bluuebunny/crossref_metadata_2025 huggingface dataset:
Further evaluation of 5‐alkyl‐5‐deaza antifolates. 5‐propyl‐ and 5‐butyl‐5‐deaza analogues of aminopterin and methotrexate
Authors: Piper James R. , Ramamurthy Balakrishnan , Johnson Cheryl A. , Maddry Joseph A. , Otter Glenys M. , Sirotnak Francis M.
Published: March 2009

5‐Propyl‐5‐deaza and 5‐butyl‐5‐deaza analogues of classical antifolates were synthesized by extensions of a previously reported general route which proceeds through 2,4‐diamino‐5‐alkylpyrido[2,3‐d]pyrimidine‐6‐carbonitrile intermediates followed by reductive condensation with diethyl N‐4‐(aminobenzoyl)‐L‐glutarnate to give diethyl esters of 5‐alkyl‐5‐deazaaminopterin types. N10‐Methyl derivatives, i.e., derivatives of 5‐alkyl‐5‐deazamethotrexate, were also prepared by reductive methylation of the N10‐H compounds. 5‐Ethyl‐5‐deazamethotrexate was prepared using an alternative route through 6‐(bromomethyl)‐2,4‐diamino‐5‐ethylpyrido[2,3‐d]pyrimidine. These antifolates were evaluated for inhibition of dihydrofolate reductase (DHFR) from L1210 cells, their effect on L1210 and S180 tumor cell growth in culture, and carrier‐mediated transport through L1210 cell membranes. Inhibitory effect on DHFR was lowered relative to methotrexate in 5‐propyl‐5‐deazaaminopterin and 5‐propyl‐5‐deazamethotrexate by 2‐ to 3‐fold (Ki = 9.3 and 11.7 pM, respectively, vs. 4.3 pM for methotrexate) and by 17‐ to 18‐fold in 5‐butyl‐5‐deaza‐aminopterin and 5‐butyl‐5‐deazamethotrexate (Ki = 74 and 78 pM, respectively). Molecular modeling using graphics derived from human DHFR show the propyl and butyl compounds interacting with the enzyme in conformations that account for these slight decreases in binding.
The synthesis of 2‐amino‐4‐aryl‐3‐ethoxycarbonyl‐4H‐naphtho[1,2‐b]pyrans revisited
Authors: Martín Nazario , Martínez‐Grau Angeles , Seoane Carlos , Marco José L.
Published: March 2009

An expeditious and unequivocal synthesis of some 2‐amino‐4‐aryl‐3‐ethoxycarbonyl‐4H‐naphtho‐[1,2‐b]pyrans 3 is reported. Previous papers describing the preparation of this type of compound have been amended and a convenient and direct procedure for its preparation is now presented.
Syntheses of substituted‐oxazolo‐1,3,4‐thiadiazoles, 1,3,4‐oxadiazoles, and 1,2,4‐triazoles
Authors: Shafiee A. , Naimi E. , Mansobi P. , Foroumadi A. , Shekari M.
Published: March 2009

Starting from readily available methyl 5‐methyloxazole‐4‐carboxylate (1) and 4‐methyl‐5‐oxazolylcar‐boxylic acid hydrazide (11) the title compounds were prepared. The reaction of compound 1 with hydrazine hydrate afforded the corresponding hydrazide 2. The reaction of compound 2 with formic acid yielded 1‐formyl‐2‐(5‐methyloxazole‐4‐carboxyl)hydrazine (3). Refluxing of the latter with phosphorus pentasulfide in xylene gave compound 5 in 62% yield. The reaction of compound 3 with phosphorus pentoxide afforded compound 4. Starting from hydrazide 11, compounds 13 and 14 were prepared similarly. Reaction of compound 2 with substituted isothiocyanate yielded compound 9 which was cyclized in basic medium to 4‐alkyl‐5‐(5‐methyl‐4‐oxazolyl)‐2,4‐dihydro‐3H‐1,2,4‐triazole‐3‐thione (10). The isomer 19 was prepared similarly. Methylation and subsequent oxidation of compound 19 gave compound 21. Reaction of the acid 7 with thiosemicarbazide in the presence of phosphorus oxychloride gave 2‐amino‐5‐(5‐methyl‐4‐oxazolyl)1,3,4‐thiadiazole (8). 2‐Amino‐5‐(4‐methyl‐5‐oxazolyl)‐1,3,4‐thiadiazole (17) was prepared from acyl chloride 15 by the usual method.
Synthesis of N‐(3,5‐dichlorophenyl)‐2‐hydroxysuccinimide‐O‐sulfate: A potential metabolite of the nephrotoxicant N‐(3,5‐dichlorophenyl)succinimide
Authors: Hong Suk K. , Rankin Gary O. , Scott Kenneth R.
Published: March 2009

The sulfate conjugate 2 of N‐(3,5‐dichlorophenyl)‐2‐hydroxysuccinimide, a potential metabolite of the nephrotoxicant N‐(3,5‐dichlorophenyl)succinimide, is prepared from the 2‐hydroxysuccinimide (1) by the reaction with chlorosulfonic acid in chloroform and ether mixture at −78°.
Structure elucidation and spectral assignment of analogs of navelbine® (8′‐noranhydrovinblastine)
Authors: Spitzer Timothy D. , Reynolds Daniel W. , Crouch Ronald C. , Shockcor John P. , Johnson Robert L. , Morrison Robert W. , Martin Gary E.
Published: March 2009

During the development of the bis‐indole alkaloid anticancer drug Navelbine® (vinorelbine), several chemical degradants of the drug were isolated and identified. These included 7′‐nor‐6′,9′‐secovinorelbine (7′,8′‐bisnor‐6′,9′‐secoanhydrovinblastine) and 4‐deacetyl‐8′‐vinorelbine (4‐deacetyl‐8′‐noranhydrovinblastine). The elucidation of the structure of 7′‐nor‐6′,9′‐secovinorelbine is described; the assignment of the proton and carbon spectra of both compounds is contrasted to the shift assignments of Navelbine.
A study of the mechanism of the oxidative cyclization of benzaldehyde semicarbazones induced by cupric perchlorate in acetonitrile
Authors: Noto Renato , Gruttadauria Michelangelo , Lo Meo Paolo , Frenna Vincenzo , Werber Giuseppe
Published: March 2009

Treatment of benzaldehyde semicarbazones 1a‐i with cupric perchlorate in acetonitrile at 40 provided selectively the corresponding 1,2,4‐triazolin‐5‐ones 2a‐i. The relative rate constants for 2a‐i formation were determined by the competitive method. The results obtained showed that electron‐donating substituents (methyl and methoxy) increase the reaction rate, while the reverse was found for electron‐withdrawing substituents (chloro and nitro group). The reactivity data are discussed on the grounds of two possible mechanisms.
A practical synthesis of 5‐(chloromethyl)furo[2,3‐b]pyridine, a key intermediate for the HIV protease inhibitor, L‐754,394
Authors: Bhupathy M. , Conlon David A. , Wells Kenneth M. , Nelson John R. , Reider Paul J. , Rossen Kai , Sager Jess W. , Volante R. P. , Dorsey Bruce D. , Hoffman Jacob M. , Joseph Sally A. , Mcdaniel Stacey L.
Published: March 2009

