bluuebunny/crossref_metadata_2025 huggingface dataset:
The crystal and molecular structure of phenothiazine‐10‐propionitrile. The effect of crystal packing on the dihedral angle of phenothiazine heterocycles
Authors: Malmstrom Mary Carl , Cordes A. W.
Published: March 2009

Phenothiazine‐10‐propionitrile, C12H8SNC2H4CN, crystallizes in the centrosymmetric monoclinic space group P21/n, with a = 5.785(1)Å, b = 15.427(3)Å, c = 14.497(4)Å, β = 92.50(1)°, Z = 4, Dmeas = 1.29(1) g cm3 and Dcalc = 1.28 g cm3 at 23°. Three dimensional X‐ray data were collected with a manual diffractometer using MoKα (λ 0.71069Å) radiation and by multiple film Weissenberg techniques using CuKα (λ 1.5418Å) radiation. The structure was determined by Patterson and Fourier methods and refined with 519 observed reflections by full matrix least‐squares methods to an R of 0.077. The dihedral angle between the two planes of the o‐phenylene rings is 135.4(3)°. In the folded heterocyclic ring the C‐S‐C angle is 97.8(7)° and the average CS bond is 1.76(1)Å. A comparison of this structure to that of phenothiazine‐10‐propionic acid shows the two chemically similar molecules have the same dihedral angles in spite of completely different solid state packing patterns.
Spirans XX. Synthesis of 8,8‐dialkylazaspiro[4.5] decanes and 9,9‐dialkylazaspiro[5.5]undecanes
Authors: Rice Leonard M. , Sheth Bhagvandas S. , Wheeler James W.
Published: March 2009

N‐(2‐Dimethylaminopropyl)‐8,8‐dimethyl‐2‐azaspiro[4.5]decane (1), N‐(2‐dimethylaminopropyl)‐8,8‐diethyl‐2‐azaspiro[4.5]decane (2), N‐(3‐dimethylaminopropyl)‐9,9‐dimethyl‐3‐azaspiro[5.5]undecane (3), and N‐(3‐dimethylaminopropyl)‐9,9‐diethyl‐3‐azaspiro[5.5]undecane (4) have been synthesized from 4,4‐dimethylcyclohexanone (5) and 4,4‐diethylcyclohexanone (6). Biological evaluation of these amines showed significant inhibition of cancer cell growth in human cancer cells grown in tissue culture.
Spirans XXI. Synthesis of silaazaspiro[4.5]decanes and silaazaspiro[5.5]undecanes
Authors: Rice Leonard M. , Sheth Bhagvandas S. , Wheeler James W.
Published: March 2009

N‐(2‐Dimethylaminopropyl)‐8,8‐dimethyl‐8‐sila‐2‐azaspiro[4.5]decane (1) and N‐(3‐dimethyl‐aminopropyl)‐9,9‐dimethyl‐9‐sila‐3‐azaspiro[5.5]undecane (2) have been synthesized from 4,4‐dimethyl‐4‐silacyclohexanone (5). Biological evaluation of 1 and 2 indicated cytotoxic action against human cancer cells grown in tissue culture.
Nitro derivatives of 1‐picrylbenzotriazole
Authors: Coburn Michael D.
Published: March 2009

The synthesis of the isomeric 4,6‐, 5,6‐, and 5,7‐dinitro‐1‐picrylbenzotriazoles has been accomplished. The nmr spectra of these compounds and the mononitro derivatives of 1‐picrylbenzotriazole were determined and the substituent effects of the nitro and picryl groups on the chemical shifts of the various benzotriazole protons are discussed.
Pyridine nucleosides related to 5‐fluorouracil
Authors: Nesnow Stephen , Heidelberger Charles
Published: March 2009

5‐Fluoro‐2‐methoxypyridine (3) synthesized from 5‐amino‐2‐methoxypyridine was converted to 4‐benzyloxy‐5‐fluoro‐2‐methoxypyridine (12) and 2,4‐dimethoxy‐5‐fluoropyridine (13) by a four step procedure employing the intermediate 5‐fluoro‐2‐methoxy‐4‐nitropyridine N‐oxide (7). Condensation of 3, 12, and 13 with 2,3,5‐tri‐O‐benzoyl‐D‐ribofuranosyl bromide gave, after removal of the protecting groups, 4‐deoxy‐5‐fluoro‐3‐deazauridine (20), 5‐fluoro‐3‐deazauridine (23) and 5‐fluoro‐4‐methoxy‐3‐deazauridine (25). Several alkylated and dealkylated derivatives of 3 and 12 were also prepared. Structure proof and anomeric configuration were determined from the uv, nmr, and CD data.
Azetidine‐2‐carboxylic acid derivatives
Authors: Phillips Barry A. , Cromwell Norman H.
Published: March 2009

An improved method for the preparation of DL‐azetidine‐2‐carboxylic acid is reported. The reaction of thionyl chloride with azetidine‐2‐carboxylic acid in methanol gave rise to 2‐carbomethoxyazetidine hydrochloride, which upon treatment with triethylamine yielded 2‐carbomethoxyazetidine. 2‐Carbomethoxyazetidine proved to be unstable and upon standing formed azetidine‐2‐carboxylic acid anhydride. The nmr and ir spectra of 2‐carbomethoxyazetidine are discussed in terms of its conformation. The conversion of azetidine‐2‐carboxylic acid to azetidine‐2‐carboxamide is also described.
Pyrrolopyridazines. II. Synthesis of the novel pyrrolo[3,2‐c]pyridazine ring system
Authors: Dan Cook P. , Castle Raymond N.
Published: March 2009

