bluuebunny/crossref_metadata_2025 huggingface dataset:
Unsymmetrical covariance processing of COSY or TOCSY and HSQC NMR data to obtain the equivalent of HSQC‐COSY or HSQC‐TOCSY spectra
Authors: Blinov Kirill A. , Larin Nicolay I. , Williams Antony J. , Mills Kent A. , Martin Gary E.
Published: March 2009

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Artifacts observed in the indirect covariance NMR spectrum of HSQC‐TOCSY data have recently been analyzed and a method for their elimination proposed. More recently, unsymmetrical covariance processing has been applied HSQC and HMBC spectral data to afford long‐range carbon‐carbon correlation information equivalent to that obtained from n, 1‐, 1, n‐ and m,n‐ADEQUATE spectra. We now wish to describe the results obtained through the application of unsymmetrical covariance processing of HSQC and COSY or TOCSY data, which affords the equivalent of HSQC‐COSY and HSQC‐TOCSY data in a fraction of the time required to record these spectra directly and with considerably higher sensitivity.
A mechanistic approach to photochemical behavior of 4‐anisyl‐4‐methyl‐2,6‐diphenyl‐4H‐thiopyran‐1,1‐dioxide
Authors: Rezanejadebardajee Ghasem , Jafarpour Farnaz , Pirelahi Hooshang
Published: March 2009

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Photoisomerization of 4‐anisyl‐4‐methyl‐2,6‐diphenyl‐4H‐thiopyran‐1,1‐dioxide is described in the presence of a sensitizer and new mechanistic features are proposed. The relative molar ratios of the stereoselective photoproducts compared in the presence and the absence of sensitizer in different concentrations of the starting material using hplc. The results observed are discussed on the basis of a triplet excited state thiadi‐π‐methane rearrangement.
Reactions of cephalosporin sulfones 3. Synthesis of 2‐phenylhydrazonocephem‐sulfones. A new potential entry to 2‐aminocephems
Authors: Gunda Tamas E. , Batta Gyula
Published: March 2009

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Reaction of cephem sulfones 1a‐e with aryldiazonium salts gives the 2‐azo compounds which immediately rearrange into the corresponding 2‐hydrazono derivatives 2a‐e.
Synthesis and activity of four (N,N‐dimethylamino)benzamide nonsteroidal anti‐inflammatory drugs based on thiazole and thiazoline
Authors: Lynch Daniel E. , Hayer Ravinder , Beddows Samantha , Howdle Joy , Thake C. Douglas
Published: March 2009

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Four compounds derived from 2‐aminothiazole and 2‐amino‐2‐thiazoline were prepared by coupling the respective bases with the acid chlorides of either 3‐ or 4‐(N,N‐dimethylamino)benzoic acid. Products were identified using infrared spectroscopy, 1H NMR spectroscopy and electrospray mass spectroscopy and in two cases by single‐crystal X‐ray diffraction. Of the four, N‐(thiazol‐2‐yl)‐3‐(N,N‐dimethylamino)‐benzamide (1), N‐(thiazolin‐2‐yl)‐4‐(N,N‐dimethylamino)benzamide (2), N‐(thiazolin‐2‐yl)‐3‐(N,N‐dimethylamino) benzamide (3) and N‐(thiazolin‐2‐yl)‐4‐(N,N‐dimethylamino)benzamide (4), the hydrochloride salts of compounds 3 and 4 showed anti‐inflammatory activity across a concentration range of 10−2−5 × 10−4 M while 3 (at a concentration of 10−5 M) was found to have no adverse effect on myocardial function. The X‐ray crystal structure of 2 and the 1:1 adduct structure of 3 with 3‐(N,N‐dimethylamino)benzoic acid are reported.
A series of 1‐[2‐aryl‐1‐diazenyl]‐3‐({3‐[2‐aryl‐1‐diazenyl]perhydrobenzo[d]imidazol‐1‐yl}methyl)perhydrobenzo[d]imidazoles. Synthesis and characterization
Authors: Glister Julie F. , Vaughan Keith
Published: March 2009

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Reaction of diazonium salts with solutions of 1,2‐diaminocyclohexane mixed with formaldehyde affords the 1‐[2‐aryl‐1‐diazenyl]‐3‐({3‐[2‐aryl‐1‐diazenyl]perhydrobenzo[d]imidazol‐1‐yl}methyl)perhydrobenzo‐[d]imidazoles (6), a new series of bis‐triazenes with different connectivity than any previous type of bis‐triazene reported. The products have been characterized principally by NMR and IR spectroscopy, elemental analysis and unequivocally by X‐ray crystallography. The methylene protons of the perhydroimidazole rings are diastereotopic giving rise to a doublet of doublets pattern in the 1H NMR spectra. However, detailed analysis of the NMR spectra shows that there is more than one set of doublet‐of‐doublet signals, suggesting the presence of different rotameric forms of the products. The 13C NMR spectral assignments were assisted by COSY and DEPT experiments with selected compounds.
Application on novel fragmentation reaction: A concise synthesis of 2,3,5‐trisubstituted furans from butenolides
Authors: Zhang Xuqing , Jackson Elieen U. , Schultz Arthur G.
Published: March 2009

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Butenolides 4, generated from a novel fragmentation reaction, function as excellent precursors to 2,3,5‐trisubstituted furans 5 by additions of alkyl or aryl metallic reagents. It can also be converted into siloxyfurans 6 by treatment with silylating reagents.
New efficient approach for the synthesis of 2‐alkyl(aryl) substituted 4H‐pyrido[1,2‐a]pyrimidin‐4‐ones
Authors: Bonacorso Helio G. , Righi Fernando J. , Rodrigues Isadora R. , Cechinel Cleber A. , Costa Michelle B. , Wastowski Arci D. , Martins Marcos A. P. , Zanatta Nilo
Published: March 2009

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A new, efficient and easy route for the preparation of a series of 2‐alkyl(aryl) substituted 4‐oxo‐4H‐pyrido‐[1,2‐a]pyrimidines, where alkyl = CH3; aryl = C6H5, 4‐FC6H4, 4‐ClC6H4, 4‐BrC6H4, 4‐CH3C6H4, 4‐OCH3C6H4, 4‐NO2C6H4in 45–80 % yield from the reaction of β‐alkoxyvinyl trichloromethyl ketones with 2‐aminopyridine under mild conditions, is then reported.
Convenient synthesis of N‐substituted 1‐alkyl and 1‐aryl‐3‐aminoisoquinolines
Authors: Cánepa Alicia S. , Bravo Rodolfo D.
Published: March 2009

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Cyclocondensation of 2‐acylphenylacetonitriles 1 with amines affords 1‐substituted 3‐aminoisoquinolines 2 in good yields.
Δ2‐Isoxazolines from β,γ‐unsaturated oximes
Authors: Mosher Michael D. , Emmerich Laura G. , Frost Katherine S. , Anderson Benjamin
Published: March 2009

