bluuebunny/crossref_metadata_2025 huggingface dataset:
Acridine derivatives. VI. Redox chemistry of novel 9‐anilinoacridines with antitumor activities
Authors: Kimura Michio , Okabayashi Ichizo , Inoue Hiroaki
Published: March 2009

In order to elucidate the mechanism of deoxyribonucleic acid (DNA) strand breaks caused by 9‐anilino‐acridine DNA intercalators, the antitumor activity of L1210, P388 and the reduction‐oxidation (redox) reaction of 9‐anilinoacridines were studied. The redox reaction induced by two electrons causing structural changes in quinone diimines of 9‐anilinoacridines is believed to be an important factor in DNA strand breaks and was examined by means of temperature‐dependent nuclear magnetic resonance and cyclic voltammetry. The redox reaction of 9‐anilinoacridines is induced by the effect of a low‐energy electron transfer from the acridine to the aniline ring. We propose that the redox reaction plays an important role in the DNA strand cleavage of 9‐anilinoacridine when it is intercalated into double‐strand DNA.
3‐Phenacylidene‐3,4‐dihydro‐1H‐pyrido[2,3‐b]pyrazin‐2‐ones and 2‐Phenacylidene‐1,2‐dihydro‐4H‐pyrido[2,3‐b]pyrazin‐3‐ones
Authors: Seki Taketsugu , Sakata Hisanori , Iwanami Yasuo
Published: March 2009

Condensation of 2,3‐diaminopyridine (1) with ethyl o‐, m‐ and p‐substituted benzoylpyruvates 2–9 gave two isomeric products. The preferential formation of one or the other isomer has been achieved by different reaction conditions. All the products appear to exist in the enamine form as evidenced by their 1H nmr and ir spectra.
Solid state structure of NH‐pyrazoles not easily amenable to crystal structure determinations: The case of 3(5)‐phenyl‐5(3)‐methylpyrazole and 3,5‐diphenyl‐4‐methylpyrazole
Authors: Elguero JosÉ , Jagerovic Nadine , Foces‐Foces ConcepciÓN , Cano Félix H. , Roux MarÍA Victoria , Aguilar‐Parrilla Francisco , Limbach Hans‐Heinrich
Published: March 2009

The structures of 3(5)‐methyl‐5(3)‐phenylpyrazole (polymorph B) and 3,5‐diphenyl‐4‐methylpyrazole in the solid state cannot be determined by X‐ray crystallography due to the lack of suitable monocrystals. The combined use of CPMAS nmr, DSC and powder diffraction provides information about the behaviour of these pyrazoles in the solid state, particularly, about N‐H ⃛N intermolecular proton transfer. 3(5)‐Methyl‐5(3)‐phenylpyrazole is an example of the influence of polymorphism on the proton exchange since polymorph A (a tetramer formed by a mixture of both tautomers) presents the phenomenon but polymorph B (formed exclusively by 3‐phenyl‐5‐methyl tautomer) is devoid of it.
Tautomeric behavior of 3‐(arylhydrazono)methyl‐2‐oxo‐1,2‐dihydroquinoxalines between the hydrazone imine and diazenyl enamine forms in acidic media. Solvent and substituent effects
Authors: Kurasawa Yoshihisa , Hosaka Tomoyoshi , Takada Atsushi , Kim Ho Sik , Okamoto Yoshihisa
Published: March 2009

The 3‐(arylhydrazono)methyl‐2‐oxo‐1,2‐dihydroquinoxalines 1a‐h and 2a‐e showed tautomeric equilibria between the hydrazone imine A and diazenyl enamine B forms in a series of mixed trifluoroacetic acid/dimethyl sulfoxide media. The substituent and solvent effects on the tautomer ratios of A to B in a series of mixed media were studied for compounds 1a‐h and 2a‐e by the nmr spectroscopy. In compounds 1a‐h and 2a‐e, the ratios of the tautomer B gradually increased with elevation of acid concentration, and the tautomer B exclusively existed in trifluoroacetic acid media. The various acid concentrations (C v/v%, C' mol/1) giving the 1:1 tautomer ratios [C(A:B = 1:1), C'(A:B = 1:1)] were obtained from all compounds (Figures 1–13), and the linear correlation of the Hammett σp values with the log C'(A:B = 1:1) values were observed for compounds 1a‐h. The larger Hammett σp values brought about the larger acid concentrations C(A:B = 1:1) in compounds 1a‐h and 2a‐e, indicating that the higher acid concentration was required for the stabilization of tautomer B possessing the electron‐withdrawing p‐substituents R1, which weakened the basicity of the azo nitrogen atom. Moreover, the ester group R2 of compounds 2a‐e was found to decrease the electron density of the azo nitrogen atom, since the acid concentration C(A:B = 1:1) of compound 2c (R1 = H, R2 = COOMe, σp = O) was 52%, whose value was larger than that of compound 1b (R1 = CN, R2 = H, σp = 0.66) [C(A:B = 1:1) = 42%].
Electron impact ionization mass spectra of 6‐carbamoyloxy‐3‐oxo‐3,6‐dihydro‐2H‐pyran and 5H‐pyrano[3,2‐d]‐oxazole‐2,6‐dione derivatives
Authors: Couladouros Elias A. , Haroutounian Serkos A.
Published: March 2009

The electron impact ionization mass spectra of 6‐carbamoyloxy‐3‐oxo‐3,6‐dihydro‐2H‐pyrans show a weak molecular ion peak and a base peak of m/z 84 resulting from a retro Diels‐Alder fragmentation. The bicyclic system 5H‐pyrano[3,2‐d]oxazole‐2,6‐dione gives a characteristic fragmentation pattern with a very stable fragment of oxazolenone.
Synthesis of 1‐(dimethylsulfamoyl)‐2‐ and 5‐imidazolecarboxaldehydes. Rearrangement of 1‐(dimethylsulfamoyl)‐5‐imidazole‐carboxaldehyde to the 4‐carboxaldehyde
Authors: Kim Jang‐Woo , Abdelaal Salma M. , Bauer Ludwig , Heimer Norman E.
Published: March 2009

Lithiation of 1‐(dimethylsulfamoyl)imidazole by n‐butyllithium, followed by substitution with dimethylformamide provided 1‐(dimethylsulfamoyl)‐2‐imidazolecarboxaldehyde in 19% yield. When 1‐(dimethylsulfamoyl)‐2‐(tert‐butyldimethylsilyl)imidazole was lithiated by sec‐butyllithium, followed by methyl formate, there was obtained 1‐(dimethylsulfamoyl)‐2‐(tert‐butyldimethylsilyl)‐5‐imidazolecarbox‐aldehyde (57%). Removal of the silyl group by acetic acid yielded 1‐(dimethylsulfamoyl)‐5‐imidazolecarbxaldehyde (11, 96%) as a gum. Isomerization of 11 took place slowly at room temperature (10 days), or faster in tetrahydrofuran solution containing triethylamine (2 hours) to form crystalline 1‐(dimethylsul‐famoyl)‐4‐imidazolecarboxaldehyde (12) in 68% yield. Proton and carbon‐13 nmr spectra were analyzed to determine the structure of the isomers. However, only X‐ray crystallography established the structure of 1‐(dimethylsulfamoyl)‐4‐imidazolecarboxaldehyde, unequivocally. A mechanism for the isomerization of 11 to 12 is proposed.
Progress in the chemistry of quinoxaline N‐oxides and N,N′‐dioxides
Authors: Kurasawa Yoshihisa , Takada Atsushi , Kim Ho Sik
Published: March 2009