The first derivatives of the pyrrolo[3,2‐c]pyridazine ring system, ethyl pyrrolo[3,2‐c]pyridazine‐6‐carboxylate 2‐oxide (5) and ethyl 3‐chloro‐6‐methylpyrrolo[3,2‐c]pyridazine‐7‐glyoxalate 1‐oxide (12), were obtained in good yields from the cyclization of 4‐ethoxymethyl‐eneamino‐3‐methylpyridazine 1‐oxide (3) and 3‐chloro‐5‐(α‐ethoxyethylideneamino)‐6‐methylpyridazine 1‐oxide (14, R  Cl, R1  OMe), respectively, with diethyl oxalate and potassium ethoxide in ether.
Bridgehead nitrogen heterocycles. VI. The reaction of 1‐amino‐ and 1,2‐diaminopyridinium salts with β‐dicarbonyl compounds
Authors: Potts K. T. , Dugas R. , Surapaneni C. R.
Published: March 2009

1,2‐Diaminopyridinium iodide underwent reaction with ethyl acetoacetate to form 1,4‐dihydro‐2‐methyl‐4‐oxopyrido[1,2‐a]pyrimidin‐1‐ium iodide, and with acetyl acetone it gave 2,4‐dimethylpyrido[1,2‐a]pyrimidin‐5‐ium iodide. Though 2‐acetylcyclohexanone gave the corresponding 5‐methyl‐1,2,3,4‐tetrahydropyrido[1,2‐a]quinazolin‐11‐ium iodide, no reaction was observed with 2,6‐dimethyl‐3,5‐heptanedione, 1‐benzoylacetone, 1,3‐diphenyl‐1,3‐propanedione and its p‐methoxyphenyl derivative. However, 1‐aminopyridinium iodide and acetyl acetone in the presence of base gave 3‐acetyl‐2‐methylpyrazolo[1,5‐a]pyridine and 1‐amino‐2‐methylpyridinium iodide yielded the corresponding 3‐acetyl‐2,7‐dimethylpyrazolo[1,5‐a]pyridine. With ethyl acetoacetate, the latter salt formed 3‐ethoxycarbonyl‐2,7‐dimethylpyrazolo[1,5‐a]pyridine but with 2,6‐dimethyl substituents in the pyridine ring no condensation occurred. Reaction of 1‐amino‐2‐methylpyridinium iodide with benzaldehyde gave N‐benzalimino‐2‐methylpyridinium iodide which, on treatment with base, resulted in the formation of 2‐picoline and benzonitrile, providing a convenient method of deamination.
Mass spectral analysis of substituted pteridines and their reduced analogs
Authors: Williams V. P. , Ayling J. E.
Published: March 2009

The reduced forms of substituted pteridines exhibit cofactor and inhibitory properties with the enzyme, phenylalanine hydroxylase (Ayling, et al., Biochemistry, 12, 2045 (1973)). Mass spectrometry has been used as a method for structure confirmation and to determine the state of purity and the extent of reduction. The structural analysis was facilitated by the use of several homologous classes of compounds. Reduced pteridines have not previously been analyzed by mass spectrometry and only a limited amount of data, much of which was from trimethylsilyl or acetyl derivatives, has been published on the mass spectral analysis of the non‐reduced compounds. Detailed mass spectral fragmentation modes are presented for the reduced and non‐reduced forms of the following compounds: 4‐aminopteridine, 4(3H)pteridinone, 6,7‐dimethyl‐4(3H)pteridinone, 2,4‐diamino‐6,7‐dimethylpteridine, 6,7‐dimethyl‐2,4(1H,3H)pteridinedione, 2‐amino‐4(3H)pteridinone, 2‐amino‐6,7‐dimethyl‐4(3H)pteridinone, 2‐amino‐6‐(L‐erythro‐1,2‐dihydroxypropyl)‐4(3H)pteridinone, 2‐amino‐4,6(3H,5H)pteridinedione, 2‐amino‐7‐methyl‐4,6(3H,5H)pteridinedione, 2‐amino‐4,7(3H,8H)pteridinedione, 2‐amino‐6‐methyl‐4,7(3H,8H)pteridinedione.
Reactions of diazo derivatives of 5‐membered heterocycles with hydrazines
Authors: Shealy Y. Fulmer , O'Dell C. Allen
Published: March 2009

Interaction of hydrazine or dimethylhydrazine with 5‐diazoimidazole‐4‐carboxamide produced, presumably via tetrazenes, high yields of 5‐azidoimidazole‐4‐carboxamide. In contrast, when semicarbazide reacted with either the diazoimidazole or the analogous diazo‐1,2,3‐triazole, the yield of the azidoheterocycle was low, and the yield of biurea, and presumably the aminoheterocycle, was high. 3‐Azidopyrazole‐4‐carboxamide was obtained from a reaction of hydrazine with the diazopyrazole. Both azido and amino derivatives were formed from reactions of diazo‐imidazole esters with hydrazine or thiosemicarbazide.
Mass spectra of C‐nucleosides II. An unusual fragmentation reaction of the heterocyclic moiety of pyrazomycin and some closely related compounds
Authors: Crain P. F. , McCloskey James A. , Lewis Arthur F. , Schram Karl H. , Townsend Leroy B.
Published: March 2009

The mass spectrum of pyrazomycin has been obtained and reveals a fragmentation pattern with several important peaks which are not normally found in the mass spectra of C‐nucleosides. It has now been established, using model compounds, that these unusual fragment ions are a direct result of the juxtaposition of the exocyclic hydroxy and carboxamido groups of the aglycon. It appears that a facile elimination of ammonia and ethanol from o‐hydroxycarboxamides and o‐hydroxyethylesters, respectively, may be a general fragmentation reaction for aromatic heterocycles. A mass spectrum of the TMS derivative of pyrazomycin has also been obtained and factors which may result in exceptions to the empirical B+30 (M‐103) rule for C‐nucleosides are discussed.
Synthesis and PMR spectra of 7‐hydroxyalkylguanosinium acetates
Authors: Roe Robert , Paul J. S. , Montgomery P. O'B.
Published: March 2009

