bluuebunny/crossref_metadata_2025 huggingface dataset:
Furopyridines. XXX. Synthesis and reaction of difuro[3,2‐c:‐ 3′,2′‐e]pyridine, a new tricyclic heterocycle
Authors: Shiotani Shunsaku , Yamaguchi Seiji , Kurosaki Masahide , Yokoyama Hajime , Hirai Yoshiro
Published: March 2009

Difuro[3,2‐c:3′,2′‐e]pyridine 1, a new tricyclic heteroaromatic, has been prepared for the first time. Bromination of 1 with molecular bromine gave 3‐bromo 7, 8‐bromo 7′ and 3,8‐dibromo derivative 8; nitration with fuming nitric acid yielded 2‐nitro compound 9, while nitration with a mixture of fuming nitric acid and sulfuric acid gave 2,7‐dinitro derivative 10; formylation with n‐butyllithium and dimethylformamide gave 2‐formyl 11, 7‐formyl 11′, and 2,7‐diformyl compound 12. The N‐oxide 14 of 1 afforded 4‐cyano compound 15 by cyanation with trimethylsilyl cyanide, 4‐chloro compound 16 by chlorination with phosphorus oxychloride, and 4‐acetoxyl compound 17 by acetoxylation with acetic anhydride.
Synthesis and antiviral evaluation of several 6‐(Methylene‐carbomethoxy)pteridine‐4,7(3H,8H)‐diones
Authors: Molina S. , Cobo J. , Sánchez A. , Nogueras M. , De Clercq E.
Published: March 2009

The reactions of 5,6‐diaminopyrimidin‐4(3H)‐one derivatives 1a‐h, with dimethyl acetylenedicarboxylate are discussed in this paper. 6‐Amino‐5‐(E)(1′,2′‐dicarbomethoxyvinyl)aminopyrimidines, 2, and 6‐(methylenecarbomethoxy)pteridinones, 3, have been obtained as main the products, which can be explained on the basis of a Michael addition on pyrimidine derivatives, and cyclization. Those compounds were evaluated for their in vitro antiviral activity.
Synthesis of spiro[1,4‐benzothiazine‐2,2′‐pyrans] starting from methyl β‐D‐arabino‐2‐hexulopyranosonate
Authors: Andersch Jens , Sicker Dieter , Wilde Horst
Published: March 2009

Dedicated to Professor Klaus Burger on the occasion of his 60th birthday Methyl β‐D‐arabono‐2‐hexulopyranosonate 1 has via the novel glycosyl donor 3 been transformed into the thiophenyl glycosides 4 and 5. Catalytic hydrogenation of the nitro compound 4 in alkaline solution led to spontaneous cyclization and deprotection to form the cyclic hydroxamic acid 7. The related lactams 8 and 9 were obtained from amine 5. The spiro[1,4‐benzothiazine‐2,2′‐pyrans] 7–9 are the first representatives of a novel class of heterocycles structurally related to bioactive natural products. As shown by the values for J3′,4′ and J4′,5′ the glycosides 4, 5 and 6 adopt a 5C2 conformation of the pyranoid ring whereas the 1,4‐benzothiazine system in 7–9 forces a conformational change into the 2C5 conformation.
Synthesis of tetracyclic and pentacyclic phenothiazines via benzotriazole methodology
Authors: Katritzky Alan R. , Agamy Samia , Yang Baozhen , Qiu Guofang
Published: March 2009

Treatment of 10‐(benzotriazol‐1‐yl)alkylphenothiazine with electron‐rich alkenes in the presence of zinc bromide gave tetracyclic phenothiazines 4 and 9 as well as pentacyclic phenothiazines 5, which have potential use in the pharmaceutical industry.
Amalgam (Na.Hg) reduction of some 4‐Substituted‐2‐amino‐3,5‐dicyano‐6‐methoxypyridines. New evidence regarding the oxidation step in their synthesis
Authors: Fuentes LuÍS , Lorenzo Ma Jesús , Márquez César , Galakhov Mikhail
Published: March 2009

The amalgam (Na.Hg) reduction of some 4‐substituted‐2‐amino‐3,5‐dicyano‐6‐methoxypyridines 3 results in the formation, in high yields of 3,4‐dihydropyridines 2. Highfield 1H and 13C nmr studies provide unambiguous support for the structures proposed. The synthesis of C‐4 deuterium labeled dihydropyridine 2c‐D, by this procedure, let us understand the role played by this dihydropyridines as intermediates in the necessary oxidation path into the synthesis of pyridines 3 from malononitrile and benzylidenemalononitriles 1 in methanol/sodium methoxide.
Behavior of 5,6‐dihydrobenzo[h]cinnolinones towards hydrazine. Synthesis of benzo[h]cinnolinones and of 4‐Aminobenzo[h]cinnolinones
Authors: Villa Stefania , Evoli Giacomo Luca , Cignarella Giorgio , Curzu Michela M. , Pinna Gérard A.
Published: March 2009

Dehydrogenation and amination of 4,4a,5,6‐tetrahydro and 5,6‐dihydrobenzocinnolinones in refluxing hydrazine hydrate to give new benzo[h]cinnolinones and 4‐aminobenzo[h]cinnolinones are reported, and reaction mechanisms proposed. Experiments were also extended to 4,4a‐dihydro‐5H‐indenopyridazinone which underwent hydrazine induced dehydrogenation to 5H‐indenopyridazin‐3‐one but not subsequent amination.
Synthesis of new 6‐Aroylpyrido[2,3‐d]pyrimidines
Authors: Quiroga Jairo , Viveros GermÁN , Insuasty Braulio , Nogueras Manuel , Sánchez Adolfo , Cobo Justo
Published: March 2009

The synthesis of 6‐dimethylaminomethylenaminopyrimidin‐4(3H)‐ones 2 and its reaction with β‐dimethyl‐aminopropiophenone hydrochloride 3 is discussed in this work. The reaction of 6‐aminopyrimidin‐4(3H)‐ones 1 with an excess of dimethylformamide dimethyl acetal gives rise to the formation of 6‐dimethylaminomethyleneaminopyrimidines 2. The heating of equimolecular quantities of 2 and 3 in dimethylformamide leads to the 6‐aroylpyrido[2,3‐d]pyrimidines derivatives 4. The structures of compounds 2 and 4 were determined on the basis of nmr measurements.
Reactivity of p‐phenyl substituted β‐Enamino compounds using K‐10/ultrasound. II. Synthesis of isoxazoles and 5‐Isoxazolones
Authors: Valduga Claudete J. , Santis Denise B. , Braibante Hugo S. , Braibante Mara E. F.
Published: March 2009

The condensation of 4‐phenyl substituted β‐enamino ketones 1a‐d and β‐enamino esters 5a‐d with hydroxylamine hydrochloride using K‐10 as the solid support under sonication was studied to evaluate the formation of isoxazole and 5‐isoxazolone rings from β‐enamino compounds with a substituted aromatic ring. Isoxazoles 2a‐c, 3c‐d and 5‐isoxazolones 6a‐c and 7a‐d were obtained. The use of K‐10/ultrasound in this reaction furnished novel results in some cases.
Phenylsulfonyl‐methylenation of aldonolactones
Authors: Alzérreca Arnaldo , Hernández Eliud , Mangual Edgar , Prieto José A.
Published: March 2009

