bluuebunny/crossref_metadata_2025 huggingface dataset:
Polycyclic arene sulfides. Preparation of 1a,2,3,11b‐tetrahydrobenz‐[5,6]anthra[1,2‐b]thiirene, 6b,7a,8,9‐tetrahydrobenzo[10,11]‐chryseno[1,2‐b]thiirene, and 7,8,8a,9a‐tetrahydrobenzo‐[10,11]chryseno[3,4‐b]thiirene
Authors: Shalom Yosef , Kogan Vladimir , Badriah Yacoub , Harvey Ronald G.
Published: March 2009

The title compounds 5, 7 and 9 which are the first arene sulfides of 7,8‐dihydrobenz[a]anthracene, 8,9‐and 10,11‐dihydrobenzo[a]pyrene, respectively, have been synthesized by treatment of the corresponding arene oxides 4, 6 and 8 with N,N‐dimethylthioformamide in the presence of catalytic amounts of trifluoroacetic acid.
The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 17. Thieno[3′,2′:4,5]thieno[2,3‐c]naphtho‐[2,1‐f]quinoline and thieno[3′,2′:4,5]thieno[2,3‐c]‐naphtho[1,2‐g]quinoline
Authors: Luo Jiann‐Kuan , Federspiel Ronald F. , Castle Raymond N. , Castle Lyle W.
Published: March 2009

The synthesis of two previously unknown novel polycyclic heterocyclic ring systems via photocyclization is described. The structural assignment of the isomeric ring systems, 4 and 5, was achieved by the total assignment of their 1H and 13C nmr spectra by the concerted usage of two‐dimensional nmr methods.
Synthesis of some novel 2‐phenylpyridazino[4,5‐b][1,5]thiazepines
Authors: Mátyus Péter , Zára‐Kaczián Erzsébet , Boros SÁNdor , Böcskei Zsolt
Published: March 2009

Synthesis of some derivatives of the pyridazino[4,5‐b][1,5]thiazepine ring system is reported. Thus, 5‐benzyl‐8‐methyl‐2‐phenyl‐2,3.4,5‐tetrahydro‐5H‐pyridazino[4,5‐b][1,5]thiazepin‐9(8H)‐one (5) was prepared by an intramolecular S‐alkylation reaction, whereas the thiazepine ring of sulfone analogue 21, and that of the novel tricyclic pyrrolidino fused ring system 22 was elaborated by an intramolecular C‐alkylation reaction. Unexpected formation of bicyclic pyrido‐ and thiazine fused pyridazine systems are also discussed.
Retro‐ene reactions. III. Alkylation of 4,5‐dichloro‐1‐hydroxymethylpyridazin‐6‐ones: Synthesis of 4,5‐dichloro‐1‐(ω‐phthalimido and saccharin‐2′‐ylalkyl)pyridazin‐6‐ones
Authors: Kim Sung‐Kyu , Cho Su‐Dong , Moon Jung‐Kyen , Yoon Yong‐Jin
Published: March 2009

4,5‐Dichloro‐1‐(ω‐phthalimido and saccharinyl‐2′‐ylalkyl)pyridazin‐6‐ones were synthesized from 4,5‐dichloro‐1‐hydroxymethylpyridazin‐6‐one and the corresponding N‐(ω‐haloalkyl)phthalimides and saccharins via a fragmentation of retro‐ene type.
A new synthesis of 1,5‐dihydropyridazino[3,4‐b]quinoxalines and 2‐(pyrazol‐4‐yl)quinoxalines
Authors: Kurasawa Yoshihisa , Takano Akiko , Kato Kyoko , Takada Atsushi , Kim Ho Sik , Okamoto Yoshihisa
Published: March 2009

The reaction of 6‐chloro‐2‐(l‐methylhydrazino)quinoxaline 1‐oxide 3 with acetylenedicarboxylates gave the 8‐chloro‐1‐memyl‐1,5‐dihydropyridazino[3,4‐b]quinoxaline‐3,4‐dicarboxylates 4a,b and 2‐(pyrazol‐4‐yl)quinoxaline 1‐oxides 5a,b. The formation of compounds 4a,b would follow the 1,3‐dipolar cycloaddition reaction, subsequent 1,2‐hydrazino migration, and then dehydrative cyclization, while the production of compounds 5a,b would proceed via the addition of the hydrazino group to acetylene‐dicarboxylate leading to the construction of a pyrazole ring, followed by rearrangement of the pyrazole ring. Compounds 5a,b were deoxidized with phosphoryl chloride/N,N‐dimethylformamide to change into the 4‐(quinoxalin‐2‐yl)pyrazole‐3‐carboxylates 8a,b.
Synthesis of heterocyclic sulfonylureas
Authors: Löwe Werner , Matzanke Norbert
Published: March 2009

We examined the scope of the previously reported one‐pot synthesis [1] of chromone‐3‐sulfonylureas. Different anilines and heterocyclic amines were thereby reacted with chlorosulfonyl isocyanate‐derived chlorosulfonylureas. These were treated with different enaminones and enamines to provide the title compounds.
Addition of trimethylsilyl azide and of “mixed anhydrides” to the N‐C(3) σ‐bond in 3‐substituted‐1‐azabicyclo[1.1.0]butanes
Authors: Marchand Alan P. , Sharma G. V. M. , Rajagopal D. , Shukla Rajesh , Mlostoń Grzegorz , Bartnik Romuald
Published: March 2009

Trimethylsilyl azide adds smoothly to the highly strained N‐C(3) σ‐bond in 3‐ethyl‐1‐azabicyclo[1.1.0]‐butane (1) to afford an adduct, 2, that reacts in situ with a variety of electrophilic reagents (i.e., ethyl chloroformate, p‐toluenesulfonyl chloride, benzoyl chloride, acetyl chloride, and oxalyl chloride) to afford the corresponding N‐substituted‐3‐azido‐3‐ethylazetidines 3–7, respectively in 62–72% yield. Similarly, 1 reacts regiospecifically with “mixed anhydrides” (i.e., p‐toluenesulfonyl acetate, methanesulfonyl acetate, and benzoyl trifluoromethanesulfonate) to afford the corresponding adducts, 8–10, respectively) in 38–68% yield. Reaction of p‐toluenesulfonyl azide with 1‐aza‐3‐phenylbicyclo[1.1.0]butane (12) produces two products: N‐(p‐toluenesulfonyl‐3‐azido‐3‐phenylazetidine (13, 15%) and a dimeric product, N‐(N'‐p‐toluenesulfonyl‐3′‐phenyl‐3′‐azetidinyl)‐3‐azido‐3‐phenylazetidine (14, 28%). Ethyl chloroformate adds to the N‐C(3) σ‐bond in 1‐aza‐3‐(bromomethyl)bicyclo[1.1.0]butane (15) to afford N‐carboethoxy‐3‐(bromomethyl)‐3‐chloroazetidine (16) in 73% yield.
Synthesis of 1‐ and 2‐(2‐quinolyl)azulenes by the friedländer reaction of acetylazulenes
Authors: Mori Takahiro , Imafuku Kimiaki , Piao Ming‐Zhu , Fujimori Kunihide
Published: March 2009

