bluuebunny/crossref_metadata_2025 huggingface dataset:
On triazoles. XXII. Synthesis of Dialkyl (3‐Q‐1,2,4‐triazol‐5‐yl)iminodithiocarbonates
Authors: Reiter József , Pongó László , Pallagi István
Published: March 2009

Isomeric dialkyl and diaralkyl[1‐, 2‐ and 4‐(alkyl, aralkyl and aryl)‐3‐Q‐1,2,4‐triazole‐5‐yl]iminodithiocarbonates 4a‐c (R ≠ H) were synthesised and their spectral data compared. The uv, cmr and ms rules elaborated helped to prove the tautomeric structure of the non‐substituted derivatives 4 (R  H). In case of dimethyl (3‐methylthio‐1,2,4‐triazole‐5‐yl)iminodithiocarbonate this is the first time ever crystalline triazole desmotropes 4a/17 and 4b/17 could be isolated. The sodium salts of 4 (R  H) could be further alkylated and aralkylated to yield the corresponding 4 (R  alkyl and aralkyl) type derivatives. Providing the above reaction in the presence of carbon disulfide the dithiocarbomethoxy derivative 7 was obtained.
A conformational analysis of the six isomers of oxybispyridine
Authors: Dunne Simon J. , Summers Lindsay A. , Von Nagy‐Felsobuki Ellak I.
Published: March 2009

Conformational energy contour maps of the six isomers of oxybispyridine have been constructed using the ab initio STO‐3G molecular orbital method. The calculations (employing a partial rigid rotor) for all six isomers indicate that the minimum energy conformers are not planar and that energy barriers between 70–1000 kJ mol−1 restrict interconversion to planar structures, thereby preventing conjugation between the p‐electrons of the oxygen atom with the π system of the pyridine rings. It is postulated that of the three mechanisms used to explain conformer interconversion about the CO bond, the disrotatory one‐ring flip mechanism is the most appropriate, since the “Morino's” structures are all within 2.5 kJ mol−1 of the minimum. Furthermore, room temperature accessibility of the “Morino's” structures suggests that the Smiles rearrangement would be possible for suitably substituted derivatives of these isomers.
The reaction of ethyl 4H‐pyran‐4‐one‐2‐carboxylate with 1,2‐diaminobenzene
Authors: Markees Diether G.
Published: March 2009

Ethyl 4H‐pyran‐4‐one‐2‐carboxylate was allowed to react with 1,2‐diaminobenzene and related diamines. The resulting products were found to be 8H‐5,6‐dihydro‐6,8‐dioxopyrido[1,2‐a]quinoxaline and derivatives. The synthesis 3H‐5,6‐dihydrobenzo[g]pyrido[1,2‐a]quinoxaline‐3,5‐dione (2c) constitutes the synthesis of a derivative of previously unknown benzo[g]pyrido[1,2‐a]quinoxaline ring system.
A new synthesis of 7‐substituted 2,3‐bis(alkylthio)naphth[1,8‐bc]‐azepines using the tris(alkylthio)cyclopropenyl cation
Authors: Kojima Hideo , Ozaki Kazuyoshi , Matsumura Noboru , Inoue Hiroo
Published: March 2009

7‐Substituted 2,3‐bis(isopropylthio)naphth[1,8‐bc]azepines 3a‐c were synthesized in good yields by the reactions of 5‐substituted 1‐naphthylamines 2a‐c with tris(isopropylthio)cyclopropenylium perchlorate (1) in acetonitrile under reflux. This reaction proceeds through the facile ring opening of 1, followed by the intermediary formation of iminium salts 5a‐c and then intramolecular cyclization.
Synthesis and biological evaluation of 5‐substituted‐4‐nitroimidazole ribonucleosides
Authors: Hasan Ahmad , Lambert Carla R. , Srivastava Prem C.
Published: March 2009

The imidazole nucleosides, 4(5)‐bromo‐5(4)‐nitro‐1‐β‐D‐ribofuranosylimidazoles, have been prepared via glycosylation of the trimethylsilylated aglycone, 4(5)‐bromo‐5(4)‐nitroimidazole, with tetra‐O‐acetyl‐β‐D‐ribo‐furanose followed by removal of the acetyl protecting groups. The 5‐bromo‐4‐nitro‐1‐β‐D‐ribofuranosylimidazole nucleoside was acetonated to produce 5‐bromo‐4‐nitro‐1‐(2,3‐O‐isopropylidene‐β‐D‐ribofuranosyl)‐imidazole which was cyclized to provide the corresponding anhydronucleoside 5,5′‐anhydro‐4‐nitro‐5‐oxo‐1‐(2,3‐O‐isopropylidene‐β‐D‐ribofuranosyl)imidazole. Sodium hydrosulfide treatment of 5‐bromo‐4‐nitroimidazole nucleoside provided 5‐mercapto‐4‐nitro‐1‐β‐D‐ribofuranosylimidazole 5‐sodium salt which was alkylated with E‐1,5‐diiodopent‐1‐ene to yield 5‐(E‐1‐iodo‐1‐penten‐5‐yl)thio‐4‐nitro‐1‐β‐D‐ribofuranosylimidazole. The corresponding iodine‐125‐labeled compound was prepared similarly using radiolabeled diiodopentene. The 5‐bromo‐4‐nitroimidazole, 5‐mercapto‐4‐nitroimidazole, and 5‐iodopentenylthio‐4‐nitroimidazole nucleosides were cytotoxic to Molt‐3 cells in vitro at concentrations higher than 10 μg/mL. The radiolabeled 5‐iodopentenylthio‐4‐nitroimidazole nucleoside showed 2‐fold higher uptake in a rapidly growing tumor as compared to uptake in a relatively slower growing tumor in mice.
Saturated heterocycles, Part 172. Synthesis of 2,6‐disubstituted‐5,6,7,8‐tetrahydropyrido[4,3‐d]pyrimidine derivatives
Authors: Lázár János , Bernáth Gábor
Published: March 2009

The title compounds were synthesized via the addition of methyl acrylate to benzylamine or to α‐aminopyridine, which gave the corresponding diesters, e.g. 12, followed by Dieckmann condensation of the latter to yield the keto‐esters 13, which were condensed with amidines and guanidines, 3, 14. Removal of the benzyl group by hydrogenolysis and subsequent alkylation of the nitrogen atom at position 6 in the resulting compound 5, with variation of the substituents on C‐2, gave a number of products with potential biological action; some of them gave analgesic and anti‐inflammatory effects.
A convenient synthesis of 1‐aryl‐3‐methyl‐1,2,4‐triazolin‐5‐ones from the reaction between acetone arylhydrazones and acetyl isocyanate
Authors: Ray Partha S. , Hank Richard F.
Published: March 2009

The reaction of acetone arylhydrazones with acetyl isocyanate gave the corresponding 4‐acetyl‐1‐aryl‐3,3‐dimethyl‐1,2,4‐triazolidin‐5‐ones which eliminated acetone upon acidic hydrolysis to give 1‐aryl‐3‐methyl‐1,2,‐4‐triazolin‐5‐ones. The above transformation can be achieved in one pot by a simple solvent swap.
Synthesis of substituted [1]benzothieno[2,3‐b]pyrazines
Authors: Cannizzo Sergio , Guerrera Francesco , Siracusa Maria Angela , Corsaro Antonino
Published: March 2009