Guanosine and 9‐methylguanine treated with epoxides in glacial acetic acid are hydroxyalkylated stereoselectively at the N7 position of the guanine moiety. Previously unreported 7‐(hydroxyalkyl)guanosinium acetates from the reactions of six epoxides with guanosine and 7‐(hydroxyalkyl)‐9‐methylguaninium acetates from the reactions of two epoxides with 9‐methyl guanine in glacial acetic acid have been prepared and characterized by their pmr spectra. By using an excess of epoxide, quantitative conversion of guanosine or 9‐methylguanine to the corresponding 7‐hydroxyalkylguanosinium or 7‐hydroxyalkyl‐9‐methylguaninium acetate was achieved. Comparisons of the pmr spectra of the 7‐(hydroxyalkyl)guanosinium acetates in DMSO‐d6 to the spectrum of guanosine reveal that the H8 and amino group proton absorptions common to guanosine are shifted to a lower field, the absorptions of the H1 proton is absent, and the coupling constant of the H′1‐H′2 protons of the ribosyl group is decreased from about 5.7 ± 0.1 Hz in guanosine to about 3.5 ± 0.1 Hz in the products. The use of the pmr spectral features of 7‐(hydroxyalkyl)‐9‐methylguaninium compounds in characterizing 7‐hydroxyalkylguanosinium compounds is discussed. Evidence is presented which suggests that extensive delocalization of positive charge exists in both the pyrimidine and imidazole rings of N7‐hydroxyalkylated guanosine and N7‐hydroxyalkylated‐9‐methylguanine. The possible effects of charge delocalization upon the hydrogen bonding potential of 7‐hydroxyalkylated guanine moieties in DNA is discussed.
S‐and Se‐dimethylarsino derivatives of thio‐ and selonopyrimidines and purines
Authors: Sarquis Arlyne M. , Zingaro Ralph A.
Published: March 2009

The synthesis of dimethylarsinothio‐and dimethylarsinoselonopyrimidines and ‐purines which utilizes diethylaminodimethylarsine is described. A series of these derivatives, with different substituents on the heterocyclic ring, has been investigated by infrared, nmr, and mass spectroscopic methods. Attempts to prepare O‐or N‐ arsinous acid derivatives from oxy‐ and aminopyrimidines were unsuccessful.
Chemical studies of potential relevance to penicillin hypersensitivity. The synthesis ofdl‐2‐phenoxymethylpenicillenic acid and ofdl‐2‐(2,6‐dimethoxyphenyl)penicillenic acid
Authors: Dudley Kenneth H. , Bius Daniel L. , Johnson Dorothy
Published: March 2009

Crystalline samples of DL‐2‐phenoxy melhylpenicillenic acid (14) and ofDL‐2‐(2, 6‐dimethoxyphenyl)penicillenic acid (21) have been synthesized by the reaction ofDL‐penicillamine with 2 phenoxymethyl‐4‐(methoxymethylene)oxazol‐5‐one and 2‐(2, 6‐dimethoxyphenyl)‐4‐(ethoxymethylene)oxazol‐5‐one, respectively. These key oxazol‐5‐one intermediates were synthesized by azlactonization of the appropriately substituted penaldic acid dialkyl acetals. The reaction of mercury(II) chloride with D‐phenoxymethylpenicillin was studied and found to be inapplicable to the synthesis ofD‐14. A comparison of crystallineDL‐ and of amorphous D‐2‐(2,6‐dimethoxyphenyl)penicillenic acid (21), which were prepared by the “oxazolone” and “mercury(11) chloride” methods, respectively, suggests a marked improvement in the purity of theDL‐material.
Fluoroalkyl‐s‐triazines
Authors: Croft Thomas S. , Snyder Carl F.
Published: March 2009

A series of symmetrically and asymmetrically substituted s‐triazines was synthesized by condensation of fluorocarbon nitriles (Scheme II, compounds 1a‐c) and by cyclodehydration of a fluorocarbon imidoylamidine utilizing a fluorocarbon anhydride (Scheme III, compounds 2a‐e). Among the new nitriles prepared for incorporation in these reaction paths were 11‐H‐4,9‐dioxahexadecylfluoroundecanenitrile (3) and 6‐chloro‐6‐H‐4‐oxaheptafluorohexanenitrile (4), prepared by Scheme 1.
Selenium heterocycles XII. Heat induced transformation of 1,2,3‐Selenadiazoles to disubstituted selenophenes
Authors: Lalezari I. , Shafiee A. , Rabet F. , Yalpani M.
Published: March 2009

4‐Aryl‐1, 2, 3‐selenadiazoles when subjected to heat afforded 2, 5‐diarylselenophenes and small quantities of 2,4‐diarylseneophenes. Monoarylacetylenes and selenium behaved similarly. Phenylacetylene and sulfur gave 2,4‐diphenylthiophene. Mechanistic aspects of these reactions are discussed.
Strained heterocyclic systems. VII. The mass spectral fragmentations of dihydrocycloalka[b]quinolines and quinoline N‐Oxides
Authors: Koch Charles W. , Milberb Richard M. , Markgraf J. Hodge
Published: March 2009

High resolution mass spectra of compounds 1‐6 were investigated. The quinolines (1‐3) all exhibit a prominent (M‐1)+ peak and subsequent loss of HCN. These processes are consistent with azatropylium ion intermediates. The N‐oxides (4‐6) all exhibit major peaks at (M‐16)+; the abundance of the latter is related to the geometry of the molecule. The four‐membered ring compounds (3 and 6) give more complex spectra, which reflect the influence of the fused strained ring.
Benzo[b]thiophene derivatives. XX. The sulfur isostere of 5,6‐Dihydroxytryptamine
Authors: Campaigne E. , Rogers Richard Brewer , Donelson A. , Bosin T. R.
Published: March 2009