A practical synthesis of 5‐(chloromethyl)furo[2,3‐b]pyridine (10), the side chain used to incorporate a key pharmacophore of the HIV protease inhibitor, L‐754,394, is described. The synthesis was accomplished in ten steps and in 15% overall yield from commercially available methyl 2‐furoate.
A facile synthesis of 2‐acetylnaphtho[2,3‐b]furan‐4,9‐dione
Authors: Koyanagi Jyunichi , Yamamoto Katsumi , Nakayama Kouji , Tanaka Akira
Published: March 2009

Reaction of the parent naphtho[2,3‐b]furan‐4,9‐dione 2 with various electrophilic reagents was difficult, and only nitration of 2 gave small amounts of 2‐nitronaphtho[2,3‐b]furan‐4,9‐dione 4. Then 2‐acetylnaphtho[2,3‐b]furan‐4,9‐dione 1 was not obtained by the acetylation of 2. On the other hand, compound 1 that is isolated from Tabebuia Cassinoides and has cytotoxic activity, was obtained from 3‐lithiofuran in five steps.
Reactions of o‐bromoacetylacylphenones with several primary amines
Authors: Nan'ya Seiko , Ishida Hirofumi , Kanie Kiyoshi , Ito Noriyuki , Butsugan Yasuo
Published: March 2009

o‐Monobromoacetylacylphenones, 3a and 3b reacted with hydroxylamine or hydrazine hydrate to produce heterocycles, 2,3‐benzoxazine or phthalazine derivatives. The reaction of bromoacetyl group of 3a and 3b with several thioamides afforded thiazole derivatives in high yields. Whereas o‐dibromoacetyl‐benzophenoe 2a reacted with aniline or cyclohexylamine to produce non‐heterocycles, 2‐substituted‐iminophenylindanones and the mechanism for the formation of these non‐heterocycles is proposed.
Synthesis and analysis of compounds having the skeleton of ergot alkaloids with the nitrogen atom in the D‐ring transposed
Authors: Stamos Ioannis K. , Kelly Elyse A. , Floss Heinz G. , Cassady John M.
Published: March 2009

Alkylation‐amination of the enamine 2 in the presence of ethyl α,α‐bis(dibromomethyl)acetate, triethyl‐amine, and methylamine lead to the construction of the aza‐transposed ergoline 3. Sequential reduction, hydrolysis, reesterification, and indolization of 3, produced three diastereomers of 6. The structure of these three diastereomers was assigned on the basis of nmr and ir spectral analysis to be (α‐cis) syn, (β‐cis) anti, and (α‐trans) syn. The isomer (β‐cis) anti was reduced with lithium aluminum hydride to the corresponding alcohol.
Synthesis and reactivity of pyrrolo[1,2‐α]quinoxalines. Crystal structure and AM1 calculation
Authors: Blache Yves , Gueiffier Alain , Elhakmaoui Ahmed , Viols Henri , Chapat Jean‐Pierre , Chavignon Olivier , Teulade Jean‐Claude , Grassy Gérard , Dauphin Gérard , Carpy Alain
Published: March 2009

2‐Methylquinoxaline reacts with ethyl bromopyruvate giving 2‐substituted pyrrolo[1,2‐α]quinoxalines. The yield of the condensation depends on the functionalization of starting materials, and optimization is obtained with 2‐dimethylamino‐3‐methylquinoxaline (1c). Reactivity of the resulting pyrrolo[1,2‐a]‐quinoxalines was investigated and supported by a theoretical approach (AM1 calculation performed with the MOPAC 6.0 software). X‐ray analysis of 5 which crystallizes in the monoclinic system, space group P21/n, with a = 9.095(1), b = 8.972(1), c = 17.749(3) A, β = 96.56(1)°, is also reported.
NMR spectroscopic investigations with ethyl 1‐(hetero)aryl‐5‐hydroxy‐1H‐pyrazole‐4‐carboxylates
Authors: Holzer Wolfgang , Schmid Eva
Published: March 2009

The synthesis of a series of ethyl N‐1‐(hetero)aryl‐5‐hydroxy‐1H‐pyrazole‐4‐carboxylates by reaction of diethyl ethoxymethylenemalonate with the appropriate hydrazines is described. According to nmr‐spectro‐scopic investigations (1H‐ and 13C‐nmr) the title compounds exist as 5‐hydroxy tautomers in deuteriochlo‐roform as well as in deuteriodimethyl sulfoxide solution.
N1‐substituted 3,5‐dimethoxy‐4‐halogeno‐1H‐pyrazoles: Synthesis and NMR study
Authors: Holzer Wolfgang , Gruber Heidi
Published: March 2009

The synthesis of 1‐methyl‐ and 1‐benzyl‐3,5‐dimethoxy‐4‐halogeno‐1H‐pyrazoles is described. Moreover, detailed nmr spectroscopic studies with the title compounds are presented. The highly shielded pyrazole C‐4 atom in the corresponding 4‐iodo congeners was found to have a 13C‐chemical shift of only −27 ppm.
Michael addition of benzoylacetonitrile to chiral α‐cyanoacrylates derived from enantiomerically pure α‐hydroxyaldehydes: Synthesis of 3‐alkoxycarbonyl‐4‐alkyl‐2‐amino‐5‐cyano‐6‐phenyl‐4H‐pyrans
Authors: Jiménez Blanca , Martín Nazario , Martínez‐Grau Angeles , Seoane Carlos , Marco José L.
Published: March 2009

We describe the Michael addition of benzoylacetonitrile to α‐cyanoacrylates 4a‐c and 5a obtained from readily available chiral α‐hydroxyaldehydes 1a‐c. The resulting polyfunctionalized 4‐alkyl‐2‐amino‐4H‐pyrans 6a‐c, 7a have been obtained in good yield and moderate diastereoselectivity.
Reduction of indolo[2,3‐a]quinolizidines with baker's yeast
Authors: Farés F. A. , Virelizier H. , Jankowski K. , Gribble G. W.
Published: March 2009

The reduction of several indolo[2,3‐a]quinolizidines with Baker's yeast (Saccharomyces cerevisiae) affords novel reduction products resulting from reduction of the indole double bond, cleavage of the C‐D ring junction, or reduction of a lactam to a carbinol amine, as determined by high resolution mass spectrometry.
Cyclization of 3‐fluorophenol and 3,3‐dimethylacrylic acid: A structure correction
Authors: Shawcross Frances , Sard Howard
Published: March 2009

Reaction of 3‐fluorophenol and 3,3‐dimethylacrylic acid in methanesulfonic acid at 90° gives predominantly 5‐fluoro‐2,2‐dimethylchroman‐4‐one, not the 7‐fluoro isomer as reported [1].
Preparation of 7‐ethoxy‐3‐hydroxy‐6‐methoxy‐1‐methyl‐4‐nitroisoquinoline
Authors: Barton Donald L. , Fabian Arthur C. , Lam Margaret M. , Sterbenz Jeffrey T.
Published: March 2009

This paper reports the large scale preparation of 7‐ethoxy‐3‐hydroxy‐6‐methoxy‐1‐methyl‐4‐nitroiso‐quinoline (RWJ 19959,2) from an available starting material, 4‐ethoxy‐3‐methoxyphenylacetic acid (9). Previously 2 was prepared via a perchlorate salt which was found to decompose exothermically.
Aldol condensation of 6‐alkoxy‐2,2‐dimethylchroman‐4‐ones with substituted benzaldehydes using tetramethylorthosilicate and potassium fluoride
Authors: Chambers R. J. , Marfat A.
Published: March 2009