The low temperature addition of dilithiomethylphenyl sulfone to 2,3‐O‐isopropylidene‐D‐erythronolactone, and to 5‐O‐(tert‐butyldimethylsilyl)‐2,3‐O‐isopropylidene‐D‐ribofuranolactone gives the lactols 2 and 3a, respectively. Dehydration of lactol 2 in the presence of boron trifluoride etherate produces tetrahydrofuranylidene sulfones 5 and 6 in good yields. The reaction of lactol 3a under the same reaction conditions proceeds with formation of the 1′,5′‐anhydro derivative 7 via competing intramolecular substitution.
The chemistry of 4H‐3,1‐benzoxazin‐4‐ones
Authors: Coppola Gary M.
Published: March 2009

The present review covers the synthesis and reactions of 4H‐3,1‐Benzoxazin‐4‐ones. Only those with carbon substituents at the 2‐position are included. Literature corverage includes publications primarily from the mid 1960's to May 1998.
Synthesis and spectral properties of 2,3‐dihydro‐2‐[(o‐ and p‐substituted)anilinylidene]‐1H‐4‐(p‐methylphenyl)‐7‐[(o‐ and p‐methyl)phenoxy]‐1,5‐benzodiazepines
Authors: Cortés Eduardo Cortés , Bravo Maria Paz Sánchez
Published: March 2009

A series of twelve new 2,3‐dihydro‐2‐[(o‐ and p‐substituted)anilinylidene]‐1H‐4‐(p‐methylphenyl)‐7‐[(o‐ and p‐methyl)phenoxy]‐1,5‐benzodiazepines, which have potentially useful pharmacological properties, has been synthesized by condensing the 3,3‐dimercapto‐1‐(p‐methylphenyl)‐2‐propen‐1‐one with 3,4‐diaminophenyl‐R‐phenyl ethers. Subsequently the 1H‐1,5‐benzodiazepine‐2‐thiones obtained were treated with the (o‐ and p‐substituted)aniline. The structure of all products was corroborated by ir, 1H nmr, 13C nmr and ms.
Complete regioselective formation of 2‐(arylsulfinyl)diphenyl sulfides from 5‐arylthianthreniumyl perchlorates
Authors: Kim Jongyup , Kim Kab Sig , Kim Kyongtae
Published: March 2009

Treatment of 5‐arylthianthreniurnyl perchlorates with potassium tert‐butoxide in dimethyl sulfoxide at room temperature gave 2‐(arylsulfinyl)diphenyl sulfides (29–79% yields), which are the first examples for complete regioselective formation of S‐monoxides from unsymmetrical arylthiodiphenyl sulfides.
N‐(2‐tetrahydrofuranyl)azole nucleoside analogs by reactions of azoles with dihalomethanes in tetrahydrofuran
Authors: Zadykowicz Jerzy , Potvin Pierre G.
Published: March 2009

The reactions of the mono‐N‐substituted bispyrazolylpyridine 2‐(1‐methyl‐4,5,6,7‐tetxahydroindazol‐3‐yl)‐6‐(2H‐4,5,6,7‐tetrahydroindazol‐3‐yl)pyridine, 3,5‐dimethylpyrazole and benzimidazole with sodium hydride and diiodomethane or dibromomethane in tetrahydrofuran produced the unexpectedN‐tetrahydrofuran‐2‐yl adducts as well as the expected diazolylmethanes. These side‐reactions are thought to involve the 2‐halo tetrahydrofuran derivative resulting from a free‐radical halogenation by the dihalomethane.
Synthesis of purinobenzodiazepine and purinobenzotriazocine derivatives, two new heterocyclic ring systems
Authors: Settimo Antonio Da , Primofiore Giampaolo , Marini Anna Maria , Settimo Federico Da , La Motta Concettina , Salerno Silvia
Published: March 2009

The preparation of two new heterocyclic ring systems, purinobenzodiazepine and purinobenzotriazocine derivatives by the condensation of 8‐aminotheophylline or 8‐hydrazinotheophylline with o‐carboxybenzaldehyde or o‐carboxyacetophenone is described.
Synthesis and NMR investigation of 3,4‐diazabicyclo[4.3.0]non‐2‐ene and N,N'‐azo‐3‐azabicyclo[3.3.0]octane. X‐ray crystal structure analysis of a new tetrazene derivative
Authors: Delalu H. , Elkhatib M. , Peyrot L. , Fenet B. , Mentzen B. F.
Published: March 2009

3,4‐Diazabicyclo[4.3.0]non‐2‐ene and N,N'‐azo‐3‐azabicyclo[3.3.0]octane are the main products of the oxidation of N‐amino‐3‐azabicyclo[3.3.0]octane by chloramine. These new compounds have been isolated and characterized. A structural study has been performed with the goal of establishing the cis—trans configuration at the bicyclic junction. Multinuclear proton decoupling carried out on the endocyclic hydrazone has allowed the determination of the coupling constant of the bridgehead hydrogens. A low temperature conformational study shows splitting of the 13C signal of the carbon atom located α with respect to the ammonia nitrogen. This result, consistent with a cis structure, was confirmed by a nmr analysis conducted on the solid tetrazene derivative. The X‐ray data collection on a single cyrstal of the tetrazene has permitted us to determine the crystallographic properties of this compound. Data processing by direct methods reveals that the geometry of the molecule presents a cis configuration for the bicyclic bridge link and a trans one for the azo group, confirming thus the main results obtained by nmr studies.
Synthesis of some 2‐substituted‐thioxanthones
Authors: Moon Jung‐Kyen , Park Jung‐Won , Lee Woo Song , Kang Young‐Jin , Chung Hyun‐A , Shin Mi‐Seon , Yoon Yong‐Jin , Park Ki Hun
Published: March 2009

This paper presents the synthesis of 2‐amino‐, 2‐acetamido‐ and 2‐benzamidothioxanthones and their 10,10‐dioxides.
Synthesis, NMR spectroscopic and X‐ray crystallographic studies of functionalized 2‐aminopyrrolin‐4‐ones
Authors: Gola Anna , Samartzi Evangelia , Bardakos Vassilios , Petroliagi Margarita , Igglessi‐Markopoulou Olga , Markopoulos John , Barkley James V.
Published: March 2009

An efficient method for the preparation of novel cyano derivatives of 4‐amino‐3‐hydroxybutenoic acids 4–8 and N‐substituted‐2‐aminopyrrolin‐4‐ones 9–18 is described; the structure of compound 13 has been elucidated with X‐ray analysis.
Synthesis of 1,1‐bis(1,2,4‐triazol‐1‐yl)‐based potential aromatase inhibitors
Authors: Katritzky Alan R. , Pastor Alfredo , Voronkov Michael V.
Published: March 2009

Reactions of bis‐(1,2,4‐triazolyl) sulfoxide 2 with various carbonyl compounds 3 led to the formation of twelve corresponding 1,1 ‐bis‐(1,2,4‐triazolyl) compounds, with structures resembling closely some previously prepared aromatase inhibitors.
Pyrrolo[3,4‐e][1,2,3]triazolo[1,5‐a]pyrimidine and pyrrolo[3,4‐d] [1,2,3]triazolo[1,5‐a]pyrimidine. New tricyclic ring systems of biological interest
Authors: Lauria Antonino , Diana Patrizia , Barraja Paola , Almerico Anna Maria , Cirrincione Girolamo , Dattolo Gaetano
Published: March 2009

