bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and reactions of heterocyclic 2,3‐epoxypropionitriles with pyrrolidine
Authors: Agarwal Kamlesh C. , Knaus Edward E.
Published: April 2009

The Darzen's reaction of 2‐(3‐)pyridinecarboxaldehydes5with chloroacetonitrile yielded a mixture of stereoisomerscis‐6andtrans‐3‐(pyridinyl)‐2,3‐epoxypropionitriles7in a ratio of approximately 1:1. Oxidation ofcis‐6andtrans‐7afforded the correspondingcis‐8andtrans‐3‐(1‐oxidopyridinyl)‐2,3‐epoxypropionitriles9in good yield. The reaction of8aand9awith pyrrolidine at 25° gave the respectivethreo‐10anderthyro‐2‐(1‐pyrrolidino)‐3‐hydroxy‐3‐(1‐oxido‐2‐pyridinyl)propionitrile (11). A number of selected compounds (7‐9a‐b) were found to be inactive in the P388 Lymphocyctic screen.
A practical synthesis of (+)‐cocaine
Authors: Lewin Anita H. , Naseree T. , Ivy Carroll F.
Published: April 2009

(+)‐Cocaine has been prepared from commercially available 3‐tropinone in four steps. Synthetic procedures and experimental details are provided.
Studies on the nef reaction induced by organic bases
Authors: Akhtar Mohammad Shamim , Sharma Vishnu Lal , Bhaduri Amiya Prasad
Published: April 2009

Studies of the Nef reaction in the presence of primary, secondary and tertiary amines have been described. A convenient synthesis of N‐substituted pyrroles and 3,6‐dimethyl‐4‐hydrazinocarbonyl‐5‐(4‐amino‐3‐nitrophenyl)‐pyridazine 16 has been developed.
Synthesis of benzimidazole derivatives as potential H1‐antihistaminic agents
Authors: Iemura Ryuichi , Kawashima Tsuneo , Fukuda Toshikazu , Ito Keizo , Tsukamoto Goro
Published: April 2009

Several types of benzimidazole derivatives were prepared and were screened forH1‐antihistaminic activity. Most of the compounds showed potent antihistaminic activityin vitro.Among them 2‐[(1‐piperazinyl)methyl]‐benzimidazoles14and 2‐[(1‐homopiperazinyi)methyl]benzimidazoles15exhibited potent activity alsoin vivo.
Synthesis of phenanthro[9,10‐g]isoquinoline
Authors: Tanga M. J. , Davis R. F. , Reist E. J.
Published: April 2009

The synthesis of phenanthro[9,10‐g]isoquinoline is presented.
1,3‐Dipolar cycloaddition synthesis of 3‐bromo‐5‐substituted isoxazoles, useful intermediates for the preparation of pharmacologically active compounds
Authors: Chiarino D. , Napoletano M. , Sala A.
Published: April 2009

Bromonitrile oxide 2, generated from easily available dibromoformaldoxime 1, reacts with monosubstituted acetylenic derivatives 4 to give 3‐bromo‐5‐substituted isoxazoles 5 in high yield. The experimental conditions necessary to overcome difficulties such as the low reactivity of acetylenic dipolarophiles and the high tendency to dimerization of bromonitrile oxide 2, are discussed; the regioselectivity of this 1,3‐dipolar cycloaddition is also studied. The obtained improvements in the synthesis of some pharmacologically active compounds are reported.
Some chemical transformations of 7a‐cyanohexahydro‐1H‐pyrrolizine into 7a‐substituted hexahydro‐1H‐pyrrolizines
Authors: Miyano Seiji , Yamashita Osamu , Sumoto Kunihiro , Shima Keiyu , Hayashimatsu Mariko , Satoh Fumio
Published: April 2009

Chemical transformations of 7a‐cyanohexahydro‐1H‐pyrrolizine (2) into 7a‐substituted hexahydro‐1H‐pyrrolizines are described. In the reaction of 2 with lithium aluminum hydride, the orientation of the lone pair of the bridgehead nitrogen against C‐CN bond can be regarded as significant.
Nitration of some 3,5‐disubstituted pyridine N‐oxides
Authors: Bissell Eugene R. , Swansiger Rosalind W.
Published: April 2009

The preparation of 3‐chloro‐5‐methoxypyridine N‐oxide and its nitration are reported. Mononitration yields 5‐chloro‐3‐methoxy‐2‐nitro‐pyridine N‐oxide while more drastic conditions give 3‐chloro‐5‐methoxy‐2,6‐dinitropyridine. Removal of various substituents by base hydrolysis is also discussed.
Meerwein arylation of methyleneglutaronitrile with anthraquinone diazonium hydrogensulfate. Synthesis of an enolizable benzanthrone lactone
Authors: Sutter P. , Weis C. D.
Published: April 2009

The Meerwein reaction of 1‐anthraquinone diazonium hydrogensulfate with 2‐methyleneglutaronitrile in methanol yielded predominantly 3‐hydroxy‐4‐(1‐anthraquinone)‐1,3‐butanedicarbonitrile (5), while the corresponding 2‐methyleneglutaric acid diethyl ester furnished a derivative of 1‐(anthraquinone)butanolide 10. Catalytic dehydrocyanation of 5 was effected with Dowex‐50 to furnish 3‐oxo‐4‐(anthraquinone)butanecarbo‐nitrile (6). Both nitriles 5,6 gave in a double cyclization reaction a benzanthrone lactone 12 from which a crystalline derivative of the enol form was isolated, the structure of which was elucidated by 1H‐ and 13C‐nmr spectra. The methylene group of the lactone ring underwent coupling reactions with aromatic diazonium salts to form hydrazone derivatives.
Synthesis of some 2,3‐benzo‐l‐oxaoctems
Authors: Arnoldi Anna , Merlini Lucio , Scaglioni Leonardo
Published: April 2009

The synthesis of some 8‐hydroxy‐2,3‐benzo‐l‐oxaoctems is reported. The imide 7, a potential β‐lactamase inhibitor, was also synthesized.
β‐Angelica lactone epoxide: Chemical behaviour and some synthetic applications
Authors: Ortuño R. M. , Cardellach J. , Font J.
Published: April 2009

A new epoxy derivative of ß‐angelica lactone has been synthesized. Its chemical behaviour towards nucleophiles has been explored in order to prepare natural products with a trisubstituted ß‐hydroxy‐γ‐methylbutyrolactone‐type constitution. Thus, some potential precursors have been obtained and an efficient and stereo‐controlled synthesis of (±)‐blastmycinone is reported.
Synthetic approaches to cularines. I. Phenolic oxidative coupling
Authors: De Lera Angel Rodriguez , Saá José M. , Suau Rafael , Castedo Luis
Published: April 2009

Ferricyanide‐promoted biogenetic‐type phenolic oxidative coupling of an 8,3′‐dihydroxytetrahydrobenzyl‐isoquinoline 19a afforded the isomeric phenolic cularines 5 and 21. Vanadium oxytrifluoride oxidation of the N‐borane complex of 19a afforded, regioselectively, the para‐coupled product 21. Moreover, when this reagent was used on the monophenolic tetrahydrobenzylisoquinoline 19b protected as its N‐borane complex, cularine 1 was regioselectively obtained in good yield. Other structural modifications and reagents were not successful.
A new route to 6‐azachromones. An improved synthesis of 2‐azaxanthone
Authors: Cordonnier Guy , Sliwa Henri
Published: April 2009