3β‐Aminoethyl‐5,6‐dihydroxybenzo[b]thiophene, the sulfur bioisostere of 5,6‐dihydroxytryptamine, a selective neurotoxin, has been synthesized and shown to have significant effect on biogenic amine levels both centrally and peripherally. A derivative, 3β‐aminoethyl‐5,6‐isopropylidenedioxybenzo[b]thiophene, showed significant but opposite activity. The syntheses and preliminary pharmacology are reported.
Réarrangements 1,3 en série hétérocyclicque. II. Synthese d'alcoxy‐5 et aryloxy‐5 phényl‐2 oxadiazoles‐1,3,4
Authors: Golfier Michel , Milcent René
Published: March 2009

La synthèse du chloro‐5 phényl‐2 oxadiazole‐1,3,4 a été mise au point. Ce produit est utilisable pour la préparation de dérivés ou O‐alkylés ou O‐arylés de l'hydroxy‐5 pheényl‐2 oxadiazole‐1,3,4.
Effects of ring substituents on the reactivity of thionphenoxide ions towards some nitro‐activated thiophene derivatives
Authors: Guanti Giuseppe , Dell'Erba Carlo , Macera Paola
Published: March 2009

The rates of nucleophilic substitution of bromine on 3‐bromo‐2‐nitrothiophene (1) and 2‐bromo‐3‐nitrothiophene (II) by o‐, m‐, and p‐substituted thiophenoxide ions bave been measured in methanol at 20.02°.

The rate of thiophenoxy‐debromination is always higher when the reaction center is in the β‐position (substrate I) rather than in α‐position (substrate II). Plots of the log k against σ°‐constants for the reaction of the substituted thiophenoxides towards I and II have ρ‐values of ‐0.78 (for substrate I) and ‐0.76 (for substrate II). Deviations from linearity for p‐substituents with strong +M and ‐M effect are discussed.

A comparison of proton basicity, carbon basicity, and nucleophilicity of the thiophenoxide ions has also been made.
Synthése de la pyrido[4,3‐e]‐as‐triazine
Authors: Plé‐Colombier Mme N. , Queguiner G. , Pastour P.
Published: March 2009

This communication describes the synthesis of a new heterocycle, pyrido[4,3‐c]‐as‐triazine, its 3‐methyl derivative, and their nmr spectral data.
Synthèse des pyrido[2,3‐d] el [3,2‐d] ‐s‐triazolo[3,4‐f] pyrimidines el de (pyrazolyl‐1')‐4 pyrido[2,3‐d] et [3,2‐d] pyrimidines
Authors: Codefroy MM. L. , Queguiner G. , Pastour P.
Published: March 2009

The synthesis of two new heterocycles is described: pyrido‐[2,3‐d]‐.s‐triazolo[ 3,4‐f] pyrimidine and pyrido[3,2‐d]‐.s‐triayzolo‐[3,4‐f] pyrimidine. 4‐[I'‐Pyrazolyl]pyrido[2,3‐d]pyrimidines and 4‐[1′‐pyrazoly1] pyrido[ 3,2‐d] pyrimidine are obtained by the action of 4‐hydrazinopyrido[2,3‐d]pyrimidine and 4‐hydrazinopyrido‐[3,2‐d]pyrimidine with several β‐diketones.
Synthese de pyridazino pyridazines
Authors: Turck A. , Queguiner G. , Pastour P.
Published: March 2009

We describe the unsubstituted pyridazino[4,5‐c]pyridazine and some hydroxy and methyl derivatives.
Synthesis of bridgehead nitrogen heterocycles
Authors: Scovill John P. , Burckhalter Joseph H.
Published: March 2009

Reductive cyclizations of N‐[2‐(2‐pyridyl)ethyl]imides were accomplished by employing a palladium on carbon catalyst in ethanolic acetic acid as the hydrogenation medium. Reduction of the corresponding N‐[2‐(2‐quinolyl)ethyl]imides ceased at the 1,2,3,4‐tetrahydroquinolyl stage. Controlled reduction of the tetrahydroquinolyl imides with sodium borohydride gave amido alcohols which afforded bridgehead nitrogen heterocycles upon cyclodehydration.
Reaction of ketenes with N,N‐disubstituted à‐aminomethyleneketones. IX. Synthesis of 2H,5H‐pyrano[3,2‐c][1]benzopyran derivatives
Authors: Mosti Luisa , Schenone Pietro , Menozzi Giulia
Published: March 2009

Cycloaddition of dichloroketene to N,N‐disubstituted 3‐aminomethylene‐4‐chromanones gave in good yield N,N‐disubstituted 4‐amino‐3,3‐dichloro‐3,4‐dihydro‐5H‐pyrano[3,2‐c][1]benzopyran‐2‐ones only in the case of aromatic N‐substitution. Dehydrochlorination with triethylamine of these adducts afforded N,N‐disubstituted 4‐amino‐3‐chloro‐5H‐pyrano[3,2‐c][1]benzopyran‐2‐ones in good to moderate yield. The cycloaddition to 3‐dimethylaminomethylene‐4‐chromanone led directly to 3‐chloro‐4‐dimethylamino‐5H‐pyrano[3,2‐c][1]benzopyran‐2‐one.
3‐Amino‐2,1‐benzoisothiazole. Synthesis of some chloro and trifluoromethyl derivatives
Authors: Gray J. , Waring D. R.
Published: March 2009

The syntheses of the 7‐chloro‐, 4,7‐dichloro‐, 5‐ and 7‐trifluoromethyl, 5‐chloro‐6‐trifluoro‐methyl‐ and 5‐chloro‐7‐trifluoromethyl‐ derivatives of 3‐amino‐2,1‐benzoisothiazole are described. Preparative details are included for a number of the precursors to the benzoisothiazole derivative which have not previously been described. Visible spectra of some azo dyes prepared from the title compounds with a selected coupler are discussed with reference to the substituent effects.
Contribution to the synthesis of (±)‐cryptopleurine and related phenanthroquinolizidines
Authors: Trigo G. G. , Gálvez E. , Söllhuber M. M.
Published: March 2009