The aldol condensation of 6‐alkoxy‐2,2‐dimethylchromanones 1 or 2 with substituted benzaldehydes in the presence of tetramethylorthosilicate and potassium fluoride affords 6‐alkoxy‐3‐benzylidene‐2,2‐dimethylchromanones 5‐10 while other conventional methods were unsuccessful.
An example of a novel formation of an oxepin
Authors: Parlow John J.
Published: March 2009

A novel formation of an oxepin, namely 9,10,11,12‐tetrafluoro‐5,6‐dihydrobenzo[b]naphth[2,1‐f]oxepin (5), starting from pentafluoroacetophenone and 1‐tetralone is described. Also, the same synthesis using 1‐indanone affords a very different ring system namely 1,2,3,4‐tetrafluoro‐5,11b‐dihydro‐7H‐benzo[c]fluoren‐7‐one (10). Both synthesis undergo an intramolecular nucleophilic substitution of an ortho‐fluorine. In one case, the oxygen displaces the fluorine to afford the oxepin 5 and the other a carbon is used as the nucleophile to give the polycyclic ring system 10.
Synthesis and anticonvulsant activity of 3H‐imidazo[4,5‐c]‐pyridazine, 1H‐imidazo[4,5‐d]pyridazine and 1H‐benzimidazole analogues of 9‐(2‐fluorobenzyl)‐6‐methylamino‐9H‐purine
Authors: Kelley James L. , Thompson James B. , Styles Virgil L. , Soroko Francis E. , Cooper Barrett R.
Published: March 2009

The 3H‐imidazo[4,5‐c]pyridazine, 1H‐imidazo[4,5‐d]pyridazine, and 1H‐benzimidazole analogues of the potent anticonvulsant purine 9‐(2‐fluorobenzyl)‐6‐methylamino‐9H‐purine (1, 78U79) were synthesized and tested for anticonvulsant activity. The 3H‐imidazo[4,5‐c]pyridazines 8 and 9 were prepared in five stages from 3,4,5‐trichloropyridazine (2). The 1H‐imidazolo[4,5‐d]pyridazine 15 was synthesized in four stages from 5‐[(benzyloxy)methyl]‐1,5‐dihydro‐4H‐imidazo[4,5‐d] pyridazin‐4‐one (10a). The benz‐imidazole analogues 18 and 20 were prepared from 2,6‐dinitroaniline in three stages. These compounds were one‐tenth or less as active as 1 in protecting rats against maximal electroshock‐induced seizures.
Synthesis of pyrrolo[3,4‐c]pyridazines
Authors: Poschenrieder Hermann , Stachel Hans‐Dietrich
Published: March 2009

We have prepared the pyrrolopyridazines 7a‐f starting from the diazo compounds 4. The synthesis involves a tandem condensation‐aza‐Wittig reaction or a combination of Wittig and aza‐Wittig reactions as key steps. Reaction of pyridazine 7d with diazomethane results in C‐methylation to yield 7g. Sodium borohydride reduces 7d to either the dihydropyridazine 12 or the hydroxylactam 13b depending of the reaction conditions.
Synthesis of 5‐(4‐substituted benzyl)‐2,4‐diaminoquinazolines as inhibitors of candida albicans dihydrofolate reductase
Authors: Jagdmann G. Erik , Chan Joseph H. , Styles Virgil L. , Tansik Robert L. , Boytos Christine M. , Rudolph Sharon K.
Published: March 2009

Several 5‐(4‐substituted benzyl)‐2,4‐diaminoquinazolines were prepared as potentially selective inhibitors of Candida albicans dihydrofolate reductase. These compounds were synthesized by a novel route, which included as a key step the displacement of a fluoro group in 2,6‐difluorobenzonitrile by the anions of ethyl or methyl 4‐substituted phenylacetates. The resultant diarylacetates were saponified and decarboxylated to the 2‐fluoro‐6‐(4‐substituted phenyl)benzonitriles. Ring closure of these benzonitriles with guanidine carbonate gave the 5‐(4‐substituted benzyl)‐2,4‐diaminoquinazolines.
Synthesis and biological evaluation of ‐n[4‐(2‐trans‐[([2,6‐diamino‐4(3H)‐oxopyrimidin‐5‐yl]methyl)thio]cyclobutyl)benzoyl] ‐l‐glutamic acid a novel 5‐thiapyrimidinone inhibitor of dihydrofolate reductase
Authors: Varney Michael D. , Romines William H. , Boritzki Theodore , Margosiak Stephen A. , Bartlett Charlotte , Howland Eleanor J.
Published: March 2009

The synthesis and biological evaluation of N‐[4‐(2‐trans‐[([2,6‐diamino‐4(3H)‐oxopyrimidin‐5‐yl]methyl)thio]cyclobutyl)benzoyl]‐L‐glutamic acid (1) is reported. Compound 1 is a potent dihydrofolate reductase (DHFR) inhibitor (Kj = 12 nM) with excellent in vitro cell culture growth inhibition (L1210, IC50 = 29 nM). Protection experiments showed that the cell growth inhibitory activity was due to DHFR inhibition. The key step in the synthesis was the coupling of a cyclobutylmethylthiol with the 5‐bromo‐2,6‐diamino‐4‐oxopyrimidine 8.
The synthesis of benzofuroquinolines. X. Some benzofuro[3,2‐c]isoquinoline derivatives
Authors: Yamaguchi Seiji , Yoshida Mika , Miyajima Izumi , Araki Toshikatsu , Hirai Yoshiro
Published: March 2009

Condensation of salicylonitrile with ethyl α‐bromo‐α‐(o‐ethoxycarbonylphenyl)acetate (4) effectively gave 5(6H)‐benzofuro[3,2‐c]isoquinolinone (2), which was converted to some 5‐substituted benzofuro‐[3,2‐c]isoquinoline derivatives 1a‐g.
Synthesis, Characterization, and crystallographic analysis of some benzoimidazole derivatives
Authors: Benvenuti Stefania , Severi Fabio , Vampa Gabriella , Malmusi Luca , Antolini Luciano
Published: March 2009

A number of benzenesulfonyl derivatives of benzoimidazol‐2‐ylamine and 1‐methyl‐benzoimidazol‐2‐ylamine were synthesized, their synthesis reactions under different experimental conditions being monitored by hptlc. The crystal and molecular structures of N‐(1‐benzenesulfonyl‐1,3‐dihydrobenzoimidazol‐2‐ylidene)benzenesulfonamide (4) and N‐(1‐benzenesulfonyl‐3‐methyl‐1,3‐dihydro‐benzoimidazol‐2‐ylidene)‐benzenesulfonamide (7) were determined by X‐ray diffraction analysis. The structure of compound 4 is made up of two crystallographically independent molecules and that of compound 7 of one molecule. In both cases, the structure contains the imido form of the molecules. There are strong conjugative effects between the imido groups and the imidazolic rings. Weak intramolecular CH···O hydrogen bonding interactions could influence the molecular conformations.
Synthesis, stereochemistry, and opioid receptor binding activity of heterocyclic analogues of BW373U86
Authors: Boswell G. Evan , Mcnutt Robert W. , Bubacz Dulce G. , Davis Ann O. , Chang Kwen‐Jen
Published: March 2009

