bluuebunny/crossref_metadata_2025 huggingface dataset:
Polycyclic pyridazines. II [3]. Synthesis of pyrazolo[4′,3′:5,6]pyrido[2,3‐d]pyrid‐azine derivatives from dimethyl pyrazolo[3,4‐d]pyrid‐azine‐5,6‐dicarboxylates as the key intermediates
Authors: Tominaga Yoshinori , Luo Jiann‐Kuan , Castle Lyle W. , Castle Raymond N.
Published: March 2009

The synthesis of the novel pyrazolo[4′,3′:5,6]pyrido[2,3‐d]pyridazine ring system and some of its derivatives has been accomplished such as 4‐amino‐1‐phenyl‐5,8‐dioxo‐, 4‐amino‐5,8‐dioxo‐, 1‐phenyl‐5,8‐dioxo‐, 5,8‐dioxo‐, 5,8‐dichloro‐1‐phenyl‐, 5‐ethoxy‐1‐phenyl‐ and 8‐ethoxy‐1‐phenylpyrazolo[4′,3′:5,6]pyrido[2,3‐d]pyrid‐azines.
A convenient synthesis of the thieno[3,2‐c]pyridine nucleus
Authors: Wikel James H. , Denney Michael L. , Vasileff Robert T.
Published: March 2009

The unsubstituted thieno[3,2‐c]pyridine ring system was prepared from thiophene‐3‐carboxaldehyde in 4 steps. The sequence is suitable for scale‐up.
Nucleic acid related compounds. 81. Syntheses of 9‐(3‐deoxy‐β‐D‐threo‐pentofuranosyl)adenine, the core nucleoside of the extraordinarily selective antibiotic agrocin 84, and simplified structural component analogues
Authors: Vinayak Ravi , Hansske Fritz , Robins Morris J.
Published: March 2009

Alternative syntheses of 9‐(3‐deoxy‐β‐D‐threo‐pentofuranosyl)adenine (4), the core nucleoside of agrocin 84 [and its 2′‐deoxy threo isomer 5] were devised: (1) direct conversion of 9‐(β‐D‐arabinofuranosyl)adenine into 9‐(2,3‐anhydro‐β‐D‐lyxofuranosyl)adenine and regioselective opening of its oxirane ring with sodium borohy‐dride to give 4 and 5(˜7.5:1); (2) treatment of adenosine with sodium hydride and 2,4,6‐triisopropylbenzene‐sulfonyl chloride, and subjection of the resulting 2′(3′)‐sulfonates to the reductive [1,2]‐hydride shift rearrangement with lithium triethylborohydride to give 4 and 5 (˜ 2:1); and (3) subjection of the phenoxythiocar‐bonyl esters of 9‐[2(3),5‐bis‐O‐(tert‐butyldimethylsilyl)‐β‐D‐arabinofuranosyl]adenine to Barton deoxygenation, and deprotection to give 4 and 2′‐deoxyadenosine (˜5:1). Methods (2) and (3) gave lower yields. Syntheses of simplified 6‐N‐ and 5′‐O‐adenosine phosphoramidate model compounds were explored to examine potential access to such features in the structure proposed for agrocin 84.
Triazolines 24. Permanganate‐catalyzed low temperature thermolysis of 5‐(4‐pyridyl) substituted 1,2,3‐triazolines
Authors: Kadaba Pankaja K. , Parmley Gordon , Crooks Peter A. , Agha Bushra
Published: March 2009

Potassium permanganate oxidation of 1‐aryl‐5‐(4‐pyridyl)‐1,2,3‐triazolines I in a benzene‐water two‐phase system using the phase‐transfer catalyst tetrabutylammonium chloride yields the corresponding 1H‐1,2,3‐tri‐azoles II. However, when the reaction is run in a single phase in anhydrous benzene alone, the products are not triazoles, but imines III that can normally be obtained only by high‐temperature thermolysis of the tri‐azolines. The presence of both potassium permanganate and tetrabutylammonium chloride to yield the benzene soluble tetrabutylammonium permanganate ion pair appears essential for imine formation, although only in catalytic amounts. Thus a reaction pathway is proposed, which involves the initial coordination of the pyridyl nitrogen with the manganese atom of the permanganate ion leading to IV, followed by loss of nitrogen and regeneration of the permanganate ion via the dihydropyridine intermediates, V and VI, to yield the enamine VII, which tautomerizes to the imine III. Supportive evidence for the formation of IV is derived from the failure of 1,5‐diaryl‐ and l‐aryl‐5‐(3‐pyridyl)triazolines to yield the respective imines; they lack the structural requirements necessary to comply with the proposed mechanism, and are recovered unchanged. Unlike the high temperature pyrolysis, the permanganate catalyzed low temperature thermolysis reactions provide cleaner products in better yields. Thus, the low temperature thermolysis may afford a route for the synthesis of clean samples of l‐arylimino‐l‐ethyl‐4‐pyridines, especially when the triazolines are on hand.
Purines. XIV. Synthesis and properties of 8‐nitroxanthine and its N‐methyl derivatives
Authors: Mosselhi Mosselhi A. , Pfleiderer Wolfgang
Published: March 2009

Xanthine (1) and its N‐methyl derivatives 2–16 have been nitrated to the corresponding 8‐nitro derivatives 17–32 under different reaction conditions. Nitration in glacial acetic acid with nitric acid works well with the N‐7 unsubstituted and some of the 9‐methylxanthines, respectively, whereas the 7‐methylxanthine derivatives react best with nitronium tetrafluoroborate in sulfolane or glacial acetic acid. The 8‐nitro group can be displaced nucleophilically to form 8‐chloro‐, 33, 34, 8‐ethoxy‐, 35,36, and uric acid derivatives 37–40, respectively. The newly synthesized 8‐nitroxanthines have been characterized by elemental analyses, pK‐determinations and uv and 1H‐nmr spectra.
Preparation of oxazolidin‐2‐ones by oxidation of oxazolidine‐2‐thiones. A proton magnetic resonance structural study
Authors: Moreno‐Mañas Marcial , Padros Imma
Published: March 2009

The preparation of a series of oxazolidine‐2‐thiones, both homochiral and racemic, as well as their oxidation to oxazolidin‐2‐ones is reported. X‐Ray and pmr studies have showed that the stereochemical integrity of the starting aminoalcohol is maintained.
Pyrimidines. 24. Analogues and derivatives of 2‐amino‐5‐bromo‐6‐phenyl‐4(3H)‐pyrimidinone (ABPP)
Authors: Fan Junyuan , Cheng C. C.
Published: March 2009

Preparation of a number of derivatives of 2‐amino‐5‐bromo‐6‐phenyl‐4(3H)‐pyrimidinone (ABPP) including the 2‐dialkylaminoalkylamino‐, 2‐hydroxyalkylamino‐, 2‐ethoxycarbonylamino‐ and 2‐alkylaminocarbonyl‐amino‐ groups substituted on the pyrimidine ring as well as preparation of 1‐(alkylaminoalkyl)‐4,6‐dioxo‐8‐phenyl‐2,3,4,6‐tetrahydro‐1H‐pyrimido[1,2‐α]pyrimidines and 3,5‐dioxo‐7‐phenyl‐1,2,3,5‐tetrahydroimidazo‐[1,2‐α]pyrimidines with or without the bromo‐substitution are reported.
Synthesis of a new series of 8‐substituted‐2,8‐diazaspiro[4.5]decan‐3‐ones
Authors: Cignarella Giorgio , Villa Stefania , Barlocco Daniela
Published: March 2009