Condensation of the morpholine enamine of 1‐benzyl‐4‐piperidone with β‐ketoesters yielded 6‐azatetrahy‐drochromones which were debenzylated and aromatized to 6‐azachromones; 2‐azaxanthone has been thus obtained with an improved yield as compared to previous syntheses.
Cyclisation of benzils
Authors: Cremlyn Richard J. , Swinbourne Frederick J. , Shode Olufemi O. , Lynch John
Published: April 2009

Treatment of several substituted benzils [3,3′‐ and 4,4′‐dimethyl‐; 2,2′‐, 3,3′‐ and 4,4′‐dichloro‐; 3,3′‐dibromo‐; 4‐(N,N‐dimethylamino)‐] with an excess of chlorosulfonic acid gave the corresponding 3‐chloro‐2‐phenylbenzofuran disulfonyl dichlorides. Disubstitution was confirmed by microanalytical and spectral data for the corresponding bis(N,N‐dimethylaminsulfonamides). The positions of electrophilic substitution were not confirmed with 3,3′‐dimethyl‐, 2,2′‐ and 3,3′‐dichlorobenzils. With 4,4′‐dichlorobenzil, a smaller amount of chlorosulfonic acid enabled the isolation of 3,6,4′‐trichloro‐2‐phenylbenzofuran‐5‐sulfonyl chloride, which was identified by X‐ray analysis of the N,N‐dimethylsulfonamide. The cyclisation failed with 3,3′‐dimethoxy‐, and 3,3′‐ and 4,4′‐dinitrobenzils. The results have been interpreted mechanistically.
New reactions of deoxyvasicinone. Part 6
Authors: Dunn A. D. , Kinnear K. I. , Norrie R. , Ringan N. , Martin D.
Published: April 2009

Several acylated derivatives of deoxyvasicinone 1 and its analogues were shown to exist as enols. The 3‐hydroxymethyl derivative of 1 was shown to undergo rapid dehydration and products derived from an intermediate 3‐methylene compound were obtained. Novel oxazepino analogues of 1 are reported.
Substituent and solvent effects on tautomeric equilibria of barbituric acid derivatives and isoterically related compounds
Authors: Jovanovic Misa V. , Biehl Edward R.
Published: April 2009

N‐Mono and N,N‐dialkyl/diarylbarbituric acids exist in solution as a single tautomer. The 13C nmr spectroscopy shows that they are present in the triketo form in a number of polar and non‐polar solvents. 2‐Thiobarbituric acid derivatives, however, show extensive tautomerization. Their 13C chemical shift assignments were achieved by utilizing models 11a, 11c, 12b and 12d and from which relative tautomer distribution ratios were determined. These ratios were correlated with the dielectric constant of the various solvents (ϵ). Thio‐barbituric acids also formed adducts with solvents having carbonyl groups, characteristic observed only with barbiturates possessing the thione or thiophenolic group. 6‐Amino and 6‐methyluracils and thiouracils exist in DMSO solution as stable “ene” forms as do orotic acid, 24, and its thio analogue 25. Compound 25 undergoes disproportionantion and tautomerization when heated or on prolonged standing in solution. Literature contradictions regarding the structure of “4,6‐dihydroxypyrimidine,” 26, were resolved and its tautomers in solution correctly assigned by 13C nmr.

Anions of barbiturics and related systems exist in one of the two possible types A and B, depending on whether ring nitrogens are substituted (type A), or not (type B). Rapid H/D exchange at C5 was evident from C‐deuterium coupling. The redistribution of charge through C4(C6) carbonyl groups shown by 13C shifts of carbonyl carbon atoms of up to 10 ppm as compared to the CO carbons of the neutral species was evident.
Novel heterocyclic systems. Part 26. The synthesis and 13C‐NMR assignment of 1,8‐diazaphenoxathiin
Authors: Lindsy Charles M. , Smith Keith , Martin Gary E.
Published: April 2009

Although the syntheses of numerous diazaphenoxathiins have been reported, only two dipyrido[1,4]‐oxathiin systems are thus far known, viz. the 1,7‐ and 1,9‐diazaphenoxathiins. The synthesis of a third, 1,8‐diazaphenoxathiin via the condensation of the dianion of 3‐hydroxypyridine‐2(1H)‐thione with 4‐nitro‐3‐chloropyridine 1‐oxide is now described. A minor quantity of 1,7‐diazaphenoxathiin was obtained as a byproduct of the reaction. Complete assignment of the 13C‐nmr spectrum was achieved and this conclusively differentiates the 1,8‐compound from the 1,7‐isomer.
Synthetic applications of 2‐chloro‐3‐formylquinoline
Authors: Srivastava Ranjan Prasad , Neelima  , Bhaduri Amiya Prasad
Published: April 2009

New examples of synthetic applications of 2‐chloro‐3‐formylquinoline, as evident from the novel and facile syntheses of 3‐aminoisooxazolo[5,4‐b]quinoline (4), 3‐hydroxyfuro[2,3‐d]theino[2,3‐b]quinoline‐2‐carboxamide (7) and 3‐hydroxymethyl‐2‐(3‐formyl)phenylquinoline (13), have been furnished.
Reactions of 2‐isocyanatobenzoyl chloride and 2‐carbomethoxyphenyl isocyanate with 5‐aminotetrazole
Authors: Peet Norton P.
Published: April 2009

Treatment of 2‐isocyanatobenzoyl chloride (4) with 5‐aminotetrazole (5‐AT) gave 3‐(5‐tetrazolyl)quinazoline‐2,4(1H,3H)‐dione (1) directly. Treatment of 2‐carbomethoxyphenyl isocyanate (5) with 5‐AT gave 2‐[((5‐amino‐1H‐tetrazol‐1‐yl)carbonyl)amino]benzoic acid methyl ester (6) as a kinetic product, which was thermally isomerized to 2‐[((1H‐tetrazol‐5‐ylamino)carbonyl)amino]benzoic acid methyl ester (7), the thermodynamically more stable urea. Cyclization of7with polyphosphoric acid gave 2‐(1H‐tetrazol‐5‐ylamino)‐4H‐3,1‐benzoxazin‐4‐one (2). Urea6was quite labile in solution, as shown by nmr, and readily reacted with methanol to give 2‐[(methoxycarbonyl)amino]benzoic acid methyl ester (10).
Nitriles in organic synthesis: A novel synthesis of benzo[h]pyrimidino[1,2‐c]‐pyridazinone and hydrazonobut‐2‐enonitrile derivatives
Authors: Hafez Ebtisam Abdel Aziz , Kandeel Zaghloul El‐Shahat , Elnagdi Mohamed Hilmy
Published: April 2009

A new synthesis of benzo[h]pyrimidino[1,2‐c]pyridazinones via coupling diazotised anthranilic acid with 1‐phenylethylidenemalononitrile (1) is reported. Synthesis of new 1‐antipyrin‐4‐yl and 1‐pyrazol‐5‐ylpyridazine derivatives utilizing 1 as starting material is also described.
The synthesis of monomethoxynaphtho[1′,2′:4,5]thieno[2,3‐c]quinolines
Authors: Pakray Sudabeh , Castle Raymond N.
Published: April 2009

