bluuebunny/crossref_metadata_2025 huggingface dataset:
Metallation of diazines. V. Synthesis of analogues of biologically active molecules
Authors: Plé N. , Turck A. , Bardin F. , Queguiner G.
Published: March 2009

2‐Chloro‐4‐methoxypyrimidine was lithiated by lithium 2,2,6,6‐tetramethylpiperidide. The resulting lithio derivative was reacted with carbonyl derivatives and iodine. Synthesis of analogues of biologically active molecules is reported.
Preparation and properties of octaalkylphthalocyanines having long alkyl side chains of odd numbers of carbons
Authors: Nishi Hisao , Azuma Natsuhiro , Kitahara Kiyoshi
Published: March 2009

2,3,9,10,16,17,23,23‐Octaalkylphthalocyanines and their copper complexes having long alkyl side chains of odd numbers of carbons (C7H12, C9H19, C11H23 and C13H27) were prepared. Their thermal properties and solubilities were examined.
Synthesis of an s‐butyldibenz[a,h]acridine. Alkyl migration in the bernthsen reaction
Authors: Klemm L. H. , Chiang Eva , O'Bannon Gerald W.
Published: March 2009

The Bernthsen reaction between N‐1‐naphthyl‐2‐naphthylamine and 2‐methylbutanoic acid and its anhydride at 200–230° for seven hours gives a low yield of 12‐ or 13‐s‐butyldibenz[a,h]acridine, instead of the expected 14‐isomer. The parent molecule dibenz[a,h]acridine results from the same reaction conducted at 270° for thirteen hours. It is suggested that alkyl migration may have occurred in some other cases where the Bernthsen reaction was reported to yield 14‐alkyldibenz[a,h]acridines.
On the synthesis of pyrido[3,2,1‐kl]phenothiazine, quino[8,1‐bc][1,4]benzothiazepine and their derivatives
Authors: Catsoulacos P. , Catsoulacos D.
Published: March 2009

This review article comprises tetracyclic rigid analogues of phenothiazine and dibenzothiazepine derivatives. In order to discover new useful drugs, the side chain of the heterocyclic nucleus is incorporated into a ring forming tetracyclic compounds. The text has been divided in thirteen sections.
Synthesis of some novel halogenated 2,4‐diaminoquinazolines
Authors: Tomažič Alenka , Hynes John B.
Published: March 2009

Three new 2,4‐diaminoquinazolines, the 5,6‐difluoro, 6,7‐difluoro and 7,8‐difluoro isomers were prepared by the reaction of the requisite trifluorobenzonitrile and guanidine carbonate. Surprisingly, 2,3,6‐trifluorobenzonitriles gave 2,4‐diamino‐5,6‐difluoroquinazoline exclusively as determined by high resolution nuclear magnetic resonance spectroscopy. On the other hand, 3‐amino‐2,6‐difluorobenzonitrile on reaction with guanidine carbonate yielded only 5‐fluoro‐2,4,8‐triaminoquinazoline. This compound was subsequently converted to 8‐chloro‐2,4‐diamino‐5‐fluoroquinazoline using the Sandmeyer procedure. The nitration of 2,4‐diamino‐8‐fluoroquinazoline occurred exclusively at position six yielding 2,4‐diamino‐8‐fluoro‐6‐nitroquinazoline, which upon reduction with stannous chloride afforded 8‐fluoro‐2,4,6‐triaminoquinazoline. In a similar fashion 7‐fluoro‐2,4‐diaminoquinazoline underwent nitration at position six and was then reduced to give 7‐fluoro‐2,4,6‐triaminoquinazoline. Finally, both of these triaminoquinazolines were converted to the 6‐chloro derivatives under Sandmeyer conditions to yield 6‐chloro‐2,4‐diamino‐8‐fluoroquinazoline and 6‐chloro‐2,4‐diamino‐7‐fluoroquinazoline, respectively.
Photochemical induced formation of α‐alkylamino or alkylaminyl radicals from secondary amines: Reaction with 4‐pyridinecarbonitrile
Authors: Caronna Tullio , Morrocchi Sergio
Published: March 2009

The direct photolysis at 254 nm of 4‐pyridinecarbonitrile in the presence of some aliphatic secondary amines brought to the substitution of the CN group and to the formation of 4‐α‐alkylaminopyridines, whereas the irradiation in the presence of benzophenone at 350 nm yields 4‐alkylaminylpyridines and 4‐diphenylketylpyridine. A mechanism is proposed to explain the different course of the reaction under the two different conditions.
Synthesis of 7‐hydroxythioridazine and 7‐hydroxysulforidazine
Authors: Singh Shyam K. , Patrick Kennedy S.
Published: March 2009

The thioridazine metabolites 7‐hydroxythioridazine(2a)and 7‐hydroxysulforidazine(2b)were synthesized. Commercial 4‐chloro‐3‐nitrophenylmethylsulfone was converted to the corresponding 4‐thiol through an intermediate xanthate ester. Subsequent zinc metal reduction provided the 3‐amino thiolate. This salt was condensed with chloroquinone to yield 7‐hydroxy‐2‐methylsulfonylphenothiazine which was then protected as the isopropyl ether.N‐Alkylation with 2‐(2‐chloroethyl)‐1‐methylpiperidine using sodium hydroxide, then ether cleavage, afforded2b. TheN‐alkylation followed by reduction with diisobutylaluminum hydride and deblocking yielded2a. These reference standards will assist in an exploration of the potential role of meta‐bolically formed2aand2bin the neuroleptic response to thioridazine.
Reaction of 6‐chloro‐2‐[1‐methyl‐2‐(N‐methylthiocarbamoyl)]‐hydrazinoquinoxaline 4‐oxide with dimethyl acetylenedicarboxylate
Authors: Kurasawa Yoshihisa , Katoh Ritsuko , Takada Atsushi , Kim Ho Sik , Okamoto Yoshihisa
Published: March 2009

The reaction of 6‐chloro‐2‐(1‐methylhydrazino)quinoxaline 4‐oxide 4a with methyl or phenyl isothiocyanate gave 6‐chloro‐2‐[1‐methyl‐2‐(N‐methylthiocarbamoyl)hydrazino]quinoxaline 4‐oxide 7a or 6‐chloro‐2‐[1‐methyl‐2‐(N‐phenylthiocarbamoyl)hydrazino]quinoxaline 4‐oxide 7b, respectively, whose reaction with dimethyl acetylenedicarboxylate afforded 6‐chloro‐2‐[N‐methyl‐N‐(5‐methoxycarbonylmethylene‐3‐methyl‐4‐oxo‐2‐thioxoimidazolidin‐1‐yl)]aminoquinoxaline 4‐oxide 8a or 6‐chloro‐2‐[N‐methyl‐N‐(5‐methoxycarbonylmethylene‐4‐oxo‐3‐phenyl‐2‐thioxoimidazolidin‐1‐yl)]aminoquinoxaline 4‐oxide 8b, respectively.
A convenient synthesis of new heterocycles from benzimidazoles and carbon suboxide
Authors: Bonsignore Leonardo , Loy Giuseppe , Secci Daniela
Published: March 2009

The reaction of carbon suboxide with 2‐substituted benzimidazoles was investigated. By this reaction 1,3‐diazino‐ (pyrimido‐), 1,3‐oxazino‐ and 1,3‐thiazinobenzimidazole‐1,3‐diones are obtained.
Synthesis of indeno[2,1‐b][1,4]benzothiazine derivatives from 2‐bromoinden‐1‐ones
Authors: Bajji Ashok C. , Nan'ya Seiko , Butsugan Yasuo
Published: March 2009