A new series of 8‐substituted‐2,8‐diazaspiro[4.5]decan‐3‐ones has been synthesized and tested inin vitroandin vivoassays predictive for cholinergic activity, in comparison with the muscarinic agent RS‐86. Preliminary pharmacological data indicate that the compounds are devoid of significant cholinergic properties.
A highly regioselective reaction of N‐fluoropyridinium salts with stabilized sulfur, oxygen, and nitrogen nucleophiles: A convenient route to 2‐substituted pyridines
Authors: Kiselyov Alexander S. , Strekowski Lucjan
Published: March 2009

2‐Substituted pyridines are efficiently obtained by the reactions of N‐fluoropyridinium tetrafluoroborate or triflate with anions derived from benzenethiols, phenols, azoles, cyanamide, and with azide anion. The results are consistent with a nucleophile addition at the position 2 of the N‐fluoropyridinium cation as the major reaction pathway.
Synthesis of imidazo[1,2‐b]pyridazines: Fenbendazole, oxifenbendazole analogs and related derivatives
Authors: Mourad Alaa E. , Wise Dean S. , Townsend Leroy B.
Published: March 2009

A series of imidazo[1,2‐b]pyridazines has been prepared and evaluated for macrofilaricidal activity against Brugia pahangi or Acanthocheilonema viteae infections in jirds. The imidazo[1,2‐b]pyridazine analogs of fen‐bendazole and oxifenbendazole are reported. In addition, several 6‐aminoimidazo[1,2‐b]pyridazine derivatives have been prepared. None of these compounds possessed significant activity against human cytomega‐lovirus (HCMV) or filarial infections.
Synthesis of 2′‐deoxyguanosine containing a N2‐polyamine
Authors: Ramasamy Kanda S. , Bakir Farid , Baker Brenda , Dan Cook P.
Published: March 2009

The synthesis of benzylated N2‐(4,7,10,13‐tetraazatridec‐1‐yl)‐2′‐deoxyguanosines 4 was accomplished by a key nucleophilic reaction of the novel unsymmetrical polyamine 2, with 3′,5′‐O‐(tetraisopropyldisiloxane‐1,3‐diyl)‐2‐chloro‐2′‐deoxyinosine (1).
The synthesis of several imidazo[4,5‐d]isothiazoles. Derivatives of a new ring system
Authors: Swayze Eric E. , Townsend Leroy B.
Published: March 2009

Several derivatives of the new imidazo[4,5‐d]isothiazole ring system have been synthesized from the appropriately substituted isothiazolediamines. The reaction of 3‐methyl‐4,5‐diaminoisothiazole (4a) with diethoxy‐methyl acetate gave a low yield of 3‐methylimidazo[4,5‐d]isothiazole (5a). However, the analogous reaction of 4,5‐diaminoisothiazole (4b) with diethoxymethyl acetate failed to yield the parent imidazo[4,5‐d]isothiazole ring system. The diamines 4a and 4b were readily cyclized with thiocarbonyldiimidazole to give the unstable thiones 6a and 6b, which were alkylated in situ to afford good yields of the corresponding 5‐methylthioimidazo[4,5‐d]isothiazoles 7a and 7b, respectively. Neither of these compounds could be reduced to the corresponding 5‐unsubstituted derivatives via treatment with Raney nickel. To the best of our knowledge, this is the first report of the imidazo[4,5‐d]isothiazole ring system.
Azidocarbonyl‐substituted cubanoureas
Authors: Gilardi Richard , George Clifford , Karle Jerome , Eaton Philip E. , Rao Munagala
Published: March 2009

Despite the angular strain associated with the assembly of small rings, 1,2‐diisocyanatocubane reacts with trimethylsilyl azide under mild conditions to form a hexacyclic ring assembly that contains an imidazolidone ring fused to one edge of cubane. This compound was identified as an azidocarbonyl‐substituted cubanourea by means of X‐ray crystal structure analysis of the nitro‐derivative, the energetic compound N‐azidocarbonyl‐N1‐nitrocubanourea.
Cyclopentene carbocyclic nucleosides related to the antitumor nucleoside clitocine and their conversion to 8‐Aza‐neplanocin analogues. Synthesis and antiviral activity
Authors: Marquez Victor E. , Lim Benjamin B. , Driscoll John S. , Snoek Robert , Balzarini Jan , Ikeda Satoru , Andrei Graciela , De Clercq Erick
Published: March 2009

Synthesis of the cyclopentene carbocyclic analogue of the naturally occurring nucleoside clitocine (1) is reported. Starting with racemic cyclopentenylamine (10), the heterocyclic moieties of the clitocine analogue 4 and related 1,6‐dihydro‐6‐oxo, 5, and 2‐amino‐1,6‐dihydro‐6‐oxo, 6, analogues were constructed. These compounds were respectively converted to 8‐aza‐neplanocin A (7), 8‐aza‐neplanocin D (8, the inosine analogue), and the corresponding 8‐aza‐guanosine analogue 9 after reduction of the nitro group followed by nitrous acid cyclization. Extensive antiviral evaluation revealed that only 8‐aza‐neplanocin A (7) had enough antiviral activity to warrant further studies. This compound showed weak antiviral activity against HSV‐1, HSV‐20 and the thymidine kinase deficient (TK‐) HSV‐1. However, it displayed good antiviral activity against human cytomegalovirus (HCMV) at a concentration of 0.40–2.50 μg/ml, well below the cytotoxicity threshold. This activity profile is consistent with a mechanism of action involving the inhibition of the enzyme adenosylhomo‐cysteine hydrolase.
Synthesis of a new class of uridine phosphorylase inhibitors
Authors: Levesque Diane L. , Wang Eng‐Chi , Wei Dau‐Chang , Tzeng Cherng‐Chyi , Panzica Raymond P. , Naguib Fardos N. M. , El Kouni Mahmoud H.
Published: March 2009

A new series of potent uridine phosphorylase inhibitors have been prepared from barbituric acid. Among them, 1‐[(2‐hydroxyethoxy)methyl]‐5‐)(m‐‐benzyloxy)benzylbarbituric acid (37, BBBA) is the most promising having a Kivalue of 1.1 ± 0.2 nMwith uridine phosphorylase from human liver. The new inhibitors are easily synthesized and are better inhibitors of human uridine phosphorylase than their uracil counterparts.
Chlorine substituent effects for indole and tryptophan in 13C NMR
Authors: Lee Minsu , Phillips Robert S.
Published: March 2009