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3,5‐Disubstituted Δ2‐isoxazolines can be prepared using the palladium‐mediated nucleometalation / methoxycarbonylation of β,γ‐unsaturated oximes. This novel route to this class of compounds is tolerant of a wide variety of functionality in the starting material, and provides a rapid route to highly functionalized isoxazolines.
Studies with condensed aminothiophenes: Further investigation on the reactivity of condensed aminothiophenes toward electron poor and acetylenes under microwave heating
Authors: Al‐Saleh Balkis , El‐Apasery Morsy A.
Published: March 2009

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The reaction of aminothienopyridazines 8a,b, aminothienocoumarin 13 and aminothienonaphthopyran 14 with enaminones 9, 17 and 20a,b under microwave irradiation affords either a mixture of both condensations C‐1 alkylation products 15 and 16 or amino moiety alkylation and diethylamine elimination or only one of these products depending on nature of substituents on the thiophene ring. On the other hand reaction of these condensed aminothiophenes with 3‐dimethylaminoacrylaldehyde afforded 24 and 25.
Some nucleophilic substitutions in 2‐cyano‐3‐nitroimidazo[1,2‐a]pyridine
Authors: Arias Lucina , Salgado‐Zamora Héactor , Campos Elena , Reyes Alicia , Cervantes Humberto , Taylor Edward C.
Published: March 2009

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In some nucleophilic substitution reactions of 2‐cyano‐3‐nitroimidazo[1,2‐a]pyridine, nitrogen (alkylamines, guanidine) and oxygen nucleophiles (alkoxides) underwent substitution of the 2‐cyano group, while sulfur nucleophiles (alkylthiols) underwent substitution of the 3‐nitro group.
Synthesis of 8‐substituted tetrahydro‐γ‐carbolines
Authors: Bridoux Alexandre , Goossens Laurence , Houssin Raymond , Héanichart Jean‐Pierre
Published: March 2009

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The Fischer reaction is applied to the synthesis of 8‐substituted tetrahydro‐γ‐carbolines with electron‐donating or electron‐withdrawing groups, using catalytic or thermal methods. The reaction conditions must be varied according to the nature of the N 1 substituent of the piperidone. The best results are observed when a releasing group is present on the arylhydrazine and a benzyl substituent on the nitrogen of piperidone. Formation of carbolines with a withdrawing substituent is observed in soft acidic conditions; in others, reaction ended at the hydrazone level or did not evolve.
A new approach to the total synthesis of (±)‐20‐ epidasycarpidone
Authors: Uludag Nesimi , Patir Suleyman , Höukelek Tuncer
Published: March 2009

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In this study, a new synthetic route to the total synthesis of (±)‐20‐ epidasycarpidone (1b) is described. This route involves acid catalyzed ring closure and the formation of the intermediate 13 in the key step. The relative stereochemistry of 13 has been confirmed by X‐ray structure analysis. The tetracyclic intermediate 13 was synthesized through several steps starting from 3. The removal of the protecting group of 13 yielded the lactam 15, which was reduced by Red‐Al® to give 16. The synthesis of (±)‐20‐ epidasycarpidone (1b) was finally completed by the oxidation of 16.
Thermolysis of N,N″‐1,ω‐alkanediyl‐bis[n′‐organylthiourea] derivatives
Authors: Hassan Alaa A. , Döupp Dietrich
Published: March 2009

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The course of microwave assisted or conventional thermal intramolecular heterocyclization of the title compounds has been found to be dependent on the length of the alkanediyl chain. While 1,3‐propanediyl‐bisthioureas 5a‐c gave both 2‐thioxoperhydropyrimidine‐1‐carbothioamides 8a‐c and 8‐amino‐3,4,5,6‐tetrahydro‐1,3,7‐thiadiazocine‐2‐thiones 10a‐c, thermolysis of 1,4‐butanediyl‐bisthioureas 6a‐c and 1,6‐hexanediyl‐bisthioureas 7a‐c under the same conditions gave solely 9‐amino‐4,5,6,7‐tetrahydro‐1,3,8‐thiadiazonine‐2‐thiones 11a‐c and 11‐amino‐1‐thia‐3,10‐diazacycloundec‐10‐ene‐2‐thiones 12a‐c, respectively. Symmetric N,N′‐diorganylthioureas 4a‐c were formed in all cases as minor byproducts.
A new method for the synthesis of substituted indeno[1,2‐b]thiophene with subsequent ring expansion to form substituted thieno[3,2‐c]quinoline
Authors: Castle Lyle W. , Elmaaty Tarek Abou
Published: March 2009

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2‐Phenacylindan‐1,3‐dione (3) was treated with Lawesson's reagent (2,4‐bis(4‐methoxyphenyl)‐1,3‐dithia‐2,4‐diphosphetane‐2,4‐disulfide) to form 2‐phenyl‐4H‐indeno[1,2‐b]thiophene‐4‐one (4). Compound 4 was subsequently reacted with hydroxyl amine to form the oxime (5), which, upon treatment with polyphosphoric acid, underwent ring expansion (Beckmann rearrangement) to give 2‐phenylthieno[3,2‐c]quinoline‐4(5H)one.
Stereochemistry, tautomerism, and reactions of acridinyl thiosemicarbazides in the synthesis of 1,3‐thiazolidines
Authors: Balentová Eva , Imrich Ján , Bernáat Juraj , Suchá Lucia , Vilková Mária , Kristian Pavol , Pihlaja Kalevi , Klika Karel D. , Pröanayová Nad'a
Published: March 2009

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Acridin‐9‐yl hydrazine upon treatment with various isothiocyanates (RNCS, R = methyl, allyl, phenyl, p‐methoxy phenyl, and p‐nitro phenyl) yielded the corresponding thiosemicarbazides with acridine substituted on the carbazide‐type side. The alkyl‐substituted compounds were present in solution as equilibria consisting of the major H‐10, H‐12 tautomer (either E or Z or both about the C13‐N14 bond) and the minor H‐10, SH tautomer (either E or Z or both). The major species for the aromatic‐substituted compounds was the H‐10, H‐12 E tautomer, with the evident minor species being the H‐10, H‐12 Z tautomer. The thiosemicarbazides were each quantitatively converted into the analogous semicarbazides upon treatment with mesitylnitrile oxide wherein all structures were present in solution as the H‐10 tautomers with Z conformation about the C13‐N14 bond. Methylation of the compounds with methyl iodide yielded S‐methylated compounds wherein the Z configuration dominated in each case over the E configuration along the N12‐C13 double bond. Treatment of the thiosemicarbazides with methyl bromoacetate resulted in the formation of 1′,3′‐thiazolidin‐4′‐ones wherein the Z configuration predominated in each case over the E configuration along the N12C13 double bond. With bromoacetonitrile as the bifunctional electrophile, the initial 1′,3′‐thiazolidin‐4′‐imines that formed spontaneously underwent Dimroth‐type rearrangement to the regiosiomeric 1′,3′‐thiazolidin‐4′‐imines.
Convenient synthesis of novel 5‐substituted 3‐methylisoxazole‐4‐sulfonamides
Authors: Filimonov Sergey I. , Korsakov Mikhail K. , Dorogov Mikhail V. , Kravchenko Dmitry V. , Tkachenko Sergey E. , Ivachtchenko Alexandre V.
Published: March 2009