1‐Acetylazulene and 3‐methyl‐, 3‐ethyl‐, and 3‐propyl‐substituted 1‐acetylazulenes were prepared by the reaction of 3‐acetyl‐2H‐cyclohepta[b]furan‐2‐one with in situ generated enamines from aldehydes and amines. These four 1‐acetylazulenes reacted with 2‐aminobenzaldehyde and its 4,5‐dimethoxy‐ and 4,5‐methylenedioxy‐substituted derivatives in the presence of sodium ethoxide to afford twelve 1‐(2‐quinolyl)azulenes. In a similar manner, three 2‐(2‐quinolyl)azulenes were also prepared from 2‐acetylazulene.
[1]Benzothienoindolizidinones and [1]benzothienoquinolizidinones: Synthesis and schmidt rearrangement into [1,3]diazepines derivatives
Authors: Daïcb Adam , Decroix Bernard
Published: March 2009

[1]Benzothienoindolizidinones 5ac,ae,bc and [1]Benzothienoquinolizidinone 5ad were synthesized from 2(3)‐bromethyl[1]benzothiophene and methyl prolinate, methyl oxoprolinate and ethyl pipecolinate. The Schmidt rearrangement of ketones 5 led exclusively to the [1,3]diazepines derivatives 6.
Diethyl N,N‐dimethylaminomethylenemalonate in the synthesis of fused heterocyclic systems
Authors: Kušar Mihael , Svete Jurij , Stanovnik Branko
Published: March 2009

The reactions of diethyl N,N‐dimethylaminomethylenemalonate (3) with N‐ and C‐ nucleophiles were studied. In the reaction of 3 with heterocyclic amines 4, with the amino group attached at α‐position in respect to the ring nitrogen atom, substitution of the dimethylamino group in 3 with the heterocyclic amino took place to give diethyl heteroarylaminomethylenemalonates 5, which can cyclize into fused azino‐ 6 or azolopyrimidinones 7. In the reaction of 3 with the compound with an active methylene group attached at α‐position in regard to the ring nitrogen atom, such as pyridinylacetonitrile (8), ethyl pyridinyl‐ (9), and quinolinylacetate (10), fused quinolizines 11 and 12, and benzo[c]quinolizine 13 were formed, respectively. Heterocyclic systems with an active or potentially active methylene group incorporated in the ring system, such as pyrazole 14, pyrimidine 15, and pyridine derivative 18, gave with 3 fused pyranones 16, 17, and 19, and dihydroxynaphthalenes 22 and 23 naphtho[2,1‐b]pyranones 24 and 25.
Aroylation of 5‐amino‐2H‐1,2,4‐thiadiazolin‐3‐ones
Authors: Cho Nam Sook , Ra Chan Soo , Ra Do Young , Song Jin Soo , Kang Sung Kwon
Published: March 2009

2‐Aroyl‐5‐aroylamino‐1,2,4‐thiadiazolin‐3‐ones (2) have been synthesized through aroylation of 5‐arruno‐2H‐1,2,4‐thiadiazolin‐3‐one (1) as an analog of cytosine. The aroylation was carried out with a substituted aroyl chloride in pyridine at 56∼58°C. It has been established that the intermediates of the reactions are 2‐aroyl‐5‐amino‐1,2,4‐thiadiazolin‐3‐ones (3) on the basis of the spectral data, additional experimental information and ab initio molecular orbital calculations.
3,6‐Thioanhydro sugar derivatives. An enantiospecific synthesis of (2R,3R,4S)‐3‐benzyloxy‐4‐hydroxy‐2‐[(R)‐1‐benzyloxy‐4‐hydroxybutyl]thiolane as the key intermediate for thioswainsonine
Authors: Izquierdo Isidoro , Plaza Maria T. , RamYírez Antonio , Aragón Fida
Published: March 2009

Methyl 2‐O‐benzyl‐3,6‐thioanhydro‐α‐D‐mannopyranoside (9) was obtained in eight steps from the commercially available methyl α‐D‐glucopyranoside. Compound 9 was transformed into (2R,3R,4S)‐3‐benzyloxy‐4‐hydroxy‐2‐[(R)‐1‐benzyloxy‐4‐hydroxybutyl]thiolane (14) by acid hydrolysis of its 2,4‐di‐O‐benzyl derivative 10 followed by reaction of the not isolated 2,4‐di‐O‐benzyl‐3,6‐thioanhydro‐D‐mannose (11) with ethoxycarbonylmethylenetriphenylphosphorane to give an = 1:1 E/Z mixture of the corresponding α,β‐unsaturated ester (12). Finally, catalytic hydrogenation of 12 to ethyl (R)‐4‐benzyloxy‐4‐[(2′R)3′R,4′S)‐3′‐benzyloxy‐4′‐hydroxythiolan‐2′‐yl]butanoate (13) and subsequent reduction with lithium aluminum hydride gave the title compound 14.
The reaction of vinyl ethers with acridine
Authors: Takano Rumi , Ishihara Yoshimi , Saito Hiroshi , Kitahara Takio , Takano Jiro
Published: March 2009

The reaction of vinyl ethers with acridine gives new acridine derivatives in the presence of an organic ammonium salt and alcohol. An organic ammonium salt such as acridinium chloride affect this reaction. All of the addition products were obtained as dihydroacridinyl derivatives. Moreover, in the reaction of ketene silyl acetal with acridine, the addition products were also obtained as the dihydroacridine derivatives.
Synthesis and chemistry of the ionophore antibiotic tetronasin
Authors: Ley Steven V. , Clase J. Andrew , Mansfield Darren J. , Osborn Helen M. I.
Published: March 2009

Studies towards the synthesis and biosynthesis of tetronasin, an acyltetronic acid ionophore are described, together with an account of some novel methodology which is more widely applicable for the synthesis of other acyltetronic acids.
The synthesis of 8‐allyl‐2‐styrylchromones by the modified baker‐venkataraman transformation
Authors: Reddy B. Parthasarathi , Krupadanam G. L. David
Published: March 2009

Substituted‐2‐hydroxy‐3‐allylacetophenones 2 react with cinnamoyl chlorides 3 in potassium carbonate‐acetone to give good yields of polyfunctional 1‐(2‐hydroxy‐3‐allylaryl)‐5‐aryl‐4‐pentene‐1,3‐diones 4 which exist in their enol forms 5. These on acid catalysed cyclodehydration gave 70–80% yields of substituted 8‐allyl‐2‐styrylchromones 6.
Haloacetylated enol ethers. 7 . Synthesis of 3‐aryl‐5‐trihalomethylisoxazoles and 3‐aryl‐5‐hydroxy‐5‐trihalomethyl‐4,5‐dihydroisoxazoles
Authors: Martins Marcos A. P. , Siqueira Geonir M. , Bastos Giovani P. , Bonacorso Helio G. , Zanatta Nilo
Published: March 2009

β‐Aryl‐β‐methoxyvinyl trihalomethyl ketones 1a‐g, 2a‐g [aryl = p‐YC6H4 where Y= H, Me, OMe, F, Cl, Br, NO2] are cyclocondensed with hydroxylamine hydrochloride to afford the 3‐aryl‐5‐hydroxy‐5‐trihalomethyl‐4,5‐dihydroisoxazoles 3a‐g, 4a‐f in good yield. The dehydratation of compounds 3a‐g with concentrated sulfuric acid, led the corresponding 3‐aryl‐5‐trichloromethylisoxazoles 5a‐g. An alternative one‐pot procedure yields 3‐aryl‐5‐trihalomethylisoxazoles 5,6a‐g directly by cyclocondesation of 1,2a‐g with hydroxylamine hydrochloride in the presence of an excess of concentrated hydrochloric acid.
Syntheses for 2‐amino and 2‐mercapto‐2H‐1,4‐benzoxazin‐3(4H)‐one and 2H‐1,4‐benzothiazin‐3(4H)‐one as aza and thio analogues of the natural product blepharigenin
Authors: Kluge Michael , Sicker Dieter
Published: March 2009