The synthesis of a series of novel 1‐unsubstituted and 1‐alkyl‐1,2,3,4‐tetrahydro[1]benzothieno[2,3‐b]‐pyrazine‐2,3‐diones 4a‐d and their corresponding dialkylaminoalkylamino derivatives 6a‐d starting from 2‐nitro‐3‐bromobenzo[6]thiophene is described. The title ring system has not been reported previously.
Synthesis of 1‐functionalized‐6‐hydroxy‐4‐methyl and 6,11‐dihydroxy‐4‐methylnaphtho[2,3‐g]isoquinoline‐5,12‐quinones
Authors: Croisy‐Delcey Martine , Bisagni Emile , Huel Christiane , Zilberfarb Danielle , Croisy Alain
Published: March 2009

Using 2‐methoxy‐ and 2,5‐dimethoxyacetophenones 8a and 8b as starting materials, 1‐chloro‐4‐methylisoquinoline‐5,8‐quinone (6) and its 6‐bromo derivative 7 were obtained via multistep sequences. Whereas Diels‐Alder condensation of the former compound with homophthalic anhydride (22) led to a mixture of the two possible isomers: 1‐chloro‐11‐hydroxy‐4‐methylnaphtho[2,3‐g]isoquinoline‐5,12‐quinone (23) and 1‐chloro‐6‐hydroxy‐4‐methylnaphtho[2,3‐g]isoquinoline‐5,12‐quinone (24), this last tetracyclic chloroquinone was specifically obtained from 6‐bromo‐1‐chloro‐4‐methylisoquinoline‐5,8‐quinone (7) and homophthalic anhydride. The 6,11‐dihydroxy derivative was then prepared by ammonium nitrate oxidation or photochemically by cycloaddition of benzocyclobutenedione (28) and 1‐chloro‐4‐methylisoquinoline‐5,8‐quinone (6). Chloro compounds were easily substituted by diamines to provide corresponding 1‐amino substituted hydroxy tetracyclic quinones.
Thermal decomposition of 3,3,5‐trisubstituted‐4,4‐dimethyl‐4,5‐dihydro‐5‐hydroperoxy‐3H‐pyrazoles: Route to β,γ‐unsaturated ketones
Authors: Baumstark Alfons L. , Vasquez Pedro C.
Published: March 2009

The thermal decomposition of a series of cyclic α‐azo hydroperoxides (3,3,5‐R1, R2, R3‐4,4‐dimethyl‐4,5‐dihydro‐5‐hydroperoxy‐3H‐pyrazoles; 2a R1 = R2 = R3 = Ph; 2b R1 = R3 = Ph, R2 = Me; 2c R1 = R3 = p‐Anisyl, R2 = Me; 2d R1 = R2 = Me, R3 = Ph; 2e R1 = R3 = Me, R2 = Ph), synthesized by oxidation of the corresponding 3,4‐dihydro‐2H‐pyrazoles, proceeded smoothly with evolution of nitrogen. The relative stability series was found to be 2a > 2c ≈︁ 2b > 2d > 2e. For 2a, the products were 1,4,4‐triphenyl‐2,2‐dimethyl‐1‐propanone and 1,1‐dimethyl‐2,2‐diphenylethylene. For 2b‐e, β,γ‐unsaturated ketones [R1‐C(= CH2)‐CMe2‐C(= O)R3, 5a‐d] were obtained as the major products in ∼60% yield from the thermolyses. The products are consistent with a free‐radical mechanism involving initial homolysis of the O‐O bond followed by loss of nitrogen to yield a free‐radical beta to the carbonyl group. For 2a, β‐scission and hydrogen‐atom abstraction of the hydroperoxy proton by the β‐keto radical (induced decomposition) are the major pathways leading to products. For 2b‐c, abstraction of a γ‐hydrogen atom of the β‐keto radicals by hydroxy radical accounts for the formation of the β,γ‐unsaturated compounds as the major product.
Synthesis of the piperidinone metabolites of piperidine type phenothiazine antipsychotic drugsviaruthenium tetroxide oxidation
Authors: Lin G. , Midha K. K. , Hawes E. M.
Published: March 2009

The lactam metabolites of the piperidine type phenothiazine antipsychotic drugs thioridazine, mesoridazine and sulforidazine were synthesized in six steps from commercially available 2‐(2‐hydroxyethyl)piperidine. The key step involved ruthenium tetroxide oxidation ofN‐protected 2‐(2‐chloroethyl)piperidine. The products were then oxidized to obtain the phenothiazine ring 5‐sulfoxide analogues.
Synthesis and properties of furo[4,3,2‐de][1]benzopyran
Authors: Tanemura Kiyoshi , Suzuki Tsuneo , Horaguchi Takaaki , Sudo Mikio
Published: March 2009

A new heterocycle, furo[4,3,2‐de][1]benzopyran (2), was synthesized. A key step in the sequence was the allylic bromination of 3,4‐dihydrofuro[4,3,2‐de][1]benzopyran (8) to give 3‐bromo‐3,4‐dihydrofuro[4,3,2‐de][1]‐benzopyran (10) using N‐bromosuccinimide under irradiation and high dilution conditions. Bromide 10 was dealt with 1,8‐diazabicyclo[5.4.0]undec‐7‐ene to afford compound 2. Several reactions of 2 were examined. Protonation of 2 in trifluoroacetic acid occurred at the 2‐position to form a pyrylium ion 12. Catalytic hydrogenation of 2 with palladium on charcoal proceeded smoothly to give 8. Reduction of 2 by sodium and ethanol afforded 3‐ethyl‐4‐hydroxybenzofuran (14). Electrophilic substitutions of 2 such as formylation, acetylation, and bromination, occurred easily at the 2‐position. The above results show that compound 2 has both properties of benzofuran and 4‐methylenepyran.
Cycloaddition‐elimination reactions of 4‐methyl‐5‐phenylimino‐Δ2‐1,2,3,4‐thiatriazoline with electrophilic nitriles
Authors: L'abbé Gerrit , Sannen Ingrid
Published: March 2009

4‐Methyl‐5‐phenyliminothiatriazoline 4 undergoes two consecutive cycloaddition‐elimination reactions with ethyl cyanoformate and p‐toluenesulfonyl cyanide in refluxing chloroform, and yields the 1,2,4‐thiadiazolines 6a,b via the isomers 5a,b. In acetone as the solvent, the reactions occur at room temperature, due to the formation of the 1,2,4‐oxathiazolidine 12 as the intermediate. When trichloroacetonitrile was used, only the decomposition products of 4, namely 7 and 8 were obtained.
Nitration of dithieno[3,4‐b:3′,2′‐d]pyridine and dithieno[2,3‐b:3′,2′‐d]pyridine
Authors: Gronowitz Salo , Szabo Kalman J. , Oluwadiya James O.
Published: March 2009

The nitration of dithieno[3,4‐b:3′,2′‐d]pyridine (2) and dithieno[2,3‐b:3′,2′‐d]pyridine (3) has been studied. Nitration of 2 occurred in both positions of the c‐fused thiophene ring, while 3 was predominantly substituted in the 2‐position. The structures of the nitro derivatives were proven by extensive use of 1H and 13C nmr spectroscopy.
A convenient synthesis of new aminomethylenedioxypyrroloindoles via an iminium salt
Authors: Bouyazza Lahboub , Lancelot Jean‐Charles , Rault Sylvain , Robba Max , Quermonne Marie Anne
Published: March 2009

Cyclization of 2‐(1‐pyrrolyl)piperonylcarboxamide derivatives gave iminium perchlorates which afforded 9‐(N‐substituted‐imino) and 9‐(N‐substituted amino)‐6,7‐methylenedioxypyrrolo[1,2‐a]indoles.
Potential DNA bis‐intercalating agents. Bridged bis‐(6‐chloropurines) and related compounds
Authors: Párkányi Cyril , Yuan Hui Liang , Tsai Meng‐Kan Michael
Published: March 2009