A series of monomethoxynaphtho[1′,2′:4,5]thieno[2,3‐c]quinolines has been prepared by photocyclization of the appropriate N‐methoxyphenyl‐1‐chloronaphtho[2,1‐b]thiophene‐2‐carboxamides. Some of the lactams obtained were converted into the thiolactams and their S‐methyl derivatives. The lactams were also converted into the corresponding 6‐chloro derivatives. Some of these were catalytically dechlorinated into the monomethoxynaphtho[1′,2′:4,5]thieno[2,3‐c]quinolines which were then quaternized into the N‐methyl quaternary salts.
Chemistry of the phenoxathiins and isosterically related heterocycles. XXXIII . The influence of intramolecular sulfur‐nitro group interactions on the reactivity at sulfur
Authors: Mehta Mehul U. , Martin Gary E. , Smith Keith
Published: April 2009

Nitro‐groups positioned ortho to thio‐esters have been shown to engage in strong, non‐bonded intramolecular interactions between the sulfur atom and one of the nitro‐group oxygens. The effect of the sulfur‐nitro group oxygen interaction on the chemical reactivity at the sulfur atom of 9‐nitro‐1‐azaphenoxathiin is reported. Conditions which normally produce the sulfone exclusively have been shown to yield the sulfoxide with only a minimal quantity of the sulfone produced. Protracted periods of reflux are required to produce the sulfone from the sulfoxide.
Synthesis of 2,4′‐dioxospiro[indoline‐3,2′‐thiazolidine]‐5′‐acetic acids: X‐ray structure of 1‐benzyl‐3′‐(4‐chlorophenyl)‐2,4′‐dioxospiro‐ [indoline‐3,2′‐thiazolidine]‐5′‐acetic acid
Authors: Popp Frank D. , Rajopadhye Miland , Brown David S. , Waddington David , Uff Barrie C.
Published: April 2009

The title compounds have been prepared by the cyclocondensation of mercaptosuccinic acid with isatin‐3‐imines. The 1‐benzyl derivatives have been synthesized by simultaneously reacting 1‐benzylisatin, substituted anilines and mercaptosuccinic acid. The structure of the products has been confirmed by X‐ray diffraction measurements.
Application of 1,2,3,5,6,7‐hexahydropyrrolizinium perchlorate in the synthesis of 7a‐substituted hexahydro‐1h‐pyrrolizines
Authors: Miyano Seiji , Yamashita Osamu , Sumoto Kunihiro , Shima Keiyu , Hayashimatsu Mariko , Satoh Fumio
Published: April 2009

The method for preparing 7a‐substituted hexahydro‐1H‐pyrrolizines 2 from 1,2,3,5,6,7‐hexahydropyrrol‐izinium Perchlorate (3) was investigated, by which introduction of a wide variety of functionalities on C(7a) could be achieved easily.
Spirolactones of xanthene. III. Formation and molecular structure of novel spirolactones of xanthene and dibenzo[c,h]xanthene
Authors: Kimura Michio
Published: April 2009

The reaction of 1‐naphthol or phenol derivatives with oxalic and sulfuric acids yielded novel spirolactones. Eight examples (2a‐h) were synthesized by this reaction. The structures of the spirolactones were established from spectral evidence and the X‐ray diffraction studies. Some of the spirolactones form the solvates with the aromatic solvent molecules, such as toluene, xylene and nitrobenzene, and the structure of the nitrobenzene solvate of 2a was determined by the X‐ray analysis.
Reactions of 1‐isopropyl‐3‐methyl‐ and 2,3‐dimethylindoles with triethyl orthoformate: New trisindolylmethanes
Authors: Pindur Ulf , Müller Johann
Published: April 2009

Indoles 1 and 2 react with triethyl orthoformate under proton–catalyzed conditions to form trisindolylmethanes. The regioisomer distribution of the products is controlled by steric and electronic factors.
Synthesis of 8‐cyano‐1,4‐dihydro‐4‐oxopyrrolo[1,2‐a]pyrimidine‐3‐carboxylic acids as potential antimicrobial agents
Authors: Abdalla Ghassan M. , Sowell J. Walter
Published: April 2009

The preparation of a variety of 8‐cyano‐1,4‐dihydro‐7‐phenyl‐4‐oxopyrrolo[1,2‐a]pyrimidine‐3‐carboxylicacids and 8‐cyano‐1,4‐dihydro‐7‐p‐fluorophenyl‐4‐oxopyrrolo[1,2‐a]pyrimidine‐3‐carboxylic acids is described.
Intramolecular hydrogen bonding in imidazole‐4(5)‐alkoxycarbonyl‐5(4)‐carboxamide derivatives
Authors: Yasuda Naohiko , Nakamura Asao , Tsuboi Masamichi
Published: April 2009

The ir spectrum of imidazole derivatives, which have an alkoxycarbonyl group and a carboxamide group at the 4‐ and 5‐positions of the imidazole ring respectively, exhibits the shift of the ester carbonyl band to a lower wave number. This phenomenon was investigated by spectroscopic measurements of a group of relevant compounds. The results indicate that the shift is caused by the intramolecular hydrogen bonds between the hydrogen atom of the amide and the carbonyl oxygen of the ester which is enhanced by the resonance stabilization of the imidazole ring.
Synthetic approaches to cularines. II. Ullmann condensation
Authors: De Lera Angel RodrÍGuez , Suau Rafael , Castedo Luis
Published: April 2009

The first total syntheses of O‐methylcularicine 9b and sarcocapnine 9c are described together with a new synthesis of cularine 9a using the Ullmann condensation reaction of the appropriate 2′‐bromo‐8‐hydroxy‐tetrahydrobenzylisoquinoline formed by phase‐transfer alkylation of Reissert compound 2. When this strategy was combined with the lead tetraacetate treatment of the tetrahydrobenzylisoquinoline it yielded 4‐hydroxycularines, from which highly oxidized members of the family can be obtained. This is exemplified by the first synthesis of 4‐hydroxysarcocapnine 19 and its transformation to the 3,4‐dioxoisocularine yagonine 20, rearrangement of which afforded the aristoisocularine aristoyagonine 21.
1,2‐Fused pyrimidines. III. Derivatives of 12H‐pyrido[1′,2′:1,2]pyrimido[4,5‐b]quinoline, a novel heterocyclic system
Authors: Roma G. , Di Braccio M. , Balbi A. , Mazzei M. , Ermili A.
Published: April 2009

Reactivities of 2‐amino‐4H‐pyrido[1,2‐a]pyrimidin‐4‐ones and 4‐amino‐2H‐pyrido[1,2‐a]pyrimidin‐2‐ones, both N,N‐dialkyl and (N‐alkyl, N‐phenyl)substituted, when treated with the N,N‐dimethylformamide/phosphorus oxychloride Vilsmeier‐Haack reagent XII were compared.