The synthesis of a series of heterocyclic analogues of (±)‐4‐((αR*)‐α‐((2S*,5R*)‐4‐allyl‐2,5‐dimethyl‐1‐piperazmyl)‐3‐hydroxybenzyl)‐N,N‐diethylbenzarrude (BW373U86) for screening against opioid receptors is described. The intermediate α‐heterocyclic benzyl alcohols24were synthesized either by low temperature reaction of lithioheterocycles with 3‐((tert‐butyldimethylsilyl)oxy)benzaldehyde (10) or by reaction of 3‐((tert‐butyldimethylsilyl)oxy)phenylmagnesium bromide (19) with heterocyclic carbaldehydes. The α‐heterocyclic benzyl alcohols24were converted to chloromethines (25) with thionyl chloride and used to alkylate withtrans‐1‐allyl‐2,5‐dimethylpiperazine (5) to give diastereomeric pairs of the target compounds. The bromoheterocycles were then derivatized to produce amides. Compounds that are potent and selective for the 5 or μ opioid receptors and some mixed δ/μ analogues are reported.
Synthesis and anti‐tetrabenazine activity of c‐3 analogues of dimethyl‐2‐phenylmorpholines
Authors: Boswell G. Evan , Musso David L. , Kelley James L. , Soroko Francis E. , Cooper Barret R.
Published: March 2009

A series of analogues of 2‐phenylmorpholines with alkyl substituents at the C‐3 position were synthesized for anti‐tetrabenazine (anti‐TBZ) testing in mice. The target compounds were prepared by reaction of (2‐bromoalkyl) phenyl ketones 21a‐h with the appropriate aminoalcohol 20a‐b to form morpholinols 22a‐h. Hydride reduction of the morpholinols gave aminodiols 23a‐h which were cyclized to morpholines 6, 8, 10–12, 14–16, 18 and 19 by acid catalaysis. Compounds 7, 9, 13 and 17 were prepared by reductive formylation. The smaller straight chain substituents of 6, 8, 12 and 15, and the beta branching of the iso‐butyl group of 16 were well tolerated; anti‐tetrabenazine ED50′s were comparable to compounds 2–5. The α‐branched, N‐methylated, and side chain aryl derivatives were less active.
Polycyclic N‐heterocyclic compounds. 48. syntheses of furo[2,3‐h]‐[1,6]naphthyridine and imidazo(or pyrimido)[2,1‐f]‐[1,6]naphthyridines with rearrangement
Authors: Sasaki Kenji , Rouf Abu Shara Shamsur , Hirota Takashi
Published: March 2009

The formation of a novel ring system, furo[2,3‐h][1,6]naphthyridine via the Smiles rearrangement and intramolecular cyclization is described. Cyclization of 5‐(ω‐hydroxyalkylamino)‐8‐methyl‐1,2‐dihydrofuro[2,3‐h][1,6]naphthyridines provided novel spiro compound with rearrangement.
Synthesis of two novel ring systems via photocyclization: Thieno[2′,3′:4,5]thieno[2,3‐c][1,10]phenanthroline and thieno[3′,2′:4,5]thieno[2,3‐c][1,10]phenanthroline
Authors: Halverson Aileen Pfleider , Castle Lyle W. , Castle Raymond N.
Published: March 2009

The synthesis of thieno[2′,3′:4,5]thieno[2,3‐c][1,10]phenanthroline (5) and thieno[3′,2′:4,5]thieno‐[2,3‐c][1,10]phenanthroline (10) are described. Each compound was obtained in four steps from known starting materials. The basic skeleton of the molecule and of the phenanthroline ring were formed via photocyclization. The total assignment of 1H‐nmr spectra was accomplished with the aid of two‐dimensional nmr methods.
Reactivity of aminopyrroles: Protonation
Authors: Cirrincione Girolamo , Almerico Anna Maria , Diana Patrizia , Barraja Paola , Mingoia Francesco , Grimaudo Stefania , Dattolo Gaetano , Aiello Enrico
Published: March 2009

The behaviour of 2‐ and 3‐aminopyrroles towards protonation is similar. In dimethyl sulphoxide/trifluoroacetic acid they are protonated at the exocyclic nitrogen, whereas in pure trifluoroacetic acid, protonation at the 5‐ and/or 3‐position of the ring takes place.
2,6‐Diarylhexahydro‐4‐pyridazinols by acid‐catalyzed cyclization of benzaldehyde aryl‐2‐(2‐propenyl)hydrazones
Authors: Bakthavatchalam Rajagopal , Ciganek Engelbert , Calabrese Joseph C.
Published: March 2009

Treatment of benzaldehyde l‐(2‐propenyl)‐4‐methylsulfonylphenylhydrazone (1f) with 45% sulfuric acid gave 2‐(4‐methylsulfonylphenyl)‐6‐phenylhexahydro‐4‐pyridazinol (2f) in 35% yield rather than the expected 1‐(4‐methylsulfonylphenyl)‐1‐(2‐propenyl)hydrazine. The halogen‐substituted hydrazones 1c‐1e and benzaldehyde 1‐(2‐methyl‐2‐propenyl)phenylhydrazone (1b) gave similar results.
Reaction of dichlorocarbene with 2,3‐dihydro‐5,6‐dimethyl‐1,4‐oxathiin and 2,3‐dihydro‐5,6‐dimethyl‐1,4‐dithiin
Authors: Brewer A. D. , Znotins A. A.
Published: March 2009

Dichlorocarbene, generated from ethyl trichloroacetate and sodium ethoxide, reacts with 2,3‐dimethyl‐5,6‐dihydro‐1,4‐oxathiin to give 7,7‐dichloro‐1,6‐dimethyl‐2‐oxa‐5‐thiabicyclo[4,1,0]heptane, and with 2,3‐dimethyl‐5,6‐dihydro‐1,4‐dithiin to give 6‐chloro‐2,3‐dihydro‐7‐methyl 5‐methylene‐5(H)‐1,4‐dithiepin. Both products were oxidised to the corresponding sulfone.
A classification of organic redox reactions and writing balanced equations for them, with special attention to heteroatoms and heterocyclic compounds
Authors: Klemm L. H.
Published: March 2009

Organic redox reactions are classified either as atom transfers (balanced by inspection) or as more complex transformations (balanced by change in oxidation number, ON, by change in DOX value, by electrochemical half‐reaction, or by simultaneous linear algebraic equations). Examples presented include not only involvement of hydrogen or oxygen but also extensions to halogens, nitrogen, phosphorus, and sulfur. Complex reactions are subdivided into ones which proceed (a) without change in the number of carbon atoms per molecule, (b) with fragmentation of the carbon assemblage in the starting material, or (c) with condensation of two or more molecules of organic starting materials.
Synthesis of some highly functionalized thiophene‐3‐carboxylates and alcohols
Authors: Coppola Gary M. , Damon Robert E. , Yu Harvey
Published: March 2009