2‐Amino‐2H‐1,4‐benzoxazin‐3(4H)‐one 3, 2‐amino‐2H‐1,4‐benzothiazin‐3(4H)‐one 4, 2‐mercapto‐2H‐1,4‐benzoxazin‐3(4H)‐one 7, and 2‐mercapto‐2H‐1,4‐benzothiazin‐3(4H)‐one 8 representing aza and thio analogues of the natural product's aglucone Blepharigenin (2‐hydroxy‐2H‐1,4‐benzoxazin‐3(4H)‐one) from Gramineae and Acantnaceae species have been synthesized for the first time from their 2‐bromo precursors 1 and 2. Attempts to similarly prepare the 4‐hydroxy derivatives of 7 and 8, which would represent new thio analogues of the naturally occurring cyclic hydroxamic acid, 2,4‐dihydroxy‐2H‐1,4‐benzoxazin‐3(4H)‐one, have failed.
Synthesis and spectral properties of isomeric [(12‐N‐methyl) and (10‐N‐methyl)]‐11‐(o, and p‐substituted‐anilino)‐5H‐dibenzo[b,e][1,4]diazepines
Authors: Cortés Eduardo Cortés , Islas Pedro Muñoz , García Marcos Martínez , Romero Mayra O. Zepeda
Published: March 2009

The preparation of sixteen novel substituted [(10‐N‐methyl) and (12‐N‐methyl)]‐11‐(o‐, and p‐substituted‐anilino)‐5H‐dibenzo[b,e][1,4]diazepines which have potentially useful pharmacological properties is described. The structure and the isomeric differences in all products was corroborated by ir, 1H‐nmr, 13C‐nmr, and mass spectra.
New trifluoromethylated pyridines from functionalized N1‐acylacetamidrazones
Authors: Cocco Maria Teresa , Congiu Cenzo , Onnis Valentina , Bernard Angela Maria , Piras Pier Paolo
Published: March 2009

Polyfunctionalized trifluoromethylpyridines 4, 5 were readily synthesized from trifluoroacetylvinyl ether 3, using N1‐acylacetamidrazones 1,2 as starting material.
Iminium carbonic acid derivative salts. IX. Synthesis of N,S‐containing heterobicycles from N‐protected 2‐methylthio‐1,3‐thiazinium and 2‐methylthiothiazolium salts part 1. Preparation of N‐protected 2‐methylthio‐1,3‐thiazinium and 2‐methylthiothiazolium salts and their reaction with CH‐acidic compounds
Authors: Hanefeld Wolfgang , Naeeni Mahmoud , Schlitzer Martin
Published: March 2009

N‐Boc‐protected 1,3‐thiazine‐2‐thiones and thiazolidin‐2‐thiones were transformed into the corresponding 2‐methylthio‐1,3‐thiazinium and 2‐methylthiothiazolium salts by methyl iodide or trimethyloxonium tetrafluoroborate. This activated species were reacted with CH‐acidic compounds forming ketene‐N,S‐acetals. The protection group was removed with trifluoracetic acid to yield the N‐unsubstituted ketene‐N,S‐acetals.
A facile preparation of some novel class II mesoionic xanthine acyclonucleosides
Authors: Giandinoto Salvatore , Mbagwu Godwin O. , Robinson Tamara A. , Ferguson Chantel , Nunez Jacqueline
Published: March 2009

The synthesis of the first examples of Class II mesoionic xanthine acyclonucleosides is described. A series of mesoionic anhydro‐(8‐methoxyalkyl‐5‐hydroxy‐7‐oxothiazolo[3,2‐a]pyrimidinium hydroxides), Class II mesoionic analogs isoconjugate with xanthine, were prepared by the thermal condensation of methoxyalkyl‐2‐aminothiazoles with substituted bis(2,4,6‐trichlorophenyl)malonic esters. The memoxyalkyl‐2‐aminothiazoles were prepared via an aromatic nucleophilic substitution reaction between 2‐bromothiazole and the appropriate methoxyalkylamine in excess. The resulting 8‐methoxyalkyl‐substituted mesoionic xanthines were demethylated using iodotrimethylsilane in acetonitrile at room temperature to afford the corresponding mesoionic anhydro‐(8‐hydroxyalkyl‐5‐hydroxy‐7‐oxothiazolo[3,2‐a]pyrimidinium hydroxides) as the Class II mesoionic xanthine acyclonucleosides.
First synthesis of 4H‐furo[3,2‐f]pyrrolo[1,2‐a][1,4]diazepines
Authors: Feng Xiao , Lancelot Jean‐Charles , Prunier Hervé , Rault Sylvain
Published: March 2009

The synthetic pathway leading to 4‐H‐furo[3,2‐f]pyrrolo[1,2‐a][1,4]diazepines is described in five steps starting from 2‐hydroxyketones via 2‐amino‐3‐furonitriles.
Synthesis and some transformations of 5‐benzotriazolyl‐3,4‐dihydropyrid‐2‐ones
Authors: Katritzky Alan R. , Shcherbakova Irina V.
Published: March 2009

5‐(Benzotriazolyl)‐substituted 3,4‐dihydropyrid‐2‐ones were obtained by condensation of 4‐benzo‐triazolyl‐5‐phenyl(methyl)‐5‐oxopentanoic acids with benzyl or aryl amines. Dehydrogenation of 3,4‐dihydropyrid‐2‐ones resulted in 5‐benzotriazolyl‐substituted pyrid‐2‐ones and/or 5‐(phenylamino)pyrid‐2‐ones, products of nitrogen elimination from the benzotriazolyl substituent. In turn, 5‐benzotriazol‐1‐yl‐substituted pyrid‐2‐ones eliminated nitrogen under Graebe‐Ullmann conditions to give indolopyridones.
Nucleophilic substitutions of 2‐chloronaphtho[2,3‐b]furan‐4,9‐dione with amines
Authors: Koyanagi Jyunichi , Ogawa Masayuki , Yamamoto Katsumi , Nakayama Kouji , Tanaka Akira
Published: March 2009

2‐Chloronaphtho[2,3‐b]furan‐4,9‐dione 4 was allowed to react with pyrrolidine to produce 2‐(1‐pyrrolidinyl)naphtho[2,3‐b]furan‐4,9‐dione 8 in 64% yield. In a similar manner, the reaction of 4 with cyclic amines (piperidine, morpholine, 4‐substituted piperazines, etc.) gave the desired compounds. 2‐Dimethylaminonaphtho[2,3‐b]furan‐4,9‐dione 20 and 2‐propylaminonaphtho[2,3‐b]furan‐4,9‐dione 23 were obtained from the reactions of 4 with amines in 67% and 48% yields, respectively. Furthermore, the reactions of 4 with acyclic amines (diethylamine, dipropylamine, isopropylamine, butylamine, etc.) gave the desired compound. Compound 4 was treated with sodium azide to give 2‐azidonaphtho[2,3‐b]furan‐4,9‐dione 28 in 42% yield. All these nucleophilic substitutions were carried out at room temperature. It was found that 4 showed high reactivity for amines. Unexpectedly, 2‐morpholinonaphtho[2,3‐b]furan‐4,9‐dione 13 was obtained from the reaction of 4 with 1‐morpholino‐1‐cyclohexene.
Synthesis and central nervous system stimulant activity of 5,8‐methanoquinazolines fused with imidazole, thiadiazole, pyrimidine and 1,3,5‐triazine
Authors: Nagai Sbin‐Ichi , Ueda Taisei , Nagatsu Akito , Nakaoka Keiko , Murakami Nobutoshi , Sakakibara Jinsaku , Fujita Michiko , Hotta Yoshihiro
Published: March 2009