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A number of novel sulfonamide derivatives of 5‐substituted‐3‐methylisoxazole were synthesized and characterized, starting from 3,5‐dimethylisoxazole. Key steps include the generation of 3,5‐dimethylisoxazole‐4‐sulfonamides followed by their reactions with N‐(dimethoxymethyl)‐N,N‐dimethylamine or various aromatic and heteroaromatic aldehydes. As a result, a series of novel aryl/heteroaryl‐ and aminovinylsubstituted derivatives of the isoxazole heterocycle were obtained. The scope and limitations of the developed approach are discussed.
Synthesis of fluorine containing N‐benzyl‐1,2,3‐triazoles and N‐methyl‐pyrazoles from conjugated alkynes
Authors: Rama Rao V.V.V.N.S. , Lingaiah B.P.V. , Yadla R. , Rao P. Shanthan , Ravikumar K. , Swamy G.Y.S.K. , Narsimulu K.
Published: March 2009

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1, 3‐Dipolar‐cycloaddition reaction of fluoro substituted 3‐aryl‐propynenitriles 1 with benzyl azide 2 afforded the expected 3‐benzyl‐5‐aryl‐3H‐[1,2,3]triazole‐4‐carbonitrile 3 and 1‐benzyl‐5‐aryl‐1H‐[1,2,3]‐triazole‐4‐carbonitrile 4 in good yield. However, 1,3‐dipolar cycloaddition of diazomethane 5 with 3‐aryl‐propynenitriles 1 resulted in the exclusive formation of N‐methyl‐pyrazole derivatives 6 and 7.
Synthesis of 2‐amino‐4‐aryl‐7,7‐dimethyl‐5‐oxo‐4H‐5,6,7,8‐tetrahydrobenzo[b]pyran derivatives in ionic liquid medium
Authors: Li Yuling , Du Baixiang , Wang Xiangshan , Shi Daqing , Tu Shujiang
Published: March 2009

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In this paper, preparation of 2‐Amino‐4‐aryl‐7,7‐dimethyl‐5‐oxo‐4H‐5,6,7,8‐tetrahydrobenzo[b]pyran derivatives from aromatic aldehyde, malononitrile or cyanoacetate and 5,5‐dimethyl‐1,3‐cyclohexanedione in ionic liquid [bmim+][BF4−] was described. Compared with other methods, this new method has the advantages of easier work‐up, milder reaction conditions, high yields and environmentally benign procedure.
One pot synthesis of substituted dihydroindeno[1,2‐b]indoles and dihydrobenzo[a]carbazoles by photostimulated reactions of o‐iodoaniline with carbanions by the SRN1 mechanism
Authors: Barolo Silvia M. , Rossi Roberto A. , Rosales Ceciréa , Angel Guío Jorge E.
Published: March 2009

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The photostimulated reaction of enolate anions of cyclic aromatic ketones such as substituted indan‐1‐ones and 3,4‐dihydro‐2H‐naphthalen‐1‐one with o‐iodoaniline in DMSO affords 1‐, 2‐, 3‐, and 4‐methoxy‐5,10‐dihydroindeno[1,2‐b]indoles (34‐40%), 1,2‐, 1,4‐, and 2,3‐dimethoxy‐5,10‐dihydroindeno[1,2‐b]‐indoles (31‐43%), and 1‐, 2‐, and 3‐methoxy‐5,11‐dihydro‐6H‐benzo[a]carbazoles (42‐61%) by the SRN1 mechanism in one pot reactions.
The synthesis of symmetrical (2‐indolyl)ethynes and reduced congeners via palladium‐catalyzed couplings of 2‐bromoindole precursors
Authors: Sercel Anthony D. , Hollis Showalter H. D.
Published: March 2009

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Starting from a series of 2‐bromo‐1‐methylindole precursors (1b‐e) activated in the 3‐position with aldehyde, ester, or amide functionality, two approaches have been developed toward the synthesis of 2,2′‐bis(indolyl)ethynes and reduced congeners via palladium(0)‐ or palladium(II)‐catalyzed couplings. The first approach utilized Sonogashira coupling of (trimethylsilyl)acetylene to introduce the two‐carbon linker followed by desilylation and further coupling with starting 2‐bromoindole. A second shorter and more efficient route engaged the starting 2‐bromoindole in a double Stille coupling with bis(tributylstannyl) acetylene or (E)‐1,2‐bis(tributylstannyl)ethylene to provide desired homodimers in one step. Subsequent transformations of dimeric intermediates led to target acids 7a‐c and derived amides 8a‐c and 9. When tested against a panel of tyrosine kinases, each target compound was found to be inactive.
Synthesis of 1‐(substituted phenylcarbonyl/sulfonylamino)‐1,2,3,6‐tetrahydropyridine‐5‐carboxylic acid diethylamides as potential anti‐inflammatory agents
Authors: Gangapuram Madhavi , Redda Kinfe K.
Published: March 2009

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Fifteen novel 1‐(substituted phenylcarbonyl/sulfonylamino)‐1,2,3,6‐tetrahydro‐ pyridine‐5‐carboxylic acid diethylamide (7, 15) were synthesized in fair to good yields via sodium borohydride reduction of the corresponding 1‐(substituted phenylcarbonyl/ sulfonylimino)‐3‐diethylcarbamoyl pyridinium ylides (6, 14) in absolute ethanol.
Structure determination of N‐methyl‐tetrahydro‐5H‐indazol‐5‐ones
Authors: Josef Kurt A. , Dandu Reddeppareddy , Tao Ming , Hudkins Robert L.
Published: March 2009

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This paper communicates the (regio) synthesis and a convenient NMR structural assignment method for N‐methyl‐tetrahydro‐5H‐indazol‐5‐one isomers. The cyclization reaction of 7‐(hydroxymethylene)‐1,4‐dioxaspiro[4,5]decan‐8‐one (3) with methylhydrazine yields, after de‐protection predominately the N‐2 methyl isomer 2. Analysis of the product ratio and structural assignments are based on NMR data including NOE difference experiments and subsequently confirmed with X‐ray crystallography. These findings are in sharp contrast with the literature. The experimental conditions used to optimize the synthesis of the individual isomers are discussed.
Unusual structures derived from N‐acridin‐9‐yl methyl N′‐acridin‐9‐yl thiourea based on the propensity of N‐10 to retain H
Authors: Klika Karel D. , Pihlaja Kalevi , Imrich Ján , Vilková Mária , Bernát Juraj
Published: March 2009