Derivatives of the new ring system pyrrolo[3,4‐e][1,2,3] triazolo[1,5‐a]pyrimidine 6 were prepared in high yields in one step by reaction of 3‐azidopyrrole 3 and substituted acetonitriles. Compound 6b rearranged, upon heating in dimethyl sulfoxide in the presence of water, to pyrrolo[3,4‐d][1,2,3]triazolo‐[1,5‐a]pyrimidine 7.
Synthesis of N‐methyl‐4‐pyridyl‐1,2,3,4‐tetrahydroisoquinolines via a pictet‐spengler cyclisation
Authors: Prat Laurence , Levacher Vincent , Dupas Georges , Quéguiner Guy , Bourguignon Jean , Bureau Ronan , Daveu Cyril
Published: March 2009

The synthesis of N‐methyl‐4‐pyridyl‐1,2,3,4‐tetrahydroisoquinolines (6a,b,c) was achieved via a Pictet‐Spengler cyclization of an activated amino group derivatized in a carbamate form. The obtained compounds have been designed as potential serotonin analogs.
An improved procedure for the synthesis of 4,4‐disubstituted‐3‐oxo‐1,2,5‐thiadiazolidine 1,1 ‐dioxides
Authors: Xiao Zejun , Timberlake Jack W.
Published: March 2009

An improved synthesis for the preparation of 3‐oxo‐1,2,5‐thiadiazolidine 1,1‐dioxides has been developed. This facile two‐step procedure fromα‐amino acid esters and chlorosulfonyl isocyanate results in excellent yields of products.
Synthesis of bicyclic azacompounds (3‐dimethylcarbamoyloxyphenyl) substituted as acetylcholinesterase inhibitors
Authors: Borioni Anna , Giudice Maria Rosaria Del , Mustazza Carlo , Gatta Franco
Published: March 2009

This paper describes the synthesis of some bicyclic 2‐(3‐dimethylcarbamoyloxyphenyl) substituted azaderivatives, obtained from 1,4‐ and 1,5‐diketones, which were cyclized with ammonium acetate, methylamine and by reductive amination. Corresponding 3‐substituted derivatives were instead prepared by reaction of 1,5‐ketoesters with formamide. The carbamates were tested as in vitro acetylcholinesterase inhibitors.
1H and 13C spectral assignment of naphtho[2′,1′:5,6]‐naphtho[2′,1′:4,5]thieno[2,3‐c]quinoline using the IDR‐GHSQC‐TOCSY experiment
Authors: Hadden Chad E. , Martin Gary E. , Luo J.‐K. , Castle Raymond N.
Published: March 2009

The assignment of the NMR spectra of the polynuclear heteroaromatic naphtho[2′,1′:5,6]naphtho‐[2′,1′:4,5]thieno[2,3‐c]quinoline is reported. The analysis was based on the homonuclear ROESY, heteronuclear direct GHSQC, IDR‐GHSQC‐TOCSY, and long‐range GHMBC experiments. The complete 1H and 13C shift assignments are reported.
Ring‐ring interconversions. Part 3. On the effect of the substituents on the thiazole moiety in the ring‐opening/ring‐closing reactions of nitrosoimidazo[2,1‐b][1,3]thiazoles with hydrochloric acid
Authors: Billi Roberta , Cosimelli Barbara , Spinelli Domenico , Leoni Alberto
Published: March 2009

The reaction of 6‐(4‐chlorophenyl)‐5‐nitrosoimidazo[2,1‐b][1,3]thiazole 1b, 6‐(4‐chlorophenyl)‐2‐methyl‐5‐nitrosoimidazo[2,1‐b][1,3]thiazole 1c, 6‐(4‐chlorophenyl)‐2,3‐dimethyl‐5‐nitrosoimidazo‐[2,1‐b][1,3]thiazole 1d and 2‐(4‐chlorophenyl)‐3‐nitrosobenzo[d]imidazo[2,1‐b][1,3]thiazole 1e with hydrochloric acid has been carried out in order to investigate the effect of substituents on the thiazole ring in a recently reported ring‐ring interconversion reaction. In every case the corresponding [1,4]‐thiazino[3,4‐c][1,2,4]oxadiazol‐3‐ones 2b‐e have been obtained. In particular, the benzoderivative 1e furnished the 4‐(4‐chlorophenyl)‐4‐hydroxy‐4H‐benzo[5,6][1,4]thiazino[3,4‐c][1,2,4]oxadiazol‐1‐one 2e, containing a new tricyclic system with a quasi‐planar geometry whose pharmacological potentialities appear promising.
Synthesis of optically active hydroxyalkylbenzothiazepinones by ring transformation of 2‐alkylidenelactons with o‐aminothiophenol
Authors: Otto Andreas , Liebscher Jürgen
Published: March 2009

A stereoselective synthesis of new optically active 3‐(hydroxyalkyl)‐2,3‐dihydro‐1,5‐benzothiazepin‐4‐ones 4 and 7 was achieved by Michael‐like addition of o‐aminothiophenol to chiral α‐alkylidenelactons 1 and 5 followed by ring chain transformation of the resulting adducts 3 and 6.
Synthesis of 2,4‐diaminopyrido[2,3‐d]pyrimidines and 2,4‐diamino‐quinazolines with bulky dibenz[b,f]azepine and dibenzo[a,d]‐cycloheptene substituents at the 6‐position as inhibitors of dihydrofolate reductases from pneumocystis carinii, toxoplasma gondii, and mycobacterium avium
Authors: Rosowsky Andre , Fu Hongning , Queener Sherry F.
Published: March 2009

The synthesis of four previously undescribed 2,4‐diaminopyrido[2,3‐d]pyrimidines (3,4) and 2,4‐diaminoquinazolines (5,6) with a bulky tricyclic aromatic group at the 6‐position is described. Condensation of dibenz[b,f]azepine with 2,4‐diamino‐6‐bromomethylpyrido[2,3‐d]pyrimidine (8) and 2,4‐diamino‐6‐bromomethylquinazoline (17) in the presence of sodium hydride afforded N‐[(2,4‐diaminopyrido[2,3‐d]‐pyrimidin‐6‐yl)methyl]dibenz[b,f]azepine (3) and N‐[(2,4‐diaminoquinazolin‐6‐yl)methyl]dibenz[b,f]‐azepine (4), respectively. Condensation of 5‐chlorodibenzo[a,d]cycloheptene (19) and 5‐chloro‐10,11‐dihydrodibenzo[a,d]cycloheptene (20) with 2,4,6‐triaminoquinazoline (13) afforded 5‐[(2,4‐diamino‐quinazolin‐6‐yl)amino]‐5H‐dibenzo[a,d]cycloheptene (5) and the corresponding 10,11‐dihydro derivative (6), respectively. The bromides 8 and 17, as hydrobromic acid salts, were obtained from the corresponding nitriles according to a standard three‐step sequence consisting of treatment with Raney nickel in formic acid followed by reduction with sodium borohydride and bromination with dry hydrogen bromide in glacial acetic acid. Compounds 3–6 were evaluated in vitro for the ability to inhibit dihydrofolate reductase from Pneumocystis carinii, Toxoplasma gondii, Mycobacterium avium, and rat liver. Compounds 3 and 4 were potent inhibitors of all four enzymes, with IC50 values in the 0.03–0.1 μM range, whereas 5 was less potent. However the selectivity of all four compounds for the parasite enzymes relative to the rat enzyme was<10‐fold, whereas the recently reported lead compound in this series, N‐[(2,4‐diaminopteridin‐6‐yl)methyl]dibenz[b,f]azepine (1) has > 100‐fold selectivity for the T. gondii and M. avium enzyme and 21‐fold selectivity for the P carinii enzyme.
Attempted synthesis of a tenidap isomer and formation of an unexpected stable water adduct
Authors: Esses‐Reiter Klára , Reiter József
Published: March 2009