Starting from 2‐[(N‐alkyl, N‐phenyl)amino] compounds IXa,b, the expected XVIa,b and XVIIa,b were obtained, which are derivatives of 12H‐pyrido[1′,2′:1,2]pyrimido[4,5‐b]quinoline, a novel heterocyclic system. When 2‐(phenylamino) compound IXc was used a mixture of 3‐formylderivative XVIII and 12H‐pyrido‐[1′,2′:1,2]pyrimido[4,5‐b]quinolin‐12‐one (XIX) resulted from the reaction. On the other hand, 2‐(dialkylamino)‐4H‐pyrido[1,2‐a]pyrimidin‐4‐ones IIIa‐c plainly afforded high yields of 3‐formylderivatives XIVa‐c.

In contrast, no significant reaction occurred when 4‐(dialkylamino) and 4‐[(N‐alkyl,N‐phenyl)amino] compounds IIa‐c and VIIIa,b were treated with the reagent XII, under the same as well as more severe conditions. A clear difference in the nucleophilic reactivity of C‐3 position between these two classes of isomers is pointed out by the above summarized results.
Polycyclic N‐hetero compounds. XXIX. Synthesis and antidepressive evaluation of 15‐thia‐11,13‐diazasteroidal analogues and their precursors
Authors: Hirota Takashi , Hamazaki Rieko , Ohdoi Takako , Sasaki Kenji , Namba Tetsuto
Published: April 2009

Syntheses of novel 15‐thia‐11,13‐diazasteroidal skeleton IV and its D‐homo analogues are described. Meso‐ionic derivatives of IV were also synthesized. Antidepressive activities of these compounds and their precursors were screened. D‐Dihomothiadiazasteroid IX and 3,4,5,6‐tetrahydrobenzo[h]quinazoline‐4‐thione (V) exhibited antireserpine action.
Synthesis and antimalarial activity of a series of 2,4‐diamino‐6‐[(N‐alkylanilino)methyl]quinazolines
Authors: Werbel Leslie M. , Elslager Edward F. , Newton Linda S.
Published: April 2009

A series of 2,4‐diamino‐6‐[(N‐alkylanilino)methyl]quinazolines were prepared by bromination of 2,4‐dibenz‐amido‐6‐methylquinazoline followed by treatment with secondary arylamines and deblocking with base. A variety of analogs demonstrated substantial activity against Plasmodium berghei infections in mice.
A convenient synthesis of nicotinate esters from 3‐cyanopyridones
Authors: Paine John B.
Published: April 2009

A convenient synthesis of alkyl‐substituted ethyl nicotinates 8 was devised, using 3‐cyano‐2(1H)‐pyridones 4. These were converted to the corresponding 2‐bromo‐3‐cyanopyridines 5 with boiling phosphorus tribromide. The resulting 5 were smoothly debrominated to 3‐cyanopyridines 6 with zinc dust in boiling ethanolic acetic acid. The nitrile function was hydrolyzed in boiling 6N hydrochloric acid, and the resulting nicotinic acid hydrochlorides 7 esterified with refluxing triethyl orthoformate, to give the ethyl nicotinates 8. A modified formylation of 2‐butanone led to the sodium salt of 2‐methyl‐3‐oxobutanal (3a) of enhanced purity.
17O NMR Investigation of cyclic aromatic ethers
Authors: Boykin David W. , Martin Gary E.
Published: April 2009

A linear relationship between the C‐O‐C angle and the molecular dihedral angle in a series of phenoxathi‐ins and azaphenoxathiins is reported. 17O nmr spectroscopic data (natural abundance in acetonitrile at 75°C) were obtained on eight cyclic aromatic ethers 1‐8, including phenoxathiins, and two model compounds, acyclic aromatic ethers 9 and 10. The chemical shifts of the cyclic aromatic ethers were very sensitive to structural variations and were dependent upon electonic and conformational effects; however, no quantitative relationship between 17O chemical shift and geometric parameters was found.
Synthesis of 1,2‐di‐(4‐pyridyl)ethylenediamine and related compounds
Authors: Braña Miguel F. , Castellano José M. , Rodriguez Maria L. López , Gálvez Magdalena , Amil Manuel R. , Rubio Enrique
Published: April 2009

Hydrolysis of N,N'‐diacyl‐1,2‐di(4‐pyridyl)ethylenediamines 1 in aqueous sulfuric acid gave the corresponding imidazolines 3. 1,2‐Di‐(4‐pyridyl)ethylenediamine 2 was prepared in 61 % yield by treating N,N'‐di‐t‐butyl‐oxycarbonyl‐1,2‐di(4‐pyridyl)ethylenediamine 4 with trifluoroacetic acid or in 94% yield by the hydrolysis under basic conditions of N,N'‐diphthaloylglycyl‐1,2‐di(4‐pyridy)ethylenediamine 13.
Furopyridines. VII. Preparation and hydrolysis of 2‐cyano and 3‐cyano derivatives of furo[3,2‐b]‐, furo[2,3‐c]‐ and furo[3,2‐c]pyridine
Authors: Morita Hiroyuki , Shiotani Shunsaku
Published: April 2009

This paper describes the preparation and hydrolysis of 2‐cyano and 3‐cyano derivatives of furo[3,2‐b]‐, furo[2,3‐c]‐ and furo[3,2‐c]pyridine. Treatment of furopyridines 1a, 1b and 1c with n‐butyllithium in hexane‐tetrahydrofuran at ‐70° and subsequent addition of N,N‐dimethylformamide yielded 2‐formyl derivatives 2a, 2b and 2c. Dehydration of the oximes 4a, 4b and 4c of 2a, 2b and 2c gave 2‐cyano compounds 5a, 5b and 5c, which were hydrolyzed to give 2‐carboxylic acids, 6a, 6b and 6c, respectively. Reaction of 3‐bromo compounds 7a, 7b and 7c with copper(I) cyanide in N,N‐dimethylformamide afforded 3‐cyano derivatives 8a, 8b and 8c. Alkaline hydrolysis of 8a, 8b and 8c gave compounds formed by fission of the 1‐2 bond of furopyridines 9a, 9b and 9c, while acidic hydrolysis gave the corresponding carboxamides, 10a, 10b and 10c.
Synthesis of novel 4‐amino‐1,4‐benzodiazepine‐2,5‐diones for anticonvulsant testing
Authors: Tita Terence T. , Kornet Milton J.
Published: April 2009

A series of novel 4‐amino‐1,4‐benzodiazepine‐2,5‐diones was synthesized via two pathways. The first method involved reductive alkylation of unsymmetrical hydrazines with glyoxylic acid, followed by Fisher esterification. The resulting N‐aminoglycinate ethyl ester was subsequently o‐nitrobenzoylated, reduced, and thermally cyclized to obtain 4‐dialkylaminobenzodiazepinones. In the second method methylhydrazine was acetylated at Nα then benzoylated at Nβ to give 1,2‐diacylhydrazines. Alkylation with ethyl bromoacetate and reduction of the nitro group, followed by thermal cyclization yielded 4‐acetamidobenzodiazepinones. All title compounds were evaluated in mice in MES seizure and sc Met seizure threshold tests for anticonvulsant activity, and in the rotorod test for neurotoxicity. Activity and toxicity were both minimal.
On the mechanism of hydrolysis of the triazolobenzodiazepine, triazolam. Spectroscopic study
Authors: Jiménez R. M. , Domínguez E. , Badía D. , Alonso R. M. , Vicente F. , Hernández L.
Published: April 2009