2‐Bromoinden‐1‐ones 2 were condensed with 6‐substituted 3‐aminopyridine‐2(1H)‐thiones to produce a new type of 4‐azaindeno[2,1‐b][1,4]benzothiazine derivatives 3. Substituted 6‐phenylindeno[2,1‐b][1,4]benzothiazines 4 were also prepared by reacting 2‐bromo‐5‐methoxy‐ and 2,6‐dibromo‐5‐methoxyinden‐1‐ones with o‐aminobenzenethiol.
Syntheses of 4‐(benzo[b]furan‐2 or 3‐yl)‐ and 4‐(benzo[b]‐thiophen‐3‐yl)piperidines with 5‐HT2 antagonist activity
Authors: Watanabe Yoshifumi , Yoshiwara Hirotaka , Kanao Munefumi
Published: March 2009

The syntheses of 4‐(benzo[b]furan‐3‐yl)piperidines, 4‐(benzo[b]furan‐2‐yl)piperidines and 4‐(benzo[b]thiophen‐3‐yl)piperidines with 5‐HT2 antagonist activity are described. Reaction of 1‐acetyl‐4‐(2,4‐difluorobenzo‐yl)piperidine 2 with methyl glycolate gave methyl 6‐fluoro‐3‐(1‐acetylpiperidin‐4‐yl)benzo[b]furan‐2‐carboxylate 3, which was converted to 2‐[2‐[4‐(benzo[b]furan‐3‐yi)piperidin‐1‐yl]ethyl‐5,6,7,8‐tetrahydro‐1,2,4‐triazolo‐[4,3‐a]pyridin‐3(2H)‐one hydrochloride 9. Analogous benzo[b]furans 17a‐d and benzo[b]thiophenes 10a,b and 18a were prepared by a similar method. Cyclization of 4‐fluoro‐2‐(4‐pyridinylmethoxy)acetophenones 20a,b afforded 4‐(benzo[b]furan‐2‐yl)pyridines 21a,b, which were converted to 2‐[2‐[4‐(benzo[b]furan‐2‐yl)‐piperidin‐1‐yl]ethyl‐5,6,7,8‐tetrahydro‐1,2,4‐triazolo[4,3‐a]pyridin‐3(2H)‐one hydrochlorides 24a,b. Among them, benzo[b]furans 9 and 17a,d and benzo[b]thiophenes 10 and 18a showed potent 5‐HT2 antagonist activity in vitro.
Stereoselective synthesis of cis and trans 2‐substituted 1‐phenyl‐3‐azabicyclo[3.1.0]hexanes
Authors: Bonnaud Bernard , Bigg Dennis C. H.
Published: March 2009

The Stereoselective synthesis of cis and trans 2‐methyl‐1‐phenyl‐3‐azabicyclo[3.1.0]hexanes and 1,2‐diphen‐yl‐3‐azabicyclo[3.1.0]hexanes from 2‐oxo‐1‐phenyl‐3‐azabicyclo[3.1.0]hexane is described. The relative stereochemistry of the products was established by nuclear magnetic resonance and molecular modeling studies.
Synthesis of (1R,4R,7S)‐ and (1S,4S,7S)‐2‐(4‐tolylsulfonyl)‐5‐phenyl‐methyl‐7‐methyl‐2,5‐diazabicyclo[2.2.1]heptanes via regioselective opening of 3,4‐epoxy‐d‐proline with lithium dimethyl cuprate
Authors: Remuzon Philippe , Bouzard Daniel , Clemencin Claire , Dussy Christian , Essiz Munir , Jacquet Jean‐Pierre , Saint‐Germain Jean
Published: March 2009

The synthesis of (1S,4S,7S)‐ and (1R,4R,7S)‐2‐(4‐tolylsulfonyl>5‐phenylmethyl‐7‐rnethyl‐2,5‐diazabicyclo‐[2.2.1]heptanes (20) and (22) from trans 4‐hydroxy‐L‐proline is described.
Nitration of dithieno[3,2‐b:3′,2′‐d]pyridine and dithieno[3,2‐b:3′,4′‐d]pyridine
Authors: Szabó Kálmán J. , Gronowitz Salo
Published: March 2009

Nitration of dithieno[3,2‐b:3′,2′‐d]pyridine (4) and dithieno[3,2‐b:3′,4′‐d]pyridine (5) has been studied. Nitration of 4 occurred in both positions of the C ring, while 5 was predominantly substituted on the 3,4‐fused ring. The structures of the nitro derivatives were proven by extensive use of 1H and 13C nmr spectroscopy.
Preparation of some substituted imidazo[1,2‐a]pyridine derivatives
Authors: Shawcross Andrew P. , Stanforth Stephen P.
Published: March 2009

2‐Bromopyridine derivatives 2a‐2c were prepared. Compounds 2b and 2c and ammonia yielded aminopyridines 3b and 3c which were converted to imidazo[1,2‐a]pyridine derivatives 4b and 4c. Compound 4b was nitrated giving the analogue 5b of metronidazole 1.
Convenient synthesis of 5‐azacoumarins
Authors: Billeret D. , Blondeau D. , Sliwa H.
Published: March 2009

2‐Formyl‐3‐hydroxypyridine and its 6‐methyl derivative have been condensed with ethoxycarbonylmethyl‐enetriphenylphosphorane and alkyl derivatives to afford 5‐azacoumarins substituted in the second case by an alkyl group at 3‐position by two different ways according to the used phosphorane.
Studies on the chemistry of thieno‐anellated O,N‐ and S,N‐containing heterocycles. 2. Synthesis of thieno[2,3‐b]diazepine derivatives with potential CNS activity
Authors: Erker Thomas
Published: March 2009

Thieno‐anellated compounds analogous to Clobazam (1) [2] and the nootropic drugs 2 and 3 [3] were synthesized. Thus, nucleophilic substitution on halogenated nitrothiophene derivatives with aniline and reaction with ethyl malonyl chloride gave after cyclisation the thieno[2,3‐b]diazepinedione derivatives 7 and 14. These compounds were methylated to give the thieno‐anellated heterocycles 8 and 9.
The synthesis of a series of 7‐amino‐1‐cyclopropyl‐8‐fluoro‐1,4‐dihydro‐4‐oxo‐1,6‐naphthyridine‐3‐carboxylic acids as potential antibacterial agents
Authors: Sanchez Joseph P. , Gogliotti Rocco D.
Published: March 2009

A series of 7‐amino‐1‐cyclopropyl‐1,4‐dihydro‐8‐fluoro‐4‐oxo‐1,6‐naphthyridine‐3‐carboxylic acids has been prepared and evaluated for antibacterial activity. These compounds were prepared by the displacement of the chloro substituent from 7‐chloro‐1‐cyclopropyl‐1,4‐dihydro‐8‐fluoro‐4‐oxo‐1,6‐naphthyridine‐3‐carboxylic acid employing the requisite nitrogen nucleophile to produce the title compounds. The naphthyridine acid was synthesized in ten steps from ethyl 2,4‐dihydroxy‐3‐nitro‐5‐pyridinecarboxylate. The key step in the sequence was a Schiemann reaction carried out using the hexafluorophosphate salt of the diazonium ion derived from ethyl 3‐amino‐2,4‐dichloro‐5‐pyridinecarboxylate.
Synthesis of cyclopentathiophenacetic acid derivatives. Reactivity of methyl 6‐oxo‐4,5‐dihydro‐6H‐cyclopenta[b]thiophen‐4‐acetate
Authors: Jilale Abderrahim , Netchitaïlo Pierre , Decroix Bernard , Vegh Daniel
Published: March 2009