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N‐Acridin‐9‐yl methyl N′‐acridin‐9‐yl thiourea spontaneously spiro cyclises via nucleophilic attack of the methylene carbon onto the C‐9 of the other acridine moiety. The thiourea, upon reaction with bromoacetonitrile, provided a spiro fused‐bicyclic product displaying unusual dynamic behavior.
Microwave‐assisted claisen rearrangement. Application to the synthesis of angelicin derivatives
Authors: Valizadeh Hassan , Shockravi Abbas
Published: March 2009

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4′‐(Hydroxy, chloro, amino, acetoxy and methoxy)‐methyl‐4,5′‐dimethylangelicins were efficiently and rapidly synthesized via Claisen rearrangement of 4‐methyl‐7‐[4‐(hydroxy, chloro, amino, acetoxy and methoxy)‐but‐2‐ynyloxy]‐coumarins respectively under microwave irradiation. Prominent among the advantages of this new method are operational simplicity, good yields in short reaction times and easy work‐up procedures employed.
Pictet‐spengler cyclization in room temperature ionic liquid: A convenient access to tetrahydro β‐carbolines
Authors: Muthukrishnan M. , More Shivaji V. , Garud Dinesh R. , Ramana C. V. , Joshi R. R. , Joshi R. A.
Published: March 2009

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1,2,3,4‐Tetrahydro‐β‐carbolines have been synthesized in moderate to good yields in short reaction time using the ionic liquid [bbim] BF4 as reaction medium and promoter. There was no need for the use of an additional catalyst normally employed in Pictet‐Spengler condensation.
The convenient synthesis of benzimidazole derivatives catalyzed by I2 in aqueous media
Authors: Sun Peipei , Hu Zhixin
Published: March 2009

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In the presence of catalytic amount of iodine, in THF‐H2O, the condensation of aldehydes with 1,2‐phenylenediamine gave the benzimidazole derivatives under mild conditions in good yields. The method can be used for the synthesis of 2‐substituted benzimidazoles or 1,2‐disubstituted benzimidazoles.
Synthesis of a library of 1,2,3,7‐tetrasubstituted indolizines using poly(ethylene glycol) as soluble support
Authors: Yue Guizhou , Chen Zuxing , Yang Guichun
Published: March 2009

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A library of 1,2,3,7‐tetrasubstituted indolizines has been synthesized using poly(ethylene glycol) (PEG) as soluble polymer support. The PEG‐bound pyridinium salts reacted with alkenes or alkynes in the presence of Et3N via 1,3‐dipolar cycloaddition to give PEG‐bound indolizine derivatives, which were cleaved by 1 % KCN/MeOH to afford 1,2,3,7‐tetrasubstituted indolizines in good to excellent yields.
Study of synthesis of 2‐(2‐alkoxyphenyl)‐1H‐imidazoles. Comparison of oxidative aromatization reactions of imidazolines
Authors: Pařík Patrik , Šenauerová Sylva , Lišková Vlasta , Handlíř Karel , Ludwig Miroslav
Published: March 2009

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The reaction of methyl salicylate with ethane‐1,2‐diamine has been used to prepare 2‐(2‐hydroxyphenyl)‐1H‐imidazoline. This compound was alkylated with alkyl halides to give five new 2‐(2‐alkoxyphenyl)‐1H‐imidazolines (alkyl = propyl, isopropyl, isobutyl, sec‐butyl, benzyl). Seven types of transformation reactions of imidazolines into the respective imidazoles were tested. Out of them successful were the dehydrogenation on palladium in toluene (several‐day refluxing), oxidation with activated manganese dioxide in toluene (several‐hour heating at 60 °C), and the oxidation with potassium nitrosodisulfonate (Fremy's salt) at room temperature. Seven new 2‐(2‐alkoxyphenyl)‐1H‐imidazoles were synthesized (alkyl = ethyl, propyl, isopropyl, butyl, isobutyl, sec‐butyl, benzyl) via mentioned methods. Comparison of individual oxidative aromatization reactions is discussed from the point of view of experimental arrangement, reaction time and conditions, purity of the products obtained, and yields.
Transformation of 4‐oxo‐4H‐[1]‐benzopyran‐3‐carboxaldehydes into pyrazolo[3,4‐B]pyridines
Authors: Stankovičová Henrieta , Gáplovský Anton , Lácová Margita , Chovancová Jarmila , Puchala Agnieszka
Published: March 2009

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Reaction of 6‐methyl‐4‐oxo‐4H‐[1]‐benzopyran‐3‐carboxaldehyde 1 with 5‐amino‐3‐methyl‐1‐phenylpyrazole 2 in alcoholic reaction media in the presence of 4‐toluenesulfonic acid as catalyst afforded 5‐(2‐hydroxy‐5‐methylbenzoyl)‐3‐methyl‐1‐phenyl‐1H‐pyrazolo[3,4‐b]pyridine 3 and 2‐methoxy‐6‐methyl‐3‐(3‐methyl‐1‐phenylpyrazol‐5‐ylaminomethylene)chroman‐4‐one 7. We explain the mechanism of formation of both products on the basis of kinetic study of individual reaction steps.
An efficient one‐pot synthesis of 5‐aryl substituted 2‐amino‐5,8‐dihydropyrido[2,3‐D] pyrimidin‐4,7‐diones under microwave irradiationl without catalyst
Authors: Tu Shujiang , Wang Qian , Xu Jianing , Zhu Xiaotong , Zhang Jinpeng , Jiang Bo , Jia Runhong , Zhang Yan , Zhang Junyong
Published: March 2009

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A series of 5‐aryl substituted 2‐amino‐5,8‐dihydropyrido[2,3‐d]pyrimidin‐4,7‐diones were synthesized through one‐pot condensation of 2,6‐diaminopyrimidin‐4‐one, aldehyde and Meldrum's acid using glycol as energy transfer agent under microwave irradiation without catalyst. The one‐pot protocol in the absence of catalyst has the advantage of good yield (86‐95%), short route and reaction time (3‐6 min) and environmentally friendly.
Synthesis of 1‐acyl‐1,2‐dihydro‐3H‐pyrazol‐3‐ones VIA lewis acid‐mediated rearrangement of 3‐acyloxypyrazoles
Authors: Maruoka Hiroshi , Yamagata Kenji , Okabe Fumi , Tomioka Yukihiko
Published: March 2009

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The unusual formation of 1‐acyl‐1,2‐dihydro‐3H‐pyrazol‐3‐ones starting from 3‐acyloxypyrazoles by Fries‐type rearrangement is described. Under normal conditions, acylation of 2,4‐dihydro‐3H‐pyrazol‐3‐ones 1 and 2 with acid chlorides or anhydrides in the presence of triethylamine gave the corresponding 3‐acyloxypyrazoles 3a‐f and 4a‐f. Treatment of 3a‐c and 4a‐f with Lewis acid, e.g. titanium(IV) chloride and tin(IV) chloride, caused migration of acyl groups to afford the corresponding 1‐acyl‐1,2‐dihydro‐3H‐pyrazol‐3‐ones 5a‐c and 6a‐f. Interestingly, the reactions of 3‐acyloxypyrazoles 3e and 3f with tin(IV) chloride provided the corresponding tin(IV) complexes 8e and 8f.
Lewis acid catalyzed nenitzescu indole synthesis
Authors: Velezheva Valeriya S. , Kornienko Albert G. , Topilin Sergey V. , Turashev Ascar D. , Peregudov Alexander S. , Brennan Patrick J.
Published: March 2009