This review describes the 1,3‐dipolar cycloaddition reaction, deoxygenation, deoxygenative transformation, ring transformation and photochemical reaction of quinoxaline N‐oxides and N,N′‐dioxides.
Carbolines. Part VII. Anisidines, convenient tools to synthesize hydroxy‐β‐carbolines
Authors: Rocca Patrick , Marsais Francis , Godard Alain , Quéguiner Guy , Adams Luqman , Alo Babajide
Published: March 2009

The paper describes a convenient synthesis of hydroxy‐β‐carbolines from commercial anisidines based on key steps such as metalation, cross‐coupling and cyclization. The first total synthesis of a major cyto‐toxic constituent of a marine bryozoan is also reported, the 8‐hydroxy‐1‐vinyl‐β‐carboline.
Synthesis of 2‐aminoquinazolines from ortho‐fluoroketones
Authors: Hynes John B. , Campbell Johnny P. , Hynes John D.
Published: March 2009

The reactions of ten ortho‐fluoroketones with guanidine carbonate in N,N‐dimethylacetamide were investigated as a new synthetic approach to 2‐amino‐4‐alkyl‐ and 2‐amino‐4‐arylquinazolines. The yields obtained ranged from low to moderate and were highly dependent upon the nature of the substituents on the reactant. Eight new quinazolines were elaborated in this study.
Rearrangements of 5‐azidoisoxazoles
Authors: Anderson David J. , Muchmore Christine R.
Published: March 2009

5‐Azidoisoxazoles are prepared via displacement of a chlorine atom in 5‐chloroisoxazoles with azide ion. These 5‐azidoisoxazoles contain an unsaturated group (olefin, aldehyde, oxime or hydrazone) in the 4‐position which participates during thermal decomposition of the azide. Two types of products are formed which are non‐interconvertible: (i) bicyclic isoxazoles which result from direct attack of the azide or nitrene on the unsaturated group; (ii) monocyclic pyrroles and pyrazoles which result from ring opening followed by bond reorganization and subsequent ring closure. Mechanisms for the two discrete processes are discussed.
Synthesis of 7H‐pyrido[2,3‐c]carbazoles from 5‐bromo‐8‐methoxyquinolines via coupling and azide cyclization reactions
Authors: Trécourt Françis , Mongin Florence , Mallet Marc , Quéguiner Guy
Published: March 2009

A new strategy for the synthesis of substituted 7H‐pyrido[2,3‐c]carbazoles has been developed from substituted 5‐bromoquinolines by using cross‐coupling reaction with (2‐aminophenyl)boric acids, followed by a regioselective azide cyclization.
The synthesis of 5‐arylpyrrolo[3,2‐b]pyridines and 7‐arylpyrrolo[3,2‐b]pyridines: Addition of 3‐aminopyrroles to aryl enaminones
Authors: Birnberg Gary H. , Fanshawe William J. , Francisco Gerardo D. , Epstein Joseph W.
Published: March 2009

A series of 5‐arylpyrrolo[3,2‐b]pyridines 1 was synthesized by addition of 3‐aminopyrroles to aryl enaminones. One example of a 7‐arylpyrrolo[3,2‐b]pyridine 2 was obtained as a minor product along with the 5‐aryl isomer, by a modification of the reaction sequence.
Total synthesis of nosiheptide. Synthesis of thiazole fragments
Authors: Koerber‐Plé Karen , Massiot Georges
Published: March 2009

The preparation of three new thiazole derivatives from natural products is described, as well as improvements in the synthesis of ethyl 2‐aminomethyl‐4‐thiazolecarboxylate.
Friedländer reaction of 3‐acetyltropolone: Synthesis of 3‐(2‐quinolyl)tropolones
Authors: Piao Ming‐Zhu , Imafuku Kimiaki
Published: March 2009

3‐Acetyltropolone (1a) reacted with 2‐aminobenzaldehydes in the presence of sodium ethoxide to afford 3‐(2‐quinolyl)tropolone (3aa) in 96% yield. Methyl‐ and isopropyl‐substituted tropolones 1b,c also gave six 3‐(2‐quinolyl)tropolones in excellent yields. The compound 3aa was allowed to stand in 40% aqueous methylamine solution to give 7‐methylamino‐2‐(2‐quinolyl)tropone (4).
Conversion of 3,n‐dithiabicyclo[n.3.1]alkatrienes to bicyclo[n.3.1]alkapentaenes
Authors: Doomes Earl , Mcknight Alice A.
Published: March 2009

The application of the Ramberg‐Backlund reaction in the conversion of several 3,n‐dithiabicyclo[n.3.1]alkatrienes to the corresponding bicyclo[n.3.1]alkapentaenes is reported. Proton magnetic resonance and ultraviolet spectra were utilized in the overall characterization of bicyclo[8.3.1]tetradeca‐2,8,10,12,1(14)‐pentaene, bicyclo[9.3.1]pentadeca‐2,9,11,1(15)‐pentaene, and their precursors. The final step in the synthesis was a Ramberg‐Backlund of bis‐α,α′‐chloro sulfone. The intermediate, 2‐chloro‐3‐thiabicyclo[9.3.1]pentadeca‐9,11,13,1(15)‐tetraene 3,3‐dioxide, was isolated and characterized. The structure and stability of the bridged α,α′‐dichloro sulfide intermediates were examined.
Theoretical study of thieno[3,4‐d]thiepin and furo[3,4‐d]thiepin as dienes in the diels‐alder reaction
Authors: Jursic Branko S.
Published: March 2009

Theoretical study of thiophene and furan c‐fused rings with unsaturated seven membered rings with oxygen or sulfur as dienes for Diels‐Alder reactions was conducted with the semiempirical Austin Model 1 (AMI). Four approaches were considered: frontier orbital theory, resonance stability of the dienophiles determined through heat of hydrogenation, progress of the reaction through bond orders, and the estimation of the reaction barriers. It was determined that the most unreactive species with the highest resonance stability are sulfur heterocyclic compounds, while furan derivatives are the most reactive. Using o‐quinonoid episulfide as an intermediate was rejected because the estimated activation energy for its formation is too high. The possibility of a three bond formation in the transition state of thieno[3,4‐d]thiepin reaction with ethylene was considered and rejected on the basis of AMI estimated activation energy. The S‐methylated derivatives of thieno[3,4‐d]thiepin were predicted to react with less reactive dienophiles like ethylene under moderate reaction conditions. If thieno[3,4‐d]thiepin is not activated through S‐methylation then a reactive dienophile and drastic reaction conditions are predicted to be necessary to force the cycloaddition reaction. The obtained results are in agreement with experimental evidence.
Nitrosation of methyl 2‐acylamino‐3‐dimethylaminopropenoates. A simple conversion of n‐acylglycines into 5‐substituted 1,2,4‐Oxadiazole‐3‐carboxylates
Authors: Kmetiĉ Matej , Stanovnik Branko
Published: March 2009