Oxodihydrocyclopentathiophenacetic acids 4, 5 and 6 were synthesized from suitable 2‐ or 3‐formylthiophenes. Reactivity of the carbonyl group or the carboxylic group of these bicyclic systems was investigated. The Beckmann rearrangement of methyl 6‐oximino4,5‐dihydro‐6H‐cyclopenta[b]thiophen‐4‐acetate 12 is an interesting route to methyl 7‐oxo‐4,5,6,7‐tetrahydrothieno[2,3‐c]pyridin‐4‐acetate (13).
A facile method for 2‐thiophenacylidenethiazoline derivatives
Authors: Kim Sung Hoon , Kim Kyongtae , Kim Jaheon , Kim Kimoon , Kim Jung‐Hyup
Published: March 2009

The reactions of 2‐alkyl‐5‐phenylisothiazole‐3‐thiones with 2‐chloro‐1,3‐dicarbonyl compounds in chloroform gave the corresponding isothiazolium chlorides which, upon treatment at room temperature with sodium borohydride in a mixture of chloroform and ethanol, underwent SN bond cleavage to give 3‐alkyl‐4,5‐disubstituted‐2‐thiophenacylidenethiazolines. Similarly, treatment of the isothiazolium chlorides with triphenylphosphite in chloroform at 60° afforded the same thiazoline derivatives.
Research in the azole series. 103. Synthesis and 13C NMR study of pyrazole‐4‐carboxaldehydes
Authors: Echevarría Aurea , Elguero José , Meutermans Wim
Published: March 2009

Ten new pyrazoles have been prepared and their 13C nmr chemical shifts compared with those of twelve other pyrazoles, some of them prepared purposely for this study. The chemical shifts are discussed statistically assuming that they are additive. A formyl group in the position 4 of the pyrazole ring produces a large effect on carbon C4 (SCS = 17.3 ppm) and medium effects on carbons C3 (SCS = 1.9 ppm) and C5 (SCS = 3.8 ppm). The azines derived from pyrazole‐4‐carboxaldehydes are of the E,E‐configuration.
On triazoles XXX. Synthesis of [1,2,4]triazolo‐[1,5‐d][1,2,4,6]tetrazepine‐5‐thiones
Authors: Barkóczy József , Reiter József
Published: March 2009

Different 2‐Q‐6,7,8,9‐(bi‐, tri‐ or tetra)substituted[1,2,4]triazolo[1,5‐d][1,2,4,6]tetrazepine‐5‐triione derivatives representing a novel ring system were synthesised. In the case of 8‐aryl‐substituted derivatives ring‐chain tautomerism was observed in DMSO‐d6 or deuteriochloroform solutions. In some cases both ring and chain tautomers could be isolated in crystalline form. The structure of products obtained was proved by nmr using also model compounds prepared for this purpose.
Acid‐catalyzed reaction of pyrazolo[1,5‐a]pyridines with aldehydes: Formation of bis(pyrazolo[1,5‐a]pyrid‐3‐yl)methane
Authors: Miki Yasuyoshi , Yagi Sanae , Hachiken Hiroko , Ikeda Masazumi
Published: March 2009

Reaction of pyrazolo[1,5‐a]pyridines with aldehydes in the presence of trifluoroacetic acid gave bis[pyrazolo[1,5‐a]pyrid‐3‐yl)methanes in high yields.
Ring chain transformations. XIV. 3‐(ω‐Aminoalkyl)‐1,2,4‐triazoles by reaction of isothiosemicarbazides with lactam acetals or lactim ethers
Authors: Radics Ute , Liebscher Jürgen
Published: March 2009

Isothiosemicarbazide hydrohalides 1 react with lactam acetals 2 or lactim ethers 3 by the formation of lactamisothiosemicarbazones 4 or ring transformed 3‐(ω‐aminoalkyl)‐1,2,4‐triazoles 6. The latter can independently by synthesized by alkylation of lactamthiosemicarbazones 9. Condensation of primary 3‐(ω‐aminoalkyl)‐1,2,4‐triazoles 6 with lactim ethers 7 can lead to 3‐lactamiminoalkyl‐1,2,4‐triazoles 8.
Alkylation of quinazoline‐2,4(1H,3H)‐diones with 1,4‐dibromo‐2‐methylbut‐2‐ene under phase‐transfer‐catalysis
Authors: Reisch Johannes , Iding Marlies , Usifoh Cyril Odianose
Published: March 2009

Quinazoline‐2,4(1H,3H)‐dione (1) was reacted with 1,4‐dibromo‐2‐methylbut‐2‐ene (2) to give two dialkylated products and two monoalkylated products. The reaction of 6,7‐dimethoxyquinazoline‐2,4(1H,3H)‐dione (8) with 1,4‐dibromo‐2‐methylbut‐2‐ene (2) resulted in the formation of three dialkylated products.
4H‐1‐benzothiopyran‐4‐one‐3‐carboxylic acids and 3,4‐dihydro‐2H‐isothiazolo[5,4‐bbenzothiopyran‐3,4‐diones as quinolone antibacterial analogs
Authors: Cecchetti Violetta , Fravolini Arnaldo , Fringuelli Renata , Schiaffella Fausto , Lorenzini Maria Cristina , Tabarrini Oriana
Published: March 2009

The endocyclic replacement of a nitrogen atom at the 1‐position of quinolone antibacterial nucleus with a sulfur atom was investigated. A series of 1‐benzothiopyran‐4‐one‐3‐carboxylic acids 14–16 and isothiazolo‐[5,4‐b][1]benzothiopyran‐3,4‐diones 22–24, suitably functionalized with a fluorine atom at C‐6 and heterocyclic base at C‐7, were prepared. The antibacterial evaluation of the target compounds showed an activity comparable to that of nalidixic acid for compounds 14–16, while an increased activity against gram‐positive bacteria was observed for compounds 22–24.
Reaction of enol type acyl cyanide with o‐aminophenol
Authors: Kurasawa Yoshihisa , Yoshishiba Noriko , Kureyama Tomomi , Takada Atsushi , Kim Ho Sik , Okamoto Yoshihisa
Published: March 2009

The reaction of 7‐chloro‐4‐(2‐cyano‐2‐hydroxyvinyl)tetrazolo[1,5‐a]quinoxaline 2a with o‐aminophenol gave 7‐chloro‐4‐(b‐hydroxyphenylcarbamoylmethylene)4,5‐dihydrotetrazolo[1,5‐a]quinoxaline 4, while the reaction of compound 2a with o‐aminophenol hydrochloride afforded 4‐[2‐(2‐benzoxazolyl)‐2‐hydroxyvinyl]‐7‐chlorotetrazolo[1,5‐a]quinoxaline 5, whose acetylation provided 4‐[2‐acetoxy‐2‐(2‐benzoxazolyl)vinyl]‐7‐chlorotetrazolo[1,5‐a]quinoxaline 6. The behavior in a deuteriodimethyl sulfoxide or deuteriotrifluoroacetic acid solution is described for compounds 4–6.
Reaction of β‐keto ethyleneacetals with hydroxylamine: A correction
Authors: Paradkar Vidyadhar M. , Latham Tamara B. , Krishnaswami Ashok
Published: March 2009