The hydrolysis of 8‐chloro‐6‐(2′‐chlorophenyl)‐1‐methyl‐4H[1,2,4]triazolo[4,3‐a][1,4]benzodiazepine (Triazolam) at room temperature, involves a reversible mechanism. The intermediate is a protonated species and the final product is the ring‐opened compound resulting from the reversible scission of the imine bond. The two compounds were determined simultaneously as a function of pH with pmr and cmr spectrometry. Spectral data of the benzophenone derivative II (ir, cmr, pmr) are reported.
Synthesis of 3‐amino‐5H‐pyrimido[5,4‐b]indol‐4‐one derivatives
Authors: Monge A. , Palop J. A. , Parrado P. , Perez‐Ilzarbe C. , Fernández‐Alvarez E.
Published: April 2009

Starting with ethyl 3‐aminoindole‐2‐carboxylate, the synthesis of 3‐amino‐5H‐pyrimido[5,4‐b]indole‐2,4‐dione 5, 3‐amino‐5H‐pyrimido[5,4‐b]indol‐4‐one 10 and some related compounds is described. Preliminary results about the inhibition of platelet aggregation by these compounds is reported.
Synthesis of 4‐oxo‐4H‐quino[2,3,4‐i,j][1,4]‐benoxazine‐5‐carboxylic acid derivatives
Authors: Chu Daniel T. W. , Maleczka Robert E.
Published: April 2009

The synthesis and antibacterial activity of 1‐substituted amino‐2‐fluoro‐4‐oxo‐4H‐quino[2,3,4‐i,j][1,4]benox‐azine‐5‐carboxylic acid derivatives is described. Key steps in the synthesis include carbon homologation and two intramolecular nucleophilic displacement cyclization reactions to generate the 4‐oxo‐4H‐quino[2,3,4‐i,j]‐[1,4]benoxazine‐5‐carboxylic acid nucleus.
MNDO and MINDO/3 study of the reactivity of 3‐pyrrolin‐2‐one tautomers and derivatives
Authors: Ribó Josep M. , Vallés Asunción
Published: April 2009

MINDO/3 and MNDO methods have been applied to the study of the reactivity of 3‐pyrrolin‐2‐one tautomers and derivatives. The different parameters that can influence the reactivity from the frontier molecular orbital point of view (atomic charge distribution, frontier orbital energy and frontier orbital reactivity indices) are compared and evaluated with respect to the experimental reactivity already known.
Reactivity of a cyclic α‐bromoiminium bromide towards nucleophiles
Authors: Donati Donato , Fusi Stefania , Macripò Maria Adelaide , Ponticelli Fabio
Published: April 2009

Piperidine‐pyrrolidine ring contraction of 1‐piperideinium bromide (1) was observed by reaction with aqueous bases, sodium methoxide, phenylhydrazine, (S)‐1‐phenylethylamine and sodium borohydride, whereas diazomethane addition mainly gave pyrrolo[3,4‐b]pyridine derivative 8. Some stereochemical features of these reactions have been investigated. 1 gave back bromine under suitable conditions.
Synthesis of 1α and 1β‐acylamino and alkylamino‐1,2,3,4,5,6‐hexahydro‐2,6‐methano‐3‐benzazocines and related compounds
Authors: Hirani Shabir K. , Parfitt Robert T.
Published: April 2009

The synthesis of series of 1α and 1β‐alkylamino‐1,2,3,4,5,6‐hexahydro‐2,6‐methano‐3‐benzazocines from the corresponding acylamino intermediates is described. Cyclization of the 1β‐chloromethylamido derivative 20 to the novel bridged benzomorphan 21 occurred whereas the corresponding 1β‐chloromethylamido derivative 19 failed to cyclize for steric reasons. In addition several related 1α‐acylamidomethyl‐ and 1β‐alkyl‐aminomethyl benzomorphans are reported.
A practical synthesis of 2,3‐dihydro‐2‐benzofurancarboxylic acid: A general route to 2,3‐dihydrobenzofurans
Authors: Edwards Colin R. , Readhead Michael J. , Tweddle Neil J.
Published: April 2009

A practical synthesis of 2,3‐dihydro‐2‐benzofurancarboxylic acid is reported in five steps and approximately 40% overall yield. The methodology offers a useful new route to 2‐substituted‐2,3‐dihydrobenzofurans.
Condensed 1,3,5‐triazines: 1,3,4‐Thiadiazolo[3,2‐a]‐1,3,5‐triazines and isoxazolo[2,3‐a]‐1,3,5‐triazines
Authors: El‐Kerdawy Mohamed M. , Bayomi Said M. , Shehata Ihsan A. , Glennon Richard A.
Published: April 2009

A convenient route is reported for the synthesis of substituted 1,3,4‐thiadiazolo[3,2‐a]‐1,3,5‐triazine‐5,7‐diones and isoxazolo[2,3‐a]‐1,3,5‐triazines. Condensation of the appropriately substituted 2‐amino‐1,3,4‐thiadiazole and 3‐aminoisoxazole with phenoxycarbonyl isocyanate provides the desired target compounds in fair yield.
Synthesis of heterocyclic compounds related to fredericamycin A – the cyclopent[g]isoquinoline system
Authors: Clive Derrick L. J. , Sedgeworth Janette
Published: April 2009

A synthetic route is described to compounds 9 and 10, which resemble the cyclopent[g]isoquinoline system of the antitumor agent, Fredericamycin A. The method is based upon directed lithiation of the pyridine 6 and conjugate addition to 2‐cyclopenten‐1‐one. Cyclization of the product 7 with base then generates the required skeleton, which can be aromatized and methylated (7 → 8 → 9).
Synthesis of 4,8‐dimethoxy‐3H‐benz[f]indol‐3‐one. Anomalous behaviour to cyclization of 1,4,5‐trimethoxy‐3‐amino‐γ‐chloroalkylnaphthalene intermediates
Authors: Malesani Giorgio , Ferlin Maria Grazia
Published: April 2009

A new linear benz[f]indole derivative 15 bearing two methoxyls in the fused naphthalene moiety was prepared as a potential chemotherapeutic agent. The anomalous behaviour of two trimethoxynaphthalene intermediates in parallel stages of the planned synthesis route is emphasized, and the corresponding mechanisms for these cyclizing reactions are proposed and discussed.
Methylation of 2‐phenylamino‐1,3,4‐thiadiazole. A structure debated
Authors: Buccheri Francesco , Cusmano Giuseppe , Noto Renato , Rainieri Rosina , Werber Giuseppe
Published: April 2009

The true identity of the 4‐methyl‐5‐phenylimino‐δ2‐1,3,4‐thiadiazoline (A) has been demonstrated. The reactions, previously reported in the literature to give A have been repeated and the structure of the compounds obtained has been established.
Tautomerism in alloxan
Authors: Millefiori Salvatore , Millefiori Arcangelo
Published: April 2009