A novel simple synthesis of 5‐substituted‐1,2,4‐oxadiazole‐3‐carboxylates 5 from N‐acylglycines 1, which are transformed with DMF in the presence of phosphorus oxychloride into 2‐substituted‐4‐dimethyl‐aminomethyleneoxazol‐5(4H)‐ones 2, followed by opening into 2‐aroylamino‐3‐dimethylamino‐propenoates 3, and nitrosation to give the oximes 4 as intermediates, which cyclize spontaneously into 5‐substituted‐1,2,4‐oxadiazole‐3‐carboxylates 5. The compounds 2 can be transformed into 5 without isolation of 3 and 4.
Synthesis of a 1,8‐naphthyridin‐5‐one derivative via an intramolecular 1,3‐dipolar cycloaddition reaction
Authors: Read Mark W. , Ray Partha S.
Published: March 2009

Synthesis of a 1,8‐naphthyridin‐5‐one derivative [(5,6,7,8‐tetrahydro‐(3‐chloro‐6‐hydroxymethyl‐8‐methyl)‐1,8‐naphthyridin‐5‐one (9)] is described starting from 2‐chloronicotinic acid using an intramolecular 1,3‐dipolar cycloaddition reaction as the key step.
The transformations of 4‐heteroarylaminomethylene‐5(4H)‐oxazolones into dehydropeptide derivatives
Authors: Aljaẑ‐Roẑiĉ Mateja , Svete Jurij , Stanovnik Branko
Published: March 2009

2‐Phenyl‐4‐heteroarylaminomethylene‐5(4H)‐oxazolones 3, which were prepared from the corresponding N,N‐dimethyl‐N'‐heteroarylformamidines 1 and hippuric acid 2 in acetic anhydride, react with amino acids giving dehydropeptide derivatives 4, 5, and 6 as products. Dehydration of N‐protected peptides 7–10, containing glycine at the C‐terminal, followed by the reaction with formamidines 1 gave 2‐substituted‐4‐heteroarylaminomethylene‐5(4H)‐oxazolones 11–14.
Thiazolo[4,3‐c][1,4]benzodiazepines. I. Synthesis of amidine derivatives
Authors: Gillard Alain‐Claude , Rault Sylvain , Boulouard Michel , Robba Max
Published: March 2009

Reactivity of 1,2,3,10,11,11a‐hexahydro‐5H‐thiazolo[4,3‐c][1,4]benzodiazepin‐5‐one‐11‐thione and 1,2,3,10,11,11a‐hexahydro‐5H‐thiazolo[4,3‐c][1,4]benzodiazepine‐5,11‐dithione was evaluated against various amines. The synthetic pathways involved in these reactions which led to new thiazolo[4,3‐c]‐[1,4]benzodiazepine amidines are described.
The magnesium bromide induced claisen condensation reaction of N‐acylpyrazoles
Authors: Kashima Choji , Takahashi Katsumi , Fukusaka Kiyoshi
Published: March 2009

N‐Acylpyrazoles formed the 5‐membered C=O‐Mg‐N‐2 chelate complexes with magnesium bromide which afforded the Claisen condensation products by the action of tertiary amine through the corresponding enolate.
Synthesis of 5H‐imidazo[5,1‐a]isoindole: Photocyclization of N,N′ ‐bis(o‐chlorobenzyl)imidazolium chloride and N‐(o‐chlorobenzyl)imidazole
Authors: Byun Young‐Seok , Jung Chang‐Hee , Park Yong‐Tae
Published: March 2009

A N‐heterocyclic compound containing two hetero atoms, imidazo[5,1‐a]isoindole, was synthesized in 40% yield by the intramolecular photocyclization of N,N'‐bis(o‐chlorobenzyl)imidazolium salts 1 in water (neutral or pH ∼4) or of N‐(o‐chlorobenzyl)imidazole 2, in aqueous acid (pH −4). However, the photocyclized compound 3 was not formed effectively in basic aqueous solution (3 equivalents of sodium hydroxide or pyridine) or in acetonitrile by the photochemical reaction of N,N'‐bis(o‐chlorobenzyl)imidazolium salts 1 or N‐(o‐chlorobenzyl)imidazole (2).
Pyrrolothieno[1,4]diazepines part III: Synthesis of amino, hydrazino and mercapto derivatives
Authors: Boulouard Michel , Rault Sylvain , Dallemagne Patrick , Alsaïdi Abdellah , Robba Max
Published: March 2009

Treatment of 2‐(2‐formyl‐1H‐pyrrol‐1‐yl)‐3‐thiophenecarbonitrile by sodium percarbonate afforded, in a one‐pot sequence and on a multigram scale, 5,6‐dihydro‐6‐hydroxy‐4H‐pyrrolo[1,2‐a]thieno‐[3,2‐f][1,4]diazepin‐4‐one whose reactivity towards various nucleophiles like amines, hydrazines and thiols was evaluated.
On the reaction of isothiosemicarbazides with heterocumulenes. Part I
Authors: Ernst Steffen , Schulze Klaus
Published: March 2009

Isothiosemicarbazides 2 react with acyl isothiocyanates under addition‐cyclization to yield 1,3,4‐thiadiazoline‐2‐imines 3 as well as the isomeric 2‐amino‐substituted 1,3,4‐thiadiazolium‐5‐acylaminides 3′. In a similar manner the 2‐hydrazino‐substituted 1,3‐thiazoline 4 adds ethoxycarbonyl isothiocyanate to give the thiosemicarbazide 5, which undergoes a rearrangement to the 1,3,4‐thiadiazoline‐2‐imine 5′. The [2+2] cycloreversion of 3d involving ethoxycarbonyl iso(thio)cyanate and the thermal induced Dimroth rearrangement of 3′f and h are also discussed.
Pharmacophoric requirements for cannabinoid side chains. Naphthoyl and naphthylmethyl substituted Δ8‐tetrahydrocannabinol analogs
Authors: Papahatjis Demetris P. , Kourouli Therapia , Makriyannis Alexandras
Published: March 2009

We have synthesized hybrids of classical cannabinoids and aminoalkylindoles by combining the dibenzopyran structure of Δ8‐tetrahydrocannabinol with the ketonaphthyl or 1‐naphthylmethyl moieties found in aminoalkylindoles in order to investigate the role of the ketonaphthyl and 1‐naphthylmethyl pharmacophores in cannabimimetic activity.
Synthesis and anti‐HIV‐1 activity of 1,5‐dialkyl‐6‐(arylselenenyl)uracils and ‐2‐thiouracils
Authors: Kim Dae‐Kee , Kim Hun‐Taek , Lim Jinsoo , Gam Jongsik , Kim Young‐Woo , Kim Key H. , Shin Young Oh
Published: March 2009

The 1,5‐dialkyl‐6‐(arylselenenyl)uracils 10a‐h and ‐2‐thiouracils 10i‐p have been synthesized as potential anti‐HIV‐1 agents. Cyclization of N‐alkyl‐N'‐[3,3‐di(methylthio)‐2‐alkylacryloyl]ureas 6a‐d and ‐thioureas 6e‐h in acetic acid either containing a catalytic amount of methanesulfonic acid at 80°or containing 1 equivalent of methanesulfonic acid at room temperature afforded 1,5‐dialkyl‐6‐(methylthio)uracils 7a‐d in 84–96% yields and 1,5‐dialkyl‐5,6‐dihydro‐6,6‐di(methylthio)‐2‐thiouracils 11a‐d in 88–99% yields, respectively. Oxidation of 7a‐d and 11a‐d with either 3‐chloroperoxybenzoic acid in benzene or aqueous sodium periodate solution in methanol gave 1,5‐dialkyl‐6‐(methylsulfonyl)uracils 8a‐d in 88–98% yields and 1,5‐dialkyl‐6‐(methylsulfinyl)‐2‐thiouracils 12a‐d in 57–73% yields, respectively, which were subsequently treated with arylselenol 9a‐b in ethanolic sodium hydroxide solution to afford 10a‐p in 6099% yields. Of these compounds, 6‐[(3,5‐dimethylphenyl)selenenyl]‐5‐isopropyl‐1‐(3‐phenylpropyl)uracil (10h) inhibited HIV‐1 replication in MT‐4 cells at a 50% effective concentration (EC50) of 0.0006 μM with a selective index of 44833, which is 7.7‐fold more potent than AZT.
Synthesis of N‐acyl‐2‐pyrrolidinones from the corresponding N‐acyl‐GABA derivatives
Authors: Rekatas George V. , Demopoulos Vassilis J. , Kourounakis Panos N.
Published: March 2009

