bluuebunny/crossref_metadata_2025 huggingface dataset:
Methyl 2‐[bis(acetyl)ethenyl]aminopropenoate in the synthesis of heterocyclic systems
Authors: Selič Lovro , Stanovnik Branko
Published: April 2009

Methyl 2‐[bis(acetyl)ethenyl]aminopropenoate (4) was prepared in 3 steps from acetylacetone (1) via 4‐(N,N‐dimethylamino)‐3‐acetylbut‐3‐en‐2‐one (2) and methyl N‐[2,2‐bis(acetyl)ethenyl]glycinate (3). Compound 4 reacts with N‐ and C‐nucleophiles to give fused heterocyclic systems. Derivatives of pyrido[1,2‐a]pyrimidones 14–16 and thiazolo[3,2‐a]pyrimidones 17 and 18 were prepared from 2‐aminopyridines and 2‐aminothiazoles, respectively. With C‐nucleophiles derivatives of pyrido[1,2‐a]‐pyridinone 19 and 2H‐1‐benzopyran‐2‐one 20–22 were prepared.
Unexpected formation of a xanthone in the synthesis of a bisbenzoxazole
Authors: Dotrong My , Lovejoy Steven M. , Wolfe James F. , Evers Robert C.
Published: April 2009

Recently we reported the synthesis in polyphosphoric acid of a graft copolymer consisting of a rigid‐rod poly[benzo(1,2‐d;4,5‐d′)bisthiazole‐2,6‐diyl]‐1,4‐phenylene backbone and flexible poly(oxy‐1,3‐phenylenecarbonyl‐1,4‐phenylene) side‐chains [1]. However, upon extension of this synthetic approach to the analogous graft copolymer with a poly[benzo(1,2‐d:5,4‐d′)bisoxazole‐2,6‐diyl]‐1,4‐phenylene backbone, we encountered some unexpected results due to methyl group migration. In order to better understand these results, we carried out the synthesis of selected benzothiazole and benzoxazole structures under appropriate reaction conditions. The results are reported in this article.
Urea cyclisation reaction studies
Authors: Niddam Valérie , Medou Martial , Dessolin Jean , Trabaud Carole , Camplo Michel , Kraus Jean‐Louis
Published: April 2009

Synthetic approaches of N‐α‐hydroxyalkyl amides or urea derivatives are described. In particularly, a new 1,4,6‐oxadiazocine‐2,5,8‐trione was obtained by condensation of glyoxylic acid on urea derivatives in acidic catalysis condition.
Synthesis of chirally pure 2,5‐disubstituted diketopiperazines derived from trisubstituted phenylalanines
Authors: Danthi Satyavijayan Narasimhan , Hill Ronald A.
Published: April 2009

Some new chirally pure 2,5‐substituted diketopiperazines were synthesized starting from 2‐methoxybenzyl alcohol. This multistep synthesis proceeds through the enzymatic synthesis of chirally pure amino acids, protection and dipeptide coupling, cyclization of dipeptide ester formates, and nitration of the resulting diketopiperazines.
Synthesis of new 1,2,3‐triazolo[1,2‐a]benzotriazole derivatives or substituted 2,3‐benzo‐1,3a,6,6a‐tetraazapentalenes. II
Authors: Biagi Giuliana , Giorgi Irene , Livi Oreste , Manera Clementina , Scartoni Valerio , Barili Pier Luigi
Published: April 2009

This paper continues the synthesis of new 1,2,3‐triazolo[1,2‐a]benzotriazoles or 2,3‐benzo‐1,3a,6,6a‐tetrazapentalenes to submit to biological assays. The derivatives were obtained by deoxycyclization reactions of appropriate nitrophenyl‐1,2,3‐triazole derivatives and by thermal decomposition of appropriate azidophenyl‐1,2,3‐triazoles (Schemes 1 and 2). Some attempts to extend these synthetic routes to the preparation of 1,2,4‐triazolo[1,2‐a]benzotriazoles (Scheme 3) and 1,2,3‐triazolo[1,2‐b]‐4H‐1,2,3‐benzo‐triazines (Scheme 4) completely failed.
Photocyclization reactions. Part 6. Solvent and substituent effects in the synthesis of dihydrobenzofuranols using photocyclization of 2‐alkoxybenzophenones and ethyl 2‐benzoylphenoxyacetates
Authors: Sharshira Essam Mohamed , Okamura Mutsuo , Hasegawa Eietsu , Horaguchi Takaaki
Published: April 2009

Photocyclization reactions were carried out on 2‐alkoxybenzophenones 1a‐h and ethyl 2‐benzoyl‐phenoxyacetates 5a‐e in three solvents of different polarity (benzene, acetonitrile and methanol) to examine solvent and substituent effects on the cyclization of 1,5‐biradical intermediates to dihydrobenzofuranols. Irradiation of 1a‐f in benzene gave dihydrobenzofuranols 4a‐f in 80–94% yields. The ratios of cis‐and trans‐isomers of 4b‐f were 12:1 to 1:0, showing stereoselective formation of cis‐isomers. On the other hand, irradiation of 1a‐f in acetonitrile and methanol gave 4a‐f in 68–81% and 7–75% yields, respectively. However, the ratios of cis‐ and trans‐isomers of 4b‐f were 3.5:1 to 1.3:1 in acetonitrile and 2.0:1 to 1:1.7 in methanol, showing decreased stereoselectivity. The decrease in stereoselectivity was attributed to intermolecular hydrogen bonding between the hydroxyl group of 1,5‐biradicals and solvents (acetonitrile and methanol). Similarly, irradiation of 5a‐e in benzene afforded cis‐dihydrobenzofuranols cis‐11a‐e stereo‐selectively. In contrast, irradiation of 5a‐e in acetonitrile and methanol gave a mixture of cis‐ and trans‐isomers of 11a‐e because of intermolecular hydrogen bonding between the hydroxyl group of 1,5‐biradicals and solvents. The cis and trans ratios of 11a‐e varied from 1.5:1 to 17.8:1 in acetonitrile and from 2.6:1 to 1:4.5 in methanol. Solvent and substituent effects on the cyclization of 1,5‐biradicals and reaction pathways are discussed.
On the synthesis and isolation of chlorocarbazoles obtained by chlorination of N‐substituted carbazoles
Authors: Bonesi Sergio M. , Erra‐Balsells Rosa
Published: April 2009

Chloro derivatives of N‐methylcarbazole (1), N‐phenylcarbazole (2), N‐acetylcarbazole (3), N‐benzoylcarbazole (4) and 2‐methoxy‐N‐methylcarbazole are synthesized. They are compounds 1a, 1b, 1c, 1d, 1e, 2a, 2b, 3a, 3b, 3c, 3d, 4a, 4b, 5a, 5b, 5c, 5d and 5e. Some of them are described for the first time. By using semiempirical PM3 method theoretical substituent effects on the chlorinating reaction are calculated. A chlorination mechanism of carbazoles and N‐substituted carbazoles are compared.
Furopyridines. XXII. Elaboration of the C‐substituents alpha to the heteronitrogen atom of furo[2,3‐b] ‐, ‐[3,2‐b] ‐, ‐[2,3‐c]‐ and ‐[3,2‐c]pyridine
Authors: Shiotani Shunsaku , Tanigochi Katsunori
Published: April 2009