An attempt to synthesize the Tenidap isomer 13 was performed starting from 2‐ethoxy‐5‐chloroindole (9). The acylation and carbamoylation reactions of 9 led to the expected intermediate 12, however the hydrolysis of 12 in acidic or alkaline media did not yielded the expected 13. Instead an unusually stable water adduct 18 or the cleavage product 16 was formed. The formation of the unexpectedly stable water adduct 18 was caused by the steric and electronic effect of the thienoyl group in position 1 as proved by the hydrolysis of 10 and 16.
Synthesis of a novel ring‐expanded nucleoside analogue containing the imidazo[4,5‐e][1,3]diazepine ring system with a guanidinocarbamoyl‐substituted cyclopropylidene group in place of a sugar moiety
Authors: Chen Huan‐Ming , Hosmane Ramachandra S. , Baldisseri Donna M.
Published: March 2009

The synthesis of a novel ring‐expanded nucleoside analogue, (Z)‐1‐((2‐Guanidinocarbamoyl‐cyclopropylidene)methyl)‐4,5,7,8‐tetrahydro‐6H‐6‐iminoimidazo[4,5‐e][1,3]diazepine‐4,8‐dione (1) has been reported. It was prepared starting from methyl imidazole‐4,5‐dicarboxylate by sequential condensations with 2‐bromo‐2‐bromomethylcyclopropane‐1‐carboxylate and guanidine. The overall yield for the two‐step synthesis is 46%.
Synthesis of 1,4,2‐benzodithiazine carboxylates via ring expansion reaction of 1,3‐benzodithioles
Authors: Stanetty Peter , Hattinger Gregor , Mihovilovic Marko D. , Mereiter Kurt
Published: March 2009

A straight forward synthesis of the 1,4,2‐benzodithiazine system bearing an ester functionality as potential inducers of systemic acquired resistance in plants was developed utilizing the ring expansion reaction of 1,3‐benzodithioles. The structure of the isomers obtained was established using x‐ray diffraction. The reactivity of the products towards activated alkynes and ring contraction reactions in the presence of base is discussed.
Syntheses of thiopyrone and pyrone derivatives by photocyclization reaction of 3‐aryl‐2‐( Benzothien‐3‐yl)propenoic acids
Authors: Sasaki Kenji , Satoh Yasuyoshi , Hirota Takashi , Nakayama Taiji , Tominaga Yoshinori , Castle Raymond N.
Published: March 2009

Naphtho[1,2‐b][1]benzothiophene‐6‐carboxylic acids, 6H‐benzo[b]naphtho[2,3‐d]thiopyran‐6‐ones and 6H‐benzo[b]naphtho[2,3‐d]pyran‐6‐ones were synthesized in one step by the photocyclization reaction of 3‐aryl‐2‐([1]benzothien‐3‐yl)propenoic acids. The photocyclization reaction did not occur when the 3‐aryl group contained the electron‐withdrawing nitro group. The assignment of the 1H and 13C nmr spectra of 6H‐benzo[b]naphtho[2,3‐d]thiopyran‐6‐one and 6H‐benzo[b]naphtho[2,3‐d]pyran‐6‐one by two‐dimensional nmr methods is described. The difference between the chemical shift values of H12 for these two compounds is attributed to different molecular geometries.
Studies on the reactivity of new types of tetracyclic‐1,5‐benzoxazepines: Part V
Authors: Sekhar Batchu Chandra , Ramana Devalla Venkata , Ramadas Sukuru Raghu
Published: March 2009

The syntheses of tetracyclic 1,5‐benzoxazepines 3a‐e from heterocyclic (3‐chloroaldehydes 1a‐e and 2‐aminophenol are reported herein (Scheme I). Attempted lithium aluminium hydride (LiAlH4) reduction of the imine double bond in 3a‐e failed to furnish the corresponding saturated compounds 5a‐e. Attempted catalytic hydrogenation of 3a‐e in the presence of acetic acid and acetic anhydride gave surprisingly only the acetoxy derivatives 6a‐e in high yields (Scheme II). Base catalysed hydrolysis of acetoxy derivatives 6a‐e furnished, as expected, the corresponding phenolic derivatives 7a‐e, in moderate yields. Attempted cyclofunctionalization of 3a‐e either with mercaptoacetic acid or its methyl ester to obtain the new penta‐cyclic heterocycles 4a‐e was, however, not successful.
Synthesis of novel 5H‐Pyrimido[5,4‐b]mdole‐(1H,3H)2,4‐diones as potential ligands for the cloned α1‐adrenoceptor subtypes
Authors: Romeo G. , Russo F. , De Blasi A.
Published: March 2009

A new series of 3‐[ω‐[4‐(4‐substituted phenyl)piperazin‐1‐yl]alkyl]‐5H‐pyrimido[5,4‐b]indole‐(1H,3H)‐2,4‐diones (3–10and12–13) were synthesized from theN‐(2‐chloroethyl)‐N'‐[3‐(2‐ethoxycarbonyl)indolyl] urea (1) or theN‐(3‐chloropropyl)‐N'‐[3‐(2‐ethoxycarbonyl)indolyl] urea (2) and a number of 1‐(4‐substi‐tuted‐phenyl)piperazines. 3‐[2‐[4‐(4‐Aminophenyl)piperazin‐1‐yl]ethyl]‐5H‐pyrimido[5,4‐b]indole‐(1H,3H)2,4‐dione (14) was obtained by reduction of the parent nitro compound8. The obtained 5H‐pyrimido[5,4‐b]indole‐(1H,3H)2,4‐dione derivatives were tested towards cloned α1A, α1Band α1Dadrenergic receptors subtypes in binding assays. Some compounds showed good affinity and selectivity for the α1D‐adrenoceptor subtype.
On triazoles XLIII. Synthesis of 1,2,4‐triazolyl isoquinolinium zwitter ions
Authors: Prauda Ibolya , Kövesdi István , Trinka PÉTer , Reiter JÓZsef
Published: March 2009

Type 8 isoquinolinium zwitter ions were synthesised by the reaction of type 1 diketones or type 2 pyrylium salts with different 5‐amino‐3‐Q‐1H‐1,2,4‐triazoles. Spectroscopic and X‐ray diffraction evidence was given for the zwitter ion structure of the products obtained. The position of the negative charge on the 1,2,4‐tiazolium ring was proved by comparison of the cmr and uv spectra of the products obtained with the three possible N‐benzyl derivatives 14–16 prepared for this purpose.
Studies on the reactivity of some N‐aryl‐ and N‐heteroaryl‐N'‐alkylthioureas towards electrophilic reagents. Synthesis of new N‐pyridylthioureas and thiazolines maría
Authors: Rodríguez‐Franco Isabel , Dorronsoro Isabel , Martínez Ana , Castro Ana
Published: March 2009