Highly functionalized thiophenes are prepared by two methods. The first uses a lithium‐halogen exchange reaction on a trisubstituted 5‐bromothiophene 25 to generate the corresponding 5‐lithiothiophene 26 which is then reacted with either dimethylformamide or formaldehyde to give the 5‐formyl 28 or 5‐hydroxymethylthiophene derivative 31 in good yields. These are further transformed to other tetrasubstituted thiophenes. The second method assembles the thiophene ring from three components: a benzyl mercaptan, an aldehyde, and a vinylphosphonate 10. Thus, the benzyl mercaptan is dilithiated then reacted with an appropriate aldehyde to afford a 2‐mercapto‐2‐phenylethanol derivative 37. Michael addition of 37 to 10 followed by oxidation of the hydroxyl group furnishes ketophosphonate 39. An intramolecular Wittig‐type reaction produces the thiophene skeleton.
Ring chain transformation of γ‐keto‐δ‐crotonolactones: A convenient synthesis of 1,4‐piperazinones, 1,4‐thiazinones and 1,4‐diazepinones
Authors: Apostolopoulos Costas D. , Georgiadis Minas P. , Couladouros Elias A.
Published: March 2009

A new procedure for the efficient synthesis of 1,4‐piperazinones, 1,4‐thiazinones and 1,4‐diazepinones is presented. The reaction is based on a ring chain transformation of γ‐keto‐δ‐crotonolactones induced by 1,2‐ or 1,3‐diamino‐ (or thiamino‐) binucleophiles. The reaction sequence of this transformation is also discussed.
Synthesis of novel heterocycles related to the dynemicin a ring skeleton
Authors: Nicolaou K. C. , Gross Jonathan L. , Kerr Michael A.
Published: March 2009

Studies directed towards the construction of the CDE ring framework of dynemycin A (1) are reported. A series of quinoline based dienophiles containing an activating group (e.g. 5, Scheme 1), reacted with acyclic dienes (e.g. 4, Scheme 1) in a Diels‐Alder fashion under increased pressure to afford a variety of heterocyclic systems related to the CDE skeleton of dynemycin A. Reaction of dienophile 15 with cyclic diene 29 led to the novel hetereocycle 34 whereas attempted decarbonylation of 41 led to a novel rhodium‐promoted intramolecular carbonylation of the terminal acetylene furnishing compound 43.
The lead tetraacetate oxidation of bisacetylhydrazones of α‐dicarbonyl compounds
Authors: Hadjiantoniou‐Maroulis Constantina P. , Vantsiouri Anastasia , Maroulis Apostolos J.
Published: March 2009

The oxidative cyclization of the title compounds results in generally two different kinds of products. The first, 1‐(N,N‐bisacetylamino)‐1,2,3‐triazole7(R3= CH3) is the primary product, while the second, 1‐N‐acetylamino‐1,2,3‐triazole8(R3= CH3), when observed, is obtainedviahydrolysis from the former during work‐up and separation of the reaction mixture. The primary products are considered as resulting from intramolecular nucleophilic attack on the acetyl group, of the presumed zwitterionic intermediate5(R3= CH3), by theNof the ambidentN‐acetylimine site of5.
Formation and crystal structure of an exocyclic enol δ‐lactone obtained from dimedone and trimethylsilylethynyl phenyliodonium triflate
Authors: Nikas Spyros , Rodios Nestor A. , Varvoglis Anastasios , Terzis Aristidis , Raptopoulou Catherine R.
Published: March 2009

The reaction between dimedone anion and trimethylsilylethynyl phenyliodonium triflate leads to the formation of 4,4‐dimethyl‐6‐(1,5‐bistrimethylsilylpentane‐1,4‐diyne‐3‐ylidene)‐δ‐valerolactone, whose crystal structure has been determined.
Reaction of 9‐substituted 1‐aminoadenine with hydrazine
Authors: Asano Shoji , Itano Keiji , Kohda Kohfuku , Yamagata Yuriko
Published: March 2009

Reaction of 9‐substituted (methyl or benzyl) 1‐aminoadenines 1 with hydrazine afforded 9‐substituted 6‐hydrazinopurines 2 and 1‐substituted 5‐ammo‐4‐(4‐amino‐1,2,4‐triazol‐3‐yl)imidazole (4). The product ratio of 2 to 4 rose with increasing amounts of methanol used as the solvent. When the same reaction was carried out using 1,9‐dimethyladenine instead of 1, compounds 2 and 4 were also obtained with N6,9‐dimethyladenine. A possible mechanism for formation of 2 and 4 is discussed.
Synthesis and reduction of 2,2‐diaryl‐1‐nitroethylenes by using a chiral and a non chiral NADH model in the pyrrolopyridine series
Authors: Levacher Vincent , Valque Claude , Coupa Sophie , Dupas Georges , Quéguiner Guy , Bourguignon Jean
Published: March 2009

Reduction of 2,2‐diphenyl‐1‐nitroethylene (1) and 2‐(2‐pyridyl)‐2‐phenyl‐1‐nitroethylene (5) is achieved by using the NADH model in the pyrrolopyridine series 2a to give 2,2‐diphenyl‐1‐nitroethane (3) and 2‐(2‐pyridyl)‐2‐phenyl‐1‐nitroethane (7) respectively in 40% yield. The asymmetric reduction of 2‐(2‐pyridyl)‐2‐phenyl‐1‐nitroethylene by the chiral NADH model 2b is studied. Thus, 2‐(2‐pyridyl)‐2‐phenyl‐1‐nitroethane (7) is obtained in 15 to 32% yield. The stereocontrol of the reduction proved to be dependent on the amount of magnesium ions.
Access to aza‐γ‐carbolines by annulation reaction of amino derivatives of imidazo[1,2‐α]pyridine
Authors: Jouanisson Anne , Couquelet Jacques , Teulade Jean‐Claude , Chavignon Olivier , Chabard Jean‐Louis , Dauphin GÉRard
Published: March 2009

Different routes of formation of aza‐γ‐carboline ring‐system are discussed. In addition the reactivity of an amino derivative in comparison with an iminophosphorane compound is investigated.
Photocyclization of 2‐[1]benzothien‐3‐yl)‐3‐phenylpropenoic acids
Authors: Tominaga Yoshinori , Castle Lyle W. , Castle Raymond N.
Published: March 2009

Photocyclization of the substituted 2‐([1]benzothien‐3‐yl)‐3‐phenylpropenoic acids 3a‐c in the presence of iodine and air in a benzene‐cyclohexane mixture afforded a separable mixture of three compounds, benzo[b]naphtho[2,1‐d]thiophene‐6‐carboxylic acids 4a‐c, 6H‐benzo[b]naphtho[2,3‐d]thiopyran‐6‐ones 5a‐c, and 10‐methoxy‐2‐methyl‐6H‐benzo[b]naphtho[2,3‐d]pyran‐6‐one (6).
Novel porphyrinoid macrocycles and their metal complexes
Authors: Vogel Emanuel
Published: March 2009

The cornucopia of novel porhyrinoid macrocycles that ‐ as a result of a symbiotic link between annulene and porphyrin chemistry ‐ has emerged from the Cologne laboratory over the last decade is reviewed.
Regioselective synthesis of 9‐substituted‐8‐azaguanines (5‐amino‐3‐substituted‐3,6‐dihydro‐7H‐1,2,3‐triazolo[4,5‐d]pyrimidin‐7‐one)
Authors: Sznaidman Marcos L. , Beauchamp Lilia M.
Published: March 2009