Two bis‐(6‐chloropurines) bridged by conformationally restricted tethers were synthesized as potential DNA bis‐intercalating agents. Reduction of 4,6‐dichloro‐5‐nitropyrimidine (1) afforded 5‐amino‐4,6‐dichloropyrimidine (2) which was then used as the starting material. Reaction of 2 with 4,4′‐diaminodiphenylmethane (3) and bis‐(4‐aminophenyl) ether (4) yielded bis‐[4‐(N‐5‐amino‐4‐chloro‐6‐pyrimidyl)aminophenyl]methane (5) and bis‐[4‐(N‐5‐amino‐4‐chloro‐6‐pyrimidyl)aminophenyl] ether (6), respectively. Acid‐catalyzed condensation of the above pyrimidines, 5 and 6, with triethyl orthoformate in N,N‐dimethylacetamide gave bis‐[4‐(6‐chloro‐9‐purinyl)phenyl]methane (7) and bis‐[4‐(6‐chloro‐9‐purinyl)phenyl] ether (8). The spectral data on the new compounds will be discussed.
Palladium‐catalyzed conjugate addition type reaction of 5‐iodopyrimidines with α,β‐unsaturated ketones
Authors: Wada Akimori , Ohki Kazuhiro , Nagai Sotoo , Kanatomo Shōichi
Published: March 2009

The reaction of various 5‐iodopyrimidines with α,β‐unsaturated ketones in the presence of palladium diacetate‐triphenylphosphine complex in triethylamine are investigated. In the reaction of 2,4‐dialkoxy(or alkylthio)‐6‐methyl‐5‐iodopyrimidine the addition of pyrimidine to the carboncarbon double bond of α,β‐unsaturated ketones occurs. In the case of other pyrimidines, according to the decrease of steric hindrance at the 5‐position on the pyrimidine ring, the ratio of conjugate addition product was decreased and the usual olefinic substituted product was increased.
Synthesis of 1′‐substituted and 1′,3′‐disubstituted (±)‐2R*, 11bS*‐9,10‐Dimethoxy‐1,3,4,6,7,11 b‐Hexahydrospiro‐[benzo[a]quinolizin‐2,5′‐imidazolidine]‐2′,4′‐diones
Authors: Menéndez J. Carlos , Söllhuber Mónica M.
Published: March 2009

The results of the reaction between (±)‐2R*,11bS*‐2‐alkyl(aryl)amino‐1,3,4,6,7,11b‐hexahydrobenzo[a]‐quinolizine‐2‐carbonitriles 2 and isocyanates under a variety of experimental conditions are discussed. The ureides 3 and iminohydantoins 4 thus obtained were used to prepare N3‐monosubstituted and N1,N3‐disubstituted derivatives of the (±)‐2R*,11bS*‐9,10‐dimethoxy‐1,3,4,6,7,11b‐hexahydrospiro[benzo[a]quinolizin‐2,5′‐imidazolidine]‐2′,4′‐dione system 1. The stereochemistry of these compounds is discussed, on the basis of spectroscopic evidence and study of their chemical reactivity.
Synthesis of functionalized N‐methylpyrroles
Authors: Barrero A. F. , Sánchez J. F. , Oltra J. E. , Teva D.
Published: March 2009

The preparation of some new N‐methylpyrroles is shown. These heterocyclic compounds were used to synthesize polyenic substances with polysubstituted pyrrole rings.
Studies of heterocyclic compounds.VIII. Synthesis, anti‐inflammatory and antiallergic activities ofn‐alkyl‐2,3,4,9‐tetrahydrofuro[2,3‐b]quinoline‐3,4‐diones and related compounds
Authors: Kuo Sheng‐Chu , Huang Shung‐Chieh , Huang Li‐Jiau , Cheng Hong‐Elk , Lin Tsung‐Ping , Wu Chun‐Hsiung , Ishii Katsumi , Nakamura Hideo
Published: March 2009

A series of newN‐alkyl‐2,3,4,9‐tetrahydrofuro[2,3‐b]quinoline‐3,4‐dione andN‐alkyl‐4,9‐dihydrofuro[2,3‐b]‐quinolin‐4‐one derivatives were prepared and evaluated for their anti‐inflammatory activity by the carrageenin hind paw edema method and antiallergic activity by the rat passive cutaneous anaphylaxis method. Among those tested compounds,N‐ethyl‐2,3,4,9‐tetrahydrofuro[2,3‐b]quinoline‐3,4‐dione was the most promising agent which could provide a novel structural prototype for antiallergic agents.
Pentacyclic triazolodiazepines as PAF‐antagonists
Authors: Walser A. , Flynn T. , Mason C.
Published: March 2009

The syntheses of two novel pentacyclic ring systems, the thieno[3,2‐f][1,2,4]triazolo[4,3‐a][1,4]diazepino‐[4,5‐a]benzimidazole and the indazolo[2,3‐d][1,2,4]triazolo[4,3‐a][1,4]benzodiazepine are described. Attachment of a propargyl linked quinolinone resulted in compounds 6 and 16 which showed PAF‐antagonist activity by the intravenous route of administration in guinea pigs. The more potent compound 16 also exhibited good oral activity with an ID50 of 0.2 mg/kg in the bronchoconstriction assay.
The Synthesis of Octahydro‐7‐phenylpyrazino[2,1‐b][3]benzazepines
Authors: Ohnmacht Cyrus J. , Mclaren Frances M.
Published: March 2009

Octahydro‐7‐phenylpyrazino[2,1‐b][3]benzazepine (1a) was prepared from 1‐methyl‐3‐phenylmethylpiperazine5aby reaction with styrene oxide followed by sulfuric acid cyclization of the resulting alcohol6a. The diastereomeric mixture1awas further separated into the diastereomers1a′and1a″. Similarly 1‐methyl‐3‐(3‐chloro‐4‐methoxyphenyl)piperazine was reacted with styrene oxide to yield6cwhich on cyclization with 1.5 equivalents of sulfuric acid in trifluoroacetic acid gave a 3:7 mixture of phenolic,1d, and methoxy,1c, octa‐hydropyrazino[2,1‐b][3]benzazepines. The reaction of the 2,5‐piperazinedione4cwith sodium acetoxyborohydride gave a 49% yield of the 2‐piperazinone7which was similarly carried on to the corresponding 1(2H)‐oxohexahydropyrazino[2,1‐b][3]benzazepine9.
On the synthesis of 3‐amino‐2,3‐dihydro‐1H‐pyrido[3,2,1‐kl]phenothiazine 5,5‐dioxide and of 3‐amino‐1,2‐dihydro‐3H‐dibenzo[c,jk]pyrido[2,1‐c]‐1,4‐thiazepine 7,7‐Dioxide
Authors: Catsoulacos P. , Pelecanou M. , Camoutsis Ch.
Published: March 2009

3‐Amino‐2,3‐dihydro‐1H‐pyrido[3,2,1‐kl]phenothiazine 5,5‐dioxide and 3‐amino‐1,2‐dihydro‐3H‐dibenzo‐[c,jk]pyrido[2,1‐c]‐1,4‐thiazepine 7,7‐dioxide were synthesized from the corresponding 3‐oxime acetates by reduction with the borane‐tetrahydrofuran complex. Reduction was not successful in the case of 2,3‐dihydro‐1H‐pyrido[3,2,1‐kl]phenothiazine‐3‐oxime acetate.
Substituted γ‐lactones: On the structural elucidation of the reaction products from 4‐aroyl‐3‐hydroxy‐2(5H)‐furanones and 1,2‐diamines
Authors: Zimmer Hans , Amer Adel , Ho Douglas , Palmer‐Sungail R.
Published: March 2009