The Grignard reaction of fused ring cyanopyridine derivatives 1a‐d with methyl‐ and phenylmagnesium bromide yielded the corresponding acylpyridine compounds 2a‐d and 3a‐d. Furopyridine N‐oxides 4a‐d were converted into the compounds having a phenyl group at the α‐position to the ring nitrogen 5a‐d. Reduction of 1a‐d and the carboxylic esters 6a‐d with diisobutylaluminium hydride yielded the corresponding amines 7a‐d and aldehydes 9a‐d. The aldehydes were converted to nitroethanol derivatives 10a‐d by condensation with nitromethane and acrylic ester compounds 11a‐d by the Wittig‐Horner reaction with methyl diethyl phosphonoacetate.
Synthesis of racemic and enantiomerically pure 2′‐thia‐2′,3′‐dideoxycytidine as potential anti‐hepatitis B virus agents
Authors: Pan Bai‐Chuan , Cheng Yung‐Chi , Chu Shih‐Hsi
Published: April 2009

A novel class of nucleosides with the C1, atom bonded to three hetero atoms was synthesized. 2′‐Thia‐2′,3′‐dideoxycytidine was the pilot compound of this series. (±)‐β‐2′‐Thia‐1′,3′‐dideoxycytidine (6) and (±)‐α‐2′‐thia‐2′,3′‐dideoxycytidine (7) were synthesized from (±)‐3‐mercapto‐1,2‐propanediol. The synthesis of the enantiomerically pure 2′‐thia‐2′,3′‐dideoxycytidines (α‐D‐form, β‐D‐form, α‐1‐form and β‐L‐form) from optically pure (S)‐(2,2‐dimethyl‐1,3‐dioxalan‐yl)methyl p‐toluenesulfonate (8) and its (R)‐isomer 18 was also described. The preliminary biological results showed that (+)‐β‐D‐2′‐thia‐2′,3′‐dideoxycytidine (26) was the most active against human hepatitis B virus with an ED50 of 3 μM.
Cyclocondensation reactions of heterocyclic carbonyl compounds.. Synthesis of 2,6‐bis(6‐azauracil‐5‐yl)aniline and its use for synthesis of some other polynuclear 1,2,4‐triazines
Authors: Hlaváč Jan , Slouka Jan
Published: April 2009

5‐(2‐Aminophenyl)‐6‐azauracil 1 was converted to 7‐(6‐azauracil‐5‐yl)isatin 3, semicarbazone 4 of which was recyclized to 2,6‐bis(6‐azauracil‐5‐yl)aniline 5. This one served as a starting compound for preparation of other noncondensed two nuclear heterocycles 7, 9, 10 and condensed 1,2,4‐triazines 11 and 12 as well.
Synthesis of tricyclic and tetracyclic thieno[3,2‐f]‐1,4‐thiazepines
Authors: Tanaka Hiroshi , Nakao Tohru
Published: April 2009

Treatment of 5‐methylthio‐2,3‐dihydrothieno[3,2‐f]‐1,4‐thiazepine (9) with acylhydrazines gave 5,6‐dihydrothieno[3,2‐f]‐1,2,4‐triazolo[4,3‐d][1,4]thiazepines 10, 11, and that of 9 with ethyl anthranilate gave 5,6‐dihydrothieno[3′,2′:6,7][1,4]thiazepino[5,4‐b]quinazolin‐8‐one (14). Reaction of 9 with hydrazine hydrate or 4‐chlorophenylhydrazine afforded 5‐hydrazino compounds 12, 15, which were subsequently cyclized to ethyl 5,6‐dihydrothieno[3,2‐f]‐1,2,4‐triazolo[4,3‐d][1,4]thiazepine‐3‐carboxylate (13), 2‐(4‐chlorophenyl)‐5,6‐dihydrothieno[3,2‐f]‐1,2,4‐triazolo[4,3‐d][1,4]thiazepin‐3(2H)‐one (16) and 2‐(4‐chlorophenyl)‐6,7‐dihydro‐2H‐thieno[3,2‐f][1,2,4]triazino[4,3‐d][1,4]thiazepine‐3,4‐dione (17). New thieno‐anellated heterocycles were prepared with the aim of studying their affinity for the benzodiazepine receptors.
Synthesis and S‐methylation of 2‐thioxopyrido[3′,2′:4,5]thieno[3,2‐d]‐pyrimidin‐4(3H)‐ones with and without a phase transfer catalyst
Authors: Dave Chaitanya G. , Shah A. B. , Shah H. C.
Published: April 2009

A number of 2‐thioxopyrido[3′,2′:4,5]thieno[3,2‐H]pyrimdin‐4(3H‐ones (5) have been synthesized by cyclocondensation of 2‐carbethoxy‐3‐amino‐4‐phenyl‐6‐substituted‐thieno[2,3‐b]pyridines (3) with various isothiocyanates. Compounds 5 were S‐methylated routinely and the reactions compared under solid‐liquid phase transfer conditions to obtain 2‐methylthiopyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidin‐4(3H)‐ones (6). The new triheterocyclic pyridothienopyrimidines were prepared with the objective to study their pharmacological properties.
Synthesis and structural study of novel 5‐aryl substituted 2‐amino‐4,7‐dioxopyrido[2,3‐d]pyrimidines
Authors: Rodríguez Rená , Suárez Margarita , Ochoa Estael , Pita Beatriz , Espinosa Remberto , Martín Nazario , Quinteiro Margarita , Seoane Carlos , Soto Jose L.
Published: April 2009

The tide compounds 4a‐c have been prepared in a one‐step procedure from 2,4‐diamino‐6‐hydroxy‐pyrimidine (1) and the corresponding arylidene substituted Meldrum's acids 2a‐e in very good yields. Semiempirical theoretical calculations (AMI) reveal two favoured conformations (A and B) for compounds 4a‐e. The 1H‐nmr determinations, by using Karplus and Altona equations, clearly indicate that conformation A, with the aryl group on C5 in a pseudoaxial position, is that predominant in solution. The calculated charge density values for the olefinic carbons are in agreement with the experimental push‐pull effect observed in the 13C‐nmr spectra.
Synthesis of pteridine derivatives related to folic acid and methanopterin from pyrazine‐2,3‐dicarbonitrile
Authors: Tada Masaru , Asawa Yasuhiro , Igarashi Mamoru
Published: April 2009

Pteridine derivatives related to folic acid and methanopterin were synthesized by two methods. The first synthesis is initiated by the radical substitution of 5‐methylpyrazine‐2,3‐dicarbonitrile (3) with the (N‐acylanilino)alkyl radical to give 6‐methyl‐5‐(N‐acylanilino)alkylpyrazine‐2,3‐dicarbonitrile (9) and was followed by the substitution of the 2‐carbonitrile with methylamine and further conversion to 1‐methyl‐2‐amino‐6‐(N‐acylanilino)‐alkyl‐7‐methylpteridin‐4(1H)‐imine 11 by the action of guanidine. The second method is initiated by radical hydroxymethylation of 5‐methylpyrazine‐2,3‐dicarbonitrile (3) to give 5‐hydroxy‐methyl‐6‐methylpyrazine‐2,3‐dicarbonitrile (15), followed by oxidation of the hydroxymethyl group, N‐phenylimination, and the substitution of the 2‐carbonitrile with methylamine to give 6‐methyl‐2‐methyl‐arnino‐5‐(N‐phenylimino)methenylpyrazine‐3‐carbonitrile (18). The reduction of the imino group and the final cyclization with guanidine gives 2‐amino‐6‐anilinomethyl‐1,7‐dimethylpteridin‐4(1H)‐imine (20).
Compounds based on meso‐tri(4‐pyridyl)‐p‐acrylamidophenylporphyrin able to interact with DNA
Authors: Li Handong , Czuchajowski Leszek , Trumble William R.
Published: April 2009