Ab initio STO‐3G, 3‐21G and 6‐31G calculations have been used to investigate the energetics of the tautomerism in alloxan. The geometries of the tautomers have been fully optimized at STO‐3G level. The results indicate that tautomerism in alloxan in the vapour is highly unlikely, the trioxo structure being by far the most stable structure. The population analysis of the alloxan anion gives evidence that the preferred protonation site is offered by the central oxygen atom, and rules out the opposite oxygen atom as a possible protonation site.
A new synthesis of 2,3‐disubstituted quinoxaline 1,4‐dioxides catalyzed by molecular sieves
Authors: Takabatake Tohru , Hasegawa Minoru
Published: April 2009

The syntheses of 2,3‐disubstituted quinoxaline 1,4‐dioxides are smoothly and efficiently carried out by the adsorption of the components on molecular sieve 3A (powder) from benzofuroxan 1 and 1,3‐diketones, 3‐oxo‐alkanoic esters, or 3‐oxoalkanamides 2.
Synthesis of indazolo[3,2‐a]isoquinoline
Authors: Stanforth S. P.
Published: April 2009

Treatment of 1‐(2′‐nitrophenyl)isoquinoline with hot triethylphosphite afforded indazolo[3,2‐a]isoquino‐line.
Cycloaddition reactions of cyclic ketene‐N,S‐acetals with 1,2,4,5‐tetrazines
Authors: Marcelis Antonius T. M. , Van Der Plas Henk C.
Published: April 2009

Reaction of 3,6‐diphenyl‐, 3,6‐bis(2‐pyridyl)‐ and the unsubstituted 1,2,4,5‐tetrazine with 4,5‐dihydro‐1‐methyl‐2‐(methylthio)pyrrole (2) and 1‐raethyl‐2‐(methylthio)‐4.5,6,7‐tetrahydroazepine (3) gives 4,7‐di‐R‐2,3‐dihydro‐1‐methylpyrrolo[2,3‐d]pyridazine (4, R = phenyl, 2‐pyridyl, hydrogen) and 6,9‐di‐R‐1‐methyl‐2,3,4,5‐tetrahydropyridazino[4,5‐6]azepine (5), R = phenyl, 2‐pyridyl, hydrogen), respectively, in reasonable to good yields. The compounds 4 (R = phenyl, hydrogen) are converted into their corresponding 1‐methylpyrrolo‐[2,3‐d]pyridazines 6 by reaction with potassium permanganate in butanone. Reaction of 3‐phenyl‐1,2,4,5‐te‐trazine with 2 and 3 leads to the exclusive formation of the 7‐phenyl isomer 4d and 9‐phenyl isomer 5d, respectively, indicating that the cycloaddition is regiospecific. The mechanism is discussed.
Pyrido[2′1′:2,3]imidazo[4,5‐c]isoquinoline and the alkylation of pyrido[2′,1′:2,3]imidazo[4,5‐c]isoquinolin‐5(6H)‐one
Authors: Paolini John P. , Palopoli Frank P. , Lendvay Louis J. , Huffman John
Published: April 2009

The reaction of 2‐aminopyridine, o‐phthaldehydic acid and potassium cyanide gave pyrido[2′,1′:2,3]imidazo[4,5‐c]isoquinolin‐5(6H)‐one, which upon treatment with propargylbromide, yielded both O and N alkylated products. 2‐Aminopyridine, o‐phthaldehyde and potassium cyanide gave 1‐cyano‐2‐(2‐pyridyl)isoindole which rearranged in acid to give the previously unreported parent pyrido[2′,1′:2,3]imidazo[4,5‐c]isoquinole. Structures were confirmed using uv, ir, nmr and x‐ray spectroscopy.
Heterocycles. 10. A facile synthesis of 7‐hydroxy‐6,7‐dihydro‐5H‐pyrrolo[1,2‐a]imidazole
Authors: Weintraub Philip M. , Tiernan Paul L. , Huffman John C.
Published: April 2009

Reaction of imidazole with acrolein gave the title compound whose structure was confirmed by X‐ray analysis.
Synthesis of 1′‐methylspiro[3H‐indole‐3,n'‐piperidines] from 1‐methyl‐n‐piperidinecarbaldehydes
Authors: Benito Y. , Canoira L. , Martinez‐Lopez N. , Rodriguez J. G. , Temprano F.
Published: April 2009

1′‐Methylspiro[3H‐indole‐3,n'‐piperidines] 2 can be obtained from the 1‐methyl‐n‐piperidinecarbaldehydes 1 by the Fischer reaction of their phenylhydrazones. The Fischer reaction provides different kinds of products ‐3H‐indole, indole and oxindole‐ which depend on the N atom position in the piperidine ring.
Ozonolysis of five‐membered heterocycles
Authors: Kashima Choji , Hibi Shigeki , Maruyama Tatsuya , Harada Kazuo , Omote Yoshimori
Published: April 2009

The relative reaction rate of five‐membered heterocycles with ozone was evaluated. These relative rates were correlated to the highest bond order value in the corresponding ring, calculated by the convenient HMO method. From this correlation, the reactivity of heterocycles with ozone was able to be predicted. Also it was concluded that the predominant product in the ozonolysis of five‐membered heterocycles containing an oxygen atom was the corresponding carboxylic acid, while nitrogen heterocycles gave the corresponding amide.
Pyridylethyl: A versatile protecting group. Part II. The protection of heterocyclic N‐H groups
Authors: Katritzky Alan R. , Khan Ghulam R. , Marson Charles M.
Published: April 2009

Pyrrole, indole, carbazole and imidazole have been protected as N‐[2‐(4‐pyridyl)ethyl] derivatives. Deprotection occurred under mild conditions after quaternisation. 3‐Bromoindole was prepared by bromin‐ation of the protected parent indole.
Nitrogen bridgehead compounds, part 68. Studies on quinolizine derivatives. Part 2. Synthesis of 1,3‐disubstituted‐4H‐quinolizine derivatives
Authors: Schwartz Angéla , Pál Zoltán , Szabó László , Simon Kálmán , Hermecz István , Mészáros Zoltán
Published: April 2009

Quinolizine compounds 1 and 2 or their monocyclic tautomers 3 and 4 have been synthesized using 2‐pyri‐dineacetic acid derivatives 6a, b, A, B and ethoxymethylenemalonic acid derivatives 7a, b, c in base catalyzed or thermic reaction. In the 6‐unsubstituted series, both the 4‐oxo and 4‐imino derivatives could have been obtained, in the 6‐substituted series, however the 4‐oxo ones only, whereas instead of the 4‐imino derivatives, their monocyclic tautomers 3, 4 have been isolated. In the 6‐unsubstituted series, the primarily formed 4‐imino compounds have been rearranged into 4‐oxo ones under stronger conditions. The structure of the isolated compounds have been proved by ultraviolet, infrared and 1H nmr spectra, that of 3B=C by X‐ray analysis as well.
Nitrogen bridgehead compounds. Part 70. Studies on quinolizine derivatives. Part 4. Ultraviolet‐visible spectra and chemical properties of some quinolizine derivatives and their monocyclic tautomers
Authors: Schwartz Angéla , Szabó László , Pusztay‐Szabó Katalin , Hermecz István , Mészáros Zoltán
Published: April 2009