5,8‐Methanoquinazolines fused with imidazoles 4a‐4b, thiadiazoles 5–6, pyrimidines 7, 9, 11 and 12, and 1,3,5‐triazine 13 were prepared starting from (5R,8S)‐2‐amino‐8,9,9‐trimethyl‐5,6,7,8‐tetrahydro‐5,8‐methanoquinazoline 3. Most compounds possessed central nervous system stimulant activities.
Novel solid‐state synthesis of dimeric 4‐aryl‐1,4‐dihydropyridines
Authors: Hilgeroth Andreas , Heinemann Frank W.
Published: March 2009

On irradiation in the solid state the 4‐aryl‐1,4‐dihydroypridines 1 undergo [2+2] cycloadditon to centrosymmetric head‐to‐tail dimers 3 and 4a. The almost exclusive formation of the cage dimers 3 via the C2‐symmetric syn‐dimers 2 takes place in nearly quantitative yields, in contrast with the cycloaddition reaction of the anti‐dimer 4a, which is accompanied by photooxidation to pyridine 5a.
A study on ester formylhydrazones
Authors: Ikizler Aykut A. , Yildirim Nuri
Published: March 2009

A series of ester formylhydrazones 2 were synthesized from the reaction of alkyl imidate hydrochlorides 1 with formylhydrazine. Treatment of 2 with hydrazine hydrate, ethyl carbazate and tert‐butyl carbazate led to the formation of 3‐alkyl‐4‐amino‐, 3‐alkyl‐4‐ethoxycarbonylamino‐ and 3‐alkyl‐4‐tert‐butoxycar‐bonylamino‐4H‐1,2,4‐triazoles 3–5, respectively. Reaction of compounds 2 with formylhydrazine gave N,N'‐diformylhydrazine 6. Compounds 2 were reacted with 2,5‐dimethoxytetrahydrofuran to afford 3‐alkyl‐4‐(1H‐pyrrol‐1‐yl)‐4H‐1,2,4‐triazoles 8.
Synthesis of spiro[2H‐indole‐2,1′‐1H‐isoindole]‐3,3′‐diones, spiro[1H‐isobenzofuran‐1,2′‐2H‐indole]‐3,3′‐diones and spiro[benzofuran‐2,1′‐isobenzofuran]‐3,3′‐diones via transannular reactions of eight membered ring intermediates
Authors: Bullington James L. , Dodd John H.
Published: March 2009

An auto oxidation‐rearrangement product 4 was isolated from a high dilution reaction of ninhydrin with 3,4,5‐trimethoxyaniline in water. A general synthesis of this compound and its derivatives 4–6 was devised by oxidation of tetrahydroindeno[1,2‐b]indol‐10‐ones 1–3 with sodium periodate to give isoindolo[2,1‐a]‐indole‐6,11‐diones 4–6 in good yield. Compounds 4–6 can be easily transformed into spiro[1H‐isobenzofuran‐1,2′‐2H‐indole]‐3,3′‐diones 8–10, spiro[2H‐indole‐2,1′‐1H‐isoindole]‐3,3′‐diones 11–13 and isoindole[1,2‐a:2′,1′‐b]pyrimidine‐5,15‐diones 15, 16 in high yields. Analogous reactions were performed on 3‐amino‐5a, 10a‐dihydroxybenzo[b]indeno[2,1‐d]furan‐10‐one (17) to give a dibenzoxocintrione 18, spiro‐[benzofuran‐2,1′‐isobenzofuran]‐3,3′‐dione 19 and an isoindol‐1‐one 20.
Haloacetylated enol ethers. 9. Synthesis of 4‐trifluoromethyl‐2‐methyl[phenyl]pyrimidines and tetrahydro derivatives
Authors: Zanatta Nilo , Fagundes Madelon B. , Ellensohn Ricardo , Marques Marcelo , Bonacorso Helio G. , Martins Marcos A. P.
Published: March 2009

The synthesis of 4‐trifluoromethyl‐2‐methyl[phenyl]pyrimidines and the corresponding tetrahydro derivatives from the cyclo‐condensation reaction of β‐alkoxyvinyl trifluoromethyl ketones 1a‐d with acetamidine or benzamidine hydrochloride, is reported. For the cyclo‐condensation of 1a‐d with acetamidine and benzamidine hydrochloride, two methods were tested: 1 M solution of sodium hydroxide (method A) and sodium alkoxide/alcohol (method B). Depending on the structure of the β‐alkoxyvinyl trifluoromethyl ketones and the reactions conditions, pyrimidines or tetrahydropyrimidines or a mixture of both compounds were obtained.
Improved preparation of N‐propargyl‐2‐(5‐benzyloxyindolyl)methylamine [a]
Authors: Marco José L.
Published: March 2009

An improved synthetic sequence for the synthesis of N‐propargyl‐2‐(5‐benzyloxyindolyl)methylamine (1) is described.
Synthesis and debenzoylation products of two perbenzoylated 2‐substituted 5‐D‐galactosyl‐1,3,4‐oxadiazoles
Authors: Cannizzaro Carina E. , Thiel Inge M. E. , D'Accorso Norma B.
Published: March 2009

The synthesis of 2‐(p‐chlorophenyl)‐5‐[1′,2′,3′,4′,5′‐penta‐O‐benzoyl‐D‐galactopentitol‐1‐yl]‐1,3,4‐oxadiazole is described. Its debenzoylation gave an equilibrium mixture of the 1,3,4‐oxadiazole derivative without protection of the hydroxyl group and the N‐benzoyl‐D‐galactono‐1,4‐lactonehydrazone. A similar equilibrium was observed by debenzoylation of 2‐phenyl‐5‐[1′,2′,3′,4′,5′‐penta‐O‐benzoyl‐D‐galactopentitol‐1‐yl]‐1,3,4‐oxadiazole. The 1H, 13C nmr and ms spectra of these compounds are presented.
Synthesis of new 6‐(4‐chlorophenyl)perhydro‐1,3‐diazepine‐2,4‐diones via ureidobutyric acids
Authors: Guillon Jean , Sonnet Pascal , Dallemagne Patrick , Miel Hugues , Rault Sylvain , Daoust Martine , Boulouard Michel
Published: March 2009

Synthesis of new 6‐(4‐chlorophenyl)perhydro‐1,3‐diazepine‐2,4‐diones was accomplished starting from 4‐amino‐3‐(4‐chlorophenyl)butyric acid (Baclofen). The chemical pathway involved the cyclisation of various 3‐(4‐chlorophenyl)‐4‐ureidobutyric acids. However, none of the new derivatives retained the anticonvulsant activity of their six‐membered ring homologues, belonging to the phenylpyrimidinedione series which we recently described.
Syntheses of new pyridonecarboxylic acid derivatives containing 3‐,5‐ or 6‐quinolyl substituents at N‐1 and their anti‐HIV‐RT activities
Authors: Oh Yoon‐Seok , Lee Chi‐Wbo , Chung Yong‐Ho , Yoon Sung‐June , Cho Sung‐ Hye
Published: March 2009