By modifying previously described methods for the synthesis of 9‐substituted‐guanines from imidazoles, we have developed a new procedure for the regioselective synthesis of 9‐substituted‐8‐azaguanines (5‐amino‐3‐substituted‐3,6‐dihydro‐7H‐1,2,3‐triazolo[4,5‐d]pyrimidin‐7‐one) from triazoles in high yields. The method seems suitable for the introduction of a variety of substituents including sugars, carbocyclic, acyclic and carboacyclic chains.
Ring transformations of heterocyclic compounds. XV. N‐(2‐hydroxyphenyl) substituted 2‐alkylamino‐4,6‐diarylbenzophenones by ring transformation of 2,4,6‐triarylpyrylium salts with anhydrobases of benzoxazolium salts
Authors: Zimmermann Thomas , Abram Ulrich , Schmidt Klaus
Published: March 2009

The synthesis of hitherto unknown N‐(2‐hydroxyphenyl) substituted 2‐alkylamino‐4,6‐diarylbenzophenones 3 from 2,4,6‐triarylpyrylium salts 1 and 3‐alkyl‐2‐methylbenzoxazolium salts 2 in the presence of triethylamine in ethanol by a 2,5‐[C4+C2] pyrylium ring transformation is reported. Structure elucidation is performed by an X‐ray crystal structure determination of the benzophenone 3a. Spectroscopic data of the transformation products and their mode of formation via anhydrobases of the salts 2 are discussed.
Ring transformations of heterocyclic compounds. XIV. Ring transformations of pyrylium and thiopyrylium salts with anhydro‐bases derived from 1H‐benzimidazolium and benzothiazolium salts: An easy access to 2‐(2,4,6‐triarylphenyl) 1H‐benzimidazolium and benzothiazolium derivatives
Authors: Zimmermann Thomas , Schmidt Klaus
Published: March 2009

The preparation of former unknown 2‐(2,4,6‐triarylphenyl) substituted 1H‐benzimidazolium perchlorates 7 and benzothiazolium perchlorates 8 from 2‐methyl substituted derivatives 5/6 by a 2,6‐[C5+C] ring transformation of 2,4,6‐triarylpyrylium and 2,4,6‐triarylthiopyrylium salts 1/9 in the presence of an appropriate base (7: sodium ethoxide, 8: sodium acetate) is reported. Spectroscopic data of the transformation products and their mode of formation via anhydrobases of the salts 5/6 are discussed.
Cycloaddition reactions of 2H‐benzo[b]thiete and conjugated cyclic dienes
Authors: Gröschl Dieter , Meier Herbert
Published: March 2009

2H‐Benzo[b]thiete 1 reacts with cyclopentadiene 3 in consecutive [8π + 2π]cycloadditions yielding the condensed heterocycles 6–8. Tetracyclone 9 on the other hand gives only the monoadduct 10. An [8π + 8π]cycloaddition can be observed for 1 and diphenylisobenzofuran 11. The related π system 13 shows again consecutive [477π + 27π]processes (1 + 13 ← 14, 15).
Synthesis and evaluation of 1H‐pyrazolo[3,4‐b]quinoxalines and 1‐aryl‐3‐quinoxalinyl‐1,2,4‐triazole as antibacterial agent
Authors: Kim Ho Sik , Chung Ju Young , Kim Eun Kyoung , Park Yong Tae , Hong Young Seuk , Lee Man Kil , Kurasawa Yoshihisa , Takada Atsushi
Published: March 2009

Novel 1H‐pyrazolo[3,4‐b]quinoxalines (flavazoles) 14, 15 and 1‐aryl‐3‐quinoxalinyl‐1,2,4‐triazole 17 were synthesized from the ester 11 via various hydrazones 12, 13 and 16. In the antibacterial screening test of compounds 12–17, compound 14 showed a relatively high antibacterial activity, wherein the MIC value was 25 μg/ml against Bacillus licheniformis KTCC 21425 and Cellulomonas sp. and 50 μg/ml against Salmonella typhimurium KCTC 1925 and Flavobacterium devolans.
Synthesis of novel 3‐alkoxy‐ and 3‐alkylthioindole and ‐benzofuran‐2‐carboxamides
Authors: Unangst Paul C. , Connor David T. , Miller Steven R.
Published: March 2009

The preparation of a series of 3,5‐substituted indole‐ and benzofuran‐2‐carboxamides is described. A 3‐alkoxy‐5‐hydroxybenzofuran was prepared by elaboration of a benzyloxy salicylate ester. A related 3‐alkylthiobenzofuran was obtained by the addition of thionyl chloride and isopropylmagnesium chloride to a benzofuran ester. A series of 3‐(methylthio)indoles was prepared from an indole sulfonium salt intermediate.
Nitroimidazoles. XII. A simple and efficient synthesis of 1‐methyl‐5‐nitroimidazole‐2‐acetic acid
Authors: Moezzi A. M. , Ghanbarpour A. , Shafiee A.
Published: March 2009

Reaction of 1‐methyl‐5‐nitroimidazole‐2‐carboxyl chloride (9) with diazomethane afforded 2‐diazo‐1‐(1‐memyl‐5‐nitro‐2‐imidazolyl)ethanone (10). Successive rearrangement of compound 10 via Arndt‐Eastert rearrangement yielded 1‐memyl‐5‐mtroimidazole‐2‐acetic acid (1), which was converted to its corresponding methyl ester 11 with etheral solution of diazomethane.
Synthesis of new proton‐ionizable dibenzocrown ethers
Authors: Kim Jong Seung , Bartsch Richard A.
Published: March 2009

A series of structurally related dibenzo‐15‐crown‐5, dibenzo‐18‐crown‐6, and dibenzo‐21‐crown‐7 compounds with oxymethylacetoxy side arms is synthesized by reaction of the corresponding crown ether alcohols with potassium hydride and bromoacetic acid. Multi‐step synthetic routes to the crown ether alcohol precursors are reported.
Reaction of 5‐amino‐1‐aryl‐3‐methylpyrazoles with benzylidene derivatives of meldrum's acid: Synthesis and characterization of pyrazolo[3,4‐b]pyridinones
Authors: Quiroga Jairo , Hormaza Angelina , Insuasty Braulio , Márquez Manuel
Published: March 2009

A series of dihydropyrazolo[3,4‐b]pyridin‐6‐ones 3 was prepared by cyclization of 5‐amino‐1‐aryl‐3‐methylpyrazoles 1 and Meldrum's acid benzylidene derivatives 2 in nitrobenzene. The structure of 4,5‐dihydropyrazolo[3,4‐b]pyridin‐6‐ones and reaction orientation were determined by nmr measurements.
The synthesis of hexahydrooxoepithiopyridinedicarboximides by the reaction of thioamides with N‐substituted maleimides
Authors: Takido Toshio , Tamura Sachiko , Sato Kenji , Kamijo Haruo , Nakazawa Toshikatsu , Seno Manabu , Hata Tadashi
Published: March 2009