A reaction of 2‐(2‐nitrobenzoylmethyl)‐1,3‐dioxolane (3) with hydroxylamine, followed by acid catalyzed cyclization, produced 5‐(2‐nitrophenyl)isoxazole (5) as the only isolable product, whereas 2‐(benzoylmethyl)‐1,3‐dioxolane (9) under identical conditions produced a 2.5:1 mixture of 3‐phenyl and 5‐phenylisoxazoles 10 and 11. These findings contradict the literature report that β‐keto ethyleneacetals on treatment with hydroxylamine produce exclusively 3‐substituted isoxazoles. As an additional proof, 3‐(2‐nitrophenyl)isoxazole (8) was prepared by an unambiguous method via the nitrile oxide route for comparison. The intermediate obtained on treatment of 2‐(2‐nitrobenzoylmethyl)‐1,3‐dioxolane (3) with hydroxylamine was found to be an isomeric mixture of 5‐hydroxy‐5‐(2‐nitrophenyl)‐2‐isoxazoline (4) and the syn and anti mono‐oximes 19 (at least in solution), either of which could give 5‐(2‐nitrophenyl)isoxazole (5) on acid treatment. A mechanistic rationale is provided to explain the anomalous results.
Syntheses and photophysical properties of fluorescent 2‐aryl‐3‐hydroxy‐4‐chromenones
Authors: Kauffman Joel M. , Aziz Mohammed A.
Published: March 2009

The particle detectors proposed for the Super‐conducting Super Collider contain polystyrene scintillation fibers as a component. Scintillation fluors soluble in styrene are required which have improved light output and response time. New 2‐aryl‐3‐hydroxy‐4‐chromenones related to 3‐hydroxyflavone were prepared which displayed these improved properties. Improved solvent systems for chromenone formation were essential in the synthesis of two of the chromenones. One chromenone produced fluorescence emission at 560 nm with a quantum yield of 0.53 and a scintillation decay time of 5 nsec.
Reaction of 2,3‐dichloro‐5,6‐dicyanopyrazine with enamines and some tertiary amines
Authors: Hou Dongfeng , Oshida Atsushi , Matsuoka Masaru
Published: March 2009

The reaction of 2,3‐dichloro‐5,6‐dicyanopyrazine (1) with enamines as well as a few tertiary amines as enamine precursors was investigated. Both reactions gave aminovinyl‐substituted pyrazine derivatives. During the attempted purification of 3c or 3d by column chromatography on silica gel, 2‐chloro‐5,6‐dicyano‐3‐(1′‐oxocyclopent‐2′‐yl)pyrazine (4) was obtained, apparently by hydrolytic cleavage. The products prepared are all of interest as potential pesticides.
Heterocycles. 13. synthesis of [1,2‐d]triazolo steroids
Authors: Weintraub Philip M.
Published: March 2009

Reaction of 1,2‐epoxy‐5α‐3‐ketosteroids with sodium azide produces a mixture of expected 2‐azido‐5α‐δ1‐3‐ketosteroids and novel [1,2‐d]triazolosteroids. A possible pathway for formation of the latter involving 1,3‐dipolar cycloaddition of sodium azide is discussed.
Synthesis of novel 1‐aryl[1]benzoxepino[5,4‐c]pyrazole and [1]benzoxepino[5,4‐d]pyrimidine derivatives
Authors: Chetoni Fabio , Da Settimo Federico , La Motta Concettina , Primofiore Giampaolo
Published: March 2009

Several 1‐aryl[1]benzoxepinopyrazoles were prepared by reaction of 4‐hydroxymethylene[1]benzoxepin‐ones with appropriate phenylhydrazine hydrochlorides. The direct condensation of hydroxymethylenebenz‐oxepinones with variously substituted amidines failed to give benzoxepinopyrimidines. These compounds were obtained via the key intermediates morpholine enaminobenzoxepinones.
An improved synthesis of cyclohexenothioxanthenones
Authors: Ran Ruicheng , Pittman Charles U.
Published: March 2009

An improved synthesis of cyclohexanothioxanthenones in high yield (70‐90%) by treatment of thiosalicylic acid (4) or 2,2′‐dithiosalicylic acid with 1,2,3,4‐tetrahydronaphthalene (5) in the presence of concentrated sulfuric acid or a mixture of 95% sulfuric acid with 27‐30% fuming sulfuric acid (in 5:1 to 2:1 v/v ratio) was described. The crude product consisted of three isomers which were isolated and identified. These isomers are 1,2‐, 2,3‐ and 3,4‐cyclohexanothioxantenone (1, 2, and 3).
Synthesis and nmr spectra of the six isomeric thieno[c]‐fused 1,7‐ and 1,8‐naphthyridines
Authors: Malm Johan , Rehn Bengt , Hörnfeldt Anna‐Britta , Gronowitz Salo
Published: March 2009

Through the use of Pd(0)‐catalyzed coupling between 2‐ and 4‐formyl‐3‐thiopheneboronic acid and 4‐iodo‐3‐aminopyridine (1) and 3‐bromo‐2‐aminopyridine, convenient one‐pot procedures for the preparation of thieno[2,3‐c]‐1,7‐naphthyridine (2), thieno[3,4‐c]‐1,7‐naphthyridine (3), thieno[2,3‐c]‐1,8‐naphthyridine (6) and thieno[3,4‐c]‐1,8‐naphthyridine (7) have been developed. Thieno[3,2‐c]‐1,7‐naphthyridine (4) and thieno[3,2‐c]‐1,8‐naphthyridine (8) were obtained through the coupling of 2‐tri‐n‐butylstannyl‐3‐thiophenaldehyde with 2,2‐dimethyl‐N‐(4‐iodo‐3‐pyridinyl)propanamide and 3‐bromo‐2‐acetamidopyridine (1). The yield of 8 was further increased when copper(II) oxide was used as the co‐reagent. The 13C nmr spectra of the six isomeric thieno[c]‐fused 1,7‐ and 1,6‐naphthyridines are discussed.
On the mechanism of the reduction of 1‐phenyl‐3‐(4‐pyridinylmethylene)‐2‐oxindole with sodium borohydride in methanol
Authors: Pierce Michael E. , Huhn George F. , Jensen James H. , Sigvardson Ken W. , Islam Qamrul , Xing Yide
Published: March 2009

Sodium borohydride reduction of 1‐phenyl‐3‐(4‐pyridinylmethylene)‐2‐oxindole1in methanol gives a high yield of the oxindole2, a precursor to linopirdine. The reduction is accelerated by methanol and the major by‐products during this reduction are the diastereomeric Michael adducts between1and2and the overreduced products,9and11. Surprisingly, indole9is not derived from further reduction of2but is formed concurrently, whereas the ring opened product11is the unexpected reduction product derived from2.
New [f]‐fused xanthines: Synthesis of 1,3‐dipropyl‐1H,3H‐pyrazino, pyrido, pyrimido and pyrrolo[2, 1‐f]purine‐2,4‐diones
Authors: Gatta Franco , Giudice Maria Rosaria Del , Borioni Anna , Mustazza Carlo
Published: March 2009