The 13C and 1H nmr spectra of chloroindoles and chlorotryptophans in methanol‐d4 were assigned based on 1‐D and 2‐D nmr techniques, including COSY, inverse‐detected direct (HMQC) and long‐range (HMBC) correlation. Chlorine substitutent effects in chemical shifts (SCS) for chlorotryptophans and chloroindoles were calculated and compared. The correlations were linear except for 4‐chlorotryptophan, which suggests structural changes on the indole ring between 4‐chlorotryptophan and 4 chloroindole. The conformational analysis based on the coupling constants of the side chain also showed a change in the fractional population of the rotamers between 4‐chlorotryptophan and the other chlorotryptophans.
New routes to selectively methylated benzimidazoles
Authors: Katritzky Alan R. , Rachwal Stanislaw , Ollmann Richard
Published: March 2009

The use of intermediate benzotriazol‐l‐yl derivatives simplified the procedures for the preparation of 5‐methoxy‐l‐methylbenzimidazole and 6‐methoxy‐l‐methylbenzimidazole starting from 4‐methoxy‐2‐nitro‐aniline. This strategy represents a novel and potentially general method for synthesis of 5‐ and 6‐substituted‐l‐methylbenzimidazoles from 4‐substituted anilines. Preparation of l‐methyl‐5‐nitrobenzimidazole by reaction of 2‐chloro‐5‐nitroaniline with methylamine and condensation of the obtained diamine with formic acid represents a special case.
Synthesis of pyrrolo[2,1‐f][1,2,4]triazine congeners of nucleic acid purines via the N‐amination of 2‐substituted pyrroles
Authors: Patil Shirish A. , Otter Brian A. , Klein Robert S.
Published: March 2009

The synthesis of several new 4‐mono‐ and 2,4‐disubstituted pyrrolo[2,1‐f][1,2,4]triazines is described. Key 1‐aminopyrrole‐2‐carbonitrile intermediates 3 and 15 were obtained by N‐amination of the corresponding pyrrole‐2‐carboxaldehyde followed by CHO → CN conversion with either hydroxylamine‐O‐sulfonic acid for 3 or O‐mesitylenesulfonylhydroxylamine for 15. Cyclization of 3 or 15 with a variety of amidine reagents or, after conversion of 3 to its corresponding amide, base‐catalyzed annulation completed the synthesis of the title products.
Syntheses for 2‐hydroxy‐2H‐1,4‐benzothiazin‐3(4H)‐one derivatives as thio analogues of natural hemiacetals
Authors: Sicker Dieter , Hartenstein Holger , Hazard Roland , Tallec André
Published: March 2009

Reductive cyclizations of methyl 2‐(2‐nitrophenylthio)acetate 2 by means of electrochemistry or by catalytic hydrogenation have been used as key steps in the syntheses of the hemiacetals 2‐hydroxy‐2H‐1,4‐benzothiazin‐3(4H)‐one 10 and its 4‐hydroxy derivative 9 representing thio analogues of allelo chemicals found in Gramineae and Acanthaceae. In contrast to its natural counterpart 2,4‐dihydroxy‐2H‐1,4‐benzoxa‐zin‐3(4H)‐one hydroxamic acid 9 did not undergo degradation by extrusion of formic acid.
Chromatographic and spectroscopic properties of regioisomers of some 1H‐1,5‐benzodiazepines
Authors: Vianna‐Rodrigues S. , Martins‐Viana L. , Quiroga J. , Insuasty B. , Abonia R. , Baumann W.
Published: March 2009

The separation of the two regioisomeric derivatives of 1H‐1,5‐benzodiazepine yielded from the reaction of 1,2‐diamino‐4‐methylbenzene with 4‐substituted acetophenones was performed by reversed phase high performance liquid chromatography, and the absorption spectra of the separated isomers have been determined for three isomer pairs which have been obtained starting from acetophenones with substituents of different electronegativity. The isomer ratio then could be estimated as well from the ratio of the peak areas as from the absorption spectra. They agree well with the known ratio determined from nmr intensities.
Studies on pyrrolidones. Synthesis and reactivity of β‐enaminomono‐esters and β‐enaminomononitriles derived from pyroglutamic acid
Authors: Fasseur Dominique , Cauliez Pascal , Couturier Daniel , Rigo Benoît , Defretin Sebastien
Published: March 2009

In the pyroglutamic acid series, β‐enaminoesters 3 were formed in the 2‐position by opening of the corresponding Meldrum's derivative 6, and β‐enaminonitriles 4 were obtained by treating carbamate vinylogous 5 by trimethytsilyl iodide. Alkylation and acylation of β‐enaminoester 3a was briefly examined.
Diels‐alder reactivity of vinylsulfoxyallenes
Authors: Wang Xiaoheng , Donovalova Jana , Hollis Andrea , Johnson Dexter , Rodriguez Augusto , Kennedy G. Davon , Krishnan Ganapathy , Banks Harold
Published: March 2009

Vinylsulfoxyallenes 3a‐c are prepared from propargylic alcohols in 47‐65% yield. Vinylsulfoxyallenes undergo facile [4 + 2] cycloadditions with methyl triazolidenedione (MTAD) and singlet oxygen to afford phenylsulfinylpyridazines and spirocyclic phenylsulfinyl‐2H‐pyran‐3(6H)‐ones in excellent yields (60‐90%). Spirocyclic phenylsulfinyl‐2H‐pyran‐3(6H)‐ones are oxidized to the corresponding phenylsulfones with peracid or can be epoxidized with basic hydrogen peroxide. Spirocyclic pyranone formation is thought to proceed via the rearrangement of a labile cyclic peroxide intermediate 14.
Aminothiazole derivatives. I. A convenient synthesis of monocyclic and condensed 5‐aminothiazole derivatives
Authors: Uchikawa Osamu , Fukatsu Kohji , Aono Tetsuya
Published: March 2009

Treatment of diamides derived from α‐amino acids with phosphorus pentasulfide or Lawesson's reagent was shown to provide a convenient method to prepare 5‐aminothiazoles. By this method, in addition to mono‐cyclic 5‐aminothiazoles 19, novel bicyclic 5‐aminothiazole derivatives such as 4,5,6,7‐tetrahydrothiazolo[5,4‐b]pyridines 11, 5,6,7,8‐tetrahydro‐4H‐thiazolo[5,4‐b]azepines 7, 4,5,6,7,8,9‐hexahydrothiazolo[5,4‐b]azocine 16 and related compounds were prepared in moderate to good yields from simple diamides, suggesting the wide versatility of the method.
3‐Oxo‐4,4,4‐trifluorobutyronitriles as building blocks of trifluoromethyl substituted heterocycles 2. Heterocyclization to 3‐aryl‐4‐trifluoromethyl‐2H‐1‐benzopyran‐2‐ones under hoesch reaction conditions
Authors: Nishiwaki Tarozaemon , Kikukawa Hirofumi
Published: March 2009

Resorcinol and 5‐methylresorcinol, respectively, react with 3‐oxo‐2‐aryl‐4,4,4‐trifluorobutyronitrile using zinc chloride as a catalyst in dibutyl ether under the Hoesch reaction conditions to give a low yield of 3‐aryl‐7‐hydoxy‐4‐trifluoromethyl‐ or 3‐aryl‐5‐hydroxy‐7‐methyl‐4‐trifluoromethyl‐2H‐l‐benzopyran‐2‐ones. However, the related reaction with m‐methoxyphenol was found to produce poor yields of 3‐aryl‐7‐methoxy‐4‐trifluoromethyl‐2H‐1‐benzopyran‐2‐one and its 3,4‐dihydro‐4‐hydroxy derivative.
Electron ionization mass spectra of some norbornane/ene‐fused 2‐N‐phenyliminoperhydro‐1,3‐oxazines
Authors: Partanen Tuula , Vainiotalo Pirjo , Stájer Géza , Pihlaja Kalevi
Published: March 2009

