyl‐1‐oxo‐1H,5H‐pyrido[1,2‐a]‐benzimidazole‐4‐carbonitrile 5a afforded its 2‐formyl derivative 10. Chlorination of 5 and 6 with phosphorus oxychloride yielded the respective 1‐chloropyrido[1,2‐a]benzimidazole‐4‐carbonitriles 11,12 which were utilized to prepare the 1‐azido, 1‐amino, 1‐piperidino and 1‐methoxy derivatives of the ring system. Compound 11a exhibited strong in vitro activity against S. aureus. Four compounds were screened against P‐388 lymphocytic leukemia in mice but were inactive.
Synthesis of N(3‐dimethylaminopropyl)‐6‐substituted naphtho[2,1‐b]thiophene‐4‐carboxamides
Authors: Ming Yang , Boykin David W.
Published: April 2009

A series of N‐(3‐dimethylaminopropyl)‐6‐substituted naphtho[2,1‐b]thiophenes‐4‐carboxamides have been synthesized. 6‐Substituted naphtho[2,1‐b]thiophene‐4‐carboxylic acids were obtained upon oxidative‐photo‐cyclization of α‐(2‐thienyl)‐β‐arylacrylic acids. The naphtho[2,1‐b]thiophene carboxylic acids were converted to the corresponding amides through their acid chlorides or, in one case, by use of 1,1‐carbonyldiimidazole coupling of the amine and the acid.
Synthesis of 2‐amino‐6,7‐dihydrothieno‐[3′,2′:5,6]pyrido[2,3‐d]pyrimidin‐4‐one
Authors: Taylor Edward C. , Pont Joseph L. , Warner John C.
Published: April 2009

2‐Amino‐6,7‐dihydrothieno[3′,2′:5,6]pyrido[2,3‐rf]pyrimidin‐4‐one (1) was prepared in three steps from S‐(3‐butynyl)thiosemicarbazide hydroiodide (3) and diethyl ketomalonate. The featured step in this synthetic sequence was an intramolecular Diels‐Alder reaction of the in situ generated 3‐(3‐butynylthio)‐6‐carboethoxy‐5‐chloro‐1,2,4‐triazine (9) to provide the key intermediate 5‐carboethoxy‐6‐chloro‐2,3‐dihydrothieno‐[2,3‐b]pyridine (6). In the course of studies directed toward the preparation of 1, thermolysis of 3‐(3‐butynyl‐thio)‐6‐carboethoxy‐1,2,4‐triazin‐5(2H)‐one (2) was found to involve competitive intramolecular Diels‐Alder and intramolecular coplanar cycloamination processes, providing the 2,3‐dihydrothieno[2,3‐b]pyridin‐6(7H)‐one (4) and the 1,3‐thiazino[3,2‐b]‐1,2,4‐triazin‐3‐one (5) derivatives, respectively.
Difference in thermal behaviour between 1‐ and 2‐alkyl‐5‐(methoxycarbonyldiazomethyl)tetrazoles
Authors: L'Abbé Gerrit , Gelinne Marleen , Toppet Suzanne
Published: April 2009

In continuation of previous work, isomeric diazoester‐substituted alkyltetrazoles 5 and 6 have been synthesized by the diazo‐transfer method and studied in thermolysis reactions. Whereas the N‐1 alkyl derivatives 5 give norcaradienes 7 in benzene solution and imidazotetrazoles 12 in acetonitrile, the more thermostable N‐2 alkyl isomers 6 yield fluxional norcaradiene‐cycloheptatriene systems, 10 – 11, and ox‐azoles 13.
The reaction of 2‐substituted‐4,5‐dichloro‐3(2H)‐pyridazinones with alkoxides and alkylthiolates
Authors: Lyga John W.
Published: April 2009

The reaction of 2‐substituted‐4,5‐dichloro‐3(2H)‐pyridazinones 1a‐b with alkoxides and alkylthiolates was investigated. Regiospecific displacement of either the 4 or 5 chlorine atom could be achieved in most cases by appropriate selection of the reaction solvent.
A convenient one pot synthesis of substituted 4‐aminobenzopyrano[3,4‐c]pyridinones
Authors: Rangnekar D. W. , Dhamnaskar S. V.
Published: April 2009