Here in we describe our findings about the behaviour of some N‐aryl‐ and N‐heteroaryl‐N'‐alkylthioureas towards electrophilic reagents. In acid medium, the treatment of thioureas bearing aryl groups with 4‐chloropyridine in 2‐propanol yielded N‐aryl‐N‐(4‐pyridyl)‐N'‐alk;ylthioureas and N‐aryl‐N'‐alkylureas, whereas the heteroarylthioureas tested under similar reaction conditions afforded N‐heteroaryl‐N'‐alkyl‐O‐(2‐propyl)isoureas. The reaction of N‐(5,6,7,8‐tetrahydronaphth‐1‐yl)‐ and N‐(2‐benzimidazolyl)‐N'‐butyl‐thiourea with propargyl bromide in acid medium led to the formation of 2‐butylimino‐3‐arylthiazolines, in a regioselective way. However, when this reaction was carried out in basic conditions the regioselectivity failed and a mixture of isomeric thiazolines was obtained. The Z‐ or E‐configuration of the imino group of the synthesized thiazolines was studied by molecular modelling and by selective nuclear Overhauser experiments in nuclear magnetic resonance.
Synthesis of unsymmetrical methylene derivatives of benzopyran‐4‐ones from mannich bases
Authors: Mazzei Mauro , Dondero Ramona , Balbi Alessandro , Bonora Gian Maria
Published: March 2009

The formation of methylene‐bis derivatives of benzopyran‐4‐ones from their Mannich bases was studied. On these grounds, unsymmetrical methylene derivatives have been synthesized by reacting Mannich bases of benzopyran‐4‐ones with structurally related compounds lacking the dialkylaminomethyl group.
One‐step preparation of some 2‐isopropenyl‐2,3‐dihydronaphtho‐[2,3‐b]furan‐4,9‐diones
Authors: Yamaguchi Seiji , Katsuki Toshiharu , Yokoyama Hajime , Hirai Yoshiro
Published: March 2009

Some 2‐isopropenyl‐2,3‐dihydronaphtho[2,3‐b]furan‐4,9‐diones la‐f,b',f were prepared by one‐step cyclizations of 2‐hydroxy‐1,4‐naphthoquinones 2a‐f with 1,4‐dibromo‐2‐methyl‐2‐butene (3).
A study of the reaction between 2,4‐disubstituted‐2,3‐dihydro‐1,5‐benzothiazepines and ketenes generated in situ from chloro and dichloroacetyl chlorides
Authors: Xing Qi‐Yi , Wang Hong‐Zhong , Zhou Xin , Jin Sheng , Li Yue‐Ming , Chan Albert S. C.
Published: March 2009

In the presence of triethyl amine, the reaction of 2,4‐disubstituted‐2,3‐dihydro‐1,5‐benzothiazepine with chloro and dichloroacetyl chlorides produced not only the expected β‐lactam derivative of the benzo‐thiazepine, but also the ring opening product. Different results were obtained when the substituent at 2‐position of the benxothiazepine varied from methyl to aryl, and the substituent on the chloroacetyl chloride varied from H to Cl, or when carrying out the reaction at different temperatures. The structures of the obtained products and the reaction mechanism are discussed.
Concise synthesis of 6‐sulfonylated 3,4‐dihydro‐2h‐thiopyrans and 7‐sulfonylated 3,4,5,6‐tetrahydrothiepines from lactols
Authors: Gallos John K. , Dellios Constantinos C.
Published: March 2009

A concise method for the synthesis of the title compounds has been developed, which involves condensation of lactols with methylthiomethyl p‐tolyl sulfone, followed by mesylation and further cyclisation of the elimination products by refluxing with excess of sodium iodide in dimethyl formamide (DMF).
Synthesis and complexing properties of double armed diaza‐15‐crown‐5 and diaza‐18‐crown‐6 ethers having 4′‐hydroxy‐3′,5′‐disubstituted benzyl groups
Authors: Habata Yoichi , Saeki Tomomi , Akabori Sadatoshi
Published: March 2009

A series of double armed diaza‐15‐crown‐5 ethers (9a ‐ 16a) and diaza‐18‐crown‐6 ethers (9b ‐ 16b) have been prepared by the Mannich reaction of 2,6‐disubstituted phenols with the corresponding N,N'‐dimethoxymethyldiaza‐crown ethers in benzene. The crystal structures of the diaza‐18‐crown‐6 ethers having iso‐propyl (10b), tert‐butyl (11b), and mixed methyl and tert‐butyl groups (12b) at positions 3′ and 5′ of the phenolic side arms were determined using X‐ray diffraction methods. Competitive transport by these ligands for sodium, potassium and cesium cations were measured under basic‐source phase and acidic‐receiving phase conditions.
Facile synthesis of 3‐substituted [1,2,4]triazino[3,4‐f]purine‐4,6,8‐trione derivatives
Authors: Settimo Federico Da , Marini Anna Maria , Pardi Gianluca , Primofiore Giampaolo , Salerno Silvia , Simorini Francesca
Published: March 2009

A new synthetic route to build the [1,2,4]triazino[3,4‐ f]purine nucleus is described. The novel [1,2,4]‐triazino[3,4‐ f]purine‐4,6,8(l H,7 H,9 H)‐trione derivatives were obtained by condensation of 8‐hydrazinotheophylline with appropriate glyoxylic acids via the intermediate hydrazones.
Synthesis and chemiluminescent activity of 8,9‐dihydrobenzo[g] pyridazino[4,5‐b]indole‐7,10(11H)‐diones
Authors: Kurumi Masateru , Sasaki Kenji , Takata Hiroko , Nakayama Taiji
Published: March 2009

Substituted and unsubstituted naphthylamines were transformed into the corresponding triazole derivatives, which were converted to dimethyl 1H‐benz[g]indole‐2,3‐dicarboxylates by photocyclization. The reaction of the diesters with hydrazine hydrate gave the corresponding 8,9‐dihydrobenzo[g]‐pyridazino[4,5‐b]indole‐7,10(11H)‐diones (5). One of compounds 5 was found to have chemiluminescent activity similar to luminol.
Synthesis of 2(3H)‐benzoxazolone and 2(3H)‐benzothiazolone derivatives as potential beta‐3‐adrenergic receptor ligands (part 2)
Authors: Delhomel J. F. , Yous S. , Depreux P. , Lesieur D.
Published: March 2009

Adrenoceptors beta‐3‐subtype mediate lipolysis and in the search for potential beta‐3‐adrenergic receptors agonists for the treatment of obesity, we designed new arylethanolamines (structures 4, 5) and aryloxypropanolamines (structures 6, 7) derived from 2(3H)‐benzoxazolone and 2(3H)‐benzothiazolone.
Synthesis of herbicidal 3‐substituted‐4(3H)‐pyrimidinones under high pressure
Authors: Jezewski Artur , Jurczak Janusz , Lidert Zev , Tice Colin M.
Published: March 2009