The synthesis of the alkaloid cryptopleurine 7b has been accomplished by a sequence involving as a key step the selective Borch reduction of an amidoester 1b to the corresponding aminoester 2b. This route is applicable to the synthesis of derivatives such as 7a.
Reactions with heterocyclic amidines VIII. Synthesis of some new imidazo[1,2‐b]pyrazole derivatives
Authors: Elnagdi Mohamed Hilmy , Hafez Ebtisam Abdel Aziz , El‐Fahham Hassan Attia , Kandeel Ezzat Mohamed
Published: March 2009

The reaction of benzoylacetonitrile (III), its phenylazo derivative (X), malononitrile and malononitrile derivatives with ethyl hydrazinoacetate was investigated. All the investigated compounds with the exception of phenylazobenzoylacetonitrile and phenylazomalononitrile afforded 1‐ethoxycarbonylmethyl‐3‐aminopyrazole derivatives when treated with I. Compounds Xa and XVIII afforded imidazoypyrazole derivatives under the same experimental conditions.
Mass spectra of some 3‐substituted coumarins
Authors: Saint‐Ruf Germain , De Asish , Brunskill John S. A. , Jeffrey Howard
Published: March 2009

The electron impact mass spectrometric fragmentation pathways for some 3‐substituted derivatives of coumarin, benzo[f]coumarin, thieno[3,2‐f]coumarin, thieno[2,3‐h]coumarin and azacoumarin, viz nitriles, carboxamides, thiocarboxamides and esters were investigated. The initial cleavage of the pyrone ring is found to be largely dependent on the stability, under electron impact, of the attached functional group.
Synthèse de nouveaux hétérocyeles indoliques
Authors: Dupas Georges , Duflos Jack , Quéguiner Guy
Published: March 2009

Ce travail décrit une approche permettant de parvenir à des hétérocycles indoliques tri et tétracycliques.
2‐Imidazolines. III (1). 1‐Aryl‐ and 1‐acyl‐2‐amino‐(ormethoxy)‐4,5‐diamino‐4,5‐dihydroimidazoles. Synthesis and properties
Authors: Citerio Luisa , Rivera Elisabetta , Saccarello Maria Luisa , Stradi Riccardo , Gioia Bruno
Published: March 2009

Diimmonium salt (5) reacts with guanidines (6) and o‐methylisoureas (7) affording 2‐amino‐4,5‐dimorpholinoimidazolines (9). 1‐Aryl‐2‐amino‐4,5‐dimorpholinoimidazolines lose the amino functionality under mild acidic conditions with formation of 2‐amino‐5‐morpholinoimidazole derivatives (10) whereas 1‐acyl derivatives undergo under the same conditions a ring expansion process leading to pyrimidine derivatives (13).
Synthesis of granatanine‐3‐spiro‐5'‐hydantoin‐N‐ω‐hydroxyalkyl esters
Authors: Trigo G. G. , Avendaño C. , Ballesteros P. , Sastre A.
Published: March 2009

Synthetic methods to prepare N‐ω‐hydroxyalkyl‐nor‐psuedopelletierine and granatanine‐3‐spiro‐5'‐hydantoin N‐ω‐hy droxyalkylbenzylic and diphenylacetic esters are analyzed. The Bucherer‐Bergs synthesis used by us to obtain some other granatanine‐spirohydantoins (2), originates the hydrolysis of the ester group.
Selenium heterocycles. XXIX. Reaction of substituted 2‐thioxo‐1,3‐thiaselenoles with ethyl diazoacetate, ethyl azidoformate and phenyl azide
Authors: Shafiee A. , Vosooghi M. , Asgharian R.
Published: March 2009

Reaction of 5‐substituted 2‐thioxo‐1,3‐thiaselenoles with ethyl diazoacetate, phenyl azide and ethyl azidoformate afforded 2‐substituted ω‐carbethoxy‐1,4‐thiaselenafulvenes (II), 5‐substituted 2‐phenylimino‐1,3‐thiaselenoles (IV) and 5‐substituted 2‐carbethoxyimino‐1,3‐thiaselenoles (V), respectively. The structure of these compounds were confirmed by spectroscopic methods and chemical analysis.
New heterocyclic ring systems. XI. Azadithiasteroid analogues
Authors: Fravolini A. , Schiaffella F. , Brunelli C. , Cecchetti V.
Published: March 2009

Synthesis of the title compounds has been achieved starting from 4‐oxo‐3,4‐dihydro‐2H,5H‐thiopyrano[3,2‐c][1]benzothiopyran 6,6‐dioxide (III), which was converted to glyoxylate (IV), β‐ketoester (V), difluoride complex (VII) and β‐diketone (XII) gave with hydrazine, hydroxyl‐amine and glycine ethyl ester several azadithiasteroid analogues.
Folate antagonists. 16. Antimalarial and antibacterial effects of 2,4‐diamino‐6‐[(heterocyclic)thio, sulfinyl, and sulfonyl]quinazolines
Authors: Elslager Edward F. , Jacob Patricia , Johnson Judith , Werbel Leslie M.
Published: March 2009

The reaction of 5‐chloro‐2‐nitrobenzonitrile with a variety of mercaptoheterocycles provided the corresponding 2‐nitro‐5‐[(heterocyclic)thio]benzonitriles. Reduction to the amine followed by cyclization with chloroformamidine hydrochloride afforded a series of 2,4‐diamino‐6‐[(hetero‐cyclic)thio]quinazolines. Bromination, oxidation, and amidine formation were accomplished with 2,4‐diamino‐6‐[(4‐phenyl‐2‐thiazolyl)thio]quinazoline (23) to provide additional analogs. Several of these compounds exhibited suppressive antimalarial activity against drug‐sensitive lines of Plasmodium berghei in mice.
Orientation de la réaction d'alkylation des pyrazoles dans des conditions neutres et en catalyse par transfert de phase
Authors: Tarrago Georges , Ramdani Abdelkrim , Elguero JosÉ , Espada Modesta
Published: March 2009