In this work, the synthesis of 1‐(pyridine‐3‐carbonyl)pyrrolidin‐2‐one (1a) and 1‐(2‐propyl‐1‐pentanoyl)pyrrolidin‐2‐one (1b) by cyclization of the corresponding GABA derivatives, is reported. Two different methods are developed. For the synthesis of 1a, the parent molecule 4‐[(pyridine‐3‐carbonyl)‐amino]butanoic acid (2a) is treated first with thionyl chloride and then with triethylamine. The second derivative, 1b, is produced by an intramolecular dehydration of 4‐(2‐propylpentanoylamino)butanoic acid (2b) using an acid catalyst.
Condensation reactions of benzils with ureas in ethylene glycol
Authors: Lee Chang Kiu , Kim Sun Hee , Kim Yong Bun
Published: March 2009

Reactions of benzils and urea in ethylene glycol at 180° for 1‐2 hours gave 2,4,5‐triaryloxazoles as major products and bicyclic imidazoimidazole‐2,5‐diones as minor products. N‐Methylurea and N‐phenylurea gave the oxazoles under similar conditions. The solvent seemed to assist the formation of oxazole by eliminating the isocyanate components as ethylene glycol biscarbamates.
Synthesis of quinoxaline 1,4‐dioxides from 4,5(6,7)‐dimethylbenzofuroxan
Authors: Takabatake Tohru , Miyazawa Tomoyuki , Hasegawa Minoru
Published: March 2009

In this study, novel substituted quinoxaline 1,4‐dioxides were synthesized from novel substituted benzofuroxan. 4,5(6,7)‐Dimethylbenzofuroxan 3 was prepared by the thermal decomposition of 2,3‐dimethyl‐6‐nitrophenylazide 2. Novel quinoxaline 1,4‐dioxides derivatives were obtained using compound 3 and the enolic form of 1,3‐diketones 4 catalyzed by silica gel or molecular sieves. These reactions gave isomeric quinoxaline 1,4‐dioxides 5 and 6. These reactions of compound 3 may involve tautomers 4,5‐dimethylbenzofuroxan 3a, 6,7‐dimethylbenzofuroxan 3b on the surface of a solid catalyst.
3‐(2,5‐Dioxopyrrolidin‐1‐yl), 3‐(2,6‐dioxopiperidin‐1‐yl), and 3‐(1,3‐dioxoisoindolin‐2‐yl)rhodanines. a novel type of rhodanine derivatives
Authors: Hanefeld Wolfgang , Schlitzer Martin , Debski Norbert , Euler Helmut
Published: March 2009

3‐Aminorhodanine 2 was reacted with cyclic anhydrides yielding 3‐(2,5‐dioxopyrrolidin‐1‐yl), 3‐(2,6‐dioxopiperidin‐1‐yl), and 3‐(1,3‐dioxoisoindolin‐2‐yl)rhodanine 6‐8, which in turn were condensated in 5 position with several aldehydes yielding the new rhodanine derivatives 9‐11.
Synthesis of 4‐chloro‐7‐ethoxy‐2(3H)‐benzoxazolone‐6‐carboxylic acid
Authors: Kato Shiro , Morie Toshiya
Published: March 2009

As a part of metabolic studies of mosapride (1), a potential gastroprokinetic agent, the synthesis of 4‐chloro‐7‐ethoxy‐2(3H)‐benzoxazolone‐6‐carboxylic acid (7) as a derivative of 4‐amino‐5‐chloro‐2‐ethoxy‐3‐hydroxybenzoic acid (6), which has served a benzoic acid part of the metabolites 4 and 5, is described. Treatment of methyl 3‐amino‐4‐substituted amino‐5‐chloro‐2‐ethoxybenzoate derivatives 11a‐c with sodium nitrate in acidic medium gave the benzotriazole derivatives 13x,y instead of the objective 3‐hydroxy counterpart. The synthesis of 7 started from o‐vanillin acetate (15) and proceeded through the intermediates 2‐hydroxy‐3‐methoxy‐4‐nitrobenzaldehyde (18), methyl 4‐amino‐2,3‐dihydroxybenzoate (23), and methyl 7‐hydroxy‐2(3H)‐benzoxazolone‐6‐carboxylate (30). Compound 30 was alternatively prepared from 23 via methyl 4‐ethoxycarbonylamino‐2‐ethoxycarbonyloxy‐3‐hydroxybenzoate (29), which is the product resulting from the migration of the ethoxycarbonyl group of methyl 4‐amino‐2,3‐diethoxycar‐bonyloxybenzoate (27).
New anti‐tumor agents. 1. Heterocyclic benzodioxole lactones
Authors: Jurd Leonard
Published: March 2009

Morpholino Mannich bases of types 5, 12 react with tetronic acid in aqueous acetic acid to yield uncyclized lactones of types 7, 13. Acetylation and methylation of these products yields monoacetyl‐monomethyl derivatives which can then be cyclized in alkali to give unsaturated lactones of types 8, 16 and saturated lactones 9b, 15. The hydroxylactone 9a can be synthesized directly by reaction of 3,4,5‐trimethoxybenzaldehyde with sesamol and tetronic acid in methanol. With few exceptions the lactones of type 8 and 16 have proven to be active inhibitors of tumor growth in the National Cancer Institute in vitro screening program against 60 diverse human cancer cell lines. The lactone 8 is particularly potent, inhibiting in vitro growth of some cancers at concentrations as low as 10−6‐10−7 moles/1.
Synthesis and reactivity of oxopyrrolidinothieno[2]azepinones: [3]Benzazepine antidepressant analogs
Authors: Mamouni AÏCha , Daïch Adam , Decroix Bernard
Published: March 2009

A synthesis of oxopyrrolidino[2]azepinones annelated to a thiophene ring 3a,b,c is described starting from succinimide and halogenomethylthiophenes 6a,b,c. Stereoselective reduction, Schmidt reaction and the Beckmann rearrangement of the oximes of the ketones 3a,b,c are studied.
Synthesis of nitrogen‐containing heterocycles. 7 Reaction of aliphatic diaminomethylenehydrazones with hindered ethoxymethylenecyanoacetate
Authors: Miyamoto Yoshiko , Yamazaki Chiji
Published: March 2009