The reaction of an N‐monosubstituted amidine with a β‐ketoester to afford a pyrimidinone is sluggish at best under normal conditions. We now report that this reaction can be effected in moderate yield under high pressure. Thus, 2,6‐dichloro‐4‐pyridyl‐(N‐prop‐2‐ynyl)carboxamidine (4b) was reacted with three α‐substituted‐β‐ketoesters (2b‐d) at 10–16 kbar to afford herbicidal 2‐(2,6‐dichloro‐4‐pyridyl)‐3‐(prop‐2‐ynyl)‐4(3H)‐pyrimidinones 5b and 5c in 15 ‐ 43% yield. This result expands the scope of reactions promoted by application of high pressure.
A practical synthesis of functionalized alkyl‐oligothiophenes for molecular self‐assembly
Authors: Michalitsch R. , Elkassmi A. , Yassar A. , Gamier F.
Published: March 2009

A synthesis for oligothiophenes that carry an alkyl sidechain with a terminal thiol group is presented. The procedure consists of three basic steps and uses well‐known and simple synthetic chemistry. Nevertheless, this strategy for preparing functionalized oligothiophenes provides overall yields that are as high as 25–30% and represents a convenient route towards this interesting class of materials.
Synthesis of some novel 3,7‐dimethyl‐4H‐pyrazolo[5,1‐c][1,2,4]triazin‐4‐ones
Authors: El‐Barbary Ahmed A. , El‐Badawi Mahmoud A. , Loksha Yasser M.
Published: March 2009

Some novel 3,7‐dimethyl‐6H‐pyrazolo[5,1‐c][1,2,4]triazin‐4‐ones were prepared (3a‐g). Compounds 3a,b were treated with hydrazines to afford various products 7a,b, 8a,b, 9 and lla,b depending on the type of hydrazine derivative and reaction conditions. The benzoyloxyimino‐pyrazolo[5,1‐c][1,2,4]triazines (13a,b) were synthesized by refluxing of compounds 3a,b with hydroxylamine hydrochloride to afford the corresponding oxime derivatives followed by treatment with benzoyl chloride.
Synthesis and biological evaluation of several 3‐(coumarin‐4‐yl)tetrahydroisoxazole and 3‐(coumarin‐4‐yl)dihydropyrazole derivatives
Authors: Emmanuel‐Giota Anne A. , Fylaktakidou Konstantina C. , Litinas Konstantinos E. , Nicolaides Demetrios N. , Hadjipavlou‐Litina Dimitra J.
Published: March 2009

A series of novel 3‐(coumarin‐4‐yl)tetrahydroisoxazoles 5a,b, 7, 9 and 3‐(coumarin‐4‐yl)dihydropyra‐zoles 13a‐d, 14,15a,b were synthesized from coumarin‐4‐carboxaldehyde 1 via the intermediate N‐methyl nitrone 3 and N‐phenyl or N‐methyl hydrazones 11a,b. These coumarin derivatives were isolated, characterized and evaluated in vitro for their ability to inhibit trypsin, β‐glucuronidase, soybean lipoxygenase and to interact with the stable radical 1,1‐diphenyl‐2‐picrylhydrazyl. The compounds were tested in vivo as anti‐inflammatory agents in the rat carrageenin paw edema assay. Compound 15a seems to be a lead molecule to be modified in order to improve the lipoxygenase inhibition. The results are discussed in terms of structural characteristics.
One pot synthesis of 6,12‐dihydro‐1,3,7,9‐tetramethyl‐5H, 11H‐dipyrido[1,2‐a:1′,2′‐d]pyrazine‐2,8‐dione by hilbert‐johnson reaction of 2‐chloromethyl‐3,5‐dimethyl‐4‐methoxypyridine
Authors: Orešić Marina , Danilovski Aleksandar , Dumić Miljenko , Košutić‐Hulita Nada
Published: March 2009

By heating 2‐chloromethyl‐3,‐5‐dimethyl‐4‐methoxypyridine (1) either neat or in solution methoxy group cleavage was achieved, followed by dimerisation to poorly soluble 6,12‐dihydro‐1,3,7,9‐tetramethyl‐5H,11H‐dipyrido[1,2‐a:1′,2′‐d]pyrazine‐2,8‐dione (3) in almost quantitative yield with methyl chloride evolution. To our knowledge this is the first example of such Hilbert‐Johnson preparation of dipyridopyrazine‐diones. Recrystallization of 3 from the hydrochloric acid yielded 6,12‐dihydro‐2,8‐dihydroxy‐1,3,7,9‐tetramethyl‐dipyrido[1,2‐a:1′,2′‐d]pyrazinediylium dichloride (4), neutralization of which gave back the pyrazine‐2,8‐dione 3. The molecular structures of both compounds 3 and 4 have been unambiguously confirmed by single crystal X‐ray structure analysis.
Spectroscopic analysis of imidazolidines. Part II: 1H NMR spectroscopy and conformational analysis of 1,2 and 1,3‐diarylimidazolidines
Authors: Salemo Alejandra , Buldain Graciela , Perillo Isabel A.
Published: March 2009

1H NMR spectra of a series of 1,2 and 1,3‐diarylimidazolidines are analyzed and correlated with their conformational features. Results were interpreted on the basis of chemical shifts and coupling constants of hydrogen atoms and confirmed by ID nOe difference experiments. 1,3‐Diarylimidazolidines (1–7) show a fast inversion of the N‐aryl nitrogen in all studied cases. 1,2‐Diaryl‐3‐methyl (or benzyl) imidazolidines (8–13) display a preferential conformation with a transoid orientation of N3 and C2 substituents.
Preparation of pyrrolo[2,1,5‐cd]indolizine Derivatives by intramolecular condensation of 3‐acyl‐5‐methylindolizines
Authors: Liang Feng , Hu Jiaxin , Zhang Lande , Hu Yuefei , Hu Hongwen
Published: March 2009

An efficient two step route has been developed to synthesize pyrrolo[2,1,5‐cd]indolizine derivatives. The reaction sequence proceeds via preparation of 3‐acyl‐5‐methylindolizines followed by an intramolecular condensation. The procedures were carried out under convenient conditions and gave the products in high yields. It could be expected to be used to prepare a broad range of potentially interesting pyrrolo[2,1,5‐cd]indolizine derivatives.
Reactions of alkyl (z)‐2‐[(E)‐2‐ethoxycarbonyl‐2‐(2‐pyridinyl)‐ethenyl]amino‐3‐dimethylaminopropenoates with C‐ and N‐nucleophiles. the synthesis of fused pyranones, pyridinones and pyrimidinones
Authors: Jukić Lucija , Svete Jurij , Stanovnik Branko
Published: March 2009

Alkyl 2‐[2‐ethoxycarbonyl‐2‐(2‐pyridinyl)ethenyl]amino‐3‐dimethylaminopropenoates 3 and 4 were transformed with C‐and N‐nucleophiles into β‐heteroaryl‐α,β‐didehydro‐α‐amino acid derivatives 13‐16, substituted 3‐amino‐4H‐quinolizin‐4‐one 17, 2H,5H‐benzo[b]pyran‐2,5‐dione 18 and 19, 2H,5H‐pyrano[4,3‐b]pyran‐2,5‐dione 20, 2H,5H‐pyrano[3,2‐c]benzo[b]pyran‐2,5‐dione 21, 2H‐1‐benzopyran‐2‐one 22 and 24, pyrido[l,2‐a]pyrimidin‐4‐one 31–34 and 39 derivatives, and N‐heteroaryl‐1H‐imidazole‐4‐carboxylates 37 and 38.
Synthesis of thiophene/phenylene co‐oligomers. III. thienyl‐capped oligophenylenes
Authors: Hotta S.
Published: March 2009