A new synthesis of substituted 4‐aminobenzopyrano[3,4‐c]pyridinones was achieved in one pot by the condensation of an o‐hydroxyaraldehyde and a cyclic or acylic methyl ketone in the presence of ammonium acetate in refluxing ethanol followed by the treatment of malononitrile and subsequent hydrolysis with hydrochloric acid in situ.
Synthesis of a novel tricyclic 4‐quinolone. Incorporation of a spiro‐cyclopropyl group at N1 by bridging to C2
Authors: Schroeder Mel C. , Kiely John S.
Published: April 2009

An important pharmacophore in many quinolone antiinfectives is the N1 cyclopropane. By incorporating the cyclopropane into a N1 to C2 bridge, the first quinolone substrate incorporating a spiro fused cyclopropane, 8,9,10‐trifluoro‐2,3,4,6‐tetrahydro‐6‐oxospiro[1H‐benzo[c]quinolizine‐1,l‐cyclopropane]‐5‐carboxylic acid, ethyl ester (8), was prepared.
A stereochemical investigation of 1,3‐diphenyl‐4‐methyl‐1,3‐diazolidines and its related compounds via NMR
Authors: Nishiyama Tomihiro , Nanno Yukio , Yamada Fukiko
Published: April 2009

Four 1,3‐diphenyl‐4‐methyl‐1,3‐diazolidines and two isomeric 2,5‐diphenyl‐3‐methyl‐1,2,5‐thiadiazolidine 2‐oxides were prepared. The pmr and cmr spectra of these compounds were obtained. On the basis of the chemical shifts due to the γ and δ‐effects, the Stereochemical structures are discussed.
Synthesis and reactions of 1,2‐fused 3‐cyanoindolizines
Authors: Matsumoto Kiyoshi , Uchida Takane , Aoyama Kinuyo , Nishikawa Masahiko , Kuroda Takeshi , Okamoto Tadashi
Published: April 2009

With the intention that annulation of carbo‐ or heteroaromatic rings at the 1,2‐positions can activate 3‐cyanoindolizines as 1,3‐dipolar species, 6‐cyanobenz[a]indolizines, pyridazino[4,5‐a]indolizines and 5‐cyano‐1,3‐diphenylthiopheno[3,4‐a]indolizine were prepared. 6‐Cyanobenz[a]indolizines smoothly ‐underwent 1,3‐dipolar cycloaddition on to dibenzoylacetylene and diacetylacetylene to afford the corresponding indolizino[3,4,5‐ab]isoindoles, whereas 5‐cyano‐1,4‐diphenylpyridazino[4,5‐a]indolizine reacted with dimethyl acetylenedicarboxylate to give the 1:2 adduct. Only a 3% yield of 5‐cyano‐1,3‐diphenylthiopheno[3,4‐a]indolizine formed upon phosphorus pentasulfide treatment of 1,2‐dibenzoyl‐3‐cyanoindolizine.
Reactions of 3‐hydrazino‐5,6‐diphenyl‐1,2,4‐triazine with 4‐arylidene‐2‐phenyl‐5(4H)‐oxazolones and 4‐benzylidene‐3‐methyl‐5(4H)‐isoxazolone
Authors: Eid Mohga M. , Badawy M. A. , Mansour A. K.
Published: April 2009

3‐Hydrazino‐5,6‐diphenyl‐1,2,4‐triazine reacts with 4‐arylidene‐2‐phenyl‐5(4H)‐oxazolones in toluene to give substituted acrylic acid hydrazides, and in glacial acetic acid to give substituted imidazolones. On the other hand the hydrazinotriazine reacts with 4‐benzylidene‐3‐methyl‐5(4H)‐isoxazolone, probably via a 1,4 addition reaction followed by an elimination reaction, to give benzaldehyde 5,6‐diphenyl‐1,2,4‐triazin‐3‐ylhydrazone and 3‐methyl‐5(4H)‐isoxazolone.
Entzündungshemmende wirkstoffe. XI. Ringschlußreaktion an 5‐phenyl‐2‐thiobiuret
Authors: Kreutzberger Alfred , Daus Silva
Published: April 2009