The 70 eV electron ionization (EI) mass spectra were recorded for eight norbornane/ene‐fused 2‐N‐phenyl‐iminoperhydro‐1,3‐oxazines, and the fragmentation patterns were studied by metastable ion analysis and exact mass measurement. Whereas the stereoisomeric unsaturated compounds could not be distinguished on the basis of their EI mass spectra, the stereoisomeric saturated compounds gave rise to clearly different spectra. The ionized unsaturated compounds decomposed mainly by two consecutive retro‐Diels‐Alder (RDA) reactions. A methyl substituent on the ring nitrogen strongly influenced the charge distribution on the RDA fragments. The ionized saturated compounds fragmented through several pathways. Loss of cyclopentadiene from the molecular ion was the energetically favoured fragmentation reaction for the saturated di‐endo‐fused compounds but was unimportant for the di‐exo‐fused compounds.
New thiophene derivatives as potential materials for non linear optics
Authors: Kirsch Gilbert , Prim Damien , Leising Frederic , Mignani Gerard
Published: March 2009

A method of synthesis of unsymmetrical 2,5‐diarylthiophenes is described using β‐chloroacroleins, prepared from acetophenones, and their condensation with sodium sulfide and various benzyl bromides.
Heterocycles with a benzothiadiazepine moiety. 3. Synthesis of imidazo[5,1‐d]pyrrolo[1,2‐b][1,2,5]benzothiadiazepine 9,9‐dioxide
Authors: Silvestri Romano , Artico Marino , Pagnozzi Eugenia , Stefancich Giorgio
Published: March 2009

The synthesis of imidazo[5,1‐d]pyrrolo[1,2‐b][1,2,5]benzothiadiazepine 9,9‐dioxide (5), a novel sulfur‐containing tetracyclic benzodiazepine, is reported starting from pyrrolo[1,2‐b][1,2,5]benzothiadiazepine 5,5‐diox‐ide (6) by cycloaddition of tosylmethyl isocyanide to the azomethine double bond. Pyrrolobenzothiadiazepine 6 was obtained by iron powder/acetic acid reduction of 1‐(2‐nitrobenzenefulfonyl)pyrrole‐2‐carboxaldehyde (7) and subsequent ring closure of intermediate aminoaldehyde or by cyclization of 1‐(2‐formamidobenzene‐sulfonyl)pyrrole (8) with phosphorus oxychloride via a Bischler‐Napieralski reaction. Formylation of 1‐(2‐ami‐nobenzenesulfonyl)pyrrole with acetic‐formic anhydride gave 8. The structure of 5 was confirmed by oxidation with activated manganese dioxide of dihydro derivative 9, obtained through cyclization of 11‐amino‐methyl‐10,11‐dihydropyrrolo[1,2‐b][1,2,5]benzothiadiazepine 5,5‐dioxide (10) with triethyl orthoformate. The last compound was prepared alternatively by catalytic reduction of nitro derivative 11, obtained by addition of nitromethane to pyrrolobenzothiadiazepine 6, or by lithium aluminum hydride/sulfuric acid reduction of amide 13, synthesized starting from ethyl 10,11‐dihydropyrrolo[1,2‐b][1,2,5]benzothiadiazepine‐11‐carboxyl‐ate 5,5‐dioxide.
Studies on the chemistry of thienoanellated O,N‐ and S,N‐containing heterocycles. 6. Synthesis of some thienoanellated [1,4]benzoxazepines
Authors: Laimer Ingrid , Erker Thomas
Published: March 2009

Substituted thieno[2,3‐b][1,4]benzoxazepine derivatives as well as thieno[3,2‐b][1,4]benzoxazepine deriva‐ tives have been synthesized. They are thienoanalogues of loxapine, a potent antipsychotic drug. Research activities concentrate on the preparation of structurally modified compounds of loxapine to minimize its undesirable extrapyramidal symptoms.
Intramolecularly hydrogen‐bonded 3‐phenacyl‐lH‐pyrido[3,4‐b]‐pyrazin‐2‐one and 2‐Phenacyl‐4H‐pyrido[3,4‐b]pyrazin‐3‐one
Authors: Seki Taketsugu , Iwanami Yasuo
Published: March 2009

Twelve phenacyl derivatives of 1H‐pyrido[3,4‐b]pyrazin‐2‐ones and 4H‐pyrido[3,4‐b]pyrazin‐3‐ones have been synthesized. In these compounds, C = N double bonds at the 3 and 4 positions in the former compounds and those at the 1 and 2 positions in the latter compounds migrate onto the side chains to form phenacyli‐dene structures. These migrations are facilitated by chelation between side chain carbonyl and the proton attached to the ring nitrogen atom which was generated by the migration. All the hydrogen‐bonded structures appear to be stable as shown by their ir spectra in the crystalline state, and by their 1H nmr spectra in solution.
The synthesis and spontaneous resolution of 2‐(2‐thioxothiazolidin‐3‐yl)thiazole
Authors: Jasmin Serge , Dalton David R. , Carroll Patrick J. , Kao Bo‐Chan
Published: March 2009

A single crystalline enantiomer of 2‐(2‐thioxothiazolidin‐3‐yl)thiazole 5 has been isolated as the major product of the pyrolysis of 3‐(2‐thiazolin‐2‐yl)thiazolidine‐2‐thione 3 (n = 1); the latter isolated as the sole product of the reaction between thiazolidine‐2‐thione 2 (n = 1) and diethyl azodicarboxylate (DEAD) in benzene.
Studies on the synthesis of some styryl‐3‐cyano‐2(1H)‐pyridinethiones and polyfunctionally substituted 3‐aminothieno[2,3‐b]‐pyridine derivatives
Authors: Ho Yuh Wen , Wang Ing Jing
Published: March 2009

The 3‐cyano‐4,6‐dimethyl‐2(1H)‐pyridinethione was condensed with benzaldehyde in basic solution leads to styryl‐3‐cyano‐2(1H)‐pyridinethiones. Treatment of cinnamicaldehyde with cyanothioacetamide to give cinnamylidencyanothioacetamide, which can be cyclized with the appropriate ketones to afford the 3‐cyano‐5,6‐polymethylene‐4‐styryl‐2(1H)‐pyridinethione derivatives. The polyfunctionally substituted 3‐aminothieno[2,3‐b]pyridine derivatives were obtained in good yield by cyclization of 3‐cyano‐2(1H)‐pyridinethione derivatives with appropriate α‐halogeno carbonyl compounds and nitrile, respectively.
Some synthetic approaches to ropinirole (sk&f 101468‐a): A potent dopamine receptor agonist
Authors: Hayler J. D. , Howie S. L. B. , Giles R. G. , Negus A. , Oxley P. W. , Walsgrove T. C. , Walsh S. E. , Dagger R. E. , Fortunak J. M. , Mastrocola A.
Published: March 2009