The reaction pathway of 4‐aroyl‐3‐hydroxy‐2(5H)‐furanones 1 with diamines depends on the nature of the amine as well as on the applied reaction conditions. Thus, the reaction of 1a‐d with 5,6‐diamino‐1,3‐dimethyluracil 5 led to the formation of two isomeric Schiff bases 7a‐d and 8a‐d. Conversely type 1 compounds reacted with 4,5‐diaminopyrimidine 9 or 2,3‐diaminopyridine 10 to form the mono acid‐base adducts 11a and 11b respectively. When type 1 compounds were reacted with aliphatic diamines 13a‐d or p‐phenylenediamine and p‐xylenediamine, respectively also an immediate formation of acid‐base adducts 15a‐f was observed. The reaction of a number of O‐methylated type 1 compounds with 1,2‐ethylenediamine afforded the novel seven‐membered ring compounds 18a‐d in good yields. The analogous reaction of O‐alkylated 1a with o‐phenylenediamine 2 or 2,3‐diaminonaphthalene gave the expected tricyclic ring systems 19 or 20.
A new procedure for regioselective synthesis of 8,9‐dichloro‐2,3,4,5‐tetrahydro‐1H‐2‐benzazepine (LY134046) and its 3‐methyl analogue as inhibitors of phenylethanolamine N‐methyltransferase (PNMT)
Authors: Grunewald Gary L. , Paradkar Vidyadhar M. , Stillions Duane M. , Ching Feei
Published: March 2009

A regioselective synthesis of 8,9‐dichloro‐2,3,4,5‐tetrahydro‐1H‐2‐benzazepine (LY134046, 10) and its 3‐methyl analogue 26 from 6,7‐dichloro‐3‐hydroxyphthalide (16) is described. The key step involved 1,4‐hydride addition to the α,β‐unsaturated nitrile 17 to give the saturated nitrile 18 using sodium borohydride in 2‐propanol. In the preparation of LY134046 10, the COOH group in 18 was first esterified and then the nitrile function was selectively reduced with borane to yield the aminoester 20. The aminoester 20 was then cyclized to the azepinone 21 which on reduction with borane provided LY134046 10 in an overall yield of 22%. The route is adaptable to the preparation of hitherto unknown 3‐substituted‐2‐benzazepines as demonstrated by the preparation of the 3‐methyl analogue 26. In this case the nitrile 18 was reacted with an excess methylmagnesium iodide to give the ketoacid 22. Esterification of 22 followed by reductive amination with sodium cyanoborohydride and ammonium acetate provided the aminoester 24, which was then converted to the target benzazepine 26 as described earlier for the title compound. The reaction conditions and the reagents used throughout the sequence are fairly mild and many functional groups may be tolerated. The only limitation to this procedure is the availability of the corresponding hydroxyphthalide. A variation in the choice of reagent in the Grignard reaction of 18 should provide an access to a variety of 3‐substituted‐2‐benzazepines.
Synthesis of novel, substituted 4H‐imidazo[1,5‐a][1,4]benzodiazepines
Authors: Fryer R. Ian , Gu Zi‐Qiang , Wang Chen‐Guang
Published: March 2009

Synthetic approaches to novel, substituted 4H‐imidazo[1,5‐a][1,4]benzodiazepines are described. The compounds prepared are, in general, derivatives of known ring systems and structures were assigned on the basis of spectroscopic evidence.
1,4,4a,10b‐Tetrahydro‐N,N‐dimethyl‐4‐phenanthridinamines and 1,4,4a,5,6,10b‐hexahydro‐N,N‐dimethyl‐4‐phenanthridinamines
Authors: Bobowski George , West Barbara , Omecinsky Diana
Published: March 2009

Synthetic procedures to prepare the title compounds are described. Diels‐Alder cycloaddition of β‐nitrostyrene derivatives5toN,N‐dimethyl‐1,3‐butadien‐1‐amine,6, gave 5‐aryl‐N,N‐dimethyl‐6‐nitro‐2‐cyclohexen‐1‐amines 7. Reduction of 7 with zinc in acetic acid gave the diamino derivatives8. Schotten‐Baumann acylation of8gave amides9. Treatment of8with alkyl isocyanates gave the aminourea derivatives10. Bischler‐Napieralski cyclodehydration procudure of9and10gave 1,4,4a,10b‐tetrahydrophenanthridinamines3andN6‐alkyl‐1,4,4a,10b‐tetrahydro‐N4,N4‐dimethyl‐4,6‐phenanthridinediamines11, respectively. Condensation of diamines8with aryl aldehydes under azeotropic conditions gave imines12which on treatment with acids yielded 6‐aryl‐1,4,4a,5,6,10b‐hexahydro‐N,N‐dimethyl‐4‐phenanthridinamines4. The stereochemistry of these materials is assigned from the proton magnetic resonance studies.
Synthesis and insecticidal activity of 4‐(aminomethyl)‐2H‐1‐benzothiopyran‐2‐ones (thiocoumarins) and related compounds
Authors: Nakazumi Hiroyuki , Kobara Yuzoh , Kitao Teijiro
Published: March 2009

Bromination of 4‐methyl‐2H‐1‐benzothiopyran‐2‐ones (4‐methylthiocoumarins) with bromine under irradiation of high‐pressure mercury lamp gave 3‐bromo‐4‐methylthiocoumarin, which reacted with secondary amine to give 4‐(aminomethyl)thiocoumarins. The structure was determined by X‐ray crystallographic analysis. A series of 4‐methylthiocoumarin and related compounds were tested for insecticidal activity, and 4,6‐dimethylthiocoumarin shows the most significant insecticidal activity against Nilaparvata lugens and Aphis gossypii. An introduction of an aminomethyl group in thiocoumarin results in improvement of activity against Tetranychus urticae and Spodoptera litura.
1,4‐Benzothiazine‐2‐carboxylic acid 1‐oxides as analogues of antibacterial quinolones
Authors: Cecchetti Violetta , Fravolini Arnaldo , Schiaffella Fausto , Tabarrini Oriana , Zhou Weicheng , Pagella Pier Giuseppe
Published: March 2009

The synthesis of 1,4‐benzothiazine‐2‐carboxylic acid 1‐oxides as agents which mimic quinolone antibacterial, are described. The key step includes intramolecular cyclization of phenylsulfinyl acrylates 17 and 18 which are prepared in six steps from 11. None of new target compounds showed interesting antibacterial activity in vitro against the tested strains.
Furopyridines. XII. Reaction of 3‐bromo, 2‐phenylthio and 2‐phenylthio‐3‐bromo derivatives of furo[2,3‐b]‐, furo[3,2‐b]‐, furo[2,3‐c]‐ and furo[3,2‐c]pyridine with several alkyllithiums
Authors: Shiotani Shunsaku , Morita Hiroyuki
Published: March 2009