L'etude de la N‐butylation et de la N‐benzylation de neuf pyrazoles, diversement substitués en positions 3 et 5, a été effectuée en milieu neutre et en milieu basique (catalyse par transfert de phase), L'orientation de la reaction depend fortement de la méthode employée, quand le pyrazole de départ porte en position 3 (ou 5) un substituant qui a une paire libre en ortho (pyrazolyle ou pyridyle). Les différents produits ont été identifiés par rmn du proton.
Studies in the heterocyclic series XVII. A new type of triazaphenothiazine heterocycle
Authors: Okafor Charles O.
Published: March 2009

The synthesis of derivatives of 1,4,6‐benzo[b]triazaphenothiazine, a novel aza‐analog of phenothiazine, is described. The parent compound was obtained by base‐catalysed condensation of 3‐amino‐2‐mercaptopyridine with 2,3‐dichloroquinoxaline in aqueous DMF. Several derivatives were also prepared by using the appropriately substituted aminomercaptopyridines and dichloro‐quinoxalines. Nitration with mixed nitric and sulfuric acids gave the corresponding 13‐nitro‐1,4,6‐benzo[b]triazaphenothiazine derivatives. The structures were elucidated by chemical evidence and by a study of their infrared, ultraviolet, pmr and mass spectra.
Synthesis of 2,3,5,6‐tetrahydroimidazo[1,2‐c]quinazoline derivatives as potential narcotic antagonists
Authors: Antonini I. , Cristalli G. , Franchetti P. , Grifantini M. , Martelli S.
Published: March 2009

The synthesis of a series of N6‐alkyl derivatives of the 2,3,5,6‐tetrahydroimidazo[1,2‐c]quinazoline as potential narcotic antagonists is reported.
Synthesis of 6‐amino‐1,2,3‐triazolo[4,5‐c] pyridin‐4(5H)one (8‐aza‐3‐deazaguanine) and 6‐amino‐1‐(β‐D‐ribofuranosyl)‐1,2,3‐triazolo[4,5‐c] pyridin‐4(5H)one (8‐Aza‐3‐deazaguanosine) via novel ring closure procedures
Authors: Meyer Ric H. B. , Revankar Ganapathi R. , Dan Cook P. , Ehler Kenneth W. , Schweizer Martin P. , Robins Roland K.
Published: March 2009

The total synthesis of 6‐amino‐1,2,3‐triazolo[4,5‐c]pyridin‐4(5H)one (8‐aza‐3‐deazaguanine, 3) and 6‐amino‐1‐(β‐D‐ribofuranosyl)‐1,2,3‐triazolo[4,5‐c]pyridin‐4(5H)one (8‐aza‐3‐deazaguano‐sine, 22) has been described for the first time by a novel base‐catalyzed ring closure of 4(5)‐cyanomethyl‐1,2,3‐triazole‐5(4)carboxamide (14) and methyl 5‐cyanomethyl‐1‐(2,3,5‐tri‐O‐ben‐zoyl‐β‐D‐ribofuranosyl)‐1,2,3‐triazole‐4‐carboxylate (17), respectively. Under the catalysis of DBU, 2,4‐dinitrophenylhydrazone of dimethyl 1,3‐acetonedicarboxylate (7) was converted to methyl 5‐methoxycarbonylmethyl‐1‐(2,4‐dinitroanilino)‐1,2,3‐triazole‐4‐carboxylate (12) via dimethyl 2‐diazo‐3‐iminoglutarate (8). Catalytic reduction of 12 gave methyl 4(5)methoxycar‐bonylmethyl‐1,2,3‐triazole‐5(4)carboxylate (11) from which methyl 4(5)carbamoylmethyl‐1,2,3‐triazole‐5(4)carboxylate (10) was obtained by ammonolysis. Dehydration of 10 provided methyl 4(5)cyanomethyl‐1,2,3‐triazole‐5(4)carboxylate (13) which on amination gave 14. The 1,2,3‐triazole nucleosides 17, 18 and 19 were obtained from the stannic chloride‐catalyzed condensation of the trimethylsilyl 13 and a fully acylated β‐D‐ribofuranose. The yield and ratio of the ribofuranosyl derivatives of 13 markedly depends on the ratio of stannic chloride used. The structures of the nucleosides 22 and 23 were established by a combination of NOE, 1H‐nmr and 13C‐nmr spectroscopy.
Cyanation and sulfonylation of 5‐substituted tetrazoles. imidoyl azides
Authors: Subba Rao O. , Lwowski Walter
Published: March 2009

Reaction of 5‐methoxy‐ and 5‐ethoxytetrazole with methanesulfonyl chloride and cyanogen bromide was found to occur in the 1‐position of the tetrazole. This is in marked contrast to other acylations of 5‐substituted tetrazoles, where high yields of the 2‐acyl derivatives are reported for dozens of examples and a variety of acylating agents. The 1‐methanesulfonyl‐ and 1‐cyano‐5‐alkoxytetrazoles ring‐open spontaneously to the corresponding imidoyl azides, which are conveniently prepared by this method.
Decarboxylation of a benzo[b] thiophene‐2‐carboxylic acid
Authors: Jackson Bernice D. , Bowlus Stephen B.
Published: March 2009