A series of new pyridonecarboxylic acid derivatives containing 3‐, 5‐ or 6‐quinolyl substituents at N‐1 were synthesized and their in vitro anti‐HIV‐RT activities were evaluated. Several compounds in this series showed better activity than Atevirdine.
Studies on pyrrolidinones. Synthesis of N‐benzhydrylpyroglutamic acids and esters
Authors: Rigo Benoît , Gautret Philippe , Legrand Anne , Hénichart Jean Pierre , Couturier Daniel
Published: March 2009

Catalyzed N‐alkylation of N,O‐bistrimethylsilyl pyroglutamic acid with trimethylsilyl benzhydryl ethers yields trimethylsilyl N‐benzhydrylpyroglutamates. Hydrolysis of these compounds or saponification of the methyl esters gives the corresponding acids.
Ring opening reactions of 6‐oxo‐substituted spiro‐pyrrolidinediones: Synthesis of 4‐substituted‐1,5‐dihydro‐3‐hydroxy‐2‐oxo‐1,5‐diphenyl‐2H‐pyrroles
Authors: Emerson David W. , Titus Richard L. , Jones Marlon D.
Published: March 2009

Reaction of 2‐oxocylalkaneglyoxylate esters with N‐phenylmethyleneaniline yields spiro compounds such as 2‐aza‐3,4,6,‐trioxo‐1,2‐diphenylspiro[4.4]nonane 4 and cycloalkane‐2‐aza‐3,4,6‐trioxo‐1,2‐diphenylspiro‐[4.5]decanes 5–7. These undergo solvolytic opening of the the oxocycloalkane ring to yield 4‐substituted‐1,5‐dihydro‐3‐hydroxy‐2‐oxo‐1,5‐diphenyl‐2H‐pyrroles 12–17.
Cycloadditions of isoquinolinium N‐arylimides to enamines
Authors: Huisgen Rolf , Durst Tony , Temme Robert
Published: March 2009

The azomethine imine group of isoquinolinium N‐arylimides 2 is partially incorporated into an aromatic ring. The nucleophilic‐electrophilic 1,3‐dipoles 2 undergo cycloadditions to ethylene derivatives bearing either electron‐withdrawing or electron‐releasing substituents. The regiochemistry is bidirectional; electron‐attracting substituents appear at the 1‐position of the tricyclic adducts. Various enamines, however, adopt an orientation such that the amino function appears at the 2‐position. The tricyclic adducts undergo an acid‐catalyzed hyrazo rearrangement.
[4+2] Cycloaddition of 2(1H)‐pyrazinones and 1,2,4‐triazoline‐3,5‐diones
Authors: Nishio Takehiko
Published: March 2009

The reaction of 2(1H)‐pyrazinones 1 and 1,2,4‐triazoline‐3,5‐diones 3 was investigated by comparing that of 1 with singlet oxygen. 2(1H)‐Pyrazinones 1 reacted in Diels‐Alder fashion with 1,2,4‐triazoline‐3,5‐diones 3 to afford [4+2]‐adducts 4–17 in high yields.
General synthetic route to benz[g]isoquinolines (2‐azaanthracenes)
Authors: Krapcho A. Paul , Gilmor Timothy P.
Published: March 2009

Benzylic zinc reagents add with high regioselectivity to 1‐(phenoxycarbonyl) salts derived from pyridine‐3‐carboxaldehyde (1a) or 3‐acetylpyridine (1b) to yield 1‐(phenoxylcarbonyl)‐4‐benzyl‐1,4‐dihydropyridine‐3‐carboxaldehydes 5a, 5c or ketones 5b, 5d. Aromatizations of these dihydro analogues with sulfur led to the corresponding aldehydes 6a, 6c or ketones 6b, 6d. An alternate synthesis to the aldehydic precursors involved additions of benzylic zinc reagents to 1‐(phenoxycarbonyl) salts formed from methyl nicotinates which led to the corresponding methyl 1‐(phenoxycarbonyl)‐4‐benzyl‐1,4‐dihydronicotinates 7a, 7b. Aromatizations of 7a, 7b led to the corresponding pyridine esters 8a, 8b which on reduction with lithium aluminum hydride yielded the corresponding carbinols 9a, 9b. Oxidation of 9a, 9b by manganese dioxide afforded aldehydes 6e, 6f. Aldehydes 6a‐f were readily converted into the benz[g]isoquinolines 10a‐f on heating in polyphosphoric acid.
Preparation of fluorinated phenoxathiin dioxide monoamine oxidase‐A inhibitors: Intramolecular radical substitution at sulfur versus the mauthner synthesis
Authors: Boros Eric E. , Hall William R. , Harfenist Morton , Kelley James L. , Reeves Mark D. , Styles Virgil L.
Published: March 2009

Five unique fluorinated analogs, 8a‐c and 15a,b, of the monoamine oxidase‐A inhibitor 3‐iso‐propoxyphenoxathiin 10,10‐dioxide (II) were prepared via oxidation of the corresponding phenoxathiins 7 and 14. 3‐Fluoro‐7‐isopropoxy‐ 7a, 2‐fluoro‐3‐isopropoxy‐ 7b, and 2,7‐difluoro‐3‐isopropoxyphenoxathiin (7c) were prepared by a modification of the Mauthner synthesis which involved cyclization of the corresponding 2‐hydroxy‐4‐isopropoxythiophenols 4 with the appropriate 2‐halonitrobenzenes 5 in the presence of potassium tert‐butoxide. Preparation of 2,8‐difluoro‐3‐isopropoxyphenoxathiin (14b) from 4b and 2,4‐difluoronitrobenzene (5c) employing similar methods failed, leading instead to a novel macrocycle 9. Attempts to obtain 2‐fluoro‐7‐isopropoxyphenoxathün (14a) and the 2,8‐difluoro analog 14b via trifluoroacetic acid deprotection of intermediate thio‐protected 2‐nitrophenyl 2‐thiophenyl ethers 11a and c followed by cyclization of the resulting thiols were also unsuccessful. Deprotection of 11a with trifluoroacetic acid produced only complex product mixtures, while similar deprotection of 11c and treatment of the resulting crude product with potassium tert‐butoxide in refluxing dimethylformamide produced the 2,7‐difluorophenoxathiin analog 7c, a result consistent with a Smiles rearrangement of the intermediate thiol 12 prior to ring closure. The phenoxathiins 14 were ultimately prepared by a modification of a relatively unexploited phenoxathiin synthesis involving the intramolecular radical substitution at sulfur of 2‐aminophenyl 2‐thiophenyl ethers 13 containing para‐methoxybenzyl and methoxymethylthio‐protecting groups.
Synthesis of bilin‐1,19‐diones and biladiene‐ac‐1,19‐diones with c(10) adamantyl and tert‐butyl groups
Authors: Kar Ari K. , Lightner David A.
Published: March 2009

Bilirubin and biliverdin analogs bearing bulky adamantyl and tert‐butyl groups at the central C(10) position were synthesized and their structures were analyzed by nmr and ultraviolet‐visible spectroscopy and by molecular mechanics calculations, all of which collectively indicated a preference for helical conformations.
A new expedient route to 2,6‐diaryl‐3‐cyano‐4‐(trifluoromethyl)pyridines
Authors: Yamaguchi Yoshihiro , Katsuyama Isamu , Funabiki Kazumasa , Matsui Masaki , Shibata Katsuyoshi
Published: March 2009