Synthesis of 1,3‐dipropyl‐1H,3H‐pyrazino, pyrido, pyrimido and pyrrolo[2,1‐f]purine‐2,4‐diones, starting from 5,6‐diamino‐1,3‐dipropylpyrimidine‐2,4‐dione1and 6‐chloro‐1,3‐dipropylpyrimidine‐2,4‐dione14is described. A new synthetic approach to 1,3‐dipropyl‐1H,3H‐pyrido(or pyrazino)[1′,2′‐1,2]pyrimido[4,5‐d]pyrimidine‐2,4,5‐triones19 e, f, hhas been also developed.
Synthesis and characterization of ruthenium(ii) complexes of 5‐hydroxyflavones
Authors: Silva Artur M. S. , Cavaleiro José A. S. , Tarrago Georges , Marzin Claude
Published: March 2009

Bis(dimethyl sulfoxide)bis(flavonato)ruthenium(II) complexes, RuL2(DMSO)2, were synthesized by the reaction of dichlorotetrakis(dimethyl sulfoxide)ruthenium(II) with the sodium salts of 5‐hydroxyflavone, 5‐hydroxy‐4′‐methoxyflavone and 5‐hydroxy‐3′,4′,5′,7‐tetramethoxyflavone, (L). The complexation was followed by 1H nmr spectroscopy. The 1:1 kinetically favoured tris(dimethyl sulfoxide)chloroflavonatoruthenium(II) complexes, RuLCl(DMSO)3, were initially formed and then transformed into the thermodynamically more stable ones. Each one of these complexes, by reacting with another equivalent of lig‐and L, also gave rise to a mixture of 1:2 kinetic species, from which the 1:2 thermodynamically more stable bis(dimethyl sulfoxide)bis(flavonato)ruthenium(II) complexes, RuL2(DMSO)2, were formed. The complexes were characterized by extensive studies involving 1H, 13C nuclear magnetic resonance, infrared and ultraviolet‐visible spectroscopy, mass spectrometry, cyclic voltammetry and elemental analysis. Such 1:2 complexes exhibited properties of two nonequivalent flavonate ligands and also of two non‐equivalent dimethyl sulfoxide ligands; one of these dimethyl sulfoxide ligands is considered to be S‐bonded and the other O‐bonded. Also two quasireversible one‐electron redox steps were observed at 0.53 to 0.57 and 0.44 to 0.41 V (vs Saturated Calomel Electrode). The spectroscopic results obtained allow for the discussion of stereochemistry of each bis(dimethyl sulfoxide)bis(flavonato)ruthenium(II) complex and to postulate its possible structure as one corresponding to the more anisochronous species.
Preparation and nitrosation of 3,4‐dimethyl‐3‐penten‐2‐one (e)‐ and (z)‐oximes. Formation of 3,3,4,5‐tetramethyl‐3H‐pyrazole 1,2‐dioxide and of 2‐isoxazoline derivatives
Authors: Hansen John F. , Novak Bennett H.
Published: March 2009

The stereoisomeric (E)‐ and (Z)‐oximes of 3,4‐dimethyl‐3‐penten‐2‐one were prepared and nitrosated with butyl nitrite in methanol. The (E)‐oxime gave 3,3,4,5‐tetramethyl‐3H‐pyrazole 1,2‐dioxide in nearly quantitative yield, while the (Z)‐oxime reacted less readily, giving a lower yield of the same product, with five other products identified as isoxazoline derivatives. Three of these were 4‐hydroxy‐, 4‐methoxy‐, and 4‐nitro‐3,4,5,5‐tetramethyl‐2‐isoxazoline. The fourth was the O‐(3,4,5,5‐tetramethyl‐2‐isoxazolin‐4‐yl) derivative of the starting (Z)‐oxime, and the fifth was 4‐methylene‐3,5,5‐trimethyl‐2‐isoxazoline.
Synthesis of some novel fused tetracyclic quinolonecarboxylic acids via 7‐methyl‐6,7,8,9‐tetrahydro‐3H‐imidazo[4,5‐f]quinoline and 6‐methyl‐5,6,7,8‐tetrahydro‐1H‐imidazo[4,5‐g]quinoline
Authors: Le Goff Corinne , Bouyssou Pascal , Chenault Jacques
Published: March 2009

A series of fused tetracyclic quinolonecarboxylic acids was prepared for biological evaluation. These compounds were synthesized by a route involving a regiospecific functionalization of 5‐fluoro‐2‐methyl‐1,2,3,4‐tetrahydroquinoline to obtain a series of new substituted 7‐methyl‐6,7,8,9‐tetrahydro‐3H‐imidazo[4,5‐f]quinolines and 6‐methyl‐5,6,7,8‐tetrahydro‐1H‐imidazo[4,5‐g]quinolines as convenient precursors of quinolones.
On the syntheses of 1,3‐disubstituted dithieno[3,4‐b:3′,2′‐d]pyridines via halogen‐metal exchange of 1,3‐dibromodithieno[3,4‐b:3′,2′‐d]pyridine
Authors: Gronowitz Salo , Temciuc Ecaterina , Hörnfeldt Anna‐Britta
Published: March 2009

Halogen‐metal exchange of 1,3‐dibromodithieno[3,4‐b:3′,2′‐d]pyridine with butyllithium under different conditions has been studied. Upon reaction with iodine, N,N‐dimethylacetamide, N,N‐dimethylformamide, dimethyl carbonate, dimethyl disulfide and thiuram disulfide, the 1,3‐diiodo‐, 1,3‐diacetyl‐, 1,3‐diformyl‐, 1,3‐dicarbomethoxy, 1,3‐di(thiomethyl)‐ and 1,3‐di(N,N‐dimethyldithiocarbamoyl)dithieno[3,4‐b:3′,2′‐d]‐pyridines, respectively, were obtained in varying yields. 3‐Monosubstituted derivatives were obtained in some cases. The formation of 3,7‐disubstituted derivatives was sometimes also observed.
Synthesis and transformations of some (heteroaryl)acetylazides, (heteroaryl)methyl isocyanates and alkyl (heteroaryl)methyl carbamates
Authors: Koĉaevar Marijan
Published: March 2009

The synthesis of two complex acetyl azides 6 and 10 having an heteroaryl residue bound to the acetyl group through the ring nitrogen, and their further transformations into the corresponding carbamates 7a‐b and 11a‐b and isocyanates 16 and 14 are described. Hydrolysis of these products results in the elimination of the substituted methyl group from the heterocyclic residue and formation of 1‐unsubstituled heterocycles. A similar transformation was also observed under mass measurement conditions.
Preparation of 4‐bromo‐1‐hydroxypyrazole 2‐oxides by nitrosation of α‐bromo‐α,β‐unsaturated ketoximes
Authors: Hansen John F. , Easter John A. , Eckert David A. , Hunt Karen J. , Little David A.
Published: March 2009

Nitrosation of the oximes of 3‐bromo‐3‐penten‐2‐one, 3‐bromo‐4‐phenyl‐3‐buten‐2‐one, and 2‐bromo‐1,3‐diphenyl‐2‐propen‐1‐one using sodium nitrite in acetic acid gave low yields of 4‐pyrazolone 1,2‐dioxides. Nitrosation using butyl nitrite in the presence of copper(II) sulfate and pyridine in aqueous ethanol produced insoluble copper complexes from which 3,5‐dimethyl‐, 3‐methyl‐5‐phenyl‐, and 3,5‐diphenyl‐4‐bromo‐1‐hydroxypyrazole 2‐oxides could be liberated by treatment with dilute potassium hydroxide, filtration, and acidification of the filtrate. High yields were obtained with the first two oximes, but, presumably due to unfavorable stereochemistry of the oxime, the diphenyl derivative gave a lower yield of the complex, accompanied by 4‐bromo‐ and 4‐nitro‐3,5‐diphenylisoxazole and 4‐oximino‐3,5‐diphenyl‐4,5‐dihydroisoxazole.
γ‐Radiolysis of 5‐fluorouracil and 5‐fluorouridine derivatives having sulfur‐containing substituents
Authors: Kuroda Tokuyuki , Hisamura Koji , Nishikawa Hiroshi , Nakamizo Nobuhiro , Otsuji Yoshio
Published: March 2009