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A novel method for Lewis acid catalyzed Nenitzescu indole syntheses of 5‐hydroxyindoles bearing different substituents in positions 1 )Alk, Bn, Ar), 2 )Me, Et, Ph), and 3 )COOEt, COMe, CONHPh) as well as tricyclic derivatives are reported. The method is simple, rapid, efficient, and allows preparation of hydroxyindoles from 1,4‐benzoquinone and enamines in good to excellent yields with the use of low‐polar solvents in the presence of weak Lewis acids catalysts. The formation of 5‐hydroxyindoles under such mild conditions is explained in terms of a non‐redox mechanism.
Aromatization and ring cyclization: A reasonable understanding on the ring cyclization mechanism of 3‐amino‐6‐hydrazino‐1,2,4‐triazin‐5(2H)‐one reacted with one‐carbon fragment reagents or nitrous acid
Authors: Hwang Long‐Chih , Tus Chun‐Hsien , Wang Jung‐Hui
Published: March 2009

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The cyclization mechanism for the title compound (2) reacting with one‐carbon fragment reagents or nitrous acid to afford heterobicyclic compounds 6‐amino‐3‐substituted‐1,2,4‐triazolo[3,4‐f][1,2,4]triazin‐8(7H)‐ones (3a∼d) or 6‐amino‐1,2,3,4‐tetrazolo[5,1‐f][1,2,4]triazin‐8(7H)‐one (4), respectively, is explored in this paper. When 3‐amino‐2‐benzyl‐6‐hydrazino‐1,2,4‐triazin‐5(2H)‐one (10), the N‐2 benzylated derivative of 2, is treated under the same conditions, ring cyclization does not occur; instead, 3‐amino‐2‐benzyl‐6‐substituted‐1,2,4‐triazin‐5(2H)‐ones (11,12,14) and 2‐N‐(2‐amino‐1‐benzyl‐4‐oxo‐1,2,4‐triazin‐5‐yl)semicarbazide (13) are formed. Alternatively, when 3‐amino‐6‐hydrazino‐2‐[(2‐hydroxyethoxy)methyl]‐1,2,4‐triazin‐5(2H)‐one (16), a compound bearing the 2‐[(2‐hydroxyethoxy)methyl] side‐chain at N‐2 of 2 by an NCO bond, reacts with glacial acetic acid or nitrous acid, the side‐chain is cleaved through acidolysis to affford the ring‐closed compound 6‐amino‐3‐methyl‐1,2,4‐triazolo[3,4‐f][1,2,4]triazin‐8(7H)‐one (3b) or compound 4, respectively. From these results, we suggest a cyclization mechanism that the ring cyclization is dependent on the aromatization of the 1,2,4‐triazine ring, which influence the reactivity and reaction behavior of the π‐deficient 1,2,4‐triazine.
One‐pot three‐component synthesis of 2‐substituted 4‐aminoquinazolines
Authors: Rad‐Moghadam Kurosh , Samavi Laleh
Published: March 2009

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A facile and rapid synthesis of the title compounds via one‐pot reaction of 2‐aminobenzonitrile, orthoesters and ammonium acetate under solvent‐free and microwave condition is described.
π‐Aryl/heteroaryl conjugated coumarin‐thiazoles: Synthesis, optical spectral and nonlinear optic properties
Authors: Mashraqui Sabir H. , Mistry Hitesh , Sundaram Subramanain
Published: March 2009

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A series of π‐aryl/heteroaryl conjugated coumarin‐thiazole systems 8a‐f has been synthesized by using Hantzsch thiazole protocol and Wittig olefination as the keys. In the UV‐Visible spectra of 8a‐f, a main absorption band associated with a dominant π‐π* transition is observed in the region of 338 to 390 nm. Qualitatively, the values of λmax have been found to correlate satisfactory with the donor/acceptor characteristics of the π‐attached chromophores. Marked changes observed in the absorption maxima of 8a under acidic conditions are rationalized on the basis of mono‐or bis‐protonation and modification of the donor/acceptor properties of chromophores undergoing protonation. The emission spectra of 8a‐f, obtained by exciting the molecules at their main absorption bands showed emission maxima in the region of 429 nm to 537 nm, with relatively high Stokes shifts of 145 and 171 nm being observed for 8a and 8e, carrying a π‐donor, dimethylaminophenyl and a π‐acceptor, p‐nitrophenyl chromophore, respectively. Although, the first hyperpolarisability β, measured by the hyper‐Reileigh scattering (HRS) technique are modest (12 to 23 × 10−30 esu), all the compounds exhibited complete transparency in the frequency doubling region at 532 nm and showed high thermal stability (Td from 330 to 365 °C).
Studies with 3‐functionally substituted 2‐arylhydrazononitriles: A new route to 3‐substituted‐2‐arylhydrazononitriles, 4‐amino‐pyrazole‐5‐carbonitriles, azadienes and cinnolines
Authors: Abdel‐Motaleb Ramadan M. , Makhloof Abdel‐Moneim A. , Ibrahim Hamada M. , Elnagdi Mohamed H.
Published: March 2009

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3‐Amino‐3‐phenyl‐2‐phenylazoacrylonitrile 6 is obtained in good yield via reaction of 5 with phenyl magnesium bromide. The compound 6 is readily converted into 4a. The so formed alkanenitrile reacted with phenylmagnesium bromide to yield 8. Compound 8 could be also obtained from reaction of 9 with phenylmagnesium bromide. The arylhydrazononitriles 8 and 4a reacted with chloroacetonitrile to yield the 4‐aminopyrazoles 12a,b. Compound 12a reacted with acetic anhydride to yield the 15a and with benzoyl chloride to yield the pyrazole 16 which was converted into 15b. Refluxing 10 in acetic acid gave a mixture of the azadiene 21 and the cinnoline 22 is obtained. The azadiene 21 is converted into 22 either thermally or photochemically.
A novel route to tetracyclic fused tetrazines and thiadiazines
Authors: Abbas Ikhlass M. , Riyadh Sayed M. , Abdallah Magda A. , Gomha Sobhy M.
Published: March 2009