The synthesis of hexahydrooxoepithiopyridinedicarboxyimide (5: X2 = N‐Ph) by the reaction of thioamides 1 with N‐substituted maleimide (2a) was examined. The reaction of primary thioamides, such as thiobenzamide and p‐toluthioamide with N‐phenylmaleimide gives compounds 5 together with corresponding 4‐hydroxy‐1,3‐thiazoles 4. However, a similar reaction of secondary thioamides, such as N‐methylthioacetamide, thiobenzanilide, with N‐phenylmaleimide did not provide compounds 5 without addition of acid. The reaction pathway and the configuration of 5 were also investigated.
Synthesis of 4‐aryl‐4,7,8,9‐tetrahydro‐6H‐pyrazolo[3,4‐b]quinolin‐5‐ones
Authors: Quiroga Jairo , Insuasty Braulio , Hormaza Angelina , Saitz Claudio , Jullian Carolina
Published: March 2009

Reaction of 5‐amino‐3‐methyl‐1‐phenylpyrazole (1a) and 5‐amino‐3‐(4‐chlorophenyl)‐1H‐pyrazole (1b) with dimedone (2) and p‐susbstituted benzaldehydes 3 in ethanol, afforded in all cases tricyclic linear 4‐aryl‐7,7‐dimethyl‐4,7,8,9‐tetrahydro‐6H‐pyrazolo[3,4‐b]quinolin‐5‐ones (4a‐j) in good yields. The linear structures and hence the regiospecificity of the reaction were established by nmr measurements.
Synthesis of some substituted dibenzodiazepinones and pyridobenzodiazepinones
Authors: Cohen Victor I. , Jin Biyun , Cohen Emil I. , Zeeberg Barry R. , Reba Richard C.
Published: March 2009

Some fluoro‐ and iodo‐derivative of 5‐[[4‐[(4‐diisobutylamino)butyl]‐1‐phenyl]acetyl]‐10,11‐dihydro‐5H‐dibenzo[b,e][1,4]diazepin‐1l‐one and 11‐[[4‐[(dialkylamino)butyl]‐1‐phenyl]acetyl]‐5,11‐dihydro‐6H‐pyrido[2,3‐b][1,4]benzodiazepin‐6‐ones 6 (Scheme 1) and their analogues were synthesized. The synthesis of dibenzodiazepinones 1 (Scheme 1) is based on the reaction between 1,4‐phenylenediamine and substituted benzoic acids. The intermediate pyridobenzodiazepinones 3 (Scheme 1) were prepared by condensation of 2‐chloro‐3‐aminopyridine with methyl anthranilate and its chlorine derivative. The condensation of 4‐[(halo)alkyl]phenylacetyl chloride with dibenzodiazepinones and pyridobenzodiazepinones followed by the reaction of mono‐ or dialkyl‐ or dialkenylamine provides 6 (Scheme 1).
New lariat ether carboxylic and hydroxamic acids: Synthesis and lanthanide ion complexation
Authors: Elshani Sadik , Noriyuki Randal , Wai Chien M. , Natale N. R. , Bartsch Richard A.
Published: March 2009

Twenty‐six new lariat ether carboxylic and hydroxamic acids based upon dibenzo‐13‐crown‐4, dibenzo‐14‐crown‐4, dibenzo‐16‐crown‐5 and dibenzo‐19‐crown‐6 ring systems are synthesized and the solid‐state structure for a dibenzo‐19‐crown‐6 lariat ether hydroxamic acid is determined. The efficiency and selectivity for lanthanide ion extraction into chloroform by these proton‐ionizable lariat ethers is strongly influenced by the crown ether ring size, lipophilic group attachment site and identity of the acidic function. In general, the lariat ether hydroxamic acids were more efficient and selective lanthanide ion extractants than the corresponding lariat ether carboxylic acids. The 1H nmr and ir binding studies indicate that both the macrocyclic polyether unit and the proton‐ionizable group are involved in lanthanide ion complexation.
Synthesis of novel 5‐aryl‐6‐cyano‐3H,8H‐pyrido[2,3‐d]pyrimidine‐4,7‐diones in the reaction of 6‐amino‐4‐pyrimidinones with benzaldehyde and ethyl cyanoacetate
Authors: Quiroga Jairo , Alvarado Mario , Insuasty Braulio , Nogueras Manuel , Sánchez Adolfo , López M. Dolores
Published: March 2009

The title compounds 4 and 5 have been prepared in one‐step reaction from 6‐amino‐4‐pyrimidinones 1, the corresponding 4‐substituted benzaldehyde 2 and ethyl cyanoacetate 3 in very good yields. The structure of the final compounds was determined on the basis of nmr measurements, especially by 1H, 1H‐, 1H,13C COSY, and DEPT.
Cyclecondensation of 3‐amino‐1,2,4‐triazole with substituted methyl cinnamates
Authors: Desenko Sergey M. , Lipson Victoria V. , Shishkin Oleg V. , Komykhov Sergey A. , Orlov Valery D. , Lakin Evgeny E. , Kuznetsov Valery P. , Meier Herbert
Published: March 2009

The reaction of 3‐amino‐1,2,4‐triazole (1) with substituted methyl cinnamates2a‐hleads selectively to the formation of 7‐aryl‐6,7‐dihydro[1,2,4]triazolo[1,5‐a]pyrimidin‐5(4H)‐ones3a‐h. The structure eluci dation of the products is based on ir,1H and13C nmr measurements and X‐ray diffraction.
Arylidene imidazothiazoles. Synthesis, structure and benzodiazepine receptor binding
Authors: Kieć‐Kononowicz Katarzyna , Szymańska Ewa , Karolak‐Wojciechowska Janina , Ksiazek Waldemar , Müller Christa E. , Geis Uli
Published: March 2009

A series of arylidene imidazo[2,1‐b]thiazoles was synthesized, in order to investigate the influence of different spatial arrangements of the arylidene substituent towards the bicyclic structure of imidazo[2,1‐b]‐thiazole on benzodiazepine receptor affinity. 1,2‐ And 2,3‐cyclized derivatives ofmono‐ anddi‐substituted Z‐5‐arylidene‐2‐thiohydantoins were investigated. As an example ofEisomersE‐5‐benzylidene‐2,3‐dihydroimidazo[2,1‐b]thiazol‐6(5H)‐one was obtained. The spatial arrangement of the arylidene sub stituent toward the bicyclic structure as well as the character of isomers had little influence on the benzo diazepine receptor affinity of the compounds. It seems that the greatest influence on biological activity has the nature and the number of substituents on the phenyl ring. All investigated imidazo[2,1‐b]thiazoles were less active than previously described arylidene imidazo[2,1‐b]thiazepinones.
Synthesis of a chiral macrocyclic dibenzodicyclohexanotetraamide‐containing stationary phase for liquid chromatography
Authors: Hu Kejiang , Bradshaw Jerald S. , Dalley N. Kent , Krakowiak Krzysztof E. , Wu Naijun , Lee Milton L.
Published: March 2009

Allyloxy‐substituted macrocyclic dibenzodicyclohexanotetraamide 2 was prepared by the following sequence. MonoBoc‐protected chiral 1,2‐cyclohexanediamine (3) was treated with isophthaloyl chloride followed by removal of the Boc group to form bisisophthalamide 5. Compound 5 was then treated with allyloxyphthaloyl chloride to form the macrocyclic tetraamide 2 in a 56% yield. Chiral selector 2 was converted to its ethoxydimethylsilane derivative and heated in a suspension of silica gel and toluene to form the chiral macrocycle‐containing silica gel phase 1. This phase separated the enantiomers of (±)‐α‐methylbenzylamine and (±)‐DL‐α‐aminobutyric acid methyl ester in a liquid chromatograph.
General preparative route to benzo[g]quinolines (1‐azaanthracenes)
Authors: Krapcho A. Paul , Gilmor Timothy P.
Published: March 2009