Ultraviolet‐visible spectra of 4‐oxo 1 and 4‐imino 2 quinolizines or their monocyclic tautomers 3, 4 have been studied in neutral, acidic and basic ethanolic solution as well as in dimethyl sulfoxide and chloroform. Ring B of 4‐oxo and 6‐unsubstituted 4‐imino compounds can be cleaved by sodium ethanolate more or less easily. Ring B of 6‐methyl‐4‐iminoquinolizines is very unstable and they are present mainly in the monocyclic form which are partly dissociated in ethanol and dimethyl sulfoxide especially in higher dilution or in the presence of sodium ethanolate. In dilute acidic ethanol or chloroform, the dissociation is suppressed and in the latter solvent and in some cases, absorption bands can be observed due to a small amount of the 4‐imino‐6‐methylquinolizines. In acidic solution of compounds 3B=C, 3D, 4E, 4F=G having simultaneously cyano and ethoxycarbonyl groups in 1 and 3 position, not simple reprotonation occurs but irreversible changes can be observed.
Synthesis and dopaminergic activity of trans‐4‐methyl‐3‐phenylpyrrolidines
Authors: Tschappat Kathryn D. , Crider A. Michael , Hassan Mohamed N. , Fahn Stanley
Published: April 2009

tran‐3‐(3,4‐Dihyroxyphenyl)‐4‐methyl‐1‐(n‐propyl)pyrrolidine 13 trans‐3‐(3‐Hydroxyphenyl)‐4‐methyl‐1(n‐propy)pyrrolidine 14 were synthesized and evaluated for dopaminergic activity. The stereochemical assignments of 13 and 14 were determined by nmr. Both 13 and 14 were either inactive or weakly active in most dopaminergic tests.
Quinazolines and 1,4‐benzodiazepines. XCVI. Compounds derived from benzodiazepine‐2‐acetic acid
Authors: Walser A. , Flynn T.
Published: April 2009

1,4‐Benzodiazepine‐2‐acetic acid derivatives were prepared and converted to compounds with a heterocyclic ring fused to the a‐face of the benzodiazepine system. Representatives of pyrido[1,2‐a][1,4]benzodiaze‐pines, pyrimido[1,6‐a][1,4]benzodiazepines and [1,3]oxazino[3,4‐a][1,4]benzodiazepines are described. Some of the compounds showed marked CNS‐activity as measured by the antimetrazole test which is a well established primary screening method for assessment of benzodiazepine type activity.
Halogenation of [2‐(trimethylsilyl)ethoxy]methyl (SEM) protected 2,2′‐Bi‐H‐imidazole
Authors: Matthews Donald P. , Whitten Jeffrey P. , Mccarthy James R.
Published: April 2009

2,2′‐Bi‐1H‐imidazole, when protected with the [2‐(trimethylsilyl)ethoxy]methyl (SEM) blocking group, on treatment with N‐bromosuccinimide or N‐chlorosuccinimide yields predominantly the monohalogenated derivatives 4a and 4b. The [2‐(trimethylsilyl)ethoxy]methyl group is subsequently removed to yield pure mono‐halo‐2,2′‐bi‐H‐imidazoles 2.
Synthesis of 1‐(1,1‐dimethylethyl)‐1H‐pyrazole‐4‐carboxylate ester derivatives
Authors: Beck James R. , Lynch Michael P.
Published: April 2009

Attempts to prepare ethyl 5‐cyano‐1‐(1,1‐dimethylethyl)‐1H‐pyrazole‐4‐carboxylate (7) by the reaction of the corresponding 5‐chloro derivative 1b with cyanide ion were unsuccessful. The chloro ester was synthesized from the corresponding amino ester la utilizing nonaqueous diazotization with nitrosyl chloride. An alternate process was developed which allowed the preparation of 7 from the corresponding 5‐methyl ester 3 in four steps. The structure of the N‐methylamide 8 synthesized from 7 was confirmed by X‐ray diffraction analysis.
Aroylnitrile oxide cyclizations. 2. Synthesis of (3‐aroylisoxazol‐5‐yl)alkanoic acids
Authors: Tegeler John J. , Diamond Craig J.
Published: April 2009

Intermolecular cyclization of 1,3‐dipolar aroylnitrile oxides to terminal alkynols followed by phase transfer catalyzed oxidation provided a short, convenient route to several novel (3‐aroylisoxazol‐5‐yl)alkanoic acids.
Synthesis of 1‐aryl‐5‐(trifluoromethyl)‐1H‐pyrazole‐4‐carboxylic acids and esters
Authors: Beck James R. , Wright Fred L.
Published: April 2009

Ethyl 1‐aryl‐5‐(trifluoromethyl)‐1H‐pyrazole‐4‐carboxylates 2 were prepared by the condensation of arylhydrazines with ethyl 3‐ethoxy‐2‐(trifluoroacetyl)‐2‐propenoate (1a) at low temperature. The corresponding acids were also synthesized. X‐ray diffraction analysis of an amide derivative 4 verified the position of the trifluoromethyl group on the pyrazole ring.
Reaction of 4‐acylaminomethylpyridine N‐oxides with phenylbutazone in the presence of acetic anhydride
Authors: Braña M. F. , Castellano J. M. , Redondo M. C. , Esplugues J.
Published: April 2009

Reaction of 4‐acylaminomethylpyridine N‐oxides with phenylbutazone in the presence of acetic anhydride is described. In the pharmacological screening one compound shows an interesting anticonvulsant activity.
Synthesis of 1,2‐benzoquinones by the oxidation of 1,4‐benzodioxins by peroxide derivatives
Authors: Kashima Choji , Tomotake Atsushi , Omote Yoshimori
Published: April 2009

The oxidation reaction of 1,4‐benzodioxin 1 by m‐chloroperbenzoic acid (m‐CPBA) and t‐butyl hydroperoxide (t‐BHP) are reported. 1,2‐Benzoquinone 2 was given in moderate yields by the m‐CPBA oxidation of 1,4‐benzodioxin 1, while 1,2‐benzoquinone 2 was predominantly formed by t‐BHP oxidation.
Synthesis of hexahydro‐5H‐benz[g]imidazo[2,1‐a]‐ isoindole 2via an intramolecular diels‐alder reaction and a novel lawesson's reagent mediated cyclization
Authors: Basha Fatima Z. , Debernardis John F.
Published: April 2009

The 2‐(5,6‐dihydroxy‐1,2,3,4‐tetrahydro‐1‐naphthyl)imidazoline 1 is a recently reported potent alpha‐adrenergic agent [1]. In continuation of our work on the synthesis of potential adrenergic agents we required imidazoisoindole 2 in order to investigate the biological effects of incorporation of additional rigidity into the parent system. This paper describes the synthesis of 2 via an intramolecular Diels‐Alder reaction and a novel Lawesson's reagent mediated cyclization.
Un equivalent synthetique de la triformyl s‐triazine
Authors: Sumera F. , Le Rouzic A. , Raphalen D. , Kerfanto M.
Published: April 2009

La tris‐dimorpholinométhyl s‐triazine 2 se comporte comme un équivalent synthétique de la triformyl s‐triazine 1. Ainsi à partir du composé 2 nous préparons des dérivés caractéristiques 5 du trialdéhyde 1: des triphénylhydrazones, la trialdoxime, la trisemicarbazone et la tris [bis (N,N‐diméthylamino‐4 phényl) méthyl] s‐triazine.
Addition of dihalocarbenes to 3H‐1,5‐benzodiazepines. Synthesis of 2H‐bisazirino[1,2‐a:2′,1′‐d][1,5]benzodiazepines
Authors: Takahashi Masahiko , Takada Tsugumasa , Sakagami Takeshi
Published: April 2009