Aliphatic diaminomethylenehydrazones 1 were reacted with ethyl 2‐cyano‐3‐ethoxy‐2‐pentenoate 2 to give a number of heterocycles in low to moderate yields, according to the substitution pattern and the size of substituent. When 1 carried a single methyl group on the terminal nitrogen, it gave preferentially 6‐oxo‐1,6‐dihydropyrimidines 4 incorporating N(4) into the ring. In contrast, the reaction between 1c or 1d and 2 led to 6‐imino‐ and 6‐oxo‐1, 6‐dihydropyrimidines 7 and 8 along with 3. When the alkylidene moiety was bulky, 1e and 1f, the similar reaction gave 3 in high yields without any cyclized product. Upon exposure to acid, compound 3 yielded 6‐oxo‐1,6‐dihydropyrimidines 6, [1,2,4]triazolo[1,5‐c]pyrimidine‐8‐carboxylate 5 and N‐alkenyl‐1,2,4‐triazoles 9 in addition to 7 and 8 in proportions dictated by the nature of the substituents of 1. The structural assignment and reaction mechanism are discussed.
Rearrangements of 5‐acetyl‐3‐benzoylamino‐6‐(2‐dimethylamino‐1‐ethenyl)‐2H‐pyran‐2‐one and 3‐benzoylamino‐6‐(2‐dimethylamino‐1‐ethenyl)‐5‐ethoxycarbonyl‐2H‐pyran‐2‐one into 1‐aminopyridine, pyrano[2,3‐b]pyridine and isoxazole derivatives
Authors: Strah Sonja , Svete Jurij , Stanovnik Branko
Published: March 2009

Rearrangements of 5‐acetyl‐3‐benzoylamino‐6‐(2‐dimethylamino‐1‐ethenyl)‐2H‐pyran‐2‐one (1) and 3‐benzoylamino‐6‐(2‐dimethylamino‐1‐ethenyl)‐5‐ethoxycarbonyl‐2H‐pyran‐2‐one (7) in the presence of N‐nucleophiles, such as ammonia, hydrazine, and hydroxylamine, into 1‐aminopyridine, pyrano[2,3‐b]‐pyridine, and isoxazole derivatives 5, 11, and 15 is described. In the reaction of compounds 1 and 7 with C‐nucleophiles, such as 5,5‐dimethyl‐1,3‐cyclohexanedione and barbituric acid, only substitution of the dimethylamino group is taking place to give the compounds 17, 18, and 20.
The birch reduction of heterocyclic compounds. 11. Birch reduction and reductive alkylation of furamides
Authors: Kinoshita Takamasa , Icbinari Daisuke , Sinya Junko
Published: March 2009

The Birch reduction‐alkylation of some N,N‐dialkylfuramides and its application to the useful intermediates for the natural product synthesis are described.
Synthesis of steroidal extranucleo 1,3,4‐oxadiazoles
Authors: Siddiqui A. U. , Satyanarayana Y. , Ahmed I. , Siddiqui A. H.
Published: March 2009

Cholest‐5en‐3β‐ol 1, 3,3‐ethylenedioxy‐androst‐4‐en‐17β‐ol 2 and 17,17‐ethylenedioxy‐1,3,5(10)‐estratrien‐3β‐ol 3 were converted into ethyl ester 1a, 2a and 3a by reaction with ethyl chloroacetate in the presence of potassium. The ethyl esters 1a, 2a and 3a on reaction with hydrazine gave hydrazides 1b, 2b and 3b, which on reaction with cyanogen bromide afforded 1,3,4‐oxadiazoles 1c, 2c and 3c.
Synthesis of mono‐cationic and dicationic analogs of hoechst 33258
Authors: Czarny Agnieszka , Wilson W. D. , Boykin David W.
Published: March 2009

The synthesis of fourteen mono‐cationic and six dicationic analogs of Hoechst 33258 is described. The monocationic benzimiazoles 7a‐7g and the dicationic benzimidazoles 9a‐9c are obtained in five steps starting from 4‐acetamidobenzonitrile. The monocationic bis‐benzimiazoles 12a‐12g are synthesized in four steps starting from 4‐amino‐3‐nitrobenzonitrile. The dicationic bis‐benzimiazoles 17a‐17c are obtained in six steps starting from 4‐amino‐3‐nitrobenzonitrile.
Synthesis and oxygen‐atom transfer reactions of 3‐hydroperoxy‐3,4,4,5,5‐pentasubstituted‐1,2‐dioxolanes
Authors: Baumstark A. , Chen Y.‐X. , Rodriguez A.
Published: March 2009

A series of 3‐hydroperoxy‐3,4,4,5,5‐pentasubstituted‐1,2‐dioxolanes 2a‐d were synthesized in good yield from the corresponding 3‐hydroxy‐1,2‐dioxolanes by reaction with concentrated hydrogen peroxide in acetonitrile with p‐toluenesulfonic acid as catalyst. The 3‐hydroperoxy‐1,2‐dioxolanes were effective oxygen‐atom transfer reagents for the oxidation of thioanisole, triethylamine and 2,3‐dimethyl‐2‐butene to the sulfoxide, N‐oxide and epoxide, respectively. The reactions occurred under mild conditions and were found to be of the second order overall. The second order rate constants (k2) were determined for oxidation of thioanisole by 2a‐d in deuteriochloroform. For 2a, k2 values for N‐oxidation and epoxidation were also measured. The 3‐hydroperoxy‐1,2‐dioxolanes were found to be less reactive than the structurally similar cyclic α‐azohydroperoxides but much more reactive than simple hydroperoxides. The mechanism of oxygen‐atom transfer is postulated to occur via nucleophilic attack of the substrate on the terminal oxygen of the hydroperoxide. Intramolecular hydrogen bonding of the hydroperoxy proton to a dioxolane oxygen appears to account for the reaction order in aprotic media.
Synthesis and tautomerism of 2‐aryl‐ and 2‐heteroaryl derivatives of benzimidazole
Authors: Lee In‐Sook Han , Jeoung Eun Hee , Lee Chang Kiu
Published: March 2009

Benzimidazoles containing furyl and thienyl substituents at C‐2 were prepared by condensation of o‐phenylenediamine and corresponding carboxylic acids in the presence of polyphosphoric acid. The 2‐heteroarylbenzimidazoles showed tautomerism in dimethyl sulfoxide solution while 2‐phenylbenzimidazole did not. The tautomerism appeared to be taking place by intermolecular relay of protons between stacked molecules.
Synthesis of 1‐(2‐hydroxyphenyl)‐2,4‐imidazolidinedione derivatives through cyclic transformations of ethyl 2‐oxo‐3(2H)‐benzoxazoleacetate derivatives
Authors: Milcent René , Akhnazarian Anna , Lensen Nathalie
Published: March 2009

A series of ethyl 2‐oxo‐3(2H)‐benzoxazoleacetate derivatives 2 have been synthesized. By reaction with ammonia, primary amines or hydrazine, these compounds 2 were transformed into 1‐(2‐hydroxyphenyl)‐2,4‐imidazolidinedione derivatives 4, 5 and 6, respectively. Some of these new hydantoins 4, treated with phosphorus oxychloride, gave 3H‐2‐oxoimidazo[2,1‐b]benzoxazole derivatives 9. Ethyl 2‐oxo‐3(2H)‐benzoxazolepropionate (10) was prepared by a Michaël reaction of ethyl acrylate with 2‐benzoxazolone (1a). With 10, no cyclic transformation was observed in the presence of ammonia or alkylamine.
Iminium carbonic acid derivative salts. XI. Synthesis of N,S‐containing heterobicycles from N‐protected 2‐methylthio‐1,3‐thiazinium and 2‐methylthiothiazoüum salts. Part 3. Reaction of N‐protected 2‐methylthio‐1,3‐thiazinium and 2‐methylthiothiazolium salts with 3‐amino‐2‐cyano‐3‐arylacrylonitriles
Authors: Hanefeld Wolfgang , Naeeni Mahmoud , Schlitzer Martin
Published: March 2009