A new type of porphyrinyl‐nucleoside was synthesized by the Heck reaction of meso‐tri(4‐pyndyl)‐p‐acrylamidophenylporphyrin with (+)5‐iodo‐2′‐deoxyuridine. The porphyrin used in this reaction was also applied in obtaining a water soluble porphyrin polymer and a copolymer with acrylamide. The porphyrinyl‐nucleoside and the polymer and copolymer were investigated for their interaction with ds DNA, oligonucleotides and oligonucleotide duplexes. The extend of the red‐shift of the Soret band of porphyrins and the slowing of the mobolity of DNA during electrophoresis of the interacting systems suggested that intercalation of cationic porphyrin units into ds DNA cannot be solely responsible for the observed phenomena.
13C‐NMR study of 4H‐1,3,4‐thiadiazino[5,6‐b]quinoxalines. A proof for the N5‐deuteration in deuteriotrifluoroacetic acid
Authors: Kim Ho Sik , Okamoto Yoshihisa , Kurasawa Yoshihisa
Published: April 2009

The carbon signals of the 2‐acylamino‐4H‐1,3,4‐thiadiazino[5,6‐b]quinoxalines 1a,b, 2‐acylamino‐4H‐1,3,4‐thiadiazino[5,6‐b]quinoxaline 1,1‐dioxides 2a,b, and 2‐amino‐4H‐1,3,4‐thiadiazino[5,6‐b]quinoxaline 3 in deuteriodimethyl sulfoxide and in deuteriotrifluoroacetic acid were assigned by the nmr (HMBC, HMQC) spectroscopy. The comparison of the carbon chemical shifts in deuteriodimethyl sulfoxide with those in deuteriotrifluoroacetic acid clarified that compounds 1a, 1b, and 3 were deuterized at the N5‐position in deuteriotrifluoroacetic acid, while the 1,1‐dioxides 2a,b did not undergo the N5‐deuteration in deuteriotrifluoroacetic acid.
Heterocyclic variants of the 1,5‐benzodiazepine system. VIII. Reaction of 4(7)‐aminobenzimidazole with ethyl 2‐alkylmalonates
Authors: Martínez Roberto , Valle Lucia , Gonzalez Marcos , Romano Claudia
Published: April 2009

Reaction of 4(7)‐aminobenzimidazole with ethyl 2‐alkylmalonates gave the novel 4,5,6,7‐tetrahydro‐5‐alkyl‐imidazo[1,5,4‐ef][1,5]benzodiazepine‐4,6‐diones, and the 2‐alkyl‐4(7)‐(2′‐ethoxycarbonyl)acetamido‐benzimidazoles. The structure of all the products was corroborated by ir, mass spectrometry and 1H‐nmr.
A new type of reaction between o‐phenylenediamines and aromatic aldehydes to give 2,3‐diarylquinoxalines
Authors: Ochoa Carmen , Rodriguez Juan
Published: April 2009

A new type of reaction between o‐phenylenediamines and aryl aldehydes at high temperature is reported. The synthesis of 2,3‐diarylquinoxalines by this procedure is described.
Synthetic studies toward phenoxan analogs
Authors: Zhang Xiaowei , Hinkle Becky , Ballantyne Lisa , Gonzales Sam , Peña Michael R.
Published: April 2009

We developed two reactions needed for a total synthesis of phenoxan, a naturally occurring compound with anti‐HIV activity. In this Note, we further examined these two issues: metallation of a 2‐methyl‐oxazole and formation of a pyran‐4‐one. We employed these methods for the preparation of a phenoxan analog.
An improved process of separation of R‐ and S‐timolol
Authors: Várkonyi‐Schlovicskó Erika , Takács Kálmán , Hermecz István
Published: April 2009

Diastereomeric timolol tartrates 4 are obtained in a one‐pot synthesis from the racemic base 2 and optically active O,O‐diacetyl‐ or O,O‐dibenzoyltartaric anhydrides 3, as only one of the diastereomers precipitates from acetone solution. Acidic hydrolysis as the corresponding 4 leads to timolol in high yield and optical purity.
The use of 4‐hetaryliden‐ and 4‐aryliden‐5(4H)‐oxazolones as dienophiles. Appropriate reagents for the synthesis of cyclic analogues of natural amino acids
Authors: Avenoza A. , Busto J. H. , Paris M. , Peregrina J. M. , Cativiela C.
Published: April 2009

This report describes the behavior of 4‐hetaryliden‐ and 4‐aryliden‐5(4H)‐oxazolones as dienophiles in the Diels‐Alder reaction with several dienes. The application of this reaction to the synthesis of different conformationally constrained cyclic analogues of natural amino acids of pharmacological interest is also described.
Synthesis of (±)‐penlanfuran
Authors: Takano Daisuke , Fukunaga Yuki , Doe Matsumi , Yoshihara Kazuo , Kinoshita Takamasa
Published: April 2009

The title compound was efficiently synthesized from 3‐furoic acid and 3‐bromoanisole via the Birch reduction.
A simple one pot synthesis of 1‐(s‐triazolo[4,3‐x]azinyl‐3)‐substituted polyols
Authors: Svete Jury , Golič Ljubo , Stanovnik Branko
Published: April 2009

Open‐chain C‐nucleosides, 1‐(s‐triazolo[4,3‐x]azinyl‐3)polyols 13–18 were prepared by one‐pot synthesis from hydrazinoazines 20a,c and various D‐aldoses 1–6. No protective groups were required for these transformations. 1‐(s‐Triazolo[4,3‐b]pyridazinyl‐3)‐D‐xylo‐tetritol (15a) was isolated and characterised in the form of its 4‐O‐triphenylmethyl derivative 19. Reaction of hydrazinopyridazines 20a,b with methyl 2,3‐di‐O‐acetyl‐L‐threuronate (22), followed by treatment with bromine, gave the corresponding (2R,3S)‐2,3‐diacetoxy‐3‐(s‐triazolo[4,3‐b]pyridazinyl‐3)propanoic acid methyl esters 24a,b. Acetonisation of 1‐(6‐chloro‐s‐triazolo[4,3‐b]pyridazinyl‐3)‐D‐gluco‐pentitol (17a) gave a mixture of isomeric bis‐acetonides 25 and 26, while acetonisation of 1‐(6‐chloro‐s‐triazolo[4,3‐b]pyridazinyl‐3)‐D‐manno‐pentitol (18a) gave acetonide 27 as a single isomer.
Regiospecific synthesis of 6‐alkyltropan‐2‐ones
Authors: Lomenzo Stacey A. , Bradley Amy L. , Zhu Naijue , Klein Cheryl L. , Trudell Mark L.
Published: April 2009