1‐Aryl‐4,4,4‐trifluoro‐1,3‐butanediones 1 react with β‐amino‐β‐arylacrylonitrile 2, readily available from acetonitrile with aryl nitriles in the presence of potassium t‐butoxide, to afford the corresponding 2,6‐diaryl‐3‐cyano‐4‐(trifluoromethyl)pyridines 3 in moderate to excellent yields.
Reaction of metallo S‐alkyl N‐cyanodithioiminocarbonates and alkyl N‐cyanocarbamates with hydrazine. A novel preparation of 5‐amino‐3‐mercapto‐1,2,4‐triazole
Authors: Marble Lyndon K. , Puckett Wallace E. , Summers William Russell
Published: March 2009

Metal salts of S‐alkyl‐N‐cyanodithioiminocarbonates 7 react as electrophiles with hydrazine hydrate to form 5‐amino‐3‐mercapto‐1H‐1,2,4‐triazole 1. The novel 4‐cyanothiosemicarbazide 9 is proposed as the intermediate which cyclizes to the aromatic triazole. The rate determining step is addition of hydrazine to the iminocarbonate and is second order. Other nucleophiles such as substituted hydrazines and amines failed to react. Exchange of either or both sulfurs with oxygen leads to decomposition or mixtures of products.
Synthesis and cyclization reactions of 2‐amino‐3‐[(methoxy‐carbonyl)methylsulfonyl]pyrroles and thiophene
Authors: Stephens Chad E. , Sowell J. Walter
Published: March 2009

The title aminopyrroles and thiophene have been prepared by condensation of methyl (cyanomethyl‐sulfonyl)acetate with various α‐amino ketones or 2‐mercaptoacetaldehyde, respectively. Subsequent cyclization of these compounds by reaction between the amine and activated methylene has led to various ester‐substituted thiazine‐ and thiadiazine‐based bicyclic derivatives. In addition, cyclization of the title compounds by intramolecular coupling of the amine and ester has led to the analogous bicyclic thiazin‐3(2H)‐ones. Attempted hydrolysis of the ester‐substituted bicyclics to the corresponding carboxylic acids was unsuccessful.
Synthesis of polycyclic pyridazinediones as chemiluminescent compounds
Authors: Tominaga Yoshinori , Sasaki Kenji , Castle Raymond N.
Published: March 2009

Reactions of 1,3‐disubstituted 5‐aminopyrazole‐4‐carbonitrile derivatives 3a‐o with dimethyl acetylenedicarboxylate in the presence of potassium carbonate in dimethyl sulfoxide gave the corresponding dimethyl 1,3‐disubstituted pyrazolo[3,4‐b]pyridine‐5,6‐dicarboxylates 4a‐o which were allowed to react with excess hydrazine hydrate under ethanol refluxing conditions followed by heating at 250‐300° to give 1,3‐disubstituted 4‐amino‐1H‐pyrazolo[4′,3′:5,6]pyrido[2,3‐d]pyridazine‐5,8(6H,7H)‐diones 7a‐s in good yields. Similarly, 1,3‐disubstituted 4‐hydroxy‐1H‐pyrazolo[4′3′:5,6]pyrido[2,3‐d]pyridazine‐5,8(6H,7H)‐diones 10a‐c were obtained from alkyl 1,3‐disubstituted 5‐aminopyrazole‐4‐carboxylates 8a‐c. These tricyclic pyridazine derivatives were alternatively synthesized from 4‐hydroxypyrrolo[3,4‐e]pyrazolo[3,4‐b]pyridine‐5,7‐diones 13a‐c prepared by reactions of 5‐aminopyrazoles (8e‐g) with methyl 1‐methyl‐4‐methylthio‐2,5‐dioxo‐1H‐pyrrole‐3‐carboxylate (11a) followed by the Gould/Jacobs reaction.

1‐Methyl‐4‐methylthio‐2,5‐dioxo‐1H‐pyrrole‐3‐carbonitrile smoothly reacted with 2‐aminobenzimidazoles to give the corresponding 5‐amino‐3‐methyl‐1H‐pyrrolo[3′4′:4,5]pyrimido[1,2‐a]benzimidazole‐1,3(2H)‐diones 16a‐e, which were readily converted to the desired 12‐aminopyridazino[4′,5′:4,5]pyrimido‐[1,2‐a]benzimidazole‐1,4(2H,3H)‐diones 17a‐e in good yields. Other pyridazinopyrimidine derivatives were also obtained by the reaction of the corresponding 2‐aminoheterocycles with the maleimide in good yields.

Substituted anilines reacted 11b in refluxing methanol to give the corresponding methyl 4‐phenylamino‐1‐methyl‐2,5‐dioxo‐1H‐pyrrole‐3‐carboxylates 25a‐e which were converted in good yields to 2‐methylpyrrolo[3,4‐b]quinoline derivatives 26a‐e by heating in diphenyl ether. Reaction of 26a‐c with hydrazine hydrate gave 10‐hydroxypyridazino[4,5‐b]quinoline‐1,4(2H,3H)‐diones 27a‐e in good yields. The desired 10‐aminopyridazino[4,5‐b]pyridazine‐1,4(2H,3H)‐diones 30a‐e were obtained in good yields by the chlorination of 4a‐e with phosphorus oxychloride followed by aminolysis with 28% ammonium hydroxide.

Some pyridazino[4,5‐a][2.2.3]cyclazine‐1,4(2H,3H)‐diones 37a,b as luminescent compounds were synthesized via several steps from indolizine derivatives. The key intermediates, dimethyl 6‐dimethylamino[2.2.3]cyclazine‐1,2‐dicarboxylates 34, 36, were synthesized by the [8 + 2] cycloaddition reaction of the corresponding 7‐dimethylaminoindolizines 33, 35 with dimethyl acetylenedicarboxylate in the presence of Pd‐C in refluxing toluene.

Some were found to be more efficient than luminol in light production. 4‐Amino‐3‐methylsufonyl‐1‐phenyl‐1H‐pyrazolo[4′,3′:5,6]pyrido[2,3‐d]pyridazine‐5,8(6H,7H)‐dione (7r), 10‐hydroxypyridazino[4,5‐b]‐quinoline‐1,4(2H,3H)‐diones 27a‐e, and 10‐aminopyridazino[4,5‐b]quinoline‐1,4(2H,3H)‐diones 30a‐e showed the greatest chemiluminescence intensity in the presence of hydrogen peroxide peroxidase in a solution of phosphate buffer at pH 8.0.
The trapping of j,x‐biradicals, photochemically produced, with 4‐cyanopyridine in neutral and acidic medium
Authors: Bernardi Rosanna , Caronna Tullio , Mele Andrea , Morrocchi Sergio , Ursini Maurizio
Published: March 2009

4‐Cyanopyridine is able to trap 1,x‐biradicals produced by direct photochemical excitation of some ketones, showing in some cases that unaspected species are formed and pyridine producs which are not explainable on the basis of actual knowledge.
Synthesis of substituted 10,11‐dihydro‐5H‐dibenz[b,f]azepines; key synthons in syntheses of pharmaceutically active compounds
Authors: Jørgensen Tine Krogh , Andersen Knud Erik , Lau Jesper , Madsen Peter , Huusfeldt Per Olaf
Published: March 2009