γ‐Radiolysis reactions of eight 5‐fluorouracil (5‐FU) derivatives having sulfonyl group‐containing substituents at the 1‐position and five 5‐fluorouridine (5‐FUR) derivatives having thioureido group‐containing substituents were studied under the conditions where hydrated electron (eaq−) and hydroxyl radical (HO·) become the principal reactive species. The 5‐FU and 5‐FUR derivatives were radiolyzed to give 5‐FU and 5‐FUR, respectively. The efficiency of the reactions depended upon the nature of reactive species and also upon the nature of substituents. The reactivity features of the γ‐radiolysis reactions are discussed.
Addition of diamines to methylthiopyridones
Authors: Hehemann David G. , Winnik Witold
Published: March 2009

Thiopyridone derivatives react with diamines: ethylenediamine, 1,3‐propylenediamine and 1,4‐butylenediamine to produce bicyclic addition compounds. Ethanolamine reacts with thiopyridone derivatives to afford only open chain adducts. Diethylenetriamine and 2‐(2‐aminoethylamino)ethanol in reaction with thiopyridones yielded seven membered ring tricyclic derivatives. The procedures described here constitute a relatively simple method to prepare these novel heterocycles.
The counter anion effect of (16‐ethyl‐5,6,7,8‐tetrahydro‐9H‐dibenzo‐[b, i][1,4,8,11]tetraazacyclotetradecinato)nickel(II) complexes
Authors: Hashimoto Mamoru , Sakata Kazunori
Published: March 2009

The eight nickel(II) complexes with 16‐ethyl‐5,6,7,8,9,14‐hexahydrodibenzo[b, i][1,4,8,11]tetraazacyclotetradecine and a counter anion have been synthesized and their spectroscopic properties were studied. The δ N‐H values of NiLCl and NiLBr are observed in a more downfield range than those of NiLPF6, NiLBF4 and NiLClO4 in acetonitrile and nitromethane solutions. The plot of δ N‐H against molar conductance is found to be approximately linear. The N‐H stretching modes of NiLBF4, NiLPF6 and NiLClO4 shift to lower frequency and those of NiLCl, NiLBr and NiLI shift to higher frequency upon metal‐coordination.
Thienopyrrolizines: New condensed triheterocyclic systems
Authors: Lancelot Jean‐Charles , Letois Bertrand , Rault Sylvain , Robba Max , Rogosca Maria
Published: March 2009

Cyclization of 3‐(1‐pyrrolyl)thiophene‐2‐carboxamide derivatives of methyl 3‐(1‐pyrrolyl)‐2‐thiophenecarboxylate afforded imminium salts and resulted in the formation of thieno[2,3‐b]pyrrolizine derivatives.
Synthetic strategies directed to the antitumour alkaloids sesbanimide A and manzamine A
Authors: Pandit Upendra K.
Published: March 2009

Synthons derived from nature's chiral pool have been utilized in developing strategies aimed at the syntheses of the alkaloids sesbanimide A and manzamine A. The route designed for sesbanimide A has provided the naturally occurring alkaloid and a facile access to several analogues for structure‐activity relationship studies. The approach to the synthesis of manzamine A has led to a strategically functionalized chiral tricyclic intermediate possessing the absolute stereochemistry of the natural product. Recent results on the synthesis of sesbanimide analogues and the progress towards the total synthesis of manzamine A is described.
Synthesis of bioactive nitrogen heterocycles from marine organisms
Authors: Hino Tohru , Nakagawa Masako
Published: March 2009

Recently many bioactive indole alkaloids have been isolated from marine organisms. Many of them have novel ring systems which are not found in the indole alkaloids isolated from higher plants and molds on the land. We have chosen β‐carboline alkaloids, eudistomins and manzamines, as targets for total synthesis.
Acylaminoacetyl derivatives of active methylene compounds. 3. C‐Acylation Reactions via the Hippuric Acid Azlactone
Authors: Hamilakis Stylianos , Kontonassios Demetrios , Sandris Constantine
Published: March 2009

The C‐acylation reactions of the active methylene compounds, methyl cyanoacetate and Meldrum's acid, with hippuric acid, using the DCC activation and the mixed anhydride conditions, are shown to proceed through initial formation of 2‐phenyl‐5(4H)‐oxazolone, the hippuric acid azlactone. The conditions of these reactions using the azlactone as the acylating agent were investigated and discussed.
A new entry to the imidazo[4,5‐d]pyrimidine system. The reaction of 1,3‐dimethyl‐6‐aminouracil with N,N‐dimethyldichloromethyleniminium chloride (phosgeniminium chloride) and trimethylsilyl azide, a novel and convenient “one pot” synthesis of 8‐N‐arylaminotheophyllines (2‐N‐arylamino‐4,6‐dimethylimidazo[4,5‐d]pyrimidine‐(4H,6H)‐5,7‐diones), starting from 1,3‐dimethyl‐6‐aminouracil
Authors: Kokel Bruno
Published: March 2009

1,3‐Dimethyl‐6‐aminouracil 2 was converted into various 8‐N‐arylaminotheophyllines (2‐N‐arylamino‐4,6‐dimethylimidazo[4,5‐d]pyrimidine‐(4H,6H)‐5,7‐diones) 17 through reaction successively, with phosgeniminium chloride (N,N‐dimethyldichloromethyleniminium chloride) (1a), trimethylsilyl azide (4) and arylamines. Starting with the synthesis of the N,N‐dimethyl(1,3‐dimethyl‐4‐aminouracil‐5‐yl)chloromethyleniminium chloride (amide chloride) 3 this new route to the imidazo[4,5‐d]pyrimidine skeleton was shown to proceed via the formation of a very unstable N,N‐dimethyl‐(1,3‐dimethyl‐4‐aminouracil‐5‐yl)azidomethyleniminium chloride (amide azide) (8) which would undergo an in situ rearrangement into very likely, a 4‐amino‐5‐(chloroformamidin‐1′‐yl)uracil and/or related compounds of types 10. Depending on reaction conditions, the latter was proved to be a very good precursor of the 8‐dimethylaminotheophylline 11 as well.
Synthesis of 1‐arylacenaphtho[1,2‐d]pyrazoles and 5,7‐Dehydro‐5H,7H‐benzo[b]acenaphtho[1,2‐e]‐1,3a,6a‐triazapentalenes
Authors: Tsuge Otohiko , Hatta Taizo , Kojima Hisashi , Miyahara Nobutaka , Sugaya Masafumi
Published: March 2009