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The reaction between 3‐amino‐2,3‐dihydro‐7,9‐dimethyl‐2‐thioxo‐pyrido[3′,2′:4,5]thieno[3,2‐d]‐pyrimidin‐4(1H)‐one 4 or its 2‐methylthio derivative 5 with hydrazonoyl halides 6 in dioxane in the presence of triethylamine under reflux has followed heterocyclization reaction to yield pyrido[3″,2″:4′,5′]‐thieno[3′,2′:4,5]pyrimido[2,1‐c][1,2,4,5]tetrazin‐6(4H)‐ones 9. On the other hand, reaction of compound 4 with hydrazonoyl halides 6 in sodium ethoxide at room temperature led to formation of hydrazonothioate compounds 10. The latter on treatment with glacial acetic acid produced tetracyclic compounds, namely 2‐arylhydrazonopyrido[3″,2″:4′,5′]thieno [3′,2′:4,5]pyrimido[2,1‐b][1,3,4]thiadiazinones 11. An alternative method was carried out to prove the structure of product 11. The mechanism of the reaction under study was proposed and the products were screened for their biological activity.
Synthesis of novel 2‐amino‐6,8‐dithioxopurine derivatives
Authors: Ikaunieks Martins , Belyakov Sergey , Madre Marina
Published: March 2009

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The synthesis of novel 2‐amino‐9‐alkoxyalkylpurine derivatives with both identical and different sulfur containing substituents at positions 6 and 8 of the purine cycle has been accomplished. The thionation and alkylation of the key intermediate ‐ 2‐[2‐(acetylamino)‐6,8‐dichloro‐9H‐purin‐9‐yl]methoxyethyl acetate or its reactions with thiolates were used. The structures of compounds obtained were confirmed by spectroscopic data and X‐ray diffraction analysis.
Azulene‐substituted pyranylium salts. Syntheses and products characterization
Authors: Razus Alexandru C. , Birzan Liviu , Pavel Claudia , Lehadus Oana , Corbu Andreea Cristina , Enache Cristian
Published: March 2009

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The synthesis of 4‐azulene‐substituted 2,6‐diphenyl‐ and 2,6‐dimethyl‐pyranylium salts and 2‐azulenesubstituted 4,6‐dimethyl‐pyranylium salts by nucleophilic substitution at pyranylium moiety with various azulenes was studied. The starting materials for 2,6‐diphenyl derivatives were 4 chlorinated pyranylium salts. They were obtained by the halogenation with PCl5 of corresponding pyranones and were used either in situ or after separation. For the synthesis of dimethyl derivatives the corresponding pyranones were treated with POCl3 and the resulted intermediate was reacted in situ with azulene. In the aim to study the influence of dihedral angle between azulene and pyranylium planes on the recorded spectra, both moieties were adequately substituted. The obtained results were in accord with the calculated values.
Synthesis of novel 1‐substituted [1,3]thiazolo[3,2‐a]‐[1,5]benzodiazepine derivatives from 1,5‐benzodiazepine‐2‐thiones and α‐halogen carbonyl compounds
Authors: Janciene Regina , Stumbreviciute Zita , Podeniene Daiva , Puodziunaite Benedikta D. , Black Steve , Husbands Stephen M.
Published: March 2009

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A number of substituted 4H,5H,6H‐thiazolo[3,2‐a][1,5]benzodiazepinium salts 2a‐h, 5, 9, which are based on the novel thiazolobenzodiazepine system, were prepared by condensation‐cyclization of 1,5‐benzodiazepine‐2‐thiones 1a‐f, h, 4 with α‐haloketones, as well as with α‐bromoacetaldehyde diethyl acetal. The structure and stereochemistry of the ring system obtained were investigated by 1H and 13C nmr spectroscopy: the additional heterocyclic nucleus was found to appreciably influence the conformational mobility of the heptatomic ring. Upon treatment of salt 2d with alkali the presence of the base enamine structure in solution has been postulated.
One‐pot synthesis of hexahydroquinolines Via a four‐component cyclocondensation under microwave irradiation in solvent free conditions: A green chemistry strategy
Authors: Tu Shujiang , Zhang Jinpeng , Zhu Xiaotong , Zhang Yan , Wang Qian , Xu Jianing , Jiang Bo , Jia Runhong , Zhang Junyong , Shi Feng
Published: March 2009

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Four‐component cyclocondensation of aromatic aldehydes, malononitrile, dimedone and ammonium acetate proceeds under microwave irradiation in solvent free conditions to give highly functionalized hexahydroquinolines in excellent yields.
A clean synthesis of polyhydroacridine and indenoquinoline derivatives catalyzed by triethylbenzylammonium chloride in aqueous media
Authors: Wang Xiang‐Shan , Zhang Mei‐Mei , Zeng Zhao‐Sen , Shi Da‐Qing , Tu Shu‐Jiang , Wei Xian‐Yong , Zong Zhi‐Min
Published: March 2009

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An efficient and convenient synthesis of benzo[a]acridines and indeno[1,2‐b]benzo[f]quinolines was achieved in high yields by the reaction of N‐arylidenenaphthalen‐2‐amine with 1,3‐dicarbonyl compounds catalyzed with triethylbenzylammmonium chloride (TEBAC) in aqueous media. The structures were established by spectroscopic data and further confirmed by X‐ray analysis. This method provides several advantages such as neutral conditions, high yields and simple work‐up procedure. In addition, water was chosen as a green and recyclable solvent.
Synthesis, properties and solid state structure of 5‐diphenylphosphino‐2‐hydroxy‐1,3‐xylyl‐18‐crown‐5
Authors: Corbin Rex A. , Crabill Todd W. , Storhoff Bruce N. , Huffman John C.
Published: March 2009

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5‐Diphenylphosphino‐2‐hydroxy‐1,3‐xylyl‐18‐crown‐5 has been synthesized from 5‐bromo‐2‐hydroxy‐18‐crown‐5 by reacting it in sequence at low temperature with n‐butyl lithium and methyl diphenylphosphonite. The phosphorous donor properties of this phenol phosphine (OH derivative) and the corresponding phenoxide (O− derivative) have been studied in the presence and absence of alkali metal ions by determining the frequencies of the A1 ν(CO) bands of Ni(CO)3L complexes. For the OH and O− derivatives, the latter generated by addition of CsOH to the former, the ν(CO) bands are observed at 2067.6 and 2063.4 cm−1, respectively, providing the trend predicted by Hammett parameters for OH and O− substituents. Addition of Na+ or K+ to the OH derivative has little effect on this stretching frequency, but the former ion shifts the O− derivative band to 2067.7 cm−1 A solid state structure has been obtained of the OH derivative, and two independent molecules were found in the unit cell. Both have a single water molecule hydrogen bonded to two across‐ring oxygen atoms and the phenol hydrogen. The crown ether ring has the usual gauche and anti arrangements for the C‐C and CO bonds.
Synthesis, crystal structure of some new 2‐(4‐methylbenzoylimino)‐3‐aryl‐4‐methyl‐1,3‐thiazolines
Authors: Saeed Aamer , Parvez Masood
Published: March 2009

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An efficient, straightforward synthesis of some new 2‐(4‐methylbenzoylimino)‐3‐aryl‐4‐methyl‐1,3‐thiazolines (2a‐i) is described. The methodology involves the cyclization of 1‐(4‐methylbenzoyl)‐3‐arylthioureas with acetone in the presence of bromine and triethylamine. The structures were confirmed by spectroscopic data, elemental analyses and in one case (2i) by the single crystal X‐ray diffraction data.
Condensation of some ketones with methylene active nitriles in varied stoichiometries
Authors: Fondjo Emmanuel Sopbué , Döpp Dietrich
Published: March 2009