A new synthetic approach for the regiospecific alkylation of the 6‐position of the tropane ring system has been developed. Alkylation, desulfonylation and deprotection of tropanes 5 and 12 furnished a series of 6‐endo‐alkyltropan‐2‐one derivatives 8a‐e, 15a‐e and 16a‐e (R = Me, Et, n‐Pr, n‐Bu, Bn) stereoselectively in good yields. The 6‐endo isomers 15a‐e and 6‐exo isomers 16a‐e were easily obtained as pure diastereoisomers.
Synthesis of [1]benzothieno[3,2‐d]pyrimidines substituted with electron donating substituents on the benzene ring
Authors: Bridges Alexander J. , Zhou Hairong
Published: April 2009

Various 2‐fluorobenzonitriles were converted to the corresponding 3‐amino[1]benzothiophenecarboxylic acid esters, which in turn were annulated with formamidine or various equivalents to produce the desired tricyclic benzothienopyrimidines. Various methoxy and nitro/amino substituents were placed on the phenyl ring, requiring several different strategies to prepare the desired benzothiophenes. Several different pyrimidone annulations were also required. The use of an electron rich 2‐bromobenzonitrile in a four‐step one‐pot low temperature lithiation sequence to produce highly electron‐rich amino[1]benzothiophenecarboxylate esters is also described. The synthesis of 7‐amino‐8‐fluoro[1]benzothieno[3,2‐d]pyriinid‐4(3H)‐one was relatively straightforward, but synthesis of the corresponding 7‐amino‐8‐protio analogue proved to be very difficult, and required several approaches before a successful one was found.
Synthesis and characterization of new crown‐type compounds with 4‐pyrone Units
Authors: Löwe Werner , Brätter Stefanie , Dietrich Christoph , Weber Manuela , Luger Peter
Published: April 2009

We report here the syntheses and characterization of new crown‐type compounds 8 and 9 incorporated with one and two 4‐pyrone units. The reaction of compound 3 with 1,5‐bis(2‐hydroxyphenoxy)‐3‐oxapentane or catechol gave the desired molecules 8 and 9 in 65% and 25% yields, respectively. Compound 3 resulted from 1 by Wohl‐Ziegler bromination in small amounts and could be separated from five bromination by‐products by column chromatography. For example, 8 binds K+ and a pyrylium salt 11 (single crystal X‐ray structure analysis) can also be prepared starting from 3 by treatment of the latter with perchloric acid in the presence of acetonitrile.
2‐Azidopyrrolo[2,1‐c][1,4]benzodiazepines. Synthesis of the first cyclic amidine derivatives
Authors: Gillard Alain‐Claude , Rault Sylvain
Published: April 2009

We report the practical synthesis of the new 5‐azidopyrrolo[2,1‐c][1,2,4]triazolo[4,3‐a][1,4]benzo‐diazepin‐8‐one and 11‐alkylamino‐2‐azidopyrrolo[2,1‐c][1,4]benzodiazepines via the corresponding hydroxy compounds.
Synthesis of new hetero[2,1]benzothiazepine derivatives
Authors: Vega Salvador , Díaz Juan A.
Published: April 2009

As part of an investigation directed to the search of new neurotropic agents we have prepared a number of hydroxy and hydroximino derivatives of the novel thieno and pyrazolo[2,1]benzothiazepine ring systems. Assignments of the Z and E hydroximino isomers were performed by study of their 1H and 13C nmr spectra and NOE experiments.
Synthesis of 2′‐amino‐17‐cyclopropylmethyl‐6,7‐dehydro‐3,14‐dihydroxy‐4,5α‐epoxy‐6,7:4′,5′‐thiazolomorphinan from naltrexone
Authors: Nan Yang , Xu Wei , Zaw Kyaw , Hughes Kathrine E. , Huang Liang‐Fu , Dunn William J. , Bauer Ludwig , Bhargava Hemendra N.
Published: April 2009

Fusion of an azole moiety at C‐6 and C‐7 of naltrexone (1) is illustrated by the synthesis of the title compound8. Bromination of 3‐O‐methylnaltrexone led to the 1,7α‐dibromo derivative which reacted with thiourea to attach the 2‐aminothiazole ring to C‐6 and C‐7 of naltrexone. After converting the amino and alcohol groups to trimethylsilyl derivatives, the aromatic bromo group was removed by halo‐lithium interchange with butyllithium, followed by hydrolysis with water. In the final step of the synthesis, the methyl ether was cleaved by boron tribromide to generate8. An alternate synthesis of8commenced with 3‐O‐acetylnaltrexone (9). Bromination of9in acetic acid in the presence of hydrobromic acid produced a mixture of 3‐O‐acetyl‐7α‐bromonaltrexone (10) and 7α‐bromonaltrexone (11), both, as hydrobromides. Reaction of this mixture with thiourea furnished8(62% from1). While1H and13C chemical shifts of all compounds are reported, those of11hydrobromide and8dihydrochloride were established unequivocally.
Saturated heterocycles, 248. Synthesis of 2,4‐dioxo and 4‐oxo‐2‐thioxo derivatives of octahydrocyclopenta[d]pyrimidines
Authors: Fülöp Ferenc , Szakonyi Zsolt , Bernáth Gábor , Sohár Pál
Published: April 2009

Unsubstituted and 1‐benzyl‐substituted cis‐cyclopenta[d]pyrirnidine‐2,4‐diones and cis‐2‐thioxo‐cyclopenta[d]pyrimidin‐4‐ones 9a,b and 10a,b were prepared from the corresponding cis‐2‐amino‐1‐cyclopentanecarboxylates 3 and 5 with potassium cyanate and thiocyanate. It was found that the cis derivatives 7a‐h readily underwent ring closure, resulting in 3‐substituted cis‐2,4‐cyclopenta[d]pyrimidinediones and cis‐2‐thioxocyclopenta[d]pyrimidin‐4‐ones 11a‐d and 12a‐d, whereas the trans counterparts 8a‐d failed to cyclize, but gave hydrolysed amino acid derivatives 13a,b and 14. This difference in the reactivities of the cis and trans isomers is a further example of the difficulty of preparing cyclopentane trans‐fused six‐membered 1,3‐heterocycles by ring closure.
Pyrrolothieno[1,4]diazepines. Part V. Study of their chemical reactivity and first synthesis of oxazino[4,3‐c]pyrrolo[1,2‐a]thieno[2,3‐f] [1,4]diazepines
Authors: Boulouard Michel , Dallemagne Patrick , Rault Sylvain
Published: April 2009

The study of the chemical reactivity of methyloxopyrrolothienodiazepinones led to new derivatives such as oximes, methyloximes, hydrazones and alcohols and also, according to an intramolecular cyclization, to new oxazino[4,3‐c]pyrrolo[1,2‐a]thieno[3,2‐f][1,4]diazepines.
Studies on methoxylation in the 7H‐naphtho[1,2,3‐I,j][2,7]naphthyridin‐7‐one system
Authors: Zjawiony Jordan K. , Kbalil Ashraf A. , Clark Alice M. , Hufford Charles D. , Buolamwini John K.
Published: April 2009