Substituted 10,11‐dihydro‐5H‐dibenz[b,f]azepines are key synthons in the syntheses of a number of pharmaceutically active compounds such as imipramine, chlorimipramine, and desimipramine analogues. A facile synthesis of substituted 10,11‐dihydro‐5H‐dibenz[b,f]azepines is described, starting out from com mercially available 2‐bromotoluenes or 2‐nitrotoluenes. Initial α‐bromination with N‐bromosuccinimide and subsequent reaction with triethylphosphite afforded the corresponding benzyl phosphonic ester deriva tives. After reaction with benzaldehyde derivatives, the expected Horner‐Emmons reaction products were obtained. Hydrogenation gave the amino derivatives which were transformed into the corresponding formamides. Under Goldberg conditions [1], the final ring closing step was performed to give the substituted 10,11‐dihydro‐5H‐dibenz[b,f]azepines in 46–75% yield.
Synthesis and properties of 1‐aryl‐2‐alkyl‐1,4,5,6‐tetrahydropyrimidines
Authors: Orelli Liliana R. , Niemevz Fernando , García María B. , Perillo Isabel A.
Published: March 2009

A general method is described for the synthesis of 1‐aryl‐2‐alkyl‐1,4,5,6‐tetrahydropyrimidines 1, by cyclization of N‐acyl‐N′‐aryltrimethylenediamines 2 with trimethylsilyl polyphosphate. Precursors 2 were obtained by aminolysis of the corresponding N‐(3‐bromopropyl)amides 3. The 1H nmr spectra of tetrahydropyrimidines 1 are analyzed, discussing the influence of substituents in positions 1 and 2 of the heterocyclic ring. Alkaline hydrolysis of compounds 1, which originates exclusively N‐acyl‐N′‐aryltrimethylenediamines 2, through an intermediate carbinolamine, was also studied. Cleavage of such an intermediate is discussed in the light of the stereoelectronic control theory. Reduction of compounds 1 with borane, leads regiospecifically to N‐alkyl‐N′‐aryltrimethylenediamines 6.
Reactions of 2,3‐dihydrospiro[1H‐4‐ and 5‐azabenzimidazole‐2,1′‐cyclohexane] with nucleophiles: A potential route to some substituted aromatic heterocycles
Authors: Reizner Ralf , Kramer Walter , Neidlein Richard , Suschitzky Hans
Published: March 2009

The readily available title compounds 2, 16 and 27 react with pseudohalogenes (cyanide, azide), carbon and heterocyclic N‐nucleophiles in the presence of manganese dioxide to give the corresponding substituted azaisobenzimidazoles (= 2H‐azabenzimidazoles) 4, 8, 23–26 and 29–33, 36 or dihydroazabenzimidazoles (= 2,3‐dihydro‐1H‐azabenzimidazoles 7, 22, 34 and 35. In 8 one of the two imidazolyl‐substituents can be replaced by nucleophiles yielding the compounds 9–15. Treatment of 6′‐bromo‐2,3‐dihydro‐4‐azabenzimidazole 16 with morpholine or piperidine results in loss of the Br‐atom presumably by an AEa‐mechanism. Reduction of the substituted azaisobenzimidazoles with sodium hydrosulfite followed by fission of the cyclohexane ring leads to substituted o‐diaminopyridines. They were cyclised in situ with various condens ing agents to give new heterocyclic systems. Equimolar mixtures of some azaisobenzimidazoles and dihydroazabenzimidazoles lead to the formation of coloured charge transfer complexes stable only in the solid state. Owing to poor electron‐acceptor properties the complex dissociates in solution.
Acylation, cyanoethylation and alkylation of methyl and phenyl indolylmagnesium salts: Influence of the substituents on the c‐ and N‐reaction products
Authors: Rodríguez J. Gonzalo , Urrutia Anahí
Published: March 2009

Analysis of the influence of the substitution on indolylmagnesium salts in the reaction with benzoyl chlo ride, acrylonitrile and methyl iodide, giving the C‐ and N‐derivatives, have been carried out. The yield in the C‐ and N‐product depends upon the electronic character and position of the substituent (methyl or phenyl) on the indole ring and of the ethereal solvent as well as the concentration and molar ratio of the reagents. The 2‐ or 3‐phenyl substituted indolylmagnesium salts with acrylonitrile always gave the 1‐(2‐cyanoethyl)indole derivative.
Semi‐empirical evaluation of substituted terthiophenes as polythiophene precursors
Authors: Stanforth Stephen P.
Published: March 2009

PM3 Semi‐empirical molecular orbital calculations have been performed on terthiophene derivatives which are also heteropentalene mesomeric betaines. The ionization potentials and band‐gaps have been determined in order to identify systems which might provide suitable monomers for conducting polythio phene derivatives.
Inhibitors of dihydrofolate reductase: Design, synthesis and antimicrobial activities of 2,4‐diamino‐6‐methyl‐5‐ethynylpyrimidines
Authors: Jones Michael L. , Baccanari David P. , Tansik Robert L. , Boytos Christine M. , Rudolph Sharon K. , Kuyper Lee F.
Published: March 2009

Novel 2,4‐diamino‐6‐methyl‐5‐ethynylpyrimidines were prepared via palladium catalyzed coupling of 2,4‐diamino‐5‐iodo‐6‐methyl‐pyrimidine with terminal acetylenes. The compounds were inhibitors of dihydrofolate reductase and showed in vitro activity against several species of opportunistic fungi and the protozoan Toxoplasma gondii.
Synthesis and reactions of 4H‐3,1‐benzothiazines
Authors: El‐Desoky S. I. , Kandeel E. M. , Abd‐El‐Rahman A. H. , Schmidt R. R.
Published: March 2009

This study is directed towards the synthesis of the pyrrolo[1,2‐α]indole skeleton which is the essential ring system of the active antitumor miomycins. To this end a number of fused heterocycles such as benzothiazines, benzoxazines, indoles and quinolines were synthesized. The structures of the new compounds were assigned by ir, 1H nmr and ms‐data.
Synthesis and absolute configuration of (‐)‐meridinol and (‐)‐3‐epimeridinol
Authors: Takano Daisuke , Doe Matsumi , Morimoto Yoshiki , Kinoshita Takamasa , Yoshihara Kazuo
Published: March 2009

The first synthesis of (‐)‐meridinol and (‐)‐3‐epimeridinol was accomplished from (S)‐malic acid. This synthesis unambiguously established the absolute stereochemistry of meridinol.
Susceptibility of morpholine substituents to photo‐oxidative decomposition‐identification of photo‐oxidative degradants of linezolid (PNU‐100766)
Authors: Martin Gary E. , Robins Russell H. , Bowman Phil B. , Duholke Wayne K. , Farley Kathleen A. , Kaluzny Brian D. , Guido Jane E. , Sims Sandra M. , Thamann Thomas J. , Thompson Brian E. , Nishimura Toshihide , Noro Yukimi , Tahara Tsutoma
Published: March 2009

Parenteral formulations of linezolid (PNU‐100766), a novel (S)‐3‐(4′‐fluorophenyl)‐5‐N‐acetamidomethyloxazolidin‐2‐one antibiotic, were subjected to photo‐stability testing as required by ICH guidelines. Direct, reversed phase chromatographic evaluation of the photo‐irradiated solutions revealed two chromatographically broad degradants. Following preparative chromatographic isolation, the structures of both degradants were determined by mass spectrometric, nmr, and vibrational spectroscopic methods. The degradant structures formed by decomposition involving photo‐oxidation of the morpholine, followed by a carbon‐carbon bond scission to a formyloxyethylformamide‐containing degradant. Facile hydrolytic cleav age of the formate ester in acidic media gave the second chromatographically broad degradant containing a N‐2‐hydroxyethylformamide group. The formamide substituent underwent further hydrolysis in acidic media to the corresponding secondary amine.
Reactions of N‐aryl‐1H‐benzotriazolyl‐1‐methanamines with allyl trimethylsilanes. A facile route to trialkylsilane tetrahydroquinolines
Authors: Katritzky Alan R. , Cui Xilin , Long Qiuhe
Published: March 2009