Three new routes to ropinirole (SK&F 101468‐A, 1) are described each involving the preparation of 3‐chlorooxindole intermediates of type 3 from β‐nitrostyrenes as the pivotal step. The superiority of sulphonate esters 17a‐c as direct precursors to 1 over the bromide 11 is also described.
Synthesis of aryl 3‐(2‐imidazolyl)propyl ketones
Authors: Davis Frank S. , Huang Liang‐Fu , Bauer Ludwig
Published: March 2009

The approach to the title compounds was via lithiation‐substitution of N‐methyl or N‐(triphenylmethyl)‐imidazole by some iodo ketals. 4‐Chloro‐4′‐halobutyrophenones (halo = F, Cl, Br) were converted by sodium iodide to the corresponding aliphatic iodides which were subsequently ketalized with ethylene glycol to provide the corresponding iodo ketals. Lithiation of either 1‐methyl‐ or 1‐(triphenylmethyl)imid‐azole with N‐butyllithium generated the corresponding 2‐lithioimidazoles, in situ, which were then reacted with these iodo ketals to form the corresponding C‐2 substituted imidazoles. Dilute aqueous acid hydrolysis released the ketone from the ketal. For N‐triphenylmethyl protected imidazoles, the triphenylmethyl group was also hydrolyzed to give triphenylmethanol and 3‐(2‐imidazolyl)propyl 4‐haloaryl ketones. These N‐unsubstituted imidazolyl ketones can be alkylated independently with triphenylmethyl chloride to form the corresponding N‐triphenylmethyl imidazole derivatives.
Synthesis of 2‐Substituted‐4‐carbethoxythiazoles
Authors: Kim Hong‐Seok , Kwon Il‐Cheon , Kim Oh‐Hwoan
Published: March 2009

In the presence of boron trifluoride etherate, aryl and alkylthioamides react with ethyl diazopyruvate to give high yields of corresponding thiazoles.
A new route to 5,6‐diarylpyridazin‐3‐ones by metalation and cross‐coupling of pyridazines
Authors: Trécourt F. , Turck A. , Plé N. , Paris A. , Quéguiner G.
Published: March 2009

Starting from 3,6‐dichloropyridazine, a new route is described to antihypertensive 5,6‐diarylpyridazin‐3‐ones. This pathway comprises the regioselective metalation followed by a substitution of the trimethylsilyl moeity. The introduction of iodine by another metalation allowed the cross coupling of arylboronic acids. The 6‐methoxy group was then cleaved to afford the pyridazinones.
Reaction products of dialkyl acetylenedicarboxylates with 2,3‐diaminopyridine
Authors: Seki Taketsugu , Iwanami Yasuo
Published: March 2009

The condensation of dialkyl acetylenedicarboxylates 1 and 2 with 2,3‐diaminopyridine (3) or its 5‐bromo derivative 4 in ethanol gave pyrido[2,3‐b]pyrazinones with a common side chain ‐CH2‐COOR at their 2‐position, 5–7, but in the presence of sulfuric acid the reaction afforded their isomers with the same side chain at the 3‐position, 8–10. All of the products were shown to exist in enamine form, in which a ring double bond has been displaced onto their side chain (CHCOOR) being facilitated by an internal chelation as demonstrated by their ir and 1H nmr spectra.
Synthesis and in vitro evaluation of some new pyrimidines and related condensed ring systems as potential anticancer agents
Authors: Badawey El‐Sayed A. M.
Published: March 2009

Several new pyrimidines 6–11, 18–20, furo‐, thieno‐, and pyrrolo[2,3‐d]pyrimidines 3, 8, 12, triazolo‐[4,3‐a]pyrimidines 14, 15, 16 and tetrazolo[1,5‐a]pyrimidine 17 were prepared from the known intermediate 5‐(2‐hydroxyethyl)‐6‐methyl‐2‐thiouracil (2). Compound 7 (4‐chloro‐5‐(2‐chloroethyl)‐2‐methylthio‐6‐methyl‐pyrimidine) exhibited weak antitumor activity in vitro.
Conformational analysis of 1,2,3,4‐tetrahydroisoquinolines
Authors: Ibañez Adriana F. , Moltrasio Iglesias Graciela Y. , Delfino José M.
Published: March 2009

Ring and nitrogen inversion account for the conformational equilibria of 3‐phenyl‐1, 2,3, 4‐tetrahydroiso‐quinolines. In order to quantitate the relative contribution of each conformer to the equilibrium, we undertook a molecular mechanics study on several substituted 3‐phenyl‐1, 2, 3, 4‐tetrahydroisoquinolines. Predictions from calculations were checked against cmr chemical shift data. No boat conformation contributed significantly to the equilibrium. A general result of our calculations is that in all cases the 3‐phenyl group in the equatorial position is strongly favored (by at least 2.50 kcal/mole). For 3‐phenyl‐1, 2, 3, 4‐tetrahydroisoquinolines without substitution at nitrogen, N‐H in equatorial position is preferred over the axial conformer, although the energy difference between both is always small (0.30–1.10 kcal/mole). For the cis‐1,3‐disubstituted compounds the le'3e conformers are the only species present (at least 99.8%). The calculated energy differences between the la′3a conformer and the le′3e conformer are always large (3.80–6.10 kcal/mole for the NHe conformers and 3.60–3.80 kcal/mole for the NHa conformers). The lack of a γ1a upfield shift at C3 also points to the preference for the pseudoequatorial‐equatorial conformer. For N‐methyl‐3‐phenyl‐1,2,3,4‐tetrahydroisoquinoline a preference for the NMe group in the equatorial position is predicted (0.60–2.00 kcal/mole). The small downfield shift at C4 (γNa = 0.5 ppm) is consistent with the equatorial NMe preference. For the cis‐1,2,3‐trisubstituted compounds no significant γ1a effect at C3 (γ1a = ‐0.2 and 1.0 ppm) or γNa effect at C4 (γNa = 0.1 and 0.4 ppm) is observed. For these compounds, deformations due to steric congestion are evidenced by the deviation from the values of the C4a‐C8a‐Cl‐N and C4a‐C4‐C3‐N torsional angles, as compared to less crowded 3‐phenyl‐1,2,3,4‐tetrahydroisoquinolines. Here the heterocyclic ring adopts a distorted half‐chair conformation.
Thiazolo[4,3‐c][1,4]benzodiazepines. II. Synthesis of fused[a]triazolo, tetrazolo and oxadiazolo derivatives
Authors: Gillard Alain‐Claude , Rault Sylvain , Boulouard Michel , Robba Max
Published: March 2009

We report the practical synthesis of the first fused[a]triazolo, tetrazolo and oxadiazolothiazolo[4,3‐c]‐[1,4]benzodiazepine‐5,11‐diones via hydrazidines and oximes.
The synthesis of 4‐benzylamino‐6‐methyl‐1H‐pyrrolo[3, 2‐c]pyridine and 4‐benzylamino‐6‐methyl‐1H‐pyrrolo[2, 3‐b]pyridine
Authors: Meade Eric A. , Beauchamp Lilia M.
Published: March 2009