Addition of dihalocarbenes, generated from haloforms using a phase transfer catalyst, to 3H‐1,5‐benzodi‐azepines gave 2H‐Bisazirino[1,2‐a:2′,1′‐d][1,5]benzodiazepines, a new ring system.
Correlation of ring nitrogen substituents with carbon‐13 nuclear magnetic resonance data in azoloazines
Authors: Pugmire Ronald J. , Smith James C. , Grant David M. , Stanovnik Branko , Tišler Miha , Verček Bojan
Published: April 2009

Carbon–13 nuclear magnetic resonance data have been acquired on 22 azoloazines. Chemical shifts have been correlated by a step–wise linear multiple regression with nitrogen substituents in both the 5‐ and 6‐membered rings using pyrrolo[1,2‐α]pyridine as the reference for chemical shift correlation. The data demonstrate that a highly correlated set of chemical shift parameters exist. Nitrogen substitution in the five–membered ring produces larger cross–ring effects than are oberved in the five–membered ring when substitution occurs in the six–membered ring. Within the six–membered ring a constant para‐ substituent parameter is noted. The meta‐ and para‐ parameters are more complex and fall into two groups for each parameter. Within the five–membered ring, a highly regular chemical shift pattern is observed which reflects an attenuated perturbation from nitrogen substitution in the six–membered ring.
Synthesis of novel 1‐phenyl‐1H‐indole‐2‐carboxylic Acids. I. Utilization of ullmann and dieckmann reactions for the preparation of 3‐hydroxy, 3‐alkoxy, and 3‐alkyl derivatives
Authors: Unangst Paul C. , Connor David T. , Stabler S. Russell , Weikert Robert J.
Published: April 2009

Methods for the synthesis of novel 3‐hydroxy, 3‐alkoxy, and 3‐alkyl indole‐2‐carboxylic acids and esters are described. Dieckmann cyclization of various 2‐[(carboxymethyl)amino]benzoic acid diesters yielded 1‐unsubstituted‐, 1‐methyl‐, and 1‐phenyl‐3‐hydroxy‐1H‐indole‐2‐carboxylic acid esters. An Ullmann reaction with bromobenzene converted 1H‐indoles to 1‐phenylindoles.
Synthesis of novel 1‐phenyl‐1H‐indole‐2‐carboxylic acids. II. Preparation of 3‐dialkylamino, 3‐alkylthio, 3‐alkylsulfinyl, and 3‐alkylsulfonyl derivatives
Authors: Unangst Paul C. , Connor David T. , Stabler S. Russell
Published: April 2009

The synthesis of novel indole‐2‐carboxylic acids with amino‐ and sulfur‐containing substituents in the indole 3‐position is described. An Ullmann reaction with bromobenzene converted 1H‐indoles with 3‐(acetylamino)‐ and 3‐(diethylamino)‐substituents into 1‐phenyl‐1H‐indoles. Reaction of 3‐unsubstituted indoles with thionyl chloride provided indole 3‐sulfinyl chlorides, which reacted with alkyl and aryl Grignard reagents to form the corresponding sulfoxides. The indole sulfoxides thus obtained were reduced to sulfides or oxidized to sulfones.
9‐deazapurine nucleosides. The synthesis of certain N‐5‐2′‐deoxy‐β‐D‐erythropentofuranosyl and N‐5‐β‐D‐arabinofuranosylpyrrolo[3,2‐d]pyrimidines
Authors: Girgis Nabih S. , Cottam Howard B. , Larson Steven B. , Robins Roland K.
Published: April 2009

A number of 2,4‐disubstituted pyrrolo[3,2‐d]pyrimidine N‐5 nucleosides were prepared by the direct glycosylation of the sodium salt of 2,4‐dichloro‐5H‐pyrrolo[3,2‐d]pyrimidine (3) using 1‐chloro‐2‐deoxy‐3,5‐di‐O‐(p‐toluoyl)‐α‐D ‐erythropentofuranose (1) and 1‐chloro‐2,3,5‐tri‐O‐benzyl‐α‐D‐arabinofuranose (11). The resulting N‐5 glycosides, 2,4‐dichloro‐5‐(2‐deoxy‐3,5‐di‐O‐(p‐toluoyl) ‐β‐D‐erythropentofuranosyl)‐5H‐pyrrolo‐[3,2‐d]pyrimidine (4) and 2,4‐dichloro‐5‐(2,3,5‐tri‐O‐benzyl‐β‐D‐arabinofuranosyl‐5H ‐pyrrolo [3,2‐d)pyrimidine (12), served as versatile key intermediates from which the N‐7 glycosyl analogs of the naturally occurring purine nucleosides adenosine, inosine and guanosine were synthesized. Thus, treatment of 4 with methanolic ammonia followed by dehalogenation provided the adenosine analog, 4‐amino‐5‐(2‐deoxyerythropentofuranosyl) ‐5H‐pyrrolo[3,2‐d]pyrimidine (6). Reaction of 4 with sodium hydroxide followed by dehalogenation afforded the inosine analog, 5‐(2‐deoxy‐β‐D‐erythropentofuranosyl) ‐5H‐pyrrolo[3,2‐d]pyrimidin‐4(3H)‐one (9). Treatment of 4 with sodium hydroxide followed by methanolic ammonia gave the guanosine analog, 2‐amino‐5‐(2‐deoxy‐β‐D‐erythropentofuranosyl) ‐5H‐pyrrolo[3,2‐d]pyrimidin‐4(3H)‐one (10). The preparation of the same analogs in the β‐D‐arabinonucleoside series was achieved by the same general procedures as those employed for the corresponding 2′‐deoxy‐β‐D‐ribonucleoside analogs except that, in all but one case, debenzylation of the sugar protecting groups was accomplished with cyclohexene‐palladium hydroxide on carbon, providing 4‐amino‐5‐β‐D‐arabinofuranosyl‐5H‐pyrrolo [3,2‐d]pyrimidin‐4(3H)‐one (18). Structural characterization of the 2′‐deoxyribonucleoside analogs was based on uv and proton nmr while that of the arabinonucleosides was confirmed by single‐crystal X‐ray analysis of 15a. The stereospecific attachment of the 2‐deoxy‐β‐D‐ribofuranosyl and β‐D‐arabinofuranosyl moieties appears to be due to a Walden inversion at the C1 carbon by the anionic heterocyclic nitrogen (SN2 mechanism).
Synthesis of 3‐phenylpyrroles by hydride reduction of 4‐hydroxypyrrolidin‐2‐ones
Authors: Hasegawa Tadashi , Nakamura Fuki , Moribe Jun‐Ichi , Yoshioka Michikazu
Published: April 2009

3‐Phenylpyrroles 2 were easily prepared in good yields by hydride reduction of 4‐hydroxypyrrolidin‐2‐ones 1, which have been prepared in high yields from the photoreaction of N,N‐dialkylbenzoylacetamides, with lithium aluminum hydride.