Studies on methoxylation in the 7H‐naphtho[1,2,3‐i,j][2,7]naphthyridin‐7‐one (sampangine) system represented by 3‐bromo‐ and 4‐bromosampangine as well as sampangine itself are described. We have found that regioselectivity of nucleophilic substitution in the sampangine system can be directed by reaction conditions. Under kinetic control (lower temperatures) substitution at C‐4 is the predominant reaction, regardless of whether 3‐bromo or 4‐bromosampangine were used. At higher temperatures, when the reaction is thermodynamically controlled, substitution of the bromine atom at C‐3 predominates. This is the first reported example of nucleophilic substitution in ring A of the 7H‐naphtho[1,2,3‐i,j][2,7]naphthyridin‐7‐one system.
Selective synthesis of some 5‐hydrazono‐5,6,7,8‐tetrahydro‐2H‐1‐benzopyran‐2‐ones
Authors: Trebše Polonca , Recelj Boris , Kočevar Marijan , Polanc Slovenko
Published: April 2009

A simple, highly selective transformation of 5,6,7,8‐tetrahydro‐2H‐1‐benzopyran‐2,5‐diones 1–3 and 14 with some phenylhydrazines and heterocyclic hydrazines to 5‐hydrazono‐2H‐1‐benzopyran‐2‐ones 4–12 and 15–16 is described. Under more severe conditions the hydrazonoquinoline derivative 17 was obtained from the benzopyran derivative 3 and Phenylhydrazine.
Synthesis of 2‐[mercapto(cyano)methylene]‐1,2,3,4‐tetrahydro‐quinazolin‐4‐ones and 2‐amino‐4‐methylpyrazolo‐[1,5‐a]quinazolin‐5(4H)‐one
Authors: Fleischer Judit , Takács Kálmán , Hermecz István
Published: April 2009

A series of 2‐[mercapto(cyano)methylene]‐1,2,3,4‐tetrahydroquinazolin‐4‐ones and 2‐amino‐4‐methylpyrazolo[1,5‐a]quinazolin‐5(4H)‐one were prepared from 2‐cyanomethylquinazolin‐4(3H)‐ones via α‐bromo derivatives 4 and amide oxime 8, respectively. The new compounds have been characterized by elemental analyses and 1H‐nmr, in some cases by ir and 13C‐nmr investigations.
Lewis acid assisted reactions of N‐(α‐ aminoalkyl)benzotriazoles and unactivated alkenes for the facile synthesis of 4‐, 2,4‐, and 3,4‐substituted 1,2,3,4‐tetrahydroquinolines
Authors: Katritzky Alan R. , Nichols Daniel A. , Qi Ming , Yang Baozhen
Published: April 2009

A range of substituted tetrahydroquinolines have been synthesized from benzotriazole derivatives and unactivated alkenes in the presence of a Lewis acid. These reactions utilize readily available starting materials and mild reaction conditions, and give high yields. The reaction mechanisms are discussed.
Synthesis of 2‐(4‐quinazolinyl)ethyl sulfides via addition of thiols to 4‐vinylquinazolines
Authors: Samaritoni Jack G. , Babbitt George E.
Published: April 2009

Reaction of vinyl and isopropenyl Grignard reagents with quinazoline results in addition to the 3,4‐imine bond to give the 4‐alkenyldihydroquinazolines 4 which are conveniently aromatized with potassium ferri‐cyanide to the 4‐alkenylquinazolines 5. Quinazolines 5 undergo addition with thiols under neutral conditions to afford the quinazolinylethyl sulfides 2 in moderate yields.
Fused 1,2,4‐triazole heterocycles. IV. Synthesis of four new heterocyclic ring systems of [1,2,4]triazolo[1,3]thiazinoquinolines
Authors: Kóródi Ferenc , Jekõ József , Szabó Zoltán
Published: April 2009

Syntheses of 5H‐[1,2,4]triazolo[5′,1′:2,3][1,3]thiazino[5,4‐c]quinolines 8, 5H‐[1,2,4]triazolo[3′,4′:2)3][1,3]thiazino[5,4‐c]quinolines 9, 5H‐[1,2,4]triazolo[5′,1′:2,3][1,3]thiazino[5,6‐c]quinolines 14 and 5H‐[1,2,4]triazolo[3′,4′:2,3][1,3]thiazino[5,6‐c]quinolines 15 are described starting from 4‐chloro‐3‐chloromethylquinaldine (4) and 1,2,4‐triazole‐5‐thiols 5 taking advantage of different reactivity of the chlorine atoms of 4 under different reaction conditions. The structures of products 8, 9, 14 and 15 and the intermediates leading to them were confirmed by desulfurization, unequivocal syntheses and nmr spectroscopy as well.
On the formation and reactivity of N(2),N(2′)‐tetrasubstituted 2,4‐diamino‐5‐(2‐amino‐4‐thiazolyl)thiazoles
Authors: Flaig Ronald , Hartmann Horst
Published: April 2009

By the reaction of weak bases with N(2)‐disubstituted 2‐amino‐4‐thiazoliniminium chlorides 3, easily available by the reaction of thioureas 1 with α‐chloroacetonitrile 2, N(2),N(2′)‐persubstituted 2,4‐diamino‐5‐(2‐amino‐4‐thiazolyl)thiazoles 8 are formed. These new bis‐thiazoles react, as exemplified with the dimorpholino derivative 8a, with different electrophilic reagent, such as phenyl isothiocyanate 9, 4‐nitro‐phenyldiazonium salt 11, or 4‐dialkylaminobenzaldehydes 13 at their 5H‐substituted thiazole moieties to give the corresponding thioanilides 10, azo compounds 12, and methine dyes 14, respectively. With sodium nitrite and the Vilsmeier reagent the thiazole 8a is transformed, via unstable intermediates, into the tricyclic 2,7‐dimorpholinothiazolo[4,5‐c]thiazolo[4,5‐e]pyridazine 16 and 2,7‐dimorpholinothiazolo[4,5‐b]thiazolo[4,5‐d]pyridine 19, respectively.
Ketene dithioacetal derivatives of 1‐phenyl‐3,5‐dioxopyrazolidine. Synthesis and NMR characterization
Authors: Molinari Aurora , Oliva Alfonso , Sánchez Lucá , Feliciano Arturo San
Published: April 2009

1‐Phenyl‐3,5‐dioxopyrazolidine 1 reacts with carbon disufide and alkyl halides in presence of excess of sodium acetate in dimethylformamide to afford the ketene dithioacetals 3a‐h. The 13C chemical shift assignments of these compounds were made on the basis of two‐dimensional nmr studies performed on the N‐methylketene dithioacetal derivative 4.
Synthesis of N‐α‐styrylcyclopropane‐5‐phenylamino‐1,2,4‐triazoles and their conversion to γ‐butyrolactones
Authors: Lee Kee‐Jung , Kim Dong‐Wook
Published: April 2009

The reaction of cyclopropyl phenyl ketone 1‐ureidoethylidenehydrazones 14 with a mixture of tri‐phenylphosphine, carbon tetrachloride, and triethylamine provides a general route to N‐α‐styrylcyclo‐propane‐5‐phenylamino‐1,2,4‐triazoles 17 via the thermal reaction of the expected azinocarbodiimide intermediates 15, and the oxidation of 17 with 3‐chloroperoxybenzoic acid affords 1,2,4‐triazole substituted y‐butyrolactones 23 directly.
The synthesis of pyrazolo[1,2‐a]pyrazoles. Regio‐ and stereo‐selective 1,3‐dipolar cycloadditions of (1Z)‐rel‐(4R,5R)‐1‐arylmethylene‐4‐benzoylamino‐5‐phenyl‐3‐pyrazolidinon‐1 ‐azomethinimines
Authors: Svete Jurij , Prešeren Andrej , Stanovnik Branko , Golič Ljubo , Golič‐Grdadolnik Simona
Published: April 2009