4‐Benzylamino‐6‐methyl‐1H‐pyrrolo[3,2‐c]pyridine (2) and 4‐benzylamino‐6‐methyl‐1H‐pyrrolo[2,3‐b]pyridine (3) were synthesized as deaza analogues of the anxiolytic agent 4‐benzylamino‐2‐methyl‐7H‐pyrrolo[2,3‐d]pyrimidine (1). The 1‐deaza analogue (2) was prepared via a multi‐step procedure from a pyrrole precursor, 1‐benzyl‐2‐formylpyrrole (4) while the 3‐deaza analogue 3 was synthesized from a pyridine precursor, 2‐amino‐3,6‐dimethylpyridine (12).
Synthesis of novel N‐acyclonucleosides: Benzotriazole, benzothiazinone and pyridooxazinone acyclonucleosides
Authors: Cho Su‐Dong , Chung Joo‐Wha , Kim Sung‐Kyu , Kweon Deok‐Heon , Park Ki‐Hoon , Yoon Yong‐Jin
Published: March 2009

Some novel benzotriazole, benzothiazinone and pyridooxazinone acyclonucleosides containing 4‐hydroxybutyl, 4‐hydroxybutoxy, 4‐iodobutyl, 2‐oxopropyl and 2,3‐epoxypropoxy groups as a side chain was prepared.
Unsymmetrically substituted furoxans. Part 16 . Reaction of benzenesulfonyl substituted furoxans with ethanol and ethanethiol in basic medium
Authors: Sorba Giovanni , Ermondi Giuseppe , Fruttero Roberta , Galli Ubaldina , Gasco Alberto
Published: March 2009

The use of benzenesulfonyl substituted furoxans as flexible intermediates for the synthesis of new functionalized furoxans interesting for their potential biological properties is discussed. Reaction of benzenesul‐fonylphenylsulfonylfuroxan isomers 7a and 7b with ethanol and ethanethiol in basic medium affords the expected ethers and sulphides respectively. Reaction of bis(benzenesulfonyl)furoxan (1) with ethanol in basic medium gives 3‐benzenesulfonyl‐4‐ethoxyfuroxan (2) or diethoxyfuroxan (3), according to the experimental procedure. In contrast the reaction of 1 with ethanethiol gives a mixture of substitution compounds and the 4‐benzenesulfonyl‐3‐ethylthiofurazan (11). The structure of the compounds has been assigned by nmr spectroscopy and, in the case of 3‐benzenesulfonyl‐4‐ethylthiofuroxan (9b), confirmed by X‐ray analysis.
New synthesis of isoxazolidines
Authors: Malamas Michael S. , Palka Cynthia L.
Published: March 2009

A new synthesis of 5‐substituted isoxazolidines was developed by direct isoxazolidine ring formation of allylic hydroxylamines under acidic conditions. The cyclization process is an electrophilic SN1 type reaction. The formed carbocation intermediate is stabilized by electron rich groups (i.e., phenyl). A moiety that mediates oxonium ion formation (i.e., para‐methoxy) accelerates the rate of product formation.
A facile entry to l‐aryl‐4,5‐dihydro[1,4]oxazepino‐[5,4‐a]isoindole‐2,7‐diones
Authors: Warawa E. J. , Ceccarelli C.
Published: March 2009

The titled compounds were prepared by reacting N‐(2‐bromoethyl)phthalimide with enolates of phenylacetic acid esters. 2,3‐Dihydrooxazolo[2,3‐a]isoindolones are believed to be intermediates in the process. An X‐ray crystallographic analysis was conducted on one of the compounds.
Pyridine Syntheses. II. Condensation Routes Toward Streptonigrin Ring C
Authors: Robinson J. Michael , Ahmed Masood , Alaniz Nicky J. , Boyles Timothy R. , Brasher Chris D. , Floyd Kimberly A. , Holland Preston L. , Maruffo Laura D. , Mcmahan Terry L. , Middleton Stan , O'Hara Kevin D. , Pack Marcia J. , Reynolds Brandon D. , Rodriquez Romelia R. , Sawyer Dennis E. , Sharp Elena , Simpson Sharai L. , Vanlandingham Clint L. , Velasquez Rebecca S. , Welch Brian M. , Wright C. David
Published: March 2009

Alternative complimentary syntheses of penta‐substituted pyridine rings with full regiochemical control of substituents were studied as a method for the synthesis of Streptonigrin (1). Various α‐substituted acetophenones 2 were reacted with enones 3 in acetic acid/ammonium acetate and air to afford penta‐substituted pyridines 4. α‐Substituents that could provide a source of exocyclic nitrogen at position 3 of these Steptonigrin ring‐C models proved to be the limiting factor. However, an inverse “3+2+1” cyclocondensation of α‐cyanochalcone 5c with 2‐furyl ethyl ketone (6b) afforded the desired model 6‐(2‐furyl)‐5‐methyl2,4‐diphenyl‐3‐pyridinecarbonitrile (4g) in 75% yield.
Synthesis of 1H‐thieno[3,4‐c]pyrazoles, thieno[3,4‐b]furans, selenolo[3,4‐b]furans and pyrrolo[3,4‐d]thiazoles
Authors: Shafiee A. , Ebrahimzadeh M. A. , Shahbazi J. , Hamedpanah S.
Published: March 2009

Starting from the readily available aryl 2‐methyl‐5‐phenyl‐3‐furyl ketones, 5‐methyl‐1H‐1‐phenylpyrazole‐4‐yl ketones and 4‐methyl‐2‐phenyl‐5‐thiazolylcarboxaldehyde, a series of 2‐phenyl‐4‐arylthieno[3,4‐b]‐furan, 2‐phenyl‐4‐(p‐methoxyphenyl)selenolo[3,4‐b]furan, 4‐aryl‐1H‐1‐phenylthieno[3,4‐c]pyrazole and 5‐benzyl‐2‐phenylpyrrolo[3,4‐d]thiazole were prepared in high yield.
1,3‐Dipolar cycloaddition of 1,2‐o‐isopropylidene‐α‐d‐xylopentadialdo‐1,4‐furanosenitrile oxide to some alkenes
Authors: Fascio Mirta L. , Montesano Verónica J. , D'Accorso Norma B.
Published: March 2009

The synthesis of five 3‐(1,2‐O‐isopropylidene‐α‐D‐xylofuranosyl)‐5‐substituted‐2‐isoxazolines obtained by 1,3‐dipolar cycloaddition are described, as well as the intermediate products from the synthetic route. The physical and spectroscopic characterization of these compounds are reported.
A novel reaction of (2a7‐trinito‐9H‐fluoren‐9‐ylidene)‐propanedinitrile with N‐arylisoindolines
Authors: Hassan Alaa A. , Döpp Dietrich , Henkel Gerald
Published: March 2009