The author reports the synthesis of thienyl‐capped oligophenylenes via improved synthetic schemes. These schemes are based on either the Grignard or Suzuki coupling reaction and enable the author to obtain the target compounds at appreciably high yields. Regarding several of these compounds, their synthesis and characterization are believed to be reported for the first time. The resulting materials have been fully characterized through the nmr and ir spectroscopy. The ir analysis is particularly useful in characterizing the materials of higher molecular weight, since those materials are difficult to dissolve in organic solvents.
Efficient one‐pot synthesis of s‐triazolo[3,4‐b]‐[1,3,5]thiadiazines containing a chiral side chain by double mannich type reaction
Authors: Shi Haijian , Shi Haoxin , Wang Zhongyi
Published: March 2009

An efficient and convenience method has been developed via a one‐pot double Mannich type reaction for the synthesis of the important chiral s‐triazole derivatives: (S)‐3‐α‐phenylethyl‐2,4‐dihydro‐5‐aryl‐oxymethyl‐1,2,4‐triazolo [3,4‐b] ‐1,3,5 ‐thiadiazines.
A library of pyranocoumarin derivatives via a one‐pot three‐component hetero diels‐alder reaction
Authors: Cravotto Giancarlo , Nano Gian Mario , Tagliapietra Silvia , Palmisano Giovanni , Pilati Tullio
Published: March 2009

A hetero Diels‐Alder reaction with inverse electron demand between 4‐hydroxycoumarin, aromatic aldehydes and electron‐rich alkenes yielded a multitude of 2,4‐disubstituted 3,4‐dihydropyranocoumarins. This route opened an easy access to coumarin anticoagulants and provided a library of pyranocoumarin derivatives.
Synthesis of 1‐methyl‐, 4‐nitro‐, 4‐amino‐and 4‐iodo‐1,2‐dihydro‐3H‐pyrazol‐3‐ones
Authors: Fiamegos Y. C. , Pilidis G. A. , Varvounis G.
Published: March 2009

4‐Aminopyrazole‐3‐ones 4b, e, f were prepared from pyrazole‐3‐ones 1b‐d in a four‐step reaction sequence. Reaction of the latter with methyl p‐toluenesulfonate gave 1‐methylpyrazol‐3‐ones 2b‐d. Compounds 2b‐d were treated with aqueous nitric acid to give 4‐nitropyrazol‐3‐ones 3b‐d. Reduction of compounds 3b‐d by catalytic hydrogenation with Pd‐C afforded the 4‐amino compounds 4b, e, f. Using similar reaction conditions, nitropyrazole‐3‐ones derivatives 2c, d were reduced into aminopyrazole‐3‐ones 5e, f. 4‐Iodopyrazole‐3‐ones 7a, 7c and 8 were prepared from the corresponding pyrazol‐3‐ones 2a, 2c and 6 and iodine monochloride or sodium azide and iodine monochloride.
Preparation of 6‐, 7‐, and 8‐substituted derivatives of 2‐Oxa‐1,3,4,10‐tetraazacyclopenta[b]fluoren‐9‐one
Authors: Bratton Larry D. , Unangst Paul C. , Rubin J. Ronald , Trivedi Bharat K.
Published: March 2009

The preparation of a variety of derivatives of 2‐oxa‐1,3,4,10‐tetraazacyclopenta[b]fluoren‐9‐one 1 is described. A series of substituted indan‐1‐ones were prepared and oxidized with N‐bromosuccinimide and dimethyl sulfoxide to the corresponding ninhydrin derivatives. Cyclization of the ninhydrins with furazan‐3,4‐diamine yielded the target tetracycles. Appropiate choice of substituents in ninhydrins led to a preference for one regioisomer in the target tetracycles. This permitted the synthesis of a variety of 8‐substituted hetero‐cycles. In those instances where isomer formation was possible, structural assignments were confirmed by X‐ray crystallography.
Synthesis of pyrazolo[1,5‐a]‐, 1,2,4‐triazolo[1,5‐a]‐ and imidazo[1,2‐a]pyrimidines related to zaleplon, a new drug for the treatment of insomnia
Authors: Mustazza Carlo , Giudice Maria Rosaria Del , Borioni Anna , Gatta Franco
Published: March 2009

This paper describes the preparation of some pyrazolo[1,5‐a]‐, 1,2,4‐triazolo[1,5‐a]‐ and imidazo[1,2‐a]‐pyrimidines substituted on the pyrimidine moiety by a 4‐[(N‐acetyl‐N‐ethyl)amino]phenyl group. A new synthesis of related benzo[h]pyrazolo[1,5‐a]‐, benzo[h]pyrazolo[5,1‐b]‐ and benzo[h]1,2,4‐triazolo[1,5‐a]‐quinazolines is also reported.
Synthesis of side‐chain‐substituted ifosfamide analogs
Authors: Paci Angelo , Guillaume Dominique , Husson Henri‐Philippe
Published: March 2009

Three analogs of the cytostatic drug ifosfamide incorporating 1‐methyl‐2‐chloroethyl side chains were designed and prepared as an attempt to obtain drugs of lower toxicity.
Synthesis of regioisomeric 2,5‐bis‐substituted‐aza‐benzothiopyranoindazoles
Authors: Krapcho A. Paul , Haydar Simon N.
Published: March 2009

The synthesis of 6‐chloro‐9‐nitro‐benzothiopyranopyridin‐5‐ones2a, 2band2chas been accomplished. Chemotype2dcould not be prepared since attempts to cyclize 3‐(2‐nitro‐5‐chlorophenoxy)pyridine‐2‐carboxylic acid (1d) led to the decarboxylation product 3‐(2‐nitro‐5‐chlorothiophenoxy) pyridine (40). Analogues2a, 2bor2con treatment with the respectively substituted hydrazine led to the 2‐(substituted)‐5‐nitro 7, 8‐ or 9‐aza substituted chemotypes3a‐7a, 8b, and9c‐13c. The reduction of the nitro groups of these substrates was effected by treatment with hydrogen gas (palladium catalyst) or by stannous chloride to yield the 5‐amino chemotypes15a‐18a, 20band21c‐24c, respectively. The conversion of these derivatives to the 2,5‐bis (alkylamino)‐7‐, 8‐ and 9‐aza benzothiopyranoindazoles listed in Table 3 was accomplished by direct alkylations, acylations, followed by reduction of the amido group with Red‐Al or lithium aluminum hydride, or by reductive alkylations in the presence of sodium cyanoborohydride. The removal of the protective BOC‐group was effected by treatment of the appropriate substrates with anhydrous hydrogen chloride to afford the respective hydrochloride salts listed in Table 4.
Synthesis of novel pyridazine nucleosides
Authors: Lee Sang‐Gyeong , Kweon Deok‐Heon , Yoon Yong‐Jin
Published: March 2009

This paper presents the synthesis of novel pyridazine nucleosides containing the dicyanomethylene group and pyrrolo[2,3‐c]pyridazine nucleoside.
Synthesis of new 2,4‐diamino‐7H‐pyrrolo[2,3‐d]pyrimidines via the Taylor ring transformation/ring annulation strategy
Authors: Rosowsky Andre , Fu Hongning , Queener Sherry F.
Published: March 2009