A convenient synthetic pathway to benzo[g]quinolines (1‐azaanthracenes) has been developed. The nickel catalyzed coupling of methyl 2‐chloronicotinate (3a) with benzylic organo zinc reagents 2a‐e led to the methyl 2‐benzylic substituted nicotinates 4a‐e. Treatment of methyl 2‐chloro‐6‐methylnicotinate (3b)with 2a in a similar manner led to methyl 2‐benzyl‐6‐methyInicotinate (4f). The coupling of 2‐chloro‐3‐acetylpyridine (5) with benzyl zinc bromide (2a) led to 2‐benzyl‐3‐acetylpyridine (4g). The coupling of the 2,5‐dichlorobenzylic organic zinc reagent (2f) with methyl 2‐choronicotinate (3a) was unselective but readily coupled with methyl 2‐bromonicotinate (6) to yield methyl 2‐(2,5‐dichlorobenzyl)nicotinate (4h). The esters 4a‐f,h on reduction with lithium aluminum hydride led to the corresponding alcohols 7a‐f,h which were subsequently oxidized with manganese dioxide to the respective 2‐benzylic substituted pyridine‐3‐carboxaldehydes 8a‐f,h. In one case the coupling of benzy] zinc bromide (2a) with 2‐chloropyridine‐3‐carboxaldehyde (9) led directly to 2‐benzylpyridine‐3‐carboxaldehyde (8a), but in poor yield. Cyclizations of the aldehydes 8a‐d,f,h or the ketone 4g with polyphosphoric acid afforded the benzo[g]quinolines 10a‐d,f‐h in high yields. Aldehyde 8e was cyclized to 10e using a solution of sulfuric acid in methanol. Several of the benzo[g]quinolines 10c,d could be readly converted into the benzo[q]quinoline‐5,10‐diones 11c,d on treatment with ammonium ceric nitrate.
Dihydrothienopsoralens: New furocoumarins as potential photoreacting agents
Authors: Zoubir B. , Refouvelet B. , Xicluna A. , Aubin F. , Humbert P.
Published: March 2009

A series of new dihydrothienopsoralen derivatives were synthesized from 6‐hydroxybenzo[b]furan in four steps in good yield. These compounds were prepared as potential photosensitizing and chemotherapeutic agents for psoriasis. The spectroscopy study in also reported and showed an absorbance at λ = 364 nm and fluorescence at λ = 440 nm with high molar absorptivity, wave length used to perform the photochemical and photobiological experiments.
A facile and convenient method for the preparation of macrocyclic diamides
Authors: Sharghi Hashem , Niknam Khodabakhsh , Massah Ahmad Reza
Published: March 2009

A number of macrocyclic diamides have been synthesized from the reaction of a diacid dicarboxylic dichloride with primary diamino compound in the presence of magnesium oxide‐silica gel at room temperature in good yields. Using urea and thiourea as well as diamines to produce the corresponding macrocycles in the range of 52–56% yields are also included in this paper. One of the major advantages of this method is simple regeneration of inorganic solid and its reuse through several cycles without a decrease in activity.
Synthesis and reactions of fluoroaryl substituted 2‐amino‐3‐cyanopyrroles and pyrrolo[2,3‐d]pyrimidines
Authors: Dave Chaitanya G. , Desai Nirmal D.
Published: March 2009

Some fluoroaryl substituted 2‐amino‐3‐cyanopyrroles 2 were synthesized from the reaction between (2‐bromo‐1‐arylalkylidene)propanedinitriles 1 and fluoroaryl substituted aromatic amines under Gewald reaction condition, which on reaction with formamide and formic acid gave 4‐aminopyrrolo[2,3‐d]pyrimidines 3 and pyrrolo[2,3‐d]‐pyrimidin‐4(3H)‐ones 4 respectively. 4‐Chloropyrrolo[2,3‐d]pyrimidines 5 were prepared by chlorination of 4 with phosphorus oxychloride, which on hydrazinolysis provided 4‐hydrazinopyrrolo[2–3‐d]pyrirnidines 6.
Reaction of E‐2‐arylidene‐1‐indanones, Z‐aurones, Z‐1‐thioaurones and Z‐2‐arylidene‐2,3‐dihydro‐1H‐indol‐3‐ones with diazomethane
Authors: Lévai Albert , Patonay Tamás
Published: March 2009

1,3‐Dipolar cycloaddition of E‐2‐arylidene‐1‐indanones 1a‐h and Z‐aurones 3a‐c with diazomethane provided trans‐spiro‐1‐pyrazolines 2a‐h and 4a‐c, respectively, as sole products. However, the same cycloaddition of Z‐1‐thioaurones 5a‐f afforded a mixture of Z‐α‐methyl‐1‐thioaurones 6a‐f and trans‐cyclopropane derivatives 7a‐f as a result of the spontaneous denitrogenation of the initially formed 1‐pyrazolines. Similar reaction of Z‐2‐arylidene‐2,3‐dihydro‐1H‐indol‐3‐ones 8a,b and diazomethane yielded trans‐cyclopropanes 9a,b. Structure and stereochemistry of the compounds synthesized have been elucidated by nmr spectroscopic measurements.
A new rigid benzene‐bridged macrotricyclic ligand
Authors: Krakowiak Krzysztof E. , Xue Guoping , Bradshaw Jerald S. , Dalley N. Kent , Nazarenko Alexander Y. , Zhang Xian X. , Izatt Reed M.
Published: March 2009

A macrotricyclic ligand composed of two benzene rings connected by four 2,2′‐oxydiphenoxide bridges (2) has been prepared by treating 1,2,4,5‐tetrakis[2‐(2‐hydroxyphenoxy)phenoxymethyl]benzene with 1,2,4,5‐tetrakis(bromomethyl)benzene in acetonitrile in the presence of potassium carbonate. Ligand 2 is of interest because of its similarity to macrocycle 1 which interacts strongly with cesium ions. The proposed more direct route of treating an excess of 2,2′‐oxydiphenol with 1,2,4,5‐tetrakis(bromomethyl)benzene to prepare 2 did not give the desired macrocycle but gave bis(tribenzo‐11‐crown‐3) (8). An X‐ray crystal structure study of 2 showed that the benzene rings which are linked by the four 2,2′‐oxydiphenoxide bridges are connected in a nonsymmetric pattern. The structure of 8 was also determined using X‐ray diffraction methods, and is reported.
Synthesis and structural study of novel 1,4,5,6,7,8‐hexahydroquinolines
Authors: Suárez Margarita , Verdecia Yamila , Ochoa Estael , Martín Nazario , Martínez Roberto , Quinteir Margarita , Seoane Carlos , Soto José L. , Novoa Héctor , Blaton Norbert , Peeters Oswald M. , De Ranter Camiel
Published: March 2009

A new series of 1,4,5,6,7,8‐hexahydroquinolines (9a‐j) has been synthesized and their structural features studied by X‐ray analysis and theoretical calculations at semiempirical and ab initio levels. A good correlation is found between the most stable conformation predicted for compounds 9 and that obtained by experimental X‐ray diffraction for 9h. The obtained geometrical features for 9 are similar to those found for other related active calcium modulators.