N‐Arylisoindolines 1a‐c reacted with (2,4, 7‐trinitro‐9H‐fluoren‐9‐ylidene)propanedinitrile (A) in pyridine with admission of air via a net α‐H‐atom abstraction and formation of [3‐(2‐aryl‐3‐arylimino‐2,3‐dihydro‐ 1H‐isoindol‐1‐ylidene)‐2‐aryl‐2,3‐dihydro‐1H‐isoindol‐1‐ylidene]propanedinitriles 2a‐c, N‐[2‐aryl‐3‐(2‐aryl‐3‐arylimino‐2,3‐dihydro‐1H‐isoindolyl‐1‐idene)‐2,3‐dihydro‐1H‐isoindol‐1‐ylidene]arenamines 3a, b, N, N'‐[2‐aryl‐1H‐isoindole‐1,3(2H)‐diylidene]bisarenamines 4a, b and N‐arylphthalimides 5a‐c in moderate yields. 2,4,7‐Trinitro‐9‐fluorenone as well as one reduction product each of the latter and of A, namely compounds 6 and 7, respectively, are also found. The structure of 2b has been unambiguously confirmed by an X‐ray crystal structure analysis. A rationale for the conversions observed is presented. These involve dehydrogenation and oxidative couplings of 1a‐c as well as transfer of N‐aryl fragment from 1a‐c to intermediate products.
The solid‐state michael addition of 3‐methyl‐1‐phenyl‐5‐pyrazolone
Authors: Li Xiao‐Liu , Wang Yong‐Mei , Tian Bing , Matsuura Teruo , Meng Ji‐Ben
Published: March 2009

A novel solid‐state Michael addition between pyrazolone 1 and 4‐arylidenepyrazolones 2 at ambient temperature produced Michael adducts, 4,4′‐arylidenebis(3‐methyl‐1‐phenyl‐5‐pyrazolones) 3. Pyrazolones 3 formed salts 4 with Cu2+ in solution, indicating the enolic structure of the pyrazolone rings. The reactivity of 2 with 1 is discussed in terms of the electronic and steric effects of the substituent on the arylidene group of compounds 2. Pyrazolone 1 also underwent the solid state Michael addition reaction with maleimide at 100° to give the adducts 7,8 and 9.
Facile synthesis of fused purines from 8‐aminotheophylline
Authors: Ueda Taisei , Oh Rikisei , Nagai Shin‐Ichi , Sakakibara Jinsaku
Published: March 2009

Fused purines 3a‐f were prepared by one‐step from 8‐aminotheophylline (1) and α,ω‐dibromoalkanes in N, N‐dimethylformamide in the presence of sodium hydride. Reaction of 3c‐e with chloroacetyl chloride followed by treatment with dimethylamine gave 6a‐c. A one‐step reaction of 1 with ethyl bromopropionate gave 1,3‐dimethyl‐1,2,3,4,6,7,8,9‐octahydropyrimido[2,1‐f]purine‐2,4,8‐trione (7b). Facile syntheses of 7a, c, d from 1 were also carried out.
Synthesis of pyrimido[4,5‐b]quinolines in the reaction of 6‐aminopyrimidines with dimedone and benzaldehydes
Authors: Quiroga J. , Hormaza A. , Insuasty B. , Ortíz A. J. , Sánchez A. , Nogueras M.
Published: March 2009

The reaction of 6‐aminopyrimidines 1a, b with dimedone (2) and p‐substituted benzaldehydes 3a‐d in ethanol afforded in all cases new regiospecific synthesis of tricyclic, linear 5‐aryl‐5,6,7,8,9,10‐hexahydropyrimido[4,5‐b]quinolines 4a‐h in good yields. The linear structures and hence the regiospecificity of the reaction were established by nmr measurements.
Synthesis of the methanesulfonates of α‐(4‐chlorophenyl)‐α‐[1‐(2‐chlorophenyl)emenyl]‐1H‐1,2,4‐triazole‐1‐ethanol and α‐[1‐(2‐chlorophenyl)ethenyl]‐α‐(2,4‐difluorophenyl)‐1H‐1,2,4‐triazole‐1‐ethanol, alpha styryl carbinol antifungal agents
Authors: Pesti Jaan A. , Downard Jill A. , Lauritsen Mark D. , Kauffman Goss S. , Bryant Walter M. , Huhn George F. , Arnett John F. , Yule Robert E. , Segretario James , Nelson Kimberly A. , Gorko Edward F. , Page Gary O. , Lloyd Lisa M. , Olson Richard E. , Bamum Christopher S. , Mrowca Joseph J.
Published: March 2009

The methanesulfonates of (α‐(4‐chlorophenyl)‐α‐[1‐(2‐chlorophenyl)ethenyl]‐1H‐1,2,4‐triazole‐1‐ethanol and α‐[1‐(2‐chlorophenyl)ethenyl]‐α‐(2,4‐difluorophenyl)‐1H‐1,2,4‐triazole‐1‐ethanol (1a, b) are orally effective α‐styryl carbinol derivatives developed for the treatment and prevention of systemic fungal infections. Practical new processes amenable for the large‐scale production of these compounds are described. Of note is the selection of dichlorostyrene as a convenient precursor of the styryl portion, modification of a sensitive Grignard addition into a realistic preparative reaction and the use of 1,2,4‐triazole simultaneously as a base transfer agent and nucleophile.
A new simple synthesis of 3,5‐disubstituted 1‐amino‐1,3,5‐triazine‐2,4,6‐triones from ethoxycarbonylhydrazones and isocyanates
Authors: Chau François , Malanda Jean‐Claude , Milcent René
Published: March 2009

The 3,5‐disubstituted 1‐amino‐1,3,5‐triazine‐2,4,6‐triones were synthesized in good yields from aromatic aldehyde or ketone ethoxycarbonylhydrazones by treatment with aryl or methyl isocyanates in boiling triethylamine followed by hydrolysis with hydrochloric acid solution.
Synthesis of 6‐cyanopyrido[2,3‐d]pyrimidinones in the reaction of 6‐amino‐4‐pyrimidinones with arylidene derivatives of malonodinitrile
Authors: Quiroga Jairo , Alvarado Mario , Insuasty Braulio , Nogueras Manuel , Sánchez Adolfo , Cobo Justo
Published: March 2009

This paper describes the synthesis of a new series of 7‐amino‐5‐aryl‐6‐cyano‐5,8‐dihydropyrido‐[2,3‐d]pyrimidin‐4(3H)‐ones 3 from the reaction of 6‐amino‐4‐pyrimidinones 1 with arylidene derivatives of malonodinitrile 2. The structure of the final compounds was determined on the basis of nmr measurements, especially by 1H, 1H‐, 1H, 13C COSY, DEPT, HMBC and HMQC experiments.
Syntheses and properties of chiral pentahomothiazacalix[3]arenes
Authors: Ito Kazuaki , Ohba Yoshihiro , Sone Tyo
Published: March 2009

Chiral calixarene analogs incorporating an aminoethanethiol unit such as L‐cysteine into their rings were prepared. Conformational analysis of the macrocycles by using 1H and 13C nmr spectroscopy revealed that their preferred conformation was a cone, which was more stable in chloroform than in toluene. The introduction of an aminoethanethiol moiety into the macrocyclic ring caused ring fluctuation, however, the carboxylic acid derivative was a highly rigid structure in the cone form. The 1H nmr and circular dichroism spectra of the macrocycles showed the existence of chirality of the phenol‐formaldehyde unit, which was induced by the chirality of the cysteine moiety.
Synthesis of the bi‐heterocyclic parent ring system 1,2,4‐triazolo[4,3‐b][1,2,4,5]tetrazine and some 3,6‐disubstituted derivatives
Authors: Chavez David E. , Hiskey Michael A.
Published: March 2009