Reaction of rel‐(4R,5R)‐4‐benzoylamino‐5‐phenyl‐3‐pyrazolidinone (4) with aromatic aldehydes 5a‐f gave the corresponding (1Z)‐rel‐(4R,5R)‐1‐arylmethylene‐4‐benzoylamino‐5‐phenyl‐3‐pyrazolidinon‐1‐azomethinimines 6a‐f. 1,3‐Dipolar cycloadditions of azomethinimines 6a‐f to various dipolarophiles, which were found to proceed regio‐ and stereo‐selectively, afforded the corresponding pyrazolo[1,2‐a]‐pyrazoles 8a‐f, 10, and 13–16. Reaction of azomethinimine 6a with hydrogen cyanide gave rel‐(5R,6R)‐6‐benzoylamino‐5,6‐dihydro‐3,5‐diphenyl‐1‐oxo‐1H,7H‐pyrazolo[1,2‐a][1,2,3]triazole (18) as a representative of a new ring system.
Synthesis of 1‐alkyl‐2,3‐dihydro‐2‐(4‐pyridinyl)‐1H‐isoindoles as potential selective serotonin reuptake inhibitors
Authors: Kapples Kevin J. , Shutske Gregory M.
Published: April 2009

Two 2,3‐dihydro‐2‐(4‐pyridinyl)‐1H‐isoindoles 2a,b have been synthesized by the reaction of isoindoline with 4‐chloropyridines. In addition, a number of 1‐alkyl‐2,3‐dihydro‐2‐(4‐pyridinyl)‐1H‐isoindoles 2c‐h were obtained from 2‐(4‐pyridinyl)phthalimide (5). The addition of alkyl Grignard reagents to 5 gave 1‐alkylhydroxyisoindolones 6a‐f which, in two cases 6a,b, were dehydrated and subjected to three separate reductions to give targets 2c,d. In three cases, the intermediate hydroxyisoindolones 6c‐e were reduced in one step to the target compounds 2c‐g with lithium aluminum hydride‐aluminum chloride. When 6f, the product of the addition of phenyl Grignard to 5, was subjected to these conditions, a hydroxyisoindoline 7 was obtained which was further reduced to 2h with triethylsilane‐trifluoroacetic acid. The lithium aluminum hydride‐aluminum chloride conditions were successfully applied to the synthesis of a 1‐benzyl‐4‐piperidine derivative 21.
Conformational analysis of novel monoaryl substituted protoporphyrins by 1D NOE, 2D NOESY and molecular modeling studies
Authors: Robinsohn Adriana E. , Buldain Graciela Y. , Maier Marta S.
Published: April 2009

Porphyrins 1–4 are monoaryl protoporphyrins substituted on C‐5 or C‐15 by a phenyl group. One‐ and two‐dimensional nOe experiments and molecular modeling studies allowed us to find the most favorable conformations for these compounds. In the four porphyrins, the exocyclic phenyl group adopts a non‐coplanar disposition relative to the plane of the macrocycle and this is reflected in the ID nOe difference and 2D NOESY results. In porphyrins 1 and 3 the macrocycle is nearly planar while nonplanar saddle conformations were obtained for porphyrins 2 and 4.
Synthesis of new fluorinated 1,5‐benzoxazepine derivatives
Authors: Cocco Maria Teresa , Congiu Cenzo , Onnis Valentina , Bernard Angela Maria , Piras Pier Paolo
Published: April 2009

A simple approach to the fluorinated 1,5‐benzoxazepine ring system is described. By reacting commercially accessible aminophenols 1 and the trifluoroacetylvinyl ether 2, high yields of enaminones 3 were obtained. Functionalization of methyl group of compounds 3 gave rise to dieneamines 4 that were cyclized in acidic environment to benzoxazepine derivatives 5.
On the preparation of substituted 4H‐ 1,3,4‐thiadiazolo[2,3‐c]‐1,2,4‐triazin‐4‐ones and 1,2,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazoles
Authors: Coppo Frank T. , Fawzi Maged M.
Published: April 2009

The reaction of benzoyl isothiocyanates and methoxycarbonyl isothiocyanate with 4‐amino‐4,5‐dihydro‐3‐(methylthio)‐1,2,4‐triazin‐5‐ones in acetonitrile gave several substituted 4H‐1,3,4‐thiadiazolo[2,3‐c]‐1,2,4‐triazin‐4‐ones VIa‐h instead of the expected thioureas. In addition, benzoyl isothiocyanate reacted with 4‐amino‐3‐(methylthio)‐5‐(trifluoromethyl)‐4H‐1,2,4‐triazole to give the benzoyl thiourea IX and with 4‐amino‐3‐mercapto‐5‐(trifluoromethyl)‐4H‐1,2,4‐triazole to give the bicyclic compound N‐[3‐(trifluoromethyl)‐1,2,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazol‐6‐yl]benzamide IX.
Synthesis and exchange reactions of 5‐alkyl‐2‐oxo‐6‐thioxo‐1,2,3,6‐hexahydropyrimidine‐4‐carboxylic acids
Authors: Batty Craig A. , Manthey Michael K. , Kirk Julie , Manthey Monika , Christopherson Richard I. , Hambley Trevor
Published: April 2009

An improved preparation of 2‐oxo‐6‐thioxo‐1,2,3,6‐hexahydropyrimidine‐4‐carboxylic acid 3, a potent inhibitor of dihydroorotase is presented. Trans‐5‐alkyl‐2‐oxo‐6‐thioxohexahydropyrimidine‐4‐carboxylic acids 12a‐c were synthesised via the thiation of the p‐methoxybenzyl esters of 5‐alkyldihydroorotic acids with Lawesson's reagent followed by subsequent de‐protection. The corresponding cisisomers were prepared by reduction of 5‐alkyl‐6‐thioxoorotic acids with zinc in acetic acid. The stability and exchange reactions of 12a‐c under physiological conditions were investigated by ultra‐violet and 1H nmr spectroscopy. The attempted synthesis of 16, a fused cyclopentyl derivative of 3 is also presented.
Synthesis of 5‐(1‐azido‐2‐haloethyl)arabinouridines
Authors: Kumar Rakesh , Wiebe Leonard I. , Knaus Edward E.
Published: April 2009

A novel class of 5‐(1‐azido‐2‐haloethyl)arabinouridines 4–6 was synthesized by the regiospecific addition of halogenoazides (XN3: X = C1, Br, I) to the vinyl substituent of 5‐vinylarabinouridine (7). The title 5‐(1‐azido‐2‐haloethyl)arabinouridines 4–6 were previously shown to exhibit significant in vitro antiviral activity against herpes simplex virus type 1, varicella zoster virus and cytomegalo virus.
Palladium‐catalyzed synthesis of 3‐(alkylamino)isoindolin‐1‐ones by carbonylative cyclization of 2‐bromobenzaldehyde with primary amines
Authors: Cho Chan Sik , Jiang Li Hong , Lee Dong Yub , Shim Sang Chul , Lee Hyung Soo , Cho Sung‐Dong
Published: April 2009