5‐Hydroxy‐3‐methylbenzo[b]thiophene‐2‐carboxylic acid can be decarboxylated by refluxing with 48% hydrobromic acid for 30 minutes. Yield and quality of the product are better than for the previously used copper‐quinoline decarboxylation. The 5‐methoxy analog of the above acid is stable to decarboxylation under these conditions; however, it demethylates readily under the reaction conditions, and the phenol thus afforded decarboxylates.
Fluorinated chromenes. Synthesis of 6,7‐dimethoxy‐2‐methyl‐2‐trifluoromethyl‐2H‐chromene
Authors: Camps F. , Coll J. , Messeguer A. , Pericás M. A.
Published: March 2009

Preparation of the title compound, a trifluoromethyl analog of the natural insect antijuvenile hormone 6,7‐dimethoxy‐2,2‐dimethyl‐2H‐chromene (precocene II), from 3,4‐dimethoxyphenol and 1,1,1‐trifluoro‐4,4‐dimethoxy‐2‐methyl‐2‐butyl mesylate is described.
Reaction of ethyl 3‐ethoxymethylene‐2,4‐dioxovalerate with monosubstituted hydrazines
Authors: Kurihara Takushi , Uno Toshiko , Sakamoto Yasuhiko
Published: March 2009

Reactions of ethyl 3‐ethoxymethylene‐2,4‐dioxovalerate (1) with phenyl‐ and methylhydrazines are described. While the reaction of 1 with phenylhydrazine gave a mixture of ethyl 4‐acetyl‐1‐phenylpyrazole‐5‐carboxylate (4) and ethyl 5‐methyl‐1‐phenylpyrazole‐4‐glyoxylate (5), 1 reacted with methylhydrazine to give ethyl 4‐acetyl‐1‐methylpyrazole‐3‐carboxylate (14) as the sole product.
Nouvelles syntheses de la thieno[2,3‐b] pyrazine
Authors: Bourguignon Jean , Lemarchand Marc , Quéguiner Guy
Published: March 2009

Deux nouvelles synthèses de la thiéno[2,3‐b]pyrazine sont décrites avec la méthyl pyrazine comme produit de départ. L'une des méthodes consiste en une voie originale d'obtention d'un cycle thiophénique dans un système à noyaux condensés.
Chemistry of sulfonyl isocyanates and sulfonyl isothiocyanates. X. Possible routes to substituted imidazolidinethiones and hexahydropyrimidinethiones
Authors: Mcfarland J. W. , Kozel T. H. , Stuhlmacher K. R. , Chevalier T. S.
Published: March 2009

4‐Toluenesulfonyl isocyanate (I) reacted with 2‐aminoethanol and 3‐amino‐l‐propanol to give 2:1 isocyanate/amino alcohol addition products. 1‐Amino‐2‐propanol and I gave 1:1 and 2:1 adducts while 2‐amino‐2‐methyl‐l‐propanol afforded only a 1:1 adduct. 4‐Toluenesulfonyl isothio‐cyanate (III) gave 1:1 adducts with 2‐aminoethanol, l‐amino‐2‐propanol and 3‐amino‐l‐propanol, the first two of which were cyclized by concentrated sulfuric acid to 1‐(4‐toluenesulfonyl)‐imidazoline‐2‐thiones and the third to 1‐(4‐toluenesulfonyl)hexahydropyrimidine‐2‐thione. A 1:2 adduct was obtained from III and 2‐amino‐2‐methyl‐l‐propanol. Amino acids reacted with I and with 4‐chlorobenzenesulfonyl isocyanate (II) to give N‐(arylsulfonyl)‐N1‐(carboxylic acid)‐ureas. N‐(4‐Toluenesulfonyl)‐N1‐(acetic acid)‐urea (XVI) was converted to the methyl ester (XIX) by concentrated sulfuric acid and methanol and to water‐soluble unrecoverable products by sulfuric acid alone. Glycine and III gave N‐(4‐toluenesulfonyl)‐N1‐(acetic acid)‐thiourea (XX) which was converted to the methyl ester (XXII) by concentrated sulfuric acid/methanol and to the cyclic 1‐(4‐toluenesulfonyl)imidazolin‐5‐one‐2‐thione (XXI) by sulfuric acid alone.
Quinoline nitroxide radicals. Ipso‐attack in the reaction between 2‐methoxy and 2‐cyanoquinoline N‐oxide, and phenylmagnesium bromide
Authors: Colonna Martino , Greci Lucedio , Poloni Marino
Published: March 2009

2‐Methoxy and 2‐cyanoquinoline N‐oxide, when treated with phenylmagnesium bromide, undergo a nucleophilic ipso‐attack at C‐2, yielding, by elimination of methoxymagnesium bromide or cyanomagnesium bromide, the corresponding 2‐phenylquinoline N‐oxides, which react with the excess of Grignard reagents forming 2,2‐diphenylquinoline 1‐oxyls. Even when the methoxy and cyano groups are in position 4, the attack by the Grignard reagent takes place at C‐2 giving 2‐phenylquinolines and 2‐phenylquinoline N‐oxides by elimination of hydroxymagnesium bromide and bromomagnesium hydride, respectively; the formation of 2,2‐diphenylquinoline l‐oxyls in these reactions is discussed.
On the reaction of phenyldisic acids with α,β‐unsaturated carbonyl compounds. Reversible non‐catalyzed michael addition and ring closure to derivatives of 2H,7H‐isoxazolo[3,2‐b][1,3]oxazine
Authors: Zvilichovsky Gury , David Mordechai , Nemes Eliahu
Published: March 2009

4‐Aryl‐3,5‐dihyroxyisoxazoles which are strong organic acids add spontaneously to mesityl oxide to form 4‐aryl‐2‐(1,1‐dimethyl‐3‐oxobutyl)isoxazolidine‐3,5‐dione. This reaction was found to be reversible and the equilibrium is solvent dependent. These acids add to 2 moles of methyl vinyl ketone. The adducts obtained from mesityl oxide undergo ketalization to form derivatives of 2H,7H‐isoxazolo[3,2‐b][1,3]oxazine on exposure to alcohols. The rate of this ring closure reaction is dependent on the nature of the alcohol and on the nature of the substituent on the phenyl group which is at position 4 of the isoxazole ring. The mechanisms of the non catalyzed Michael addition and of the ketalization reaction are discussed. The structure of the polymers which are obtained by the reaction of phenyldisic acids with acrolein and crotonaldehyde is also discussed.
Reaction of hydrazonoyl halides with N‐aryl substituted benzamidines
Authors: Anzani Fulvio , Croce Piero Dalla , Stradi Riccardo
Published: March 2009