Die Umsetzung von 5‐Phenyl‐2‐thiobiuret (1) mil α‐Chlorcarbonylverbindungen 2 führt zu den N‐Phenyl‐N′‐(2‐thiazolyl)harnstoffen (3). Unter den neuen Verbindungen finden sich besonders die entzundungshemmende, anthelminthische und trichomonazide Wirksamkeit stark ausgeprägt.
A one step synthesis of 4‐substituted imidazoles. An important observation when N‐alkylating imidazoles
Authors: Whitten Jeffrey P. , Matthews Donald P. , Mccarthy James R. , Barbuch Robert J.
Published: April 2009

Imidazoles substituted in the 2‐position with methyl, 1e, phenyl, 1a, 2‐imidazole, 1b‐d, or t‐butyldiphenylsilyl, If, react with soft electrophiles 2 to give modest yields of 4(5)‐C‐alkylated‐imidazoles 3 and N‐alkylated products 5. These two products are readily separated by flash chromatography.
Synthesis and single‐crystal X‐ray diffraction studies of 1‐β‐D‐ribofuranosyl‐1,2,4‐triazole‐3‐sulfonamide and certain related nucleosides
Authors: Hanna Naeem B. , Dimitrijevich Slobodan D. , Larson Steven B. , Robins Roland K. , Revankar Ganapathi R.
Published: April 2009

1‐β‐D‐Ribofuranosyl‐ 21, 1‐(2‐deoxy‐β‐D‐erytftro‐pentofuranosyl)‐ 27 and 1‐β‐D‐arabinofuranosyl‐ 29 derivatives of 1,2,4‐triazole‐3‐sulfonamide (19) have been prepared. Glycosylation of the silylated 19 with 1,2,3,5‐tetra‐0‐acetyl‐β‐D‐ribofuranose (5) in the presence of trimethylsilyl triflate gave the corresponding blocked nucleoside (20), which on ammonolysis afforded 1‐β‐D‐ribofuranosyl‐1,2,4‐triazole‐3‐sulfonamide (21). Stereospecific glycosylation of the sodium salt of 19 with either 1‐chloro‐2‐deoxy‐3,5‐di‐O‐p‐toluoyl‐α‐D‐erythro‐pentofuranose (22) or 1‐chloro‐2,3,5‐tri‐0‐benzyl‐α‐D‐arabinofuranose (23) provided the corresponding protected nucleosides 26 and 28. Deprotection of 26 and 28 furnished 1‐(2‐deoxy‐β‐D‐erythro‐pentofuranosyl)‐1,2,4‐triazole‐3‐sulfonamide (27) and 1‐β‐D‐arabinofuranosyl‐1,2,4‐triazole‐3‐sulfonamide (29), respectively. 2‐0‐D‐Ribofuranosyl‐1,2,4‐triazole‐3(4H)‐thione (7) and 4‐β‐D‐ribofuranosyl‐1,2,4‐triazole‐3(2H)‐thione (9) were also prepared utilizing either an acid catalyzed fusion of 1,2,4‐triazole‐3(1H,2H)‐thione (4) with 5, the reaction of 5 with silylated 4 in the presence of trimethylsilyl triflate, or by ring closure of 4‐(2,3,5‐tri‐0‐benzoyl‐β‐D‐ribofuranosyl)thiosemicarbazide (10) with mixed anhydride and subsequent deacylation. The synthesis of 1‐β‐D‐ribofuranosyl‐3‐benzylthio‐1,2,4‐triazole (15) has also been accomplished by the silylation procedure employing 3‐benzylthio‐1,2,4‐triazole (13) and 5 to give 1‐(2,3,5‐tri‐0‐acetyl‐β‐D‐ribofuranosyl)‐3‐benzylthio‐1,2,4‐triazole (14). Deacetylation of 14 furnished 15. The structural assignments of 7, 14 and 21 were made by single‐crystal X‐ray diffraction analysis and their hydrogen bonding characteristics have been studied. The sulfonamido‐1,2,4‐triazole nucleosides are devoid of any significant antiviral or antitumor activity in cell culture.
A facile and improved synthesis of tubercidin and certain related pyrrolo[2,3‐d]pyrimidine nucleosides by the stereospecific sodium salt glycosylation procedure
Authors: Ramasamy Kandasamy , Imamura Nobutaka , Robins Roland K. , Revankar Ganapathi R.
Published: April 2009