2‐Bromobenzaldehyde reacts with an excess of primary amines under a carbon monoxide in the presence of a catalytic amount of bis(triphenylphosphine)palladium(II) chloride together with triethylamine to give the corresponding 3‐(alkylamino)isoindolin‐1‐ones in good yields.
A short and unequivocal synthesis of 5‐aminotetrazolo[1,5‐a]‐quinazoline as a tricyclic analogue of 4‐(3‐bromoanilino)‐6,7‐dimethoxyquinazoline (PD 153035)
Authors: Bencteux Edith , Houssin Raymond
Published: April 2009

The discovery of 4‐(3‐bromoanilino)‐6,7‐dimethoxyquinazoline (PD 153035) as an extremely potent inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor led to the preparation of several fused tricyclic quinazoline analogues. The present paper reports a new tricyclic derivative: 5‐(3‐bromoanilino)‐7,8‐dimethoxytetrazolo[1,5‐a]quinazoline. This compound was synthesized by two different pathways viaa 1,3‐dipolar cycloaddition of an azide at carbon 2 of the quinazoline ring.
Synthesis of 1,2,3‐triarylpyrroles from 1‐benzylbenzotriazoles via [1 + 2 + 2] annulation
Authors: Katritzky Alan R. , Wang Zouquan , Li Jianqing , Levell Julian R.
Published: April 2009

1,2,3‐Triarylpyrroles 7 have been synthesized by sequential lithiation and alkylation of 1‐benzylbenzo‐triazoles 1 with 2‐bromoacetaldehyde diethyl acetal (2) and N‐benzylideneaniline (4), followed by treatment with formic acid in ethanol.
Investigation of azoxides and olefins [3 + 2] cycloaddition to 1,2,3‐oxadiazolidines by a combination of density functional theory and semiempirical methods
Authors: Jursic Branko S.
Published: April 2009

Theoretical studies of the aspects of an azoxide addition to olefins is presented. The stability of the 1,2,3‐oxadiazolidine ring is discussed in regard to its capability to undergo a retro cycloaddition reaction. The structural features necessary to increase the stability of the heterocycle is proposed and evaluated. The computational results are supported with experimental observations.
Average deviation from ideal bond order as a measure for aromaticity. AMI commuted aromatic properties of five‐membered C4H4X ring systems
Authors: Jursic Branko S.
Published: April 2009

Average bond order deviation from that in an ideal aromatic system was proposed as a parameter for evaluation of aromaticity in general. The validity of this approach was examined by studying a series of aromatic five‐membered heterocycles. The geometries and bond orders were computed with AM1 semiem‐pirical method. The usefulness of AM1 semiempirical method for computation of these parameters was also discussed.
3,3,3‐Trifluoro‐2,2‐dihydroxypropanesulfonamides as building blocks for trifluoromethyl‐containing pyrazoles and benzimidazoles
Authors: Takahashi Masahiko , Muta Shigeru , Nakazato Hiroshi
Published: April 2009

1‐Alkyl‐3‐trifluoromethylpyrazole‐4‐sulfonamides 10, (2‐trifluoromethyl‐2,3‐dihydrobenzimidazol‐2‐yl)methanesulfonamides 12, and (2‐benzimidazolyl)metbanesulfonamides 13 were prepared starting from 3,3,3‐trifluoro‐2,2‐dihydroxypropanesulfonamides 1.
Synthesis of C‐5 benzoyl and azido functionalized 2,2′‐dithiobis‐and 2,2′‐diselenobis(1H‐indoles)
Authors: Sun Li , Rubin J. Ronald , Kraker Alan J. , Showalter H. D. Hollis
Published: April 2009

Novel methods for the synthesis of C‐5 benzoyl and azido analogues of 2,2′‐dithiobis(1H‐indole), 1, and 2,2′‐diselenobis(1H‐indole), 2, are described to further explore the structure activity relationships in this region of the molecule. Analogues 3‐i displayed inhibitory activity (IC50 = 0.45‐2.03 μ) toward the catalytic domain of the epidermal growth factor receptor tyrosine kinase that was equivalent to or better than that of unsubstituted compounds 1 and 2. The regiochemistry of Friedel‐Crafts benzoylation onto 1 was determined by X‐ray crystallography. To test the potential for compounds of this class to interact with the epidermal growth factor receptor tyrosine kinase via a sulfhydryl exchange mechanism, reaction of a 2,2′‐dithiobis(1H‐indole) with glutathione was carried out and the product characterized.
Synthesis and characterization of some heterocyclic derivatives by cyclization of carbohydrate thiosemicarbazones. Part I
Authors: Alho M. A. Martins , Accorso N. B. D'
Published: April 2009

We report the synthesis of 2,3‐dihydro‐1,3,4‐thiadiazoles and 1,3,4‐thiadiazoles from 1,2:3,4‐di‐O‐iso‐propylidene‐α‐D‐galacto‐1,6‐hexodialdo‐1,5‐pyranose thiosemicarbazone. The physical and spectro‐scopic characterizations of the heterocyclic derivatives as well as the intermediate product are described. We present the prefered conformation in solution using computational calculations and spectroscopic data. The possibilities of chiral induction of the cyclization reaction are discussed.
Synthesis of substituted 3‐amino‐4‐cyano‐1‐oxo‐1,2,5,10‐tetrahydroazepino [3,4‐b]indoles
Authors: Troschütz Reinhard , Hoffmann Annin
Published: April 2009

The preparation of 3‐amino‐ and 3‐dialkylamino‐4‐cyanoazepino[3,4‐fc]indoles bearing substituents on the aromatic nucleus and N10 is outlined. Starting from suitable substituted ethyl 3‐formylindole‐2‐carboxy‐latcs 2, condensation with malononitrile (3) and subsequent sodium borohydride‐reduction yielded ethyl 3‐(2,2‐dicyanoethyl)indole‐2‐carboxylates 5 and 19, respectively, which were cyclized in boiling alkoxides to 3‐alkoxy‐4‐cyanoazepino[3,4‐b]indoles 10,11,20 and 21. This sequence constitutes a novel and flexible route to functional azepino[3,4‐b>]indoles. The aminolysis of 10,11,20 and 21 with different amines and ammonia yielded the title compounds which were screened for their possible biological activity.
A study of the behaviour of 2,4‐substituted thiosemicarbazides toward orthoesters: Formation of mesoionic compounds
Authors: Buccheri Francesco , Cusmano Giuseppe , Gruttadauria Michelangelo , Noto Renato , Werber Giuseppe
Published: April 2009

The reactions beetwen 2,4‐disubstituted thiosemicarbazides and orthoesters in refluxing xylene led to the formation of the 1,2,4‐triazoline‐5‐thione ring and to the 1,2,4‐triazolium‐5‐thiolate ring. The formation of the mesoionic componds is due to rearrangement of the easily available 2,4‐disubstituted thiosemicarbazides to 1,4‐disubstituted thiosemicarbazides under the reaction conditions adopted. This method can be usefully used for the synthesis of mesoionic compounds, especially in the case of the 2‐methyl‐4‐phenylthiosemicarbazide.
Reactivity of p‐phenyl substituted β‐enamino compounds using K‐10/ultrasound. I. Synthesis of pyrazoles and pyrazolinones
Authors: Valduga Claudete J. , Braibante Hugo S. , Braibante Mara E. F.
Published: April 2009