N‐Boc‐protected 2‐memylthio‐1,3‐thiazinium 1 and 2‐methylthiothiazolium iodides 2, 3 obtained from the corresponding 3,4,5,6‐tetrahydro‐2H‐1,3‐thiazine‐2‐thiones and thiazolidine‐2‐thiones by the action of methyl iodide were reacted with 3‐armno‐2‐cyano‐3‐arylacrylonitriles forming the cyclic isothioureas 5–7. The protection group was removed with trifluoroacetic acid whereupon the desired cyclisation to 3,4‐dihydro‐2H,6H‐pyrimido[2,1‐b][1,3]thiazines 8a‐c, 8a′‐c′ and thiazolo[3,2‐b]pyrimidines 9a,b, 9a′,b′, 10a,b took place.
Furopyridines. XVIII. Photocycloaddition of furo[2,3‐c]pyridin‐7(6H)‐one with acrylonitrile
Authors: Shiotani Shunsaku , Tsukamoto Youichi , Kawahara Yukiko , Saitoh Hideo , Ishida Toshimasa , In Yasuko
Published: March 2009

The photocycloaddition of furo[2,3‐c]pyridin‐7(6H)‐one (1) and its N‐mefhyl derivative (1‐Me) to acrylonitrile has been studied. The structures of the photoadducts isolated by colum chromatography were determined by the nuclear magnetic resonance spectroscopy and single crystal X‐ray analysis. The cyclo‐addition of 1 afforded an adduct 2 at the carbonyl oxygen and 8‐cyano‐8,9‐dihydrofuro[d]azocin‐7(6H)‐one (3), and the addition of 1‐Me the N‐methyl derivative 3‐Me of 3, (9S*)‐9‐cyano‐6‐methyl‐3a,7a‐dihydro‐3a,7a‐ethanofuro[2,3‐c]pyridin‐7(6H)‐one (4), (2S*, 2aR*, 7bR*)‐ (5) and (1R*, 2aS*, 7bS*)‐2‐cyano‐3‐methyl‐4‐oxo‐1,2,2a,3,4,7b‐hexahydrocyclobuta[e]furo[2,3‐c]pyridine (6).
Synthesis of new pyridine intermediates as precursors for the elaboration of streptonigrin analogues by the metalation‐cross‐coupling strategy
Authors: Pomel V. , Rovera J. C. , Godard A. , Marsais F. , Quéguiner G.
Published: March 2009

Starting from available 2‐amino‐6‐chloro‐3‐nitropyridine, synthesis of 3‐amino‐6‐pyridinecarboxylic acid derivatives precursor for pyridine ring C of streptonigrin analogues is described.
Preparation of triazamacrocycles containing only secondary amine functions using both tosyl and boc protecting groups
Authors: Krakowiak Krzysztof E. , Yi Guoliang , Bradshaw Jerald S.
Published: March 2009

1,8,15‐Triazacycloheneicosane (1); 1,9,17‐triazacyclotetracosane (2) and 1,10,19‐triazacycloheptacosane (3) were prepared by treating the appropriate N,N‐bis(ω‐bromoalkyl)toluenesulfonamide 8–10 with the appropriate N,N′‐ditosyl‐α,ω‐diaminoalkane 11–13 in dimethylformamide using sodium hydride as the base followed by phenol and 33% hydrobromic acid in acetic acid to remove the tosyl protecting groups. 2‐Allyloxymethyl‐4,11,18‐ triazaoxacycloheneicosane (4) was prepared in two ways. First, N,N′,N″‐tritosylbis(hexamemylene)triamine (18) was treated with 2‐allyloxymethyl‐3‐oxa‐1,6‐hexanediol ditosylate (23) and cesium carbonate in dimethylformamide followed by sodium amalgam to remove the tosyl protecting groups. The second preparation of 4 was done by treating the tri‐BOC analog of 18 with 23 followed by hydrochloric acid in isopropyl alcohol to remove the BOC protecting groups. The overall yields of 4 using these two processes were very close.
Synthesis and anticonvulsant activity of 2‐aryl‐3,4‐dialkyltetrahydro‐1,3,4‐oxadiazines and 2‐aryl‐3,4‐dialkyltetrahydro‐1,3,4‐oxadiazin‐5‐ones
Authors: Kornet Milton J.
Published: March 2009

Several 2‐aryl‐3,4‐dialkyltetrahydro‐1,3,4‐oxadiazines have been synthesized from 2‐(1,2‐dialkylhydrazino)ethanol (2) and aromatic aldehydes. Also, three 2‐aryl‐3,4‐dialkyltetrahydro‐1,3,4‐oxadiazin‐5‐ones were obtained from the reaction of 1,2‐dialkylglycolylhydrazine (5) and aromatic aldehydes. These compounds exhibited activity in the maximal electroshock seizure test.
Conformational behavior on 2,2,3‐trisubstituted 1,2,3,4‐tetrahydroquinoline alkaloids, virantmycin, benzastatins, and their congeners, evaluated by semi‐empirical molecular orbital calculations
Authors: Morimoto Yoshiki
Published: March 2009

The conformational behaviors on ring inversion between two half‐chair conformers a and b in physiologically active 2,2,3‐trisubstituted 1,2,3,4‐tetrahydroquinoline alkaloids, virantmycin (1), benzastatin C (6), benzastatin D (7), and their congeners 2–5, which were revealed by their nmr studies have been quantitatively evaluated by semi‐empirical molecular orbital calculations (PM3). The geometries of respective half‐chair conformers a and b in compounds 1–7 were optimized and it was found that their thermodynamic distributions are approximately valid in comparison with the coupling constants observed in their nmr experiments. Furthermore, these calculations estimated the energy barriers for ring inversion in compounds 1–7 in the range of ca. 4.86–11.13 kcal/mol, which were compatible with rapid interconversions between a and b at room temperature.
Synthesis of nonsymmetrically 3,4‐disubstituted 1,2,5‐thiadiazole dioxides
Authors: Martinez Ana , Castro Ana , Arán Vicente J. , Cardelús Ignacio , Llenas Jesús , Palacios José M.
Published: March 2009

A synthetic pathway for obtaining arylamino, alkylamino 3,4‐disubstituted 1,2,5‐thiadiazole dioxide derivatives has been developed. This methodology could be applied to obtain potential biologically active molecules.
New isomeric N‐substituted hydrazones of 2‐, 3‐and 4‐pyridinecarboxaldehydes
Authors: Wyrzykiewicz Elżbieta , Prukała Dorota
Published: March 2009

Eighteen compounds unknown in the literature, N‐(E)‐stilbenyloxyalkylcarbonyl‐ and N‐(E)‐stilbenyloxyalkylcarbonylaminoalkylcarbonyl‐substituted hydrazones of 2‐, 3‐ and 4‐pyridinecarboxaldehydes have been prepared. The stereochemical behavior of these compounds in dimethyl‐d6 sulfoxide solution has been studied by 1H‐nmr technique. The E geometrical isomers and cisltrans amide conformers have been found for N‐substituted‐hydrazones 1–16.
Synthesis and reactions of 1,3‐dicarbonyl‐substituted troponoids: Conversion to tropolones having an isoxazole or a pyrazole ring
Authors: Nasu Tomoyuki , Tagawa Tomoko , Imafuku Kimiaki
Published: March 2009