A simple synthesis of tubercidin (1), 7‐deazaguanosine (2) and 2′‐deoxy‐7‐deazaguanosine (14) has been accomplished using the sodium salt glycosylation procedure. Reaction of the sodium salt of 4‐chloro‐ and 2‐amino‐4‐chloro‐pyrrolo[2,3‐d]pyrimidine, 3 and 4, respectively, with 1‐chloro‐2,3‐0‐isopropylidene‐5‐0‐(t‐butyl)dimethylsilyl‐α‐D‐ribofuranose (5) gave the corresponding protected nucleosides 6n and 7 with β‐anomeric configuration. Deprotection of 6 provided 8, which on heating with methanolic ammonia gave tubercidin (1) in excellent yield. Functional group transformation of 7, followed by deisopropylidenation gave 2‐aminotubercidin (10) and 2‐amino‐7‐β‐D‐ribofuranosylpyrrolo[2,3‐d]pyrimidine‐4(3H)‐thione (11). Treatment of 7 with 1N sodium methoxide followed by exposure to aqueous trifluoroacetic acid, and ether cleavage furnished 7‐deazaguanosine (2). 2′‐Deoxy‐7‐deazaguanosine (14) and 2′‐deoxy‐7‐deaza‐6‐thioguano‐sine (18) were also prepared by using similar sequence of reactions employing 4 and 1‐chloro‐2‐deoxy‐3,5‐di‐O‐p‐toluoyl‐α‐D‐erythro‐pentofuranose (15).
A convenient synthesis of 2′‐deoxy‐6‐thioguanosine,ara‐guanine,ara‐6‐thioguanine and certain related purine nucleosides by the stereospecific sodium salt glycosylation procedure
Authors: Hanna Naeem B. , Ramasamy Kandasamy , Robins Roland K. , Revankar Ganapathi R.
Published: April 2009

A simple and high‐yield synthesis of biologically significant 2′‐deoxy‐6‐thioguanosine (11),ara‐6‐thioguanine (16) andaraG (17) has been accomplished employing the Stereospecific sodium salt glycosylation method. Glycosylation of the sodium salt of 6‐chloro‐ and 2‐amino‐6‐chloropurine (1and2, respectively) with 1‐chloro‐2‐deoxy‐3,5‐di‐O‐(p‐toluoyl)‐α‐D‐erythro‐pentofuranose (3) gave the corresponding N‐9 substituted nucleosides as major products with the β‐anomeric configuration (4and5, respectively) along with a minor amount of the N‐7 positional isomers (6and7). Treatment of4with hydrogen sulfide in methanol containing sodium methoxide gave 2′‐deoxy‐6‐thioinosine (10) in 93% yield. Similarly,5was transformed into 2′‐deoxy‐6‐thioguanosine (β‐TGdR,11) in 71 % yield. Reaction of the sodium salt of2with 1‐chloro‐2,3,5‐tri‐O‐benzyl‐α‐D‐arabinofuranose (8) gave N‐7 and N‐9 glycosylated products13and9, respectively. Debenzylation of9with boron trichloride at −78° gave the versatile intermediate 2‐amino‐6‐chloro‐9‐β‐D‐arabinofuranosyl‐purine (14) in 62% yield. Direct treatment of14with sodium hydrosulfide furnishedara‐6‐thioguanine (16). Alkaline hydrolysis of14readily gave 9‐β‐D‐arabinofuranosylguanine (araG,17), which on subsequent phosphorylation with phosphorus oxychloride in trimethyl phosphate affordedaraG 5′‐monophosphate (18).
Synthesis of some heterocyclic skeletons via organoiron complexes. Crystal and molecular structure of (5a,6,7,8,9,9a‐η6‐1,4‐benzoxathiino[3,2‐b]pyridine)(η5‐cyclopentadienyl)iron hexafluorophosphate
Authors: Sutherland Ronald G. , Piórko Adam , Lee Choi Chuck , Simonsen Stanley H. , Lynch Vincent M.
Published: April 2009