2‐Benzoyl‐ 5 and 2‐acetylacenaphthenone 6, prepared from the corresponding 1‐acyl‐2‐(1‐pyrrolidinyl)‐acenaphthylenes 2 and 3, reacted with arylhydrazines 8 under acidic conditions to give the corresponding 1‐arylacenaphtho[1,2‐d]pyrazoles 9 and 10. Novel heteropentalene mesomeric betaines, 5,7‐dehydro‐5H,7H‐benzo[b]acenaphtho[1,2‐e]‐1,3a,6a‐triazapentalenes 13 and 14 were prepared by reductive cyclization of 1‐(o‐nitrophenyl)acenaphtho[1,2‐d]pyrazoles 9d and 10d, respectively.
Synthesis and transformations of some quinolines and 1H‐pyrido[3,2‐c]azepines containing amino acid units
Authors: Anžič Borut , Kočevar Marijan , Polanc Slovenko
Published: March 2009

The synthesis of two complex acetyl azides 5 and 12 having quinoline or pyrido[3,2‐c]azepine ring bound to the acetyl group through the ring nitrogen, and their further transformations into the corresponding carbamates 6 and 13, isocyanates 7 and 14 and 1‐unsubstituted heterocyclic compounds 8 and 15 are described. The later compounds were debenzoylated on heating in concentrated sulfuric acid to give the corresponding products 9 and 16.
Demethylation reactions of 4‐amino‐N‐(2,6‐dimethoxy‐4‐pyrimidinyl)benzenesulfonamide (sulfadimethoxine) in strongly basic aqueous solution
Authors: Miura Tadayoshi , Ono Makoto , Yoshida Atomi , Kato Masahiro , Yoshioka Toshiyuki , Tachi Hiroshi , Eguchi Shoji
Published: March 2009

Hydrolysis of 1 in strongly basic aqueous solution afforded mono‐ and didemethylated products 2,3 and 4, that are postulated as the metabolites of 1 in some animals. This hydrolytic demethylation was shown to proceed stepwise via mono‐demethylation to give 2 and 3, followed by their further demethylation to 4. The hydrolytic reactivity of 1–3 was rationalized based on MO calculation results and 13C nmr data.
Synthesis of nitrogen‐containing heterocycles 6. Formation and structures of imidazolinones and related compounds through cyclization of diaminomethylenehydrazones with dimethyl acetylenedicarboxylate
Authors: Miyamoto Yoshiko , Yamazaki Chiji
Published: March 2009

Diaminomethylenehydrazones 1 of aromatic and aliphatic carbonyl compounds react with dimethyl acetylenedicarboxylate (DMAD) at room temperature to give four types of heterocycles, (5‐oxoimidazolin‐4‐ylidene) acetates 2, 3 and 6, (2‐imino‐5‐oxoimidazolidin‐4‐ylidene) acetate 4 and 6‐oxo‐1,6‐dihydropyrimidine‐4‐carboxylates 5 according to the substitution patterns of 1 in moderate to high yields. Amino (N,N‐dimethylamino)methylenehydrazones of ketones give exclusively (5‐oxoimidazolin‐4‐yl‐idene) acetates, both (Z)‐ and (E)‐isomers 2 and 3 about the exocyclic alkenic linkage, with the (Z)‐isomer 2 generally being predominant, while those of aldehydes give 5. Diamino‐ and amino (N‐methylamino)methylenehydrazones produce 5 and/or 6 and di (N‐methylamino) methylenehydrazone gives (2‐imino‐5‐oxoimidazolidin‐4‐ylidene) acetate 4 as the sole cyclized product.
Approaches toward the synthesis of 2,5‐disubstituted‐1,3‐thiazolidines
Authors: Faury Philippe , Camplo Michel , Charvet Anne‐Sophie , Mourier Nicolas , Barthelemy Philippe , Graciet Jean‐Christophe , Kraus Jean‐Louis
Published: March 2009

Synthetic approaches for new 2,5‐disubstituted‐1,3‐thiazolidines are described. Steric and electronic effects of the N‐substituent of the thiazolidine ring represent the major parameter in the rearrangement process. The nmr studies demonstrate that N‐unsubstituted 2,5‐disubstituted‐1,3‐thiazolidines exist as epimeric mixture, while the corresponding N‐acetylated analogues exist as a conformer mixture.
Synthesis of N‐alkoxycarbonyl and N‐carboxamide derivatives of anti‐inflammatory oxindoles
Authors: Robinson Ralph P. , Donahue Kathleen M.
Published: March 2009

The synthesis of N‐alkoxycarbonyl and N‐carboxamide derivatives of anti‐inflammatory oxindoles is described. These compounds, sought as potential prodrugs of the parent anti‐inflammatory agents, were obtained by ring opening of the oxadiazine dione intermediates formed by the treatment of 1‐unsubstituted 3‐acyloxindoles with chlorocarbonyl isocyanate.
Synthesis of oxazolo[4,5‐c]quinolones by thermolytic degradation of 4‐azido‐2(1H)‐quinolones
Authors: Steinschifter Waltraud , Fiala Werner , Stadlbauer Wolfgang
Published: March 2009

4‐Azido‐2(1H)‐quinolones 1 are thermolyzed in the presence of carboxylic acids and polyphosphoric acid to yield oxazolo[4,5‐c]quinolones 3. Formation of other possible isomeric ring closure products such as oxazolo[5,4‐c]quinolones 2 or isoxazolo[4,3‐c]quinolones 4 could be excluded by independent syntheses.
Reactivity of nucleophilic uracil derivatives
Authors: Grangier Géraldine , Aitken David J. , Guillaume Dominique , Husson Henri‐Philippe , Tomas Alain , Viossat Bernard
Published: March 2009

The reactivity of uracil derivatives bearing acidic methylene groups at N1 was investigated. On treatment with strong base, compounds with nitrile as the activating group underwent extensive dimerisation to give new tricyclic systems. Ester‐activated compounds also produced dimers in the absence of an external electrophile, but their monomeric carbanions could be trapped by prompt addition of benzyl bromide to give normally alkylated products.
Synthesis of 1,3‐dihydro‐3,3‐dimethyl‐2H‐indol‐2‐one derivatives as possible nonsteroidal cardiotonics
Authors: Lee An‐Rong , Huang Wen‐Hsin , Lin Tung‐Liang , Shih Kun‐Min , Lee Hsiao‐Feng , Lin Cheng‐I
Published: March 2009

New substituted 1,3‐dihydro‐3,3‐dimethyl‐2H‐indol‐2‐one derivatives19–29and34–43were synthesized and examined for their inotropic activity in isolated dog ventricular tissues. Among them, compound26(2‐(2,3‐dimethoxybenzylamino)‐N‐(3,3,7‐trimethyl‐2‐oxo‐2,3‐dihydro‐1H‐indol‐5‐yl)acetamide) showed very potent activity.
Reaction of ninhydrin with β‐dicarbonyl compounds
Authors: Peet Norton P. , Huber Edward W. , Huffman John C.
Published: March 2009

The reactions of ninhydrin (1) with β‐ketoesters and β‐diketones were studied. Two kinds of products were observed, which were either simple adducts of the dicarbonyl compounds to the center carbonyl group of ninhydrin, or tricyclic indeno[1,2‐b]furans. Treatment of methyl 3‐aminocrotonate (2) with ninhydrin led in analogous fashion to an indeno[1,2‐b]pyrrole (3) which was reduced to a complex tetracyclic dihydropyridine 12. A mechanism for the production of 12 is presented. Structures for the novel heterocycles are supported by high resolution nmr studies and X‐ray crystallography.
Facile aerial oxidation of a porphyrin. Part 18. N‐alkylation of the oxidised product derived from Meso‐tetrakis(3,5‐di‐t‐butyl‐4‐hydroxyphenyl)porphyrin
Authors: Milgrom Lionel R. , Hill Jonathan P. , Yahioglu Gokhan
Published: March 2009