The synthesis of the previously unknown parent ring system was developed. Treatment of 3‐hydrazino‐1,2,4,5‐tetrazine (4) with diethoxymethyl acetate gave the parent ring system. Similar treatment of 3‐(3,5‐dimethylpyrazol‐1‐yl)‐6‐hydrazino‐1,2,4,5‐tetrazine (2) with one carbon cyclizing reagents gave 3,6‐di‐substituted derivatives of the 1,2,4‐triazolo‐1,2,4,5‐tetrazine ring system.
Reactions of 2‐aryl‐4‐methoxy‐9‐oxocyclohepta[b]pyrylium perchlorates with hydroxylamine and hydrazines
Authors: Wang Dao‐Lin , Imafuku Kimiaki
Published: March 2009

2‐Aryl‐4‐methoxy‐9‐oxocyclohepta[b]pyrylium perchlorates1a‐creacted with hydroxylamine hydrochloride and hydrazine sulfate in the presence of triethylamine to afford 2‐aryl‐4,9‐dihydrocyclohepta[b]pyran‐4,9‐dione 4‐oximes3a‐cand 4‐hydrazones4a‐cin good yields, respectively. On the other hand, the reactions with methylhydrazine and phenylhydrazine gave respectively 1‐methyl‐ and 1‐phenyl‐substituted 5‐aryl‐3‐(3‐tropolonyl)pyrazoles5a‐cand6a‐cin excellent yields. Treatment with 4‐nitrophenylhydrazine gave 2‐aryl‐4,9‐dihydrocyclohepta[b]pyran‐4,9‐dione 4‐(4‐nitrophenyl)hydrazones7a‐cin good yields.
Cryptolepinone vs. Hydroxycryptolepine: Resolution of a question of substituent functionality and double bond isomerization
Authors: Sharaf Maged H. M. , Schiff Paul L. , Tackie Albert N. , Martin Gary E.
Published: March 2009

An indolo[3,2‐b]quinoline alkaloid bearing an N‐methyl substituent at N5, and an oxygen moiety at the 11‐position has been variously described as both cryptolepinone and 11‐hydroxycryptolepine by independent research groups. The structure of this alkaloid is unequivocally confirmed as the former, cryptolepinone, with substantial changes in double bond isomerization relative to that which would be required if it were indeed the latter. The structure of the alkaloid was confirmed by, total assignment of the 1H, 13C, and 15N nmr spectra at natural abundance using 3 mm micro inverse nmr probe technology at 400 and 500 MHz.
Chemoselective synthesis of 1‐alkyl‐4‐(4‐amino‐2,6‐dichlorophenoxy)‐5‐halopyridazin‐6‐ones
Authors: Kweon Deok‐Heon , Chung Ju‐Wha , Cho Su‐Dong , Kim Sung‐Kyu , Yoon Yong‐Jin
Published: March 2009

Some 1‐alkyl‐4‐(4‐amino‐2,6‐dichlorophenoxy)‐5‐halopyridazin‐6‐ones were synthesized chemoselectively from 1‐alkyl‐4,5‐dihalopyridazin‐6‐ones and 4‐amino‐2,6‐dichlorophenol via a fluoride ion‐assisted reaction.
Pyridazines. XV. Synthesis of 6‐aryl‐5‐amino‐3(2H)‐pyridazinones as potential platelet aggregation inhibitors
Authors: Estevez Isabel , Raviña Enrique , Sotelo Eddy
Published: March 2009

Several 3(2H)‐pyridazinones with amino groups at the 5‐position of the pyridazine nucleus have been prepared. The 6‐aryl‐5‐halo‐3(2H)‐pyridazinones obtained from mucochloric and mucobromic acid lead to the corresponding 5‐alkylamino‐3(2H)‐pyridazinones, which were tested as platelet aggregation inhibitors.
Computational investigation of the suitability of heterocyclic aromatic compounds with two heteroatoms in the 1 and 3 ring positions as dienes for the diels alder reaction
Authors: Jursic Branko S.
Published: March 2009

Semiempirical and density functional theory computational studies were carried out with the target determining the reactivity of five membered heterocycles with heteroatoms in the 1 and 3 positions as dienes for Diels‐Alder reactions. The relative reactivity was evaluated in their reaction with acetylene, ethylene, and cyclopropene as dienophiles for cycloaddition. Qualitative criteria such as uniformity of heterocycle bond orders, change of bond orders and frontier molecular orbital energies in transformation of reactants into transition state structures were used to determine the relative reactivity in comparison with furan. These results are compared with the computed activation barriers as well as with experimental findings, where available. If cycloaddition is feasible with these heterocycles, a new synthetic transformation of simple organic compounds to valuable prostaglandin derivatives can be accomplished.
Synthesis of pyrazolecarbonylaminopyridinecarboxamides as herbicides
Authors: Parlow John J.
Published: March 2009

Target compounds from a herbicide lead area, pyrazolecarboxamides, were selected and synthesized. These targets were chosen based on 1) “structural” similarities of 2a‐c with other known bleaching herbicides, and 2) the structure activity relationship previously established with analogs of the lead compound 2a. Syntheses of three target compounds were accomplished, two of which involved various transformations and regioselective additions with a pyridine nucleus to afford novel pyridine derivatives. These targets were tested in whole plant assays with the herbicidal data reported.
Steric promotion of cyclization reactions: Substituent effect studies in the furan intramolecular diels‐alder reaction
Authors: Mcnelis Brian J. , Starr Jeremy T. , Dang Hung
Published: March 2009

Seven alkyl and aryl substituted N‐allyl‐N‐(methylfuran)‐sulfonamide compounds have been synthesized and their rates of cyclization and equilibrium product concentrations determined. Increased steric bulk on the sulfonamide substituent has been shown to increase both the rate of cyclization and yields of these reactions. A three‐fold increase in rate and 15% increase in yield was observed as the substituent was varied from methyl to triisopropylbenzene.
A convenient synthesis of 2‐amino‐4H‐1,3,4‐oxadiazino[5,6‐b]‐quinoxaline derivatives
Authors: Kim Ho Sik , Kim Tong Eun , Lee Seong Uk , Kim Dong Il , Han Sung Wook , Okamoto Yoshihisa , Mitomi Takako , Kurasawa Yoshihisa
Published: March 2009

The reaction of 6‐chloro‐2‐(1‐methylhydrazino)quinoxaline 4‐oxide 5 with a 2‐fold molar amount of ethyl chloroglyoxalate gave ethyl 8‐chloro‐4‐methyl‐4H‐1,3,4‐oxadiazino[5,6‐b]quinoxaline‐2‐carboxylate 6, whose reaction with hydrazine hydrate afforded the C2‐hydrazinocarbonyl derivative 7. The reaction of compound 7 with nitrous acid provided the C2‐acylazide derivative 8, which was converted into the C2‐amino 9, C2‐carbamate 11a‐c, 12a,b, and C2‐ureido 13a‐c, 14 derivatives. The mass spectral fragmentation patterns were examined for compounds 10–14, wherein the molecular ion peak did not appear in the mass spectra of compounds 10c, 11a‐c, 12a,b, 13c, and 14.