This paper describes reactions of 3‐bromo‐ 1a‐d, 2‐phenylthio‐ 5a‐d and 2‐phenylthio‐3‐bromofuropyridines 6a‐d with n‐butyl‐, t‐butyl‐ and methyllithium and lithioacetonitrile. Lithiation of compounds 1a‐d with n‐butyl‐ or methyllithium gave the parent furopyridines 2a‐d and o‐ethynylpyridinols 3a‐d. Reaction of compounds 5a‐d with methyllithium afforded o‐(phenylthioethynyl)pyridinols 7a‐d, which were also yielded by reaction of compounds 6a‐d with t‐butyl‐ or methyllithium. The phenylthio group in compounds 7a‐d were substituted with t‐butyl group by the reaction with excess t‐butyllithium. In contrast, 2‐phenylthio group in compounds 5a‐d and 6a‐d was substituted with cyanomethyl group by reaction with lithioacetonitrile to give compounds 11a‐d and 10b, c respectively.
Synthesis of porphyrinyl‐nucleosides
Authors: Czuchajowski Leszek , Habdas Jan , Niedbala Halina , Wandrekar Vinay
Published: March 2009

Several porphyrinyl‐nucleosides were prepared in the reaction of the OH group of one, two or four meso‐p‐hydroxyphenyl substituents of porphyrin with 5′‐O‐tosylates of 2′,3′‐O‐isopropylidene‐adenosine or ‐uridine, or 5′‐O‐tosylthymidine; the remaining porphyrin meso‐substituents were p‐tolyl, p‐hydroxyphenyl or 4‐pyridyl. The following porphyrinyl‐nucleosides were obtained with 8–17% yield: meso‐di(p‐tolyl)di(p‐phenylene‐5′‐O‐2′,3′‐O‐isopropylidene‐adenosine) (or ‐uridine)porphyrins 1,2, the respective meso‐tetranucleosideporphyrins 3,4‐meso‐mono(p‐phenylene‐5′‐O‐thymidine)porphyrins 5–7, meso‐di(p‐tolyl)di(p‐phenylene‐5′‐O‐thymidine)porphyrins 8,9 and the meso‐di(p‐hydroxyphenyl)di(p‐phenylene‐5′‐O‐thymidine)porphyrins 10. Other compounds prepared belonged to the series: meso(4‐pyridyl)4−n(p‐phenylene‐5′‐O‐2′,3′‐O‐isopropylideneuridine)nporphyrin, n = 1, 2 or 4, 11–13. N‐Methylation gave the water soluble iodide salts: (N‐methyl‐4‐pyridinium)44−n(p‐phenylene‐5′‐O‐2′,3′‐isopropylideneuridine)nporphyrins, n = 1, 2 or 4, 14–16. The ms fab showed in most cases stepwise detachment of the CH2(5′)‐nucleoside fragments.

The porphyrins meso disubstituted by thymidine represent a convenient substrate for the build‐up of both nucleoside units into the oligo/polynucleotide chains.
Pyrimidine derivatives. VII. Nucleophilic reactions of 5‐bromo‐1‐(bromoalkyl)‐6‐bromomethyl‐2,4(1H,3H)‐pyrimidinediones
Authors: Kinoshita Toshio , Takaishi Yumiko , Okunaka Tomoko , Ohwada Takehiro , Furukawa Sunao
Published: March 2009

The reactions of 1‐(bromoalkyl)‐5‐bromo‐6‐bromomethyl‐3‐methyl‐2,4(1H,3H)‐pyrimidinedione (1) with several nucleophiles were examined as follows: by reaction with sodium methoxide, 6‐(bismethoxy)methyl‐5‐debrominated derivatives 2, 3, and 4 were prepared; the corresponding di‐substituted compounds (side chains in 1‐and 6‐positions) 5, 6, 7, and 9 were obtained by treatment with silver nitrate, silver acetate, potassium thiocyanate, and potassium thioacetate; the reaction with thioacetamide and iso‐butylamine gave bicyclic compounds [1,4]thiazino[4,3‐c]‐ 11, pyrazino[1,2‐c]‐ 12, and [1,4]diazepino[1,2‐c]pyrimidinedione 13, respectively; pyrrolidine, morpholine, and sodium azide afforded the corresponding 6‐substituted compounds 14, 15, and 16.
Synthesis and structure of N1‐e‐benzo‐4,7,13,16,21,26‐hexaoxa‐1,10‐diazabicyclo[8.8.8]hexacos‐23‐yl‐N2‐phenylthiourea. Derivative of a bifunctional complexing agent
Authors: Pettit William A. , Iwai Yoshihisa , Barfknecht Charles F. , Swenson Dale C.
Published: March 2009

A cryptand with an aminobenzo group 4,7,13,16,21,24‐hexaoxa‐5,6‐(4′‐aminobenzo)‐1,10‐diazabicyclo‐[8.8.8]hexacosane, has been synthesized as a bifunctional complexing intermediate for investigation of the labeling of proteins with metal radionuclides. This amine, although unstable, can be prepared as the stable stannic salt. The free base was converted to the corresponding phenylthiourea by 1) reaction with phenyliso‐thiocyanate and 2) conversion to its isothiocyanate followed by reaction with aniline. The thiourea structure was confirmed by X‐ray crystallographic analysis.
Synthesis of some novel azido/tetrazolothienopyrimidines and their reduction to 2,4‐diaminothieno[2,3‐d]pyrimidines
Authors: Shishoo C. J. , Jain K. S.
Published: March 2009

A variety of novel 2,4‐diaminothieno[2,3‐d]pyrimidines has been prepared through the reduction of the corresponding azido/tetrazolothienopyrimidines under acidic conditions.
N‐15 NMR analysis of 1,2,3‐thiadiazoles
Authors: L'abbé Gerrit , Delbeke Pieter , Bastin Lieve , Dehaen Wim , Toppet Suzanne
Published: March 2009

The 15N nmr spectra of a series of 1,2,3‐thiadiazoles reveal the strong influence of substituents at C‐5 on the N‐2 resonance. Upon methylation, the two thiadiazole nitrogen resonances are shielded, but the most dramatic shift is observed for the methylated nitrogen, Δδ > 140 ppm. The 15N chemical shifts of some mesoionic thiadiazoles were also determined and explained by the dual effect of 5‐substitution and salt formation. By disconnecting these effects, the 15N chemical shifts of 10 and 11 were found to be unusual and to reflect a thiapentalene character.
Reactivity of 4‐azido‐ and 4‐amino‐6‐methyl‐2H‐pyran‐2‐one. Preparation of 1‐(6‐methyl‐2‐oxopyran‐4‐yl)‐1,2,3‐triazoles and 5‐oxopyrano[4,3‐b]pyridines
Authors: Malet R. , Serra N. , Abramovitch R. A. , Moreno‐Mañas M. , Pleixats R.
Published: March 2009

1,3‐Dipolar cycloadditions of stable 4‐azido‐6‐methyl‐2H‐pyran‐2‐one 1 with electron‐rich alkenes and alkynes lead to 4,5‐substituted 1‐(6‐methyl‐2‐oxopyran‐4‐yl)‐1,2,3‐triazoles. Iminophosphoranes derived from 1 have also been synthesized. 5‐Oxopyrano[4,3‐b]pyridines are prepared by reaction of 4‐amino‐6‐methyl‐2H‐pyran‐2‐one 2 with β‐dicarbonyl compounds.
Cis‐trans isomerization of styrylpyrroles by stray light
Authors: Lee Chang Kiu , Yu Ji Sook , Kim Young Hie
Published: March 2009