Synthesis of the heterocyclic skeletons of some biologically active compounds from (η6‐o‐dichlorobenzene)(η5‐cyclopentadienyrl)iron hexafluorophosphate in a two step procedure is described. Cyclopentadienyliron hexafluorophosphate complexes of 1,4‐benzodioxino[2,3‐b]pyridine, 1,4‐benzoxathiino[3,2‐b]pyridine, 10H‐pyrido[3,2‐b]benzoxazine, benzo[b]naphtho[2,3‐e][1,4]dioxin, 4‐methylbenzo[b]benzopyran‐2‐one[7,6‐e][1,4]dioxin and benzo[b]anthracen‐9,10‐diono[1,2‐e][1,4]dioxin were isolated and characterized. Upon pyrolytic sublimation of these complexes the free heterocycles were obtained and characterized. (η6‐1,4‐Benzoxathiino[3,2‐b]pyridine)(η5‐cyclopentadienyl)iron hexafluorophosphate crystalizes in the orthothombic system, space group Pbca; the dihedral angle between the planes of outer rings was found to be 176.8 (1).
The synthesis of heterocyclic analogs of bisantrene
Authors: Fields T. L. , Lin Yang‐i , Warren J. D. , Lang S. A.
Published: April 2009

Bisguanylhydrazones of anthracene‐9,10‐dicarboxaldehyde have demonstrated excellent antitumor activity. Heterocyclic analogs were synthesized in an effort to expand or modify the activity profile.
Novel diazinyl 3‐pyridyl ketones: Efficient synthesis and complete assignment of 1H and 13C NMR spectra
Authors: Heinisch Gottfried , Langer Thierry , Lukavsky Peter
Published: April 2009

The preparation of six diazinyl 3‐pyridyl ketones 3–8 is described. Detailed 1H and 13C nmr data of these novel building blocks are given.
Nitrogen bridgehead compounds. Part88. Synthesis of 3H, 7H‐[1,4]diazepino[3,4‐b]quinazoline‐3,7‐diones
Authors: Szabó Mónika , Kökösi József , Örfi László , Kovács Attila , Hermecz István
Published: April 2009

3H,7H‐[1,4]Diazepino[3,4‐b]quinazolone‐3,7‐diones 9, 11 were synthesized starting from 2‐(1‐bromo‐ethyl)quinazolin‐4(3H)‐ones 3 and 17via2‐[1‐(4‐methoxyphenylamino)ethyl]quinazolin‐4(3H)‐ones 4 and 18. Cyclization of 3‐[2‐(1‐bromoethyl)‐4‐oxo‐3,4‐dihydroquinazolin‐3‐yl)propionic acid 14 by the action of triethylamine provided the first representative of the tricyclic 7H‐[1,4]oxazepino[3,4‐b]quinazoline‐3,7‐dione system, compound 15. The new tricyclic derivatives 9, 11 and 15 are characterized by uv, ir and1H nmr spectroscopy.
Synthesis of regioisomeric 6,9‐(chlorofluoro)‐substituted benzo[g]quinoline‐5,10‐diones, benzo[g] isoquinoline‐5,10‐diones and 6‐chloro‐9‐fluorobenzo[g]quinoxaline‐5,10‐dione
Authors: Krapcho A. Paul , Gallagher Cynthia E. , Hammach Abdelhakim , Ellis Michael , Menta Ernesto , Oliva Ambrogio
Published: April 2009

Treatment of difluoro or chloro fluoro‐substituted benzyl bromides 5a‐c with zinc dust in tetrahydro‐furan leads to the corresponding benzylic zinc bromides 6a‐c. These organometallics on treatment with chlorosubstituted heterocyclic esters 4A and 4B mediated by nickel catalysis undergo couplings to yield dihalobenzyl substituted heterocyclic esters 7Aa‐c and 7Ba‐c. Treatment of 4c with 6c under Pd catalysis leads to 7Cc. The acids 8, prepared by hydrolysis of these esters, with treatment of fuming sulfuric acid undergo cyclizations and oxidations to yield the desired regioisomeric dihalo‐substituted heterocyclic quinones 2.