The reactivity of the β‐enamino ketones, 3‐amino‐1‐(p‐phenyl‐substituted)‐2‐buten‐1‐ones 1a‐d and β‐enamino esters, ethyl 3‐amino‐3‐(p‐phenyl‐substituted)‐2‐propenoates 5a‐d was systematically studied when allowed to react with hydrazine and methylhydrazine under solid support K‐10/ultrasound conditions and in homogeneous media (reflux in ethanol or dichloromethane). The products were pyrazoles 2a‐d, N‐methylpyrazoles 3a‐d, 4a‐d and N‐methylpyrazolinones 6a‐c and 7a‐c. The regiochemistry of the cyclization reactions showed dependence upon the reaction conditions employed as well as upon the sub‐stituent in the aromatic ring.
An expeditious procedure for the synthesis of purines from aminoimidazolecarbaldehydes
Authors: Perandones Francisco , Soto José L.
Published: April 2009

Reactions of 4‐amino‐1,2‐dimethylimidazole‐5‐carbaldehyde (1) and 5‐amino‐1‐methylimidazole‐4‐car‐baldehydes 3 with nitriles, in the presence of dry hydrogen chloride afforded to the formation of purine derivatives. This constitutes a facile and versatile one‐pot synthesis of purines. The use of formamide instead of nitriles leads to the respective purines without substituents on the pyrimidine ring, 2d and 4e,f.
A ring opening reaction of benzisothiazolones. A new route to unsymmetrical disulfides
Authors: Sanchez Joseph P.
Published: April 2009

A series of unsymmetrical disulfides has been prepared by employing a reaction involving a ring opening, nucleophilic attack of a thiol on a 1,2‐benzisothiazol‐3‐one. The benzisothiazolones were in turn prepared by an intramolecular ring closure of an amide on a sulfenyl thiocarbonate. The sulfenyl esters were synthesized as intermediates for preparing mixed‐disulfides, but the benzisothiazolone ring closure occurred spontaneously. It was initially thought that the mixed‐disulfides were being formed from the sulfenyl ester, but the isolation and stepwise reaction of the benzisothiazolones provided proof for the reaction mechanism.
Voltammetric behaviour of heterocyclic systems. Pyridyl‐substituted benzimidazoles, benzoxazoles and benzothiazoles
Authors: Savarino P. , Viscardi G. , Quagliotto P. , Perracino P. , Barni E.
Published: April 2009

The voltammetric properties, measured at a dropping mercury electrode, have been studied for a series of 18 pyridyl‐substituted heterocyclic bases [benzimidazoles, benzoxazoles and benzothiazoles]. The corresponding quarternary salts, obtained by reaction with methyl iodide, were also studied. The reduction potential was found to be dependent on the nature of the benzimidazole, benzoxazole or benzothiazole moiety and on its position on the pyridine ring as well as on the presence of a positive charge. The reversibility of the voltammetric waves was found to be function of the system structure. The effects of proton donors on the voltammetric behaviour of the bases was also investigated.
Tandem rearrangement involving a β‐hydroxysulfoxide and cyclization processes toward the 1‐benzenesulfonyl‐5‐benzenethio‐1,2,2a,3,4,5‐hexahydrobenz[c,d]indole oxygenated at the 4‐position
Authors: Stamos Ioannis K.
Published: April 2009

Treatment of compound 4 with trifluoroacetic anhydride under reflux in chlorobenzene underwent a tandem rearrangement to produce compound 5. When the acetylated derivative of 4, was treated with trifluoroacetic anhydride in the presence of Lewis acids produced two cis cyclized conformers 7a and 7b, presumably through the intermediate B.
Unusual nitration of substituted 7‐amino‐1,8‐naphthyridine in the synthesis of compounds with antiplatelet activity
Authors: Ferrarini Pier Luigi , Mori Claudio , Badawneh Muwaffag , Manera Clementina , Martinelli Adriano , Romagnoli Federico , Saccomanni Giuseppe , Miceli Mauro
Published: April 2009

Several 1,8‐naphthyridine derivatives have been diazotizated to obtain the corresponding hydroxy derivatives or mixture of hydroxy and hydroxy nitro derivatives. The respective amounts of hydroxy and hydroxy nitro derivatives depends on the nature of the substituents, on their position on the naphthyridine nucleus, on the amount of sodium nitrite and on the reaction temperature. A study of the electronic density of some molecules suggests a possible explanation of the effects induced by the nature of the substituents and of their position. Some of the compounds were tested for their ability to inhibit human platelet aggregation in vitro induced by arachidonic acid. Only compound 26 showed interesting antiplatelet activity.
Synthesis of new indoyl‐1,3,4‐oxadiazole and oxadiazine derivatives. Potential monoamine oxidase inhibitor activity
Authors: Pérez Silvia , Lasheras Berta , Oset Carmen , Monge Antonio
Published: April 2009

New indolyl‐1,3,4‐oxadiazole and oxadiazine derivatives were prepared as reversible monoamine oxidase inhibitors. The compound 5‐(3‐methylindolyl)‐1,3,4‐oxadiazol‐2(3H)one was shown to be a good monoamine oxidase B inhibitor.
Syntheses of substituted 2‐(l‐methyl‐2‐imidazolyl)quinolines
Authors: Khazan Minoo , Hadizadeh Farzin , Shafiee Abbas
Published: April 2009

Reaction of methyllithium with 1‐methy1‐2‐imidazolecarboxaldehyde afforded the corresponding alcohol 2. Oxidation of compound 2 with manganese dioxide gave 2‐acety1‐1‐methylimidazole (3). Using compound 3 and substituted isatins 4, the corresponding quinoline‐4‐carboxylic acids (5) were prepared. The reaction of acid imidazolides of 5 with appropriate amines yielded the amides 6. Carbamic acid esters 10 were prepared by the Curtius rearrangement in good yield. Substituted quinolin‐4‐amines 13 were obtained by the acid hydrolysis of compound 10 (R1 = t‐Bu). Alkylation of amines 13 with diakylaminoalkyl chlorides gave compounds 14.
The preparation of N‐(1H‐pyrazol‐3‐yl)arylamides and 1H‐pyrazol‐3‐amines from polylithiated C(α),N‐thiosemicarbazones and C(α),N‐semicarbazones
Authors: Beam Charles F. , Davis Sharon E. , Cordray Tracy L. , Chan Kam W. , Kassis Camille M. , Davis Joanna G. Freeman , Latham G. Mark , Guion Tina S. , Hildebran Karen C. , Church A. Cameron , Koller Madlene U. , Metz Clyde R. , Pennington William T. , Schey Kevin L.
Published: April 2009

C(α),N‐Thiosemicarbazones or C(α),N‐semicarbazones were polylithiated with excess lithium diiso‐propylamide, and the resulting cyclized intermediates were condensed with aromatic esters to afford N‐(1H‐pyrazol‐3‐yl)arylamides. The polylithiated intermediates were also quenched with aqueous acid to give 5‐substituted, 1H‐pyrazol‐3‐amines.