N‐Aryl‐1H‐benzotriazolyl‐1‐methanamines 1, easily accessible from the condensation of anilines with formaldehyde and benzotriazole, undergo Lewis acid assisted reactions with allyl trimethylsilanes to give 4‐(trimethylsilyl)methyl‐1,2,3,4‐tetrahydroquinolines 2 in good to high yields.
Borane complexes of 2‐(1‐Methyl‐1,2,5,6‐tetra‐hydropyridin‐3‐yl)benzoxazoles
Authors: Jung Myung Hee , Park Jewn‐Giew , Ryu Bok‐Sim , Cho Kui‐Woong
Published: March 2009

2‐Pyridin‐3‐ylbenzoxazoles were synthesized by the reaction between 3‐pyridinecarboxaldehyde and substituted o‐aminophenols in the presence of iodobenzene diacetate. The resulting benzoxazoles 3 were treated with methyl iodide to give the corresponding pyridinium salts 4 which underwent the hydride reduction with sodium borohydride or sodium cyanoborohydride to produce 2‐(1‐methyl‐1,2,5,6‐tetrahy‐dropyridin‐3‐yl)benzoxazole borane complex derivatives.
Synthesis and spectral properties of 5‐methylthio‐4H‐1‐(p‐substituted‐phenyl)‐3a‐(p‐substituted‐phenyl)‐9‐[(m‐; and p‐substituted)‐phenoxy]‐3a,4‐dihydro[1,2,4]oxadiazolo[4,5‐a][1,5]benzodiazepines
Authors: Cortés Eduardo CortÉS , Cruz Elide HernÁNdez , Mellado Olivia GarcÍA
Published: March 2009

The preparation of eight novel substituted [1,2,4]oxadiazolo[4,5‐a][1,5]benzodiazepines which have potentially useful pharmacological properties; by 1,3‐cycloaddition of benzonitrile oxides, generated in situ from benzohydroxamoyl chloride and triethylamine, to 1,5‐benzodiazepine derivatives is described. The structure of all products was corroborated by ir, 1H‐nmr, 13C‐nmr and ms.
New compounds in the reaction of aromatic amines and 5‐hydroxy‐4‐pyrone‐2‐carboxylate. The influence of a methoxy group
Authors: Kožul M. , Stiplošek Z. , Orhanović Z. , Jakopčić K. , Nagl A. , Hergold‐Brundić A.
Published: March 2009

Unlike most of other aromatic amines, 4‐methoxyaniline with methyl comenate (1) in the mixture of acetic acid and methanol (1:1) gave two unexpected products with azomethyne moiety. The structures of new compounds were determined from their characteristic spectroscopic behaviour and were confirmed by X‐ray crystallographic measurements.
Studies on the preparation of 3,4‐disubstituted 2‐methoxypyridines
Authors: Pelisson Marcelo M. M. , Silva Gil Valdo José Da , Clive Derrick L. J. , Coltart Don M. , Hof Fraser A.
Published: March 2009

The synthesis of 2‐methoxy‐4‐methylpyridine‐3‐carbonitrile (3) and its conversion, by way of alkylation of the C(4) methyl group, into the pyrodyl acetic acid ester 6 is described.
Synthesis and spectral data of unknown lilolidine spiro derivatives
Authors: Palma R Alirio , Silva Javier , Stashenko Elena , Martínez Jairo René , Kouznetsov Vladimir
Published: March 2009

A new series of halo and methyl substituted spiro annulated tetrahydropyrrolo[3,2,1‐ij]quinolines, analogues of lilolidine alkaloids has been prepared in a two‐step route from easily accessible dihydroquinoline precursors.
2‐Aryl‐7,7‐dimethyl‐5,6,7,8‐tetrahydrothieno[3,2‐c]azepin‐4‐ones from 5,5‐dimethyl‐1,3‐cyclohexanedione
Authors: Martinez Roberto , Durán L Ma. Esther , Cortés L César , Avila Z J. Gustavo
Published: March 2009

A novel synthesis of substituted thieno[3,2‐c]azepinones is described. This new approach uses 5,5‐dimethyl‐1,3‐cyclohexanedione (dimedone) as the starting material. Oxime intermediates are obtained in three steps from the aforementioned diketone. Using these intermediates, the title compounds are synthesized in moderate yields.
Synthesis of new pyrazolo[4,3‐c]quinolin‐3‐one derivatives and some oxazolo[4,5‐c]quinoline‐2,4‐diones
Authors: Ismaïli Lhassane , Refouvelet Bernard , Robert Jean François
Published: March 2009

The new pyrazolo[4,3‐c]quinolin‐3‐one derivatives 3a‐c and 6a‐c were prepared by the following three steps: first the preparation of ethyl 4‐hydroxyquinoline‐3‐carboxylate derivatives 1 and 4 by reaction of isatoic anhydrides and ethyl malonate and ethyl acetoacetate respectively, then chloration of 1 and 4 with phosphorus oxychloride to give 2 and 5 and finally the condensation of 2 and 5 with hydrazine and its derivatives. In addition, the successful synthesis of oxazolo[4,5‐c]quinoline‐2,4‐diones 9a‐f are reported.
Synthesis of pyrido[4,3,2‐de]quinazolines via nitro‐substituted tetrahydroquinolines
Authors: Katritzky Alan R. , Strah Sonja , Tymoshenko Dmytro O. , Johnson Graham
Published: March 2009

The simple and efficient synthesis of novel dihydropyrido[4,3,2‐de]quinazolines in four steps from m‐nitroaniline is described.
Polycyclic N‐heterocyclic compounds. 55. A novel reaction of N‐(5,6‐dihydro[1]benzothiepino[5,4‐d]pyrimidin‐4‐yl)amidine or its amide oxime derivatives with hydroxylamine
Authors: Zhang Ying‐Xue , Sasaki Kenji , Hirota Takashi
Published: March 2009

The reactions of N‐(5,6‐dihydro[1]benzothiepino[5,4‐d]pyrimidin‐4‐yl)amidines or its amide oxime derivatives with hydroxylamine hydrochloride under basic condition gave abnormal cyclization products via a ring cleavage of pyrimidine component accompanied with a ring closure of [1,2,4]oxadiazole.
Sulfenylation of heterocyclic 1,3‐dicarbonyl systems: 4‐Hydroxy‐2‐pyrones, 6‐hydroxy‐4‐pyrimidones, 4‐hydroxy‐2‐pyridones, 4‐hydroxy‐6‐pyridazinones, and 5‐hydroxy‐3‐pyrazolones
Authors: Schnell Barbara , Kappe Thomas
Published: March 2009

Anions of enolized heteroaromatic 1,3‐dicarbonyl systems, such as the title compounds 1, 9,14, and 19, react in dimethylformamide in the presence of potassium carbonate with diaryl disulfides 2 to yield arylsulfenyl derivatives (3, 10, 15, 20). The arylthiolate anions 4 formed in this reaction can be oxidized by air to yield the starting disulfides 2 again. Tetraalkylthiuram disulfides 7 react in the same manner to yield dialkylaminothiocarbonylthio derivatives (8, 13, 18) of the title compounds. Oxidation of the arylsulfenyl derivatives with hydrogen peroxide in sodium hydroxide solution usually leads to sulfoxides (5, 11, 16), whereas oxidation with peracetic acid affords sulfones (6, 12, 17).