In basic solutions, the oxidised porphyrin 2 readily undergoes macrocyclic N‐alkylation, with up to four bulky alkyl groups, including decyl and substituted benzyl moieties, being accomodated: an argument is presented to show that N‐di‐alkylation occurs on opposite nitrogen atoms, on the same side of the macrocycle.
Alkoxide‐induced reactions of N‐substituted saccharins. Synthesis of 1,2‐benzothiazocine 1,1‐dioxide and 2,3‐dihydropyrrolo[1,2‐b]‐[1,2]benzisothiazole 5,5‐dioxide derivatives
Authors: Blanco Mercedes , Perillo Isabel A. , Schapira Celia B.
Published: March 2009

The reactions of saccharin derivatives 1 with sodium alkoxides were studied. Under mild conditions, compounds 1a‐f gave the corresponding open sulfonamides 5a‐f. Under drastic conditions, β‐(saccharin‐2)propionic acid derivatives 1a,b reacted with sodium ethoxide affording saccharin and β‐ethoxypropionic acid derivatives 4a,b. γ‐(Saccharin‐2)butyric acid derivatives 1c,d and γ‐(saccharin‐2)‐butyrophenone 1f reacted with sodium t‐butoxide in dimethyl sulfoxide affording 5‐substituted 6‐hydroxy‐3,4‐dihydro‐2H‐1,2‐benzothiazocine 1,1‐dioxides 9. From mother liquors, 1‐substituted 2,3‐dihydro‐pyrrolo[1,2‐b][1,2]benzisothiazole 5,5‐dioxides 10 were isolated several hours later, though not detected immediately after completing the reaction. When the reactions were carried out in t‐butyl alcohol, the yields of 9 diminished and those of 10 increased with product ratio inversion. Different experimental observations on the possible pathway generating 9 and 10 are discussed.
Facile synthesis of (±)‐, (+)‐, and (‐)‐galanthamine
Authors: Szewczyk Jerzy , Wilson Joseph W. , Lewin Anita H. , Carroll F. Ivy
Published: March 2009

The Amarylidacea alkaloid galanthamine (1a) is an acetylcholinesterase inhibitor that has been evaluated as a potential agent for the treatment of Alzheimer's disease. We report a very efficent synthesis of (±)‐galanthamine [(±)‐1a] from readily available isovanillin and tyramine. We have separated racemic galanthamine into its diastereoisomeric (1S)‐camphanate esters and obtained both natural (‐)‐ and unnatural (+)‐galanthamine by lithium aluminum hydride removal of the acyl group.
Synthesis and conformational study of acridine derivatives related to 1,4‐dihydropyridines
Authors: Martín Nazario , Quinteiro Margarita , Seoane Carlos , Soto José L. , Mora Arturo , Suárez Margarita , Ochoa Estael , Morales Alhmed , Bosque Jose R. Del
Published: March 2009

Novel acridine derivatives have been synthesized from dimedone and different aromatic aldehydes by following the classical Hantzsch's procedure. The particular substitution pattern of these compounds is responsible for the observed strong push‐pull effect. Quantum chemical calculations were carried out on these molecules by using the AM1 method with complete geometry optimization. The calculated heats of formation reveal two equally favoured conformations. The parameter of planarity and the charge density calculations are in agreement with the 13C nmr spectroscopic data.
Synthesis of nevirapine and its major metabolite
Authors: Grozinger K. G. , Fuchs V. , Hargrave K. D. , Mauldin S. , Vitous J. , Campbell S. , Adams J.
Published: March 2009

Several synthetic methods were developed during the process optimization for the large scale synthesis of nevirapine (1), a non‐nucleoside inhibitor of HIV‐1 Reverse Transcriptase. The synthesis of its putative major metabolite 11‐cyclopropyl‐5,11‐dihydro‐4‐hydroxymethyl‐6H‐[3,2‐b:2′,3′‐e][1,4]diazepin‐6‐one (2) and the oxidation of 2 to the corresponding aldehyde 3, are described.
Electron ionization mass spectra and crystal structures of some [1,2,4]triazolo[1,2‐b]‐ and [1,3,4]thiadiazolo[3,4‐b]phthalazines
Authors: Joutsiniemi Karoliina , Ahlgrén Markku , Vainiotalo Pirjo , Morgenstem Olaf , Meusel Mario
Published: March 2009

The mass spectra of ten 1,3‐dithioxo[1,2,4]triazolo[1,2,‐b]phthalazines, five 3‐iminosubstituted 1‐thioxo‐[1,3,4]thiadiazolo[3,4‐b]phthalazines, three 3‐iminosubstituted‐1‐thioxo[1,2,4]triazolo[1,2‐b]phthalazines, and 1,3‐dithioxo‐5,10‐dihydro[1,3,4]thiadiazolo[3,4‐b]phthalazine were recorded under electron ionization. The fragmentation pathways were elucidated by metastable ion analysis and exact mass measurements. The changes in the ring‐system had little effect on the fragmentation mechanism, but the effect on peak intensities was considerable. The most important fragmentations began with the opening of the triazole ring. Substituents at nitrogen atoms also had a marked effect on the mass spectral behavior. The aryl substituents prompted a whole new fragmentation. The X‐ray crystal structure was determined for a few compounds. Two of the three structures of the 1,3‐dithioxo[1,2,4]triazolo[1,2‐b]phthalazines that were studied proved to be relatively planar, whereas the structure of 1,3‐dithioxo‐5,10‐dihydro[1,3,4]thiadiazolo[3,4‐b]phthalazine was considerably bent similarly to the 2‐(4‐chlorophenyl)‐1,3‐dithioxo‐2,3,5,10‐tetrahydro[1,2,4]triazolo[1,2‐b]‐phthalazine. The triazole and the thiadiazole rings had a strong double bond nature.
The synthesis of cycloalkylpyrido[1,2‐a]benzimidazole carbonitrile analogs
Authors: Russell Ronald K. , Van Nievelt Caroline E.
Published: March 2009

The preparation of various sustituted cycloalkylpyrido[1,2‐a]benzimidazolecarbonitrile analogs is described as well as the X‐ray of the cycloheptyl analog 13a.
Synthesis of some N‐[pyridyl(phenyl)carbonylamino]hydroxyalkyl‐(benzyl)‐1,2,3,6‐tetrahydropyridines as potential anti‐inflammatory agents
Authors: Rao Kode Nageswara , Redda Kinfe K. , Onayemi Folakemi Y. , Melles Hailemichael , Choi Jongoh
Published: March 2009

1,2,3,6‐Tetrahydropyridines are known to possess analgesic, anti‐inflammatory, hyperglycemic and hypoglycemic activities. Substituted 2,4‐dinitrophenylpyridinium chlorides 3 were formed by reacting 1‐chloro‐2,4‐dinitrobenzene with hydroxypropyl, hydroxymethyl and benzyl substituted pyridines 2. Attack of the pyridinium chlorides 3 with pyridylcarbonyl hydrazides or benzoyl hydrazides 4 gave the isolable 2,4‐dinitroanilino derivative 5 which underwent hydrolysis when refluxed in water:p‐dioxane mixture (1:4 v/v) to afford the pyridinium ylides 6. Sodium borohydride reduction of 6 in absolute ethanol at 0° for 4–6 hours resulted in the isolation of the 1,2,3,6‐tetrahydropyridines 7 in good yields.