A series of substituted N‐methylstyrylpyrroles (H, p‐Br, p‐CN, o,p‐diCl, m‐CH3, m‐CN, m‐NO2) were prepared via the Wittig reaction of 1‐methylpyrrole‐2‐carboxaldehyde and substituted benzyltriphenylphosphonium bromides. Both cis and trans isomers were found to be present in the reaction mixture and they were separable by column chromatography in a few cases (H, p‐Br, m‐CN, m‐NO2). Photochemical isomerizations of cis‐styrylpyrroles to trans isomers were observed when the substituents were o,p‐diCl and m‐NO2, while the opposite was the case with compounds having H, p‐Br, m‐CH3, m‐CN. It was difficult to separate the cis and trans mixture of p‐cyanostyrylpyrroles and the equilibrium ratio did not change under similar photochemical reaction conditions.
Synthesis and analysis of 1,2,3,4‐tetrahydro‐(9H)‐pyrido[3,4‐b]indole
Authors: Rodríguez J. G. , Gil‐Lopetegui P.
Published: March 2009

The synthesis of 1,2,3,4‐tetrahydro‐(9H)‐pyrido[3,4‐b]indole derivatives was carried out in one pot, by condensation of tryptamin with cycloalkanones in the presence of a polyphosphate ester as the catalyst in moderate to low yields, the aldol condensation being the main products. Reaction of tryptamine and cyclic ketones was also carried out in two stage through the imine intermediate with protic catalysis giving the tetrahydro‐β‐carbolines 8–14, in good yields. 2‐Methyl derivatives 15–21, of the tetrahydro‐β‐carbolines, were obtained in good yields, using methyl iodide in dimethyl sulphoxide‐potassium carbonate.
Convenient synthesis of 4‐trifluoroacetylpyrazoles from aldehyde tert‐butylhydrazones
Authors: Kamitori Yasuhiro , Hojo Masaru , Masuda Ryōichi , Fujishiro Masaki , Nakamura Isao , Yamamoto Katsumasa
Published: March 2009

Several 1‐(tert‐butyl)‐4‐trifluoroacetylpyrazoles 3 were synthesized by the reaction of aldehyde tert‐butylhy‐drazones 2 with 4‐ethoxy‐1,1,1‐trifluoro‐3‐buten‐2‐one (1). The tert‐butyl group could be readily removed by treatment of 3 with 90% sulfuric acid.
The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 11. Synthesis and total assignment of the 1H and 13C NMR spectra of isomeric benzothienonaphthoquinolines using multiple inverse detected two‐dimensional NMR methods
Authors: Luo Jiann‐Kuan , Zektzer Andrew S. , Castle Raymond N. , Crouch Ronald C. , Shockcor John P. , Martin Gary E.
Published: March 2009

Two novel heterocyclic ring systems, namely, [1]benzothieno[2,3‐c]naphtho[1,2‐f]quinoline and [1]benzothieno[2,3‐c]naphtho[2,1‐g]quinoline have been synthesized and characterized by inverse detected two‐dimensional nmr methods. Unequivocal total assignments of the proton and carbon nmr spectra were made through the concerted utilization of HMQC (Heteronuclear Multiple Quantum Correlation) and a combination of HMBC (Heteronuclear Multiple Bond Correlation) and HMQC‐TOCSY (HMQC with proton TOtal Correlation Spectroscopy).
Research on nitrogen containing heterocyclic compounds. XIX: Synthesis of 8H‐imidazo[2,1‐c]‐s‐triazolo[4,3‐a]‐[1,4]benzodiazepine and its 1‐derivatives
Authors: Stefancich Giorgio , Silvestri Romano , Artico Marino
Published: March 2009

Reaction of 2‐nitrobenzyl iodide with 1H‐imidazole, in the presence of potassium tert‐butoxide and 18‐crown‐6, gave 1‐(2‐nitrobenzyl)‐1H‐imidazole. Trichloroacetylation of this compound furnished trichloroacet‐ylimidazole 8, which on treatment with sodium ethoxide was transformed into the corresponding ethoxycarbonyl derivative 9. Catalytic reduction of the nitro group to the amino group yielded 10, which was then cyclized to 10,11‐dihydro‐11‐oxo‐5H‐imidazo[2,1‐c][1,4]benzodiazepine 11. Treatment of this lactam with di‐4‐morpholinylphosphinic chloride followed by reaction of the intermediate 12 with formylhydrazine gave the title compound or its 1‐derivatives when acetylhydrazine or isonicotinoylhydrazine were used instead of formylhydrazine.
On the orientation in lithiation and bromination of dithieno[3,4‐b:3′,2′‐d]pyridine
Authors: Gronowitz Salo , Hörnfeldt Anna‐Britta , Temciuc Ecaterina
Published: March 2009

The 3‐position of dithieno[3,4‐b:3′,2′‐d]pyridine was found to be most reactive with regard to lithiation, bromination and halogen‐metal exchange. The lithium compounds were trapped as the formyl derivatives by reaction with N,N‐dimethylformamide.
The investigation of the mannich reaction of 4,5‐dimethyl‐1,2‐dithiole‐3‐thione
Authors: Vaccher Claude , Berthelot Pascal , Debaert Michel
Published: March 2009

4,5‐Dimethyl‐1,2‐dithiole‐3‐thione 1 reacts with primary amines and formaldehyde to give the mono‐, retro‐, bis‐Mannich bases in moderate yield.
Synthesis of 3‐alkoxycarbonylaminomethylcarbonylamino‐4‐benzoyl‐1,2‐dihydropyridines and their cyclization to 5‐phenyl‐1,3,8,9‐tetrahydro‐2H‐pyrido[3,4‐e]‐1,4‐diazepin‐2‐ones
Authors: Fiakpui Charles Y. , Arora Vinod K. , Knaus Edward E.
Published: March 2009

The regiospecific reaction of 3‐benzyloxycarbonylaminomethylcarbonylamino‐4‐benzoylpyridine (6a), or 3‐t‐butoxycarbonylaminomethylcarbonylamino‐4‐benzoylpyridine (6b), with either acetyl chloride or ethyl chloroformate, and either n‐butylmagnesium chloride or phenylmagnesium bromide afforded the respective 1‐acetyl (or ethoxycarbonyl)‐2‐n‐butyl (or phenyl)‐3‐benzyloxy (or t‐butoxy) carbonylaminomethylcarbonylami‐no‐4‐benzoyl‐1,2‐dihydropyridines 7 in 60‐75% yield. Reaction of 1‐acetyl (or ethoxycarbonyl)‐2‐n‐butyl (or phenyl)‐3‐t‐butoxycarbonylaminomethylcarbonyl‐4‐benzoyl‐1,2‐dihydropyridines 7b, 7f, 7d, 7h with trifluoroacetic acid gave the corresponding 5‐phenyl‐8‐acetyl (or ethoxycarbonyl)‐9‐n‐butyl (or phenyl)‐1,3,8,9‐tetrahydro‐2H‐pyrido[3,4‐e]‐1,4‐diazepin‐2‐ones 8a, 8b, 8c, 8d respectively in 45–63% yield. N1‐Methylation of 5‐phenyl‐8‐acetyl‐9‐n‐butyl (or phenyl)‐1,3,8,9‐tetrahydro‐2H‐pyrido[3,4‐e]‐1,4‐diazepin‐2‐ones 8a, 8b using sodium hydride and iodomethane yielded the corresponding N1‐methyl derivatives 9a (48%) and 9b (54%). Oxidation of 5,9‐diphenyl‐8‐ethoxycarbonyl‐1,3,8,9‐tetrahydro‐2H‐pyrido[3,4‐e]‐1,4‐diazepin‐2‐one (8d) using p‐chloranil afforded 1,3‐dihydro‐5,9‐diphenyl‐2H‐pyrido[3,4‐e]‐1,4‐diazepin‐2‐one (10). 5‐Phenyl‐8‐acetyl‐9‐n‐butyl‐1,3,8,9‐tetrahydro‐2H‐pyrido[3,4‐e]‐1,4‐diazepin‐2‐one (8a) and the corresponding 8‐ethoxycarbonyl analog 8c exhibited weak anticonvulsant activity indicating that 8a and 8c may be acting at the same site as the 7‐halo‐1,4‐benzodiazepin‐2‐one class of compounds.
Structural study of methyl 2,6‐diphenyl‐N‐methyl‐4‐oxopiperidine‐3,5‐dicarboxylate enolic forms
Authors: Fernàndez M. J. , Casares J. M. , Gálvez E. , Bellanato J.
Published: March 2009