3‐Acetyltropolone (1) was treated with diethyl oxalate in the presence of sodium ethoxide to afford 3‐(2‐ethoxalyl‐1‐oxoethyl)tropolone (2) as a minor product and its cyclized 2‐ethoxycarbonyl‐4,9‐dihydrocyclohetpa[b]pyran‐4,9‐dione (3) as the major one. The former was readily converted to the latter. Then, as a stable synthon bearing a 1,3‐dicarbonyl group, 2‐(2‐ethoxalyl‐1‐oxoethyl)‐7‐methylaminotropone (5) was prepared. The reactions of compound 5 with hydroxylamine, hydrazine, and methylhydrazine were carried out to give troponoids possessing an isoxazole or a pyrazole ring. The parent compounds, 3‐(3‐pyrazolyl)tropolone (13) and 3‐(1‐methylpyrazol‐3‐yl)tropolone (21), were obtained via hydrolysis and decarboxylation. Similarly, 2‐ethoxycarbonyl‐4,9‐dihydrocyclohepta[b]pyran‐4,9‐dione (3) reacted with hydroxylamine, hydrazine, and methylhydrazine to yield troponoids possessing a heterocyclic ring.
Synthesis of pyrazoles
Authors: Makino Kenzi , Kim Ho Sik , Kurasawa Yoshihisa
Published: March 2009

This review summarizes the synthesis of various pyrazoles reported by us and some other research groups in 1981–1989.
Facile synthesis of benzene‐bridged azaoxamacrobicyclic ligands
Authors: Bradshaw Jerald S. , Krakowiak Krzysztof E.
Published: March 2009

Five new barrel‐shaped macrobicyclic compounds capable of complexation with anions have been prepared. Intermediate triamines were prepared in one‐step using a triple Mitsonobu reaction, thereby shortening the overall synthetic sequence. A previously prepared benzene‐bridged hexaazamacrocycle was prepared in only four‐steps.
Acylation of 5‐amino‐3H‐1,3,4‐thiadiazolin‐2‐one
Authors: Ra Do Young , Cho Nam Sook , Cho Jae Joo
Published: March 2009

Acylation of 5‐amino‐3H‐1,3,4‐thiadiazolin‐2‐one (2) was undertaken selectively at either the 3‐NH position or at 5‐amino group depending on reaction conditions. The 3‐NH is highly acidic and acylation takes place with acid anhydrides at this position in high yields in the presence of pyridine or triethylamine. The diacylation of both the 3‐position and the 5‐amino group was only possible via the 5‐amino‐3‐acyl‐1,3,4‐thiadiazolin‐2‐one intermediates 4. Under neutral conditions, acylation only occurs at the 5‐amino group with acyl chlorides forming 5‐acylamino‐3H‐1,3,4‐thiadiazolin‐2‐ones 5. 5‐Acetylamino‐3H‐1,3,4‐thiadiazolin‐2‐one can also be synthesized by the thermal transformation of 5‐amino‐3‐acetyl‐1,3,4‐thiadi‐azolin‐2‐one in acetic acid.
Functionalization of 4,5‐dihalopyridazin‐6‐ones using 1‐(1,1‐dibromo‐2‐oxopropyl) derivatives
Authors: Kang Young‐Jin , Chung Hyun‐A , Kweon Deok‐Heon , Cho Su‐Dong , Lee Sang‐Gyeong , Kim Sung‐Kyu , Yoon Yong‐Jin
Published: March 2009

Functionalization of 4,5‐dihalopyridazin‐6‐ones using 1‐(1,1‐dibromo‐2‐oxopropyl)‐4,5‐dihalopyridazin‐6‐ones with some nucleophiles gave regioselectively only 5‐halo‐4‐substituted‐pyridazin‐6‐ones.
Synthesis and structure of novel 1,2‐dihydro‐phthalazine containing betaines
Authors: Saczewski Franciszek , Gdaniec Maria
Published: March 2009

1,2‐Dihydro‐2‐(4,5‐dihydroimidazol‐2yl)phthalazin‐1‐ol 1 reacts exothermically with dialkyl acetylenedicarboxylates to give 3‐[2‐(4,5‐dihydro‐1H‐imidazol‐3‐iurn‐2‐yl)‐1,2‐dihydro‐1‐phthalazin]‐1,4‐dialkoxy‐1,4‐dioxo‐2‐buten‐2‐olates 7 and 8. Enolic ester compounds underwent further transesterification reactions with formation of the betaines 9 and 10. The unequivocal structural assignement of these compounds was achieved by spectroscopic 1H and 13C nmr methods as well as X‐ray analysis of 7.
Synthesis of functionalized 3‐pyridyl methyl ketones
Authors: Wright S. W. , Hageman D. L. , McClure L. D.
Published: March 2009

A synthesis of 3‐pyridyl methyl ketones is described that employs a palladium‐catalyzed olefination of 3‐bromopyridines with butyl vinyl ether followed by acid hydrolysis of the intermediate pyridyl vinyl ether in situ. This method has been applied to bromoquinoline substrates as well. The reaction is compatible with a variety of functional groups.
Synthesis of five‐membered 2‐heteroaryl 2‐heteroaromatic carboxylates and attempted cyclization to bisheteroaryl[2,3‐b:3′,2′‐d]pyran‐2‐one
Authors: Lee Chang Kiu , Yu Ji Sook , Kim Sun Hee
Published: March 2009

2‐Heteroaryl 2‐heteroaromatic carboxylates were prepared by reactions of 2‐heteroaromatic carbonyl chlorides and 2(5H)‐furanone, 2(5H)‐thiophenone, and 1‐methyl‐2(5H)‐pyrrolone in triethylamine. The 1H nmr spectra of the esters showed that the electronic effect of both heteroaromatic rings did not cause any sizable shift from each other except for 1‐methyl‐2‐pyrrolyl 1‐methyl‐2‐pyrrolecarboxylate (5c). Attempts to cyclize the esters to heteroaryl‐fused pyran‐2‐ones were unsuccessful. The results may be explained by the most stable conformation of the esters in which two heteroatoms are anti along the C0 bond of the ester group.
Formation of basic compounds during the indole cyclization of ketone phenylhydrazones
Authors: Boido Caterina Canu , Boido Vito , Novelli Federica , Sparatore Fabio
Published: March 2009

On the basis of previous occasional findings, the Fischer indole cyclization of ten ketone phenylhydrazones containing moieties of increasing bulkiness was investigated in order to isolate eventual side products. In the cases of the three 2‐, 3‐ and 4‐acetylpyridine phenylhydrazones the corresponding 2‐pyridylindoles were the sole compounds so far isolated. In all the remaining cases, beside the indoles a mixture of basic compounds was obtained. In all cases aniline and a 2‐substituted (2‐methyl or 2‐phenyl)benzimidazole were formed, the last resulting through an apparent ortho‐semidinic rearrangements of phenylhydrazones. Starting from methyl isopropyl ketone phenylhydrazone a compound of formula C11H15NO was also isolated, to which the structure of 3‐(4‐aminophenyl)‐3‐methylbutanone was assigned on the basis of ir, nmr spectra and of the chemical reactivity. The formation of this compound seems related to a para‐benzidine‐like rearrangement of phenyl hydrazone.
A short and stereoselective synthesis of carbocyclic alpha‐l‐dideoxyhomonucleosides
Authors: Girard F. , Lee M.‐G. , Agrofoglio L. A. , Fridland A.
Published: March 2009