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Condensations of some ketones, such as cyclopentanone, cyclohexanone, indan‐1,3‐dione, 2‐acetyl‐1‐naphthol, 1‐acetyl‐2‐naphthol, with some active methylene compounds, such as malononitrile and cyanoacetate, in the presence of amine bases, diethylamine or triethylamine, were studied. The structures of the Knoevenagel condensation products were determined by spectral analyses.
Isothiazolo[5,4‐d]isoxazole S,S‐dioxides and pyrazolo [3,4‐d]‐isothiazole S,S‐dioxides through cycloaddition reaction on 3‐benzylaminoisothiazole S,S‐dioxides
Authors: Clerici Francesca , Gelmi Maria Luisa , Monzani Cristiano , Pocar Donato , Sala Alessandro
Published: March 2009

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By reacting 4,5‐unsubstituted isothiazole dioxides with diazoalkanes and nitrile oxides bicyclic pyrazolo[3,4‐d]isothiazole and isothiazolo[5,4‐d]isoxazole S,S‐dioxides were obtained in good yield through a regioselective cycloaddition reaction. Through cycloaddition reaction of 3‐benzylamino‐4‐bromo‐isothiazole S,S‐dioxide labile cycloadducts were formed that underwent in situ dehydrobromination affording the corresponding aromatized compounds.
Synthesis of imidazole and imidazolium porphyrins
Authors: Seng Virginia , Wang Xiulan , Ali Rukya , Fang Weici , Charles‐Pierre Farah , Bhagan Salome , Hyslop Alison G.
Published: March 2009

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A new porphyrin compound, where an imidazole group was attached through the 1‐position nitrogen to a phenyl ring located on the porphyrin periphery has been synthesized and characterized. The second nitrogen on the imidazole is available for further chemistry as demonstrated by the attachment of bromopentane forming the imidazolium porphyrin complex. This is the first example of an imidazolium group covalently attached to the porphyrin periphery in which the porphyrin is attached through the nitrogen on the imidazole ring rather than a carbon atom.
Microbial screening of novel synthesized formazans having amide linkagesΦ
Authors: Desai Krunal G. , Desai Kishor R.
Published: March 2009

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Formazans 5(a‐j) have been prepared by the condensation between schiff base 3 and diazonium salt of substituted 2‐amino benzothiazole 4(a‐j). The intermediate schiff base 3 was synthesized by the condensation of p‐nitrobenzolyhydrazide 1 with thiophene‐2‐aldehyde 2. All the compounds have been screened for their antifungal activity against Candida albicans (ATCC‐64550), Candida krusei (ATCC‐14243) and Candida parapsilosis (ATCC‐22019) and antibacterial activity against Escherchia coli (ATCC‐6538), Staphylococcus aureus (ATCC‐6538), Pseudomonas aeruginosa (ATCC‐1539) and Bacillus substilis (ATCC‐6633). The structures of the synthesised compounds 5(a‐j) have been characterized on the basis of their elemental analysis and spectral data (UV, IR, 1H NMR, 13C NMR and Mass).
Facile synthesis of pyrrolo[2,1‐c][1,4]benzodiazepine‐5,11‐dione dimer
Authors: Al‐Said Naim H.
Published: March 2009

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Efficient synthesis of biological important pyrrolo[2,1‐c][1,4]benzodiazepine‐5,11‐dione dimer linked through the C‐2 positions by fumarate group is described.
Synthetic approaches to bridgehead nitrogen methanesulfonamide derivatives of 3‐amino‐2‐thioxo‐2,3‐dihydrothieno[2,3‐d]pyrimidin‐4(1H)‐ones, potential cox‐2 selective inhibitors
Authors: Granata Giuseppe , Barbagallo Salvatore , Perdicaro Antonio , Marrazzo Agostino , Santagati Andrea , Lombardo Laura , Cardile Venera
Published: March 2009

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Methane sulfonamide derivatives of 3‐amino‐2‐thioxo‐2,3‐dihydrothieno[2,3‐d]pyimidin‐4(1H)‐one, potential selective COX‐2 inhibitors, were synthesized and their structural elucidation is here reported. Some derivatives, at 10 μM concentration, showed a significant percentage of inhibition in somein vitroexperiments.
Reaction of malonates with camphoranile synthesis of 4‐hydroxy‐2‐pyridones attached to the bornane ring system
Authors: Kafka Stanislav , Aigner Rudolf , Kappe Thomas
Published: March 2009

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The reaction of camphoraniles 3a,b with “magic malonates” (bis‐2,4,6‐trichlorophenylmalonates) 4a,b leads to 4‐hydroxy‐2(1H)‐pyridones attached to bornane ring system 6a‐c in good yields. Less satisfactory yields were obtained with the diethyl malonate 5b. The reaction of an excess of diethyl malonate 5 itself with 3b yields the pyrono derivative 7, which can readily be degraded via the acetyl derivative 8 to the basic structure 9.
One‐pot synthesis of 2‐aminobenzothiazoles using a new reagent of [bmim]br3in [bmim]BF4
Authors: Le Zhang‐Gao , Xu Jian‐Ping , Rao Huo‐Yu , Ying Min
Published: March 2009

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The one‐pot direct synthesis of 2‐aminobenzothiazoles from phenyl isothiocyanate and amines using a new reagent of 1‐butyl‐3‐methylimidazolium tribromide ([Bmim]Br3) in ionic liquid 1‐butyl‐3‐methylimidazolium tetraflouoroborate ([Bmim]BF4) is described.
Lithiation of N‐protected‐dihydro‐1,4‐benzoxaziness
Authors: Lu Yansong J. , Hu Bin , Prashad Mahavir , Kabadi Shaum , Repič Oljan , Blacklock Thomas J.
Published: March 2009

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Lithiation of N‐protected‐2,3‐dihydro‐1,4‐benzoxazines is described. Lithiation of N‐(tert‐butoxycarbonyl)‐2,3‐dihydro‐1,4‐benzoxazine (1) with BuLi/TMEDA occurred in the α‐position to nitrogen on the heterocyclic ring, leading to the unexpected ring‐opened product 3. On the other hand, lithiation of N‐methyl‐2,3‐dihydro‐1,4‐benzoxazine (4) took place at the oxygen‐adjacent ortho‐position of the aromatic ring.
Reactions of 2‐amino‐4h‐1‐benzopyran‐4‐one with 4‐oxo‐4h‐1‐benzopyran‐3‐carbaldehydes
Authors: Ghosh Tarun , Bandyopadhyay Chandrakanta
Published: March 2009