Selected examples 2,4‐diamino‐7H‐pyrrolo[2,3‐d]pyrimidines with a phenyl or benzyl group at the 5‐position were synthesized as inhibitors of dihydrofolate reductase (DHFR) from Pneumocystis carinü and Toxoplasma gondii, two potentially life‐threatening opportunistic pathogens associated with AIDS and other disorders of the immune system. Aldol condensation of paraformaldehyde with substituted benzaldehydes or with phenylacetaldehyde afforded α‐hydroxyketones with a phenyl or benzyl group at the 4‐position. Further reaction of the hydroxyketones with malononitrile afforded 2‐aminofuran‐3‐carbonitriles, which upon heating with guanidine underwent ring transformation/ring annulation to produce 2,4‐diamino‐7H‐pyrrolo[2,3‐d]pyrimidines rather than 2,4‐diaminofuro[2,3‐d]pyrimidines. One of the target compounds obtained in this manner, 2,4‐diamino‐5‐(3,4,5‐trimethoxyphenyl)‐7H‐pyrrolo[2,3‐d]pyrimidine (1d), may be viewed as a conformationally restricted analogue of trimethoprim, an antimicrobial agent widely used in combination with a sulfa drug to treat P. carinii and T. gondii opportunistic infections in patients with AIDS. Compound 1d inhibited P. carinii and T. gondii DHFR with IC50 values of 8.3 and 14 μM, respectively. This potency was somewhat greater than that of trimethoprim. However, because this compound was also more potent than trimethoprim against mammalian (rat liver) DHFR rat liver it lacked species selectivity. The other 2,4‐diamino‐7H‐pyrrolo[2,3‐d]pyrimidines synthesized were neither potent nor selective.
Non‐biaryl atropisomers. part 1. configurationally stable 1,2‐diaryl‐3‐methyl‐1,4,5,6‐tetrahydropyrimidinium salts
Authors: García Maria B. , Perillo Isabel A. , Orelli Liliana R.
Published: March 2009

In the present communication we describe two examples of a new kind of configurationally stable non‐biaryl atropisomers in which the Ar‐N bond is the chiral axis, namely 1‐(o‐nitrophenyl)‐2‐aryl‐3‐methyl‐1,4,5,6‐tetrahydropyrimidinium iodides 1. Stereochemical features of such compounds are analyzed on the basis of their 1H and 13C one‐ and two‐dimensional nmr spectra. A comparison is made with the corresponding amidines 2.
Inverse‐electron demand [π2 + σ2 + σ2] cycloaddition reaction of dimethyl oxaquadricyclane‐2,3‐dicarboxylate with cyclooctyne
Authors: Matsumoto Kiyoshi , Taketsuna Hiroyuki , Kim Jong Chul , Kakehi Akikazu
Published: March 2009

A first example of an inverse‐electron demand [π2 + σ2 + σ2] cycloaddition reaction of dimethyl oxaquadricyclane‐2,3‐dicarboxylate was reported: cyclooctyne underwent cycloaddition with dimethyl oxaquadricyclane‐2,3‐dicarboxylate to afford the corresponding adducts one of whose structure was confirmed by a single crystal X‐ray analysis.
Ring transformations of heterocyclic compounds. XXII. Pyrido[1,2‐a]indolium salts from 2‐methyl‐3H‐indoles by pyrylium mediated three carbon annelation
Authors: Zimmermann Thomas , Hennig Lothar
Published: March 2009

The synthesis of pyrido[1,2‐a]indolium perchlorates 8,11 from 2,4,6‐triarylpyrylium perchlorates 1 and 2‐methyl‐3H‐indoles 6,9 in the presence of a basic condensing agent (anhydrous sodium acetate, piperidine acetate, triethylamine/acetic acid, triethylamine) in ethanol by a 2,4‐[C3+C2N] pyrylium ring transformation is reported. Spectroscopic data of the transformation products and their mode of formation are discussed.
The influence of the size and position of the alkyl groups in alkylimidazole molecules on their acid‐base properties
Authors: Lenarcik Beniamin , Ojczenasz Piotr
Published: March 2009

Dissociation constants of HL+ acids, where L stands for 1‐alkylimidazole, 1‐alkyl‐2‐methylimidazole, 1‐alkyl‐2‐ethylimidazole, 1‐alkyl‐2‐propylimidazole, 1‐alkyl‐4‐methylimidazole and 1‐alkyl‐2‐ethyl‐4‐methylimidazole, were determined potentiometrically. For each of the homologous series of these bases, a relationship has been derived between the pKa value and the number of carbon atoms in the hydrocarbon group for (CH2)n ≤ 13. The basicity of the alkylimidazoles has been found to increase linearly with increasing carbon chain length. The slopes of straight plots of pKa = f(nCH2) have been found to increase with increasing basicity of homologous series of the alkylimidazoles.
Synthesis of the azocino[4,3‐b]indole core structure for the synthesis of strychnos alkaloids
Authors: Ergün Yavuz , Okay Gürol , Patir Süleyman
Published: March 2009

The synthesis of compound 12 which has a hexahydro‐1,5‐methanoazocino[4,3‐b]indole structure for the synthesis of pentacyclic strychnos type alkaloids (tubifolin and tubifolidine) is described. Many new compounds 5–12 have also been synthesized.
Furopyridines. XXXI. Birch reduction of furopyridines
Authors: Yamaguchi Seiji , Hamade Eriko , Yokoyama Hajime , Hirai Yoshiro , Shiotani Shunsaku
Published: March 2009

Birch reduction of four furopyridines 1a‐d effected the characteristic cleavage of the furan ring, giving ethnylpyridinols 2a‐d, vinylpyridinols 3b,d, and ethylpyridinols 4a‐d, and the reduction of the furan ring, giving dihydrofuropyridine 5c,d.
Oxygen analogues of the benzodiazepine alkaloids sclerotigenin and circumdatin F
Authors: Witt F. Anette , Bergman Jan
Published: March 2009

A new type of fused oxazepinones 9a and 9b, which are analogues of sclerotigenin and circumdatin F, were obtained in a two step synthesis from 2‐(2‐amino‐benzoylamino)‐benzoic acid or the corresponding methyl ester. Secondly a new synthesis of circumdatin F arose from this work, where 2‐(2‐propionylamino‐benzoylamino)‐benzoic acid methyl ester was used as an intermediate.
Synthesis of some symmetrically substituted compounds derived from 1,3‐bis(6‐azauracil‐1‐yl)benzene and 1,3,5‐tris(6‐azauracil‐1‐yl)benzene
Authors: Bílek Petr , Slouka Jan
Published: March 2009

The 3,5‐bis(5‐carboxy‐6‐azauracil‐1‐yl)aniline (7) and 1,3,5‐tris(5‐carboxy‐6‐azauracil‐1‐yl)benzene (10) were prepared from 3‐amino‐5‐nitroacetanilide (1) via intermediates 2–6. A series of other substituted 6‐azauracil derivatives 9, 11‐14 were also prepared.
Synthesis of 4,7,8a,9‐tetrahydro‐3H‐diimidazo‐[1,5‐a:4′,5′‐d]pyridine derivatives
Authors: Braña Miguel F. , Guisado Cristina , Pérez‐Castells Javier , Pérez‐Serrano Leticia
Published: March 2009

The synthesis and evaluation of new ligands for the H3receptor of histamine is described. These new compounds are diimidazopyridine derivatives readily prepared by a condensation reaction of spinacine and isocyanates.