The methyl 2,6‐diphenyl‐1‐methyl‐4‐oxopiperidine‐3,5‐dicarboxylates 1 were synthesized by the Mannich procedure from methyl 3‐oxoglutarate, benzaldehyde and methylamine. Keto‐enol tautomerism as well as configurational isomerism at C‐2 were observed. The stereochemistry of the Ib and Ic enolic forms were determined by 1H and 13C nmr data.
Studies on pyrrolidinones. Synthesis of 2‐(5‐oxo‐2‐pyrrolidinyl)‐1,3,4‐oxadiazoles and 2‐(5‐oxo‐2‐pyrrolidinyl)benzimidazoles
Authors: Cauliez Pascal , Couturier Daniel , Rigo Benoît , Fasseur Dominique , Halama Patrice
Published: March 2009

The condensation of pyroglutamic acids with 1,2‐phenylenediamine leads to 2‐(5‐oxo‐2‐pyrrolidinyl)benzimidazoles and the cyclization of disilylated diacylhydrazines derived from the same acids gives 2‐(5‐oxo‐2‐pyrrolidinyl)‐1,3,4‐oxadiazoles. These compounds show weak antifungal activity.
Studies related to alkylations of enolate anions of 1,4‐benzodiazepinones
Authors: Fryer R. Ian , Pinto Julia C. , Upasani Ravindra B.
Published: March 2009

Treatment of 1,4‐benzodiazepinone derivatives with a Wittig‐Horner reagent, led to the desired carboncarbon bond formation at the amide carbonyl carbon atom in reasonable yield. An examination of this reaction has shown that only secondary amides can be used, indicating that this process requires the amide proton. This observation would exclude the accepted mechanism for Wittig‐Horner type reactions (four membered spiro ring intermediate), and an alternate mechanism, that involves cleavage of the anion prior to addition of the reagent to substrate is proposed.
Natural product chemistry. Part 158. Reactions of ethyl 4‐hydroxy‐1‐methyl‐3‐quinolin‐2(1H)‐onecarboxylate with 1,4‐dibromo‐2‐methyl‐2‐butene
Authors: Reisch Johannes , Iding Marlies , Von Bassewitz Ingo
Published: March 2009

Ethyl 4‐hydroxy‐1‐methyl‐3‐quinolin‐2(1H)‐onecarboxylate (1) which is obtained conveniently by the condensation of N‐methylisatoic anhydride with diethyl malonate [4], was reacted with 1,4‐dibromo‐2‐methyl‐butene (2) to give the main products 3 and 4 and the dimeric derivatives 5 and 6.
Polycyclic N‐heterocyclic compounds. XLV. Synthesis of 4‐substituted 5,6‐dihydrobenzo[h]quinazolines and 6,7‐dihydro‐5H‐benzo[6,7]cyclohepta[1,2‐d]pyrimidines and their inhibitory activity on platelet aggregation
Authors: Sasaki Kenji , Sekiya Yuhki , Fujiwara Hideko , Ohtomo Hiromi , Nakayama Taiji , Hirota Takashi
Published: March 2009

The synthesis of 4‐substituted 5,6‐dihydrobenzo[h]quinazolines and 6,7‐dihydro‐5H‐benzo[6,7]cyclohepta‐[1,2‐d]pyrimidines with substituents which are an electron‐attracting group such as a nitrite, an amide, a thione, or a carboxyl group is described. Their inhibitory activity against collagen‐induced platelet aggregation was also investigated.
Synthesis of 5‐substituted 1‐aryl‐1H‐pyrazole‐4‐acetonitriles, 4‐methyl‐1‐phenyl‐1H‐pyrazole‐3‐carbonitriles and pharmacologically active 1‐aryl‐1H‐pyrazole‐4‐acetic acids
Authors: Menozzi Giulia , Schenone Pietro , Mosti Luisa , Mattioli Franceses
Published: March 2009

Lithium aluminum hydride reduction of 5‐substituted or unsubstituted ethyl or methyl 1‐aryl‐1H‐pyrazole‐4‐carboxylates gave, generally in excellent yields, 5‐substituted or unsubstituted 1‐aryl‐1H‐pyrazole‐4‐methanols which afforded the corresponding 1‐aryl‐4‐(bromomethyl)‐1H‐pyrazoles with hydrobromic acid in acetic acid solution. These crude intermediates gave by reaction with potassium cyanide in dimethylsulfoxide solution 1‐aryl‐1H‐pyrazole‐4‐acetonitriles only in the case of 5‐unsubstituted compounds, otherwise mixtures of 5‐substituted 1‐aryl‐1H‐pyrazole‐4‐acetonitriles and 4‐methyl‐1‐phenyl‐1H‐pyrazole‐3‐carbonitriles were generally obtained. Acetonitriles IIIa,b,i,l gave in excellent yields the corresponding 1‐aryl‐1H‐pyrazole‐4‐acetic acids Va,b,i,l by alkaline hydrolysis. Compounds Vb,i,l showed in the writhing test appreciable analgesic properties, associated with low acute toxicity; moreover, compound VI exhibited a statistically significant antiinflammatory activity in the carrageenan‐induced edema assay.
Synthesis of new 4‐quinolone‐type compounds in the benzo[b]thiophene series
Authors: Février B. , Dupas G. , Bourguignon J. , Quéguiner G.
Published: March 2009

Some new derivatives of 1,4‐dihydro‐4‐oxo‐3‐pyridinecarboxylic acid (quinolone‐type compounds) 5 and 13 have been prepared in the benzo[b]thiophene series. The key step was the construction of the pyridine ring starting from 2‐aminobenzo[b]thiophene derivatives. The synthesis of amine 9, was performed by using an original “animation” reaction.
Electron impact ionization mass spectra of 2,4,5,5‐tetrasubstituted 1,2,4‐triazolidine‐3‐thiones. The effect of the ethoxycarbonyl group at position 4
Authors: Mäki Esa , Pihlaja Kalevi , Schulze Klaus , Richter Christian
Published: March 2009

The electron impact ionization mass spectra of 2,4,5,5‐tetrasubstituted 1,2,4‐triazolidine‐3‐thiones studied confirmed that the substituent at position 4 has the most dramatic influence on the fragmentation pattern. When the substituent is a methylallyl group the molecular ions exhibit four main routes of fragmentation, but when it is an ethoxycarbonyl/acetyl or a methyl group these direct decompositions of the molecular ion become less abundant. Interestingly all 4‐ethoxycarbonyl derivatives and the 4‐acetyl derivative exhibited the ions [M‐R4‐COOC2H4]+ and [M‐R4‐COCH2]+, respectively, with the same composition.
Michael addition of N‐isobutylidene‐t‐butylamine to dimethyl methoxymethylenemalonate and a new synthesis of some fused pyrazole derivatives from the adduct
Authors: Ito Kunio , Ihara Shogo , Miyajima Shingo
Published: March 2009