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The title aldehyde 1 reacts smoothly with the enamine moiety of 2‐aminochromone 2 to produce hitherto unreported 3‐(2‐hydroxybenzoyl)‐5H‐1‐benzopyrano[2,3‐b]pyridin‐5‐one (azaxanthone) 5. This reaction has been extended for the synthesis of bisazaxanthone 9.
Synthesis of novel quinazoline non‐nucleosides analogues of the HIV drug emivirine
Authors: El‐Brollosy Nasser R.
Published: March 2009

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Novel quinazoline non‐nucleosides analogues of Emivirine were described. Compounds 1a‐c were silylated and reacted with the appropriate chloroethers (2a‐c) in the presence of CsI to give the corresponding non‐nucleosides 3a‐h and 4a‐h. Silylation of 1a‐c and treatment with bis(allyloxy)methanes (5a,b) afforded the corresponding 1‐(allyloxymethyl)quinazolines 6a‐f. 1‐(Propargyloxymethyl)‐quinazolines 8a,b were obtained by treatment of the silylated 1a,b with bis(propargyloxy)methane (7) in the presence of TMS triflate.
Synthesis of 7‐azabicyclo[2.2.1]heptane derivatives by transformation of tropinone
Authors: Gómez‐Sénchez Elena , Marco‐Contelles José
Published: March 2009

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The bromination (CuBr2, AcOEt/CHCI3) plus Favorskii rearrangement (EtONa, EtOH) of N‐carbethoxytropinone (4), readily available from tropinone (3), affords mixtures of exo‐ and endo‐isomers of 2,7‐dicarbethoxy‐7‐azabicyclo[2.2.1]heptane (1b) in variable and moderate chemical yield (maximum 37%). The bromination (Br2, HBr/AcOH) reaction of compound 4 gives ethyl trans‐2,4‐dibromo‐3‐oxo‐8‐azabicyclo[3.2.1]octane‐8‐carboxylate (5) in 99% yield, a product that on Favorskii rearrangement (EtONa/EtOH) affords ethyl 2,2‐diethoxy‐3‐oxo‐8‐azabicyclo[3.2.1]octane‐8‐carboxylate in moderate yield (6) (52%).
Catalyst and pressure dependent reductive cyclizations for the diastereo‐selective synthesis of hexahydropyrrolo[1,2‐a]quinoline‐5‐carboxylic esters
Authors: Bunce Richard A. , Schammerhorn James E. , Slaughter Legrande M.
Published: March 2009

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A diastereoselective synthesis of 1,2,3,3a,4,5‐hexahydropyrrolo[1,2‐a]quinoline‐5‐carboxylic esters has been developed using a tandem reduction‐double reductive amination reaction. The nitro dicarbonyl cyclization substrates were synthesized by alkylation of methyl (2‐nitrophenyl)acetate with 2‐bromomethyl‐1,5‐hexadiene derivatives, followed by ozonolysis. Catalytic hydrogenation of each substrate gave the target heterocycle, along with a deacylated product and an adduct resulting from capture of the intermediate hydroxylamine by the side chain carbonyls. The product ratio varied dramatically with the catalyst and the hydrogen pressure. Cyclization to the title compounds was highly diastereoselective, producing each hexahydropyrrolo[1,2‐a]‐quinoline as a single stereoisomer with the all‐cis geometry. The competing processes have not been observed in previous heterocyclization studies but can be attributed to greater strain in the system, which slows the final ring closure.
Synthesis of ethyl 6‐aryl‐4‐oxo‐4,6‐dihydro‐1(12)(13)h‐pyrimido‐[2′,1′:4,5][1,3,5]triazino[1,2‐a]benzimidazole‐3‐carboxylates
Authors: Dolzhenko Anton V. , Chui Wai‐Keung , Dolzhenko Anna V.
Published: March 2009

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The synthesis of ethyl 6‐aryl‐4‐oxo‐4,6‐dihdro‐1(12)(13)H‐pyrimido[2′,1′:4,5][1,3,5]triazino[1,2‐a]‐benzimidazole‐3‐carboxylates (4a‐p) was described via pyrimidine ring annulation to 4‐aryl‐3,4‐dihydro[1,3,5]triazino[1,2‐a]benzimidazole‐2‐amines (2a‐p) which were obtained from 2‐guanidinobenzimidazole (1). Tautomerism in the prepared compounds was investigated using nmr spectroscopy. Compounds 2a‐p were found to be present in dimethyl sulfoxide solution predominantly as 3,4‐dihyhydro tautomeric form. Compounds 4a‐p existed in dynamic equilibrium of 1‐, 12‐ and 13H‐forms. It was found that methylation of 4a‐d led to 13‐methyl substituted derivatives 9a‐d exclusively.
Synthesis of 2,6‐diamino‐5‐[(2‐substituted phenylamino)ethyl]pyrimidin‐4(3h)‐one as inhibitors of folate metabolizing enzymes
Authors: Gangjee Aleem , Wang Ying , Queener Sherry F. , Kisliuk Roy L.
Published: March 2009

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A series of eleven novel 2,6‐diamino‐5‐[(2‐substituted phenylamino)ethyl]pyrimidin‐4(3H)‐one derivatives were synthesized as potential inhibitors of dihydrofolate reductase (DHFR) and thymidylate synthase (TS). The synthesis of analogues 2a‐f, 3a and 3e was achieved via an improved method. Commercially available anilines 12a‐f were used as starting materials which on reaction with chloroacetaldehyde followed by cyanoacetate and cyclocondensation with guanidine afforded 2,6‐diamino‐5‐[(2‐substituted phenylamino)ethyl]pyrimidin‐4(3H)‐one 2a‐f in three steps. The N‐methyl analogues 3a‐3e were prepared by reductive methylation. These compounds were evaluated against dihydrofolate reductase from Escherichia coli, Toxoplasma gondii, Pneumocystis carinii, human, and rat liver. Few compounds were marginally active against dihydrofolate reductase. The most potent inhibitor, (2c) which has a 1‐naphthyl substituent on the side chain, has an IC50 = 150 μM and 9.1 μM against Escherichia coli and Toxoplasma gondii DHFR, respectively.
Synthesis of 8,9‐dialkoxybenzodiazepines and 7,8‐dialkoxyisoquinolines
Authors: Pongó Lészló , Reiter Józef , Simig Gyula , ágai Béla , Faigl Ferenc
Published: March 2009

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o‐Aroylarylacetone type 1,5‐diketone derivatives (5, 6) were synthesised from arylacetones (1) protected as 1,3‐dioxolanes (4) through directed ortho lithiation followed by acylation with aroyl chlorides. 8,9‐Dialkoxy‐2,3‐benzodiazepines 9 were obtained by cyclisation of diketones 6 with hydrazine. The reaction of diketones 6 with ammonia gave 7,8‐dialkoxyisoquinolines 11. Reaction of ketals 5 with hydrazine hydrochloride and hydroxylamine hydrochloride afforded N‐amino‐7,8‐dialkoxyisoquinolinium chlorides (10) and 7,8‐dialkoxyisoquinolinium oxides (12), respectively.