A stereoselective five‐step total synthesis of the hitherto unknown carbocyclic alpha‐L‐dideoxyhomonu‐cleosides starting from readily available (1R,5S)‐2‐oxabicyclo[3.3.0]oct‐6‐en‐3‐one is described.
Synthesis and biological activity of 1,5‐dihydropyridazino‐[3,4‐b]quinoxalines and a new class of quinolones
Authors: Kurasawa Yoshihisa , Kim Ho Sik
Published: March 2009

A new class of quinolones, 1,4‐dihydro‐4‐oxopyridazino[3,4‐b]quinoxaline‐3‐carboxylic acids and related compounds, were synthesized via oxidation of 1,5‐dihydropyridazino[3,4‐b]quinoxalines obtained from 2‐hydrazinoquinoxaline 4‐oxides. Some of the 1,5‐dihydropyridazino[3,4‐b]quinoxalines, 1,4‐dihydro‐4‐oxopyridazino[3,4‐b]quinoxaline‐3‐carboxylic acids, and related compounds showed biological activity.
Design, synthesis, and photophysical characterization of novel pentacyclic red shifted azine dyes
Authors: Gloster Daniel F. , Cincotta Louis , Foley James W.
Published: March 2009

As part of our continuing efforts to develop second generation photodynamic therapeutic agents [1], we synthesized three pentacyclic azine dyes that were designed with the aid of MNDO calculations to absorb visible light having wavelengths longer than 600 nm. Photophysical measurements for the azine dyes 1,4,8,11‐tetraethyl‐1,2,3,4,8,9,10,11,13‐nonahydrodipyrazino[2,3‐b:2′, 3′‐i] phenazinium acetate, 13, 1,4,8,11‐tetraethyl‐2,3,4,8,9,10,11,12,13‐octahydro‐13‐methyldipyrazino[2,3‐b:2,3′‐i]phenazinium iodide, 14, and l,4,8,11,13‐pentaethyl‐2,3,4,8,9,10,11,12,13‐octahydrodipyrazino[2,3‐b:2′,3′‐i]phenazinium iodide, 15, are highlighted by a 35 nm red shift in their absorption spectra and a 5–7 fold increase in their singlet oxygen quantum yield relative to tricyclic model compounds 3,7‐bis(diethylamino)phenazinium chloride, 20, and 3,7‐bis(diethylamino)‐5‐ethyl‐phenazinium iodide, 21, which were also synthesized for this study. Incorporation of rigid peripheral tetrahydropyrazino ring systems in the pentacyclic azines 13, 14, and 15 are responsible for the improved fluorescence and singlet oxygen quantum yields relative to the tricyclic azines 20 and 21.
Infrared study of hydrogen bonds involving N‐heterocyclic bases and phenols
Authors: Goethals Muriel , Zeegers‐Huyskens Thérese , Czarnik‐Matusewicz Boguslawa
Published: March 2009

The hydrogen bond complexes between phenols and N‐heteroaromatic bases 2,4,6‐tri(2‐pyridyl)‐1,3,5‐triazine, 2,2′,2′‐terpyridine, quinoxaline, pyrido[2,3‐b]pyrazine, pyzazino [2,3f]quinoxaline and 5‐nitrozphenanthroline are investigated by infrared spectroscopy in 1,2‐dichloroethane. The stability constants of the complexes involving N‐heteroaromatic bases characterized by tow vicinal nitrogen atoms having lone pairs pointing to each other are higher than predicted from their basicity. Possible differences between protonation and hydrogen bond formation are discussed. Nheteroaromatic bases such as tri(2‐pyridyl)‐1,3,5‐triazine or phenanthrolines cannot be considered as proton sponges but their behaviour is intermediate between that of the classical heteroaromatic bases and the proton sponges.
A convenient synthesis of the novel 5H‐thieno[2,3‐e]‐4,1,2‐oxathiazepine ring systemviaan alkoxycarbenium ion intermediate
Authors: Dantanarayana Anura P. , Dupre Brian , May Jesse A. , Lynch Vincent M.
Published: March 2009

3‐(Methoxymethoxymethyl)‐2‐thiophenesulfonamides and 3‐hydroxymethyl‐N‐methoxymethyl‐2‐thiophenesulfonamides have been shown to undergo cyclization when treated under anhydrous acidic conditions to provide the novel 2,3‐dihydro‐5H‐thieno[2,3‐e]‐4,1,2‐oxathiazepine ring system. Incorporation of a primary sulfonamide group into position seven of the molecule provided compounds which inhibit human carbonic anhydrase II.
Haloacetylated enol ethers. 11. Synthesis of 1‐methyl‐ and 1‐phenyl pyrazole‐3(5)‐ethyl esters. A one‐pot procedure
Authors: Martins Marcos A. P. , Freitag Rogério A. , Da Rosa Adriano , Flores Alex F. C. , Zanatta Nilo , Bonacorso Helio G.
Published: March 2009

A one‐pot synthesis of 1‐methyl‐ and 1‐phenylpyrazole‐3(5)‐ethyl esters 2,3a‐e by the cyclocondensation of β‐alkoxyvinyl trichloromethyl ketones 1a‐e with methyl and phenyl hydrazine hydrochloride under mild conditions, is reported. A study using compounds 1a‐e with different substituents proved that these are versatile building blocks for the synthesis of pyrazole derivatives, having a 3(5)‐ethoxycarbonyl substituent in good yields (60–89%). The hydrazine and β‐alkoxyvinyl trichloromethyl ketone substituent effects on the reaction regiochemistry on the formation of the 1,3‐ and 1,5‐isomer were observed.
Synthesis of β‐butylsulfanyl α‐oligothiophenes from 3‐butylsulfanyl‐2,2′‐bithiophene
Authors: Iarossi Dario , Mucci Adele , Schenetti Luisa , Sodini Valerio
Published: March 2009

β‐Butylsulfanyl tetra‐, sexa‐, and octathiophenes were synthesized by oxidative coupling with iron(III) chloride from 3‐butylsulfanyl‐2,2′‐bithiophene. Tetrathiophene was also generated through coupling reac tions. The nmr characterization of oligomers is reported and discussed.
Retro‐ene reaction. V. Functionalization of 4,5‐dihalopyridazin‐6‐ones using 1‐hydroxymethyl‐4,5‐dihalopyridazin‐6‐ones as 1–0, 3‐n, 5–0 ene‐adducts
Authors: Chung Hyun‐A , Kang Young‐Jin , Chung Joo‐Wha , Cho Su‐Dong , Yoon Yong‐Jin
Published: March 2009

Functionalization of 1‐hydroxymethyl‐4,5‐dihalopyridazin‐6‐ones via a retro‐ene reaction with some nucleophiles gave regioselectively only 5‐halo‐4‐substitutedpyridazin‐6‐ones.
Synthesis of pyrazoles and condensed pyrazoles
Authors: Makino Kenzi , Kim Ho Sik , Kurasawa Yoshihisa
Published: March 2009

This review introduces the synthesis of various pyrazoles reported by us and some other research groups during 1989–1998. Some of papers in this review deal with the development of potent pyrazoles or with the synthesis of potential pyrazoles aiming at agrochemicals and/or drugs.