N‐Isobutylidenemethylamine reacted with dimethyl methoxymethylenemalonate to afford the N‐alkylation product 3a exclusively. Exchanging the N‐substituent of the Schiff's base from methyl to t‐butyl altered the course of the reaction, allowing Michael addition to take place predominantly. The Michael adduct 4c on reaction with hydrazinoalkanols 6a,b, 6c,d and 6e gave tetrahydropyrazolo[5,1‐b]oxazoles 9a,b, tetrahydro‐pyrazolo[5,1‐b][1,3]oxazines 9c,d and hexahydropyrazolo[5,1‐b][1,3]oxazepine 9e, respectively.
Cycloaddition behavior of 3,4‐diazacyclopentadienone dioxides toward bicyclo[2.2.1]heptadiene derivatives. X‐ray analysis of the cycloadduct and reaction pathway
Authors: Eto Masashi , Harano Kazunobu , Yoshitake Yasuyuki , Hisano Takuzo
Published: March 2009

The cycloaddition behavior of 2,5‐disubstituted 3,4‐diazacyclopentadienone dioxide 1a‐c toward epoxy‐naphthalene (2a) and norbornadiene (2b) was investigated. The structures of the products were determined on the basis of the 1H‐ and 13C‐nmr spectral data and the X‐ray analysis data. The stereospecific formation of the endo‐exo 1,3‐dipolar cycloadducts from 2a indicates that the cycloadduct resulted from the direct 1,3‐dipolar cycloaddition. The cycloaddition behavior of 1 toward 2 is discussed on the basis of the PM3‐calculated transition‐state structures.
Bathochromic 1‐amino‐2(1H)‐pyrimidinimines and hydrazones by substitution/dimroth rearrangement of 1‐amino‐2‐methylthiopyrimidinium salts
Authors: Riemer Beate , Hassoun Ahmed , Liebscher JÜRgen , Jones Peter G. , Chrapkowski Axel
Published: March 2009

1‐Amino‐2‐methylthiopyrimidinium salts 1 and 9 react with hydrazines 2 or alkylamines 6 by substitution of the methylthio group and Dimroth rearrangement affording violet or purple 2(1H)‐pyrimidinehydrazones 5 and 7 or orange hydrazones 8, rather than the non‐rearranged hydrazones 10 or zwitterionic 1‐amido‐2‐hydrazinopyrimidinium ylides 4 as previously reported.
A synthetic route to 3‐(dialkylamino)phenothiazin‐5‐ium salts and 3,7‐disubstituted derivatives containing two different amino groups
Authors: Strekowski Lucjan , Hou Dong‐Feng , Wydra Roman L. , Schinazi Raymond F.
Published: March 2009

Phenothiazin‐5‐ium tetraiodide hydrate (2), the suggested oxidation product of phenothiazine with iodine, is treated with two equivalents of a dialkylamine to give 3‐(dialkylamino)phenothiazin‐5‐ium triiodides, 3‐6. 3,7‐Disubstituted phenothiazin‐5‐ium iodides, 7‐9, are obtained by the reaction of 3‐6 with an amine.
New quinoxalines with nitrogen functions in the side chain. Potential inhibitors of 5‐HT3
Authors: Monge A. , Palop J. A. , Del Castillo J. C.
Published: March 2009

Starting with benzofuroxane1, 2‐ethoxy‐carbonyl‐3‐methylquinoxaline 1,4‐dioxide7is obtained. From this compound different amides5a‐qand amino esters6a‐care obtained. From 2‐amino‐3‐cyanoquinoxaline 1,4‐dioxide7, new amidines9, [5,4‐b]pyrimido10and [6,5‐b]diazepinoquinoxalines11were prepared.
Unusual schmidt rearrangement of 7,7a,8,9,10,12‐hexahydro benzo[h]pyrrolo[1,2‐b]‐isoquinoline‐7,10‐dione
Authors: Mérour Jean‐Yves , Piroëlle Simone , Faure Robert
Published: March 2009

The reaction of 7,7a,8,9,10,12‐hexahydrobenzo[h]pyrrolo [1,2‐b]isoquinoline‐7,10‐dione 2 with sodium azide in sulfuric acid afforded the unexpected cyano derivative 5. The proposed structure for 5 is supported by 13C nmr, 1H nmr and HMBC spectra.
The synthesis of β‐heteroarylamino‐α,β‐dehydro‐α‐amino acid derivatives via thiazolones
Authors: Smodiŝ Janez , Stanovnik Branko , Tiŝler Miha
Published: March 2009

2‐Alkoxy‐4‐heteroarylaminomethylene‐5(4H)‐thiazolones 4 were converted with various nucleophiles into β‐heteroarylamino‐α,β‐dehydro‐α‐amino acid derivatives 11, 14, 15, 16, 17, 18, and 19. Reduction of 4 with sodium borohydride in ethanol saturated with gaseous ammonia afforded the corresponding β‐heteroaryl‐amino substituted alanyl amides 20. Thiazoledione derivative 7a was transformed with sodium methoxide in methanol into 1‐(4,6‐dimethylpyrimidinyl‐2)‐4‐mercaptocarbonylimidazol‐2(3H)‐one (8a).
Reaction of 5‐aminopyrazole derivatives with ethoxymethylene‐malononitrile and its analogues
Authors: Nagahara Katsuhiko , Kawano Hiroko , Sasaoka Shinji , Ukawa Chisa , Hirama Tamaki , Takada Atsushi , Cottam Howard B. , Robins Roland K.
Published: March 2009

A one‐pot synthesis using 5‐aminopyrazole derivatives 1 with ethoxymethylenemalononitrile (EMMN), ethyl ethoxymethylenecyanoacetate (EMCA) or diethyl ethoxymethylenemalonate (DEMM) gave pyrazolo‐[1,5‐a]pyrimidine compounds 2,4,8. Also, the one step reaction of EMCA with hydrazine hydrate afforded ethyl(4‐ethoxycarbonyl‐5‐pyrazolyl)aminomethylenecyanoacetate 3c. On the other hand, the reaction of 1‐substituted 5‐aminopyrazole‐4‐carboxamide 9 with EMMN afforded pyrazolo[3,4‐d]pyrimidine compounds 10.
Regioselective acetylation of some N‐methylpyrrole derivatives with isopropenyl acetate and different acetic anhydrides
Authors: Gizur Tibor , Harsányi KÁLmán
Published: March 2009

We studied the reactions of some N‐methylpyrrole derivatives with isopropenyl acetate and different acetic anhydrides. We have found that the reaction with isopropenyl acetate afforded 5‐acetylpyrrole derivatives while with acetic anhydrides acetylation occurred on the α‐carbon atom of the side‐chain of pyrrole‐2‐acetic acid derivatives.
Synthesis of a 2,5‐diaryloxazoline as a potential platelet‐activating factor antagonist
Authors: Peet Norton P. , Burkhart Joseph P. , Broersma Robert J. , Heminger Eileen F.
Published: March 2009

2,5‐Bis‐(3,4,5‐trimethoxyphenyl)‐2‐oxazoline (5, MDL 100,270) was designed as a potential platelet‐activating factor (PAF) antagonist on the basis of computer modeling comparison studies with known PAF antagonists. An efficient, four‐step synthesis of oxazoline5was developed, starting from 3,4,5‐trimethoxybenzaldehyde (6). Oxazoline5was found to inhibit the PAF‐induced aggregation of human platelets with an IC50value of 708 μM.