The reaction between hydrazonoyl halides and N‐arylbenzamidines leads to the simultaneous formation of products derived from a substitution and a cycloaddition reaction via two independent paths.
Tetracyclic heterocycles as CNS agents
Authors: Moffett Robert Bruce
Published: March 2009

A considerable number of new tri and tetracyclic heterocycles (II) and open chain intermediates were synthesized. These were tested in a battery of assays designed to reveal central nervous system (CNS) activity. However, none showed useful activity greater than known analogs.
Carbocyclic analogs of cytosine nucleosides
Authors: Shealy Y. Fulmer , O'Dell C. Allen
Published: March 2009

The carbocyclic analogs of cytidine, 2′‐deoxycytidine, and 3′‐deoxycytidine were synthesized from the analogous uracil derivatives. The route consists of complete benzoylation of the uracil derivative, selective removal of a benzoyl group attached to the pyrimidine ring, conversion of the 4‐oxo to a 4‐chloro group with the dimethylformamide‐thionyl chloride reagent, and replacement of the chloro group with an amino group in methanolic ammonia. When the total products of the deoxychlorination reaction were employed, the desired cytosine derivatives were frequently accompanied by small amounts of the corresponding N,N‐dimethylcytosine derivatives, which could be removed by ion‐exchange chromatography. Carbodine (VIa), the carbocyclic analog of cytidine, was obtained in 84% yield from the pure 4‐chloropyrimidinone intermediate, after the latter was prepared by deoxychlorination in carbon tetrachloride. Carbodine has antileukemic, antiviral, and antibacterial activity.
1,4‐Benzodiazepine und 1,5‐benzodiazocine. III Oxydation eines 2‐Chloromethyl‐1,4‐benzodiazepinderivates
Authors: Milkowski W. , Hüschens R. , Kuchenbecker H.
Published: March 2009

7‐Chlor‐l‐methyl‐2‐chlormethyl‐5‐phenyl‐2,3‐dihydro‐1H‐1,4‐benzodiazepin (1) wird mit Kaliumpermanganat und Chromsäure oxydiert. Die Oxydationsprodukte werden diskutiert. Während man mit Kaliumpermanganat in verd. Salzsäure als Hauptprodukt das 7‐Chlor‐l‐methyl‐5‐phenyl‐1,3‐dihydro‐2H‐1,4‐benzodiazepin‐2‐on (3) erhält, beobachtet man mit Chromsäureanhydrid in Pyridin in zunehmendem Maße Oxydation der N‐Methylgruppe sowie einen zusätzlichen Angriff am C3.
N‐acyl (substituted) phenylglycine derivatives
Authors: Edwards M. L.
Published: March 2009

Amidoalkylation of three benzoheterocycles, benzimidazole‐2‐one, 1,3‐dihydrobenzo[c]‐thiophene 2,2‐dioxide and 1,3‐dihydro‐2,1,3‐benzothiadiazole using N‐acylhippuric acids was successful. The corresponding phenylglycine analogs were prepared by removal of the N‐acyl protecting group.
A new synthesis of 2‐pyrazolin‐5‐ones from the condensation of C(α),N‐dilithiophenylhydrazones with diethyl carbonate
Authors: Wilson Jana D. , Fulmer Tammy D. , Dasher Lisette P. , Beam Charles F.
Published: March 2009

C(α),N‐Dilithiophenylhydrazones were prepared from phenylhydrazones in an excess of lithium diisopropylamide and condensed with diethyl carbonate followed by an acid cyclization to give 2‐pyrazolin‐5‐ones.
The photoinitiated substitution reactions of 2‐pyridinecarbonitrile with benzophenone in aqueous 2‐propanol
Authors: Caronna Tullio , Morrocchi Sergio , Vittimberga Bruno M.
Published: March 2009

The photoinitiated reaction of 2‐pyridinecarbonitrile and benzophenone in acidic 4:1 2‐propanol‐water yields substitution product 3 and bicyclic product 4. In nonacidic solution 3 is the principal product in addition to small amounts of a bipyridyl compound 5.
Mononuclear heterocyclic rearrangements. Part 4 Synthesis and characterization of the E‐isomer phenylhydrazone of 3‐benzoyl‐5‐phenyl‐1,2,4‐oxadiazole
Authors: Vivona Nicolò , Ruccia Michele , Frenna Vincenzo , Spinelli Domenico
Published: March 2009

3‐Benzoyl‐5‐phenyl‐1,2,4‐oxadiazole (I) with phenylhydrazine in acetic acid gives the two geometrical isomers, phenylhydrazones II‐Z and II‐E, which have been characterized by uv‐visible, ir, and nmr spectra. The possible II‐E ⇌ II‐Z isomerization as well as the rearrangement of II‐Z and of II‐E into 2,5‐diphenyl‐4‐benzoylamino‐1,2,3‐triazole (III) has been pointed out.
Photochemical reactions of β‐aminovinyl aryl thioketones
Authors: Nishio Takehiko , Nakajima Naoko , Omote Yoshimori
Published: March 2009

Irradiation of β‐aminovinyl aryl thioketones (1a‐b) afforded β‐aminovinyl aryl ketones (2a‐b). 2H‐Thiopyran derivatives (4a‐b) were obtained when β‐aminovinyl phenyl thioketone (1a) was irradiated with methyl acrylate and acrylonitrile. 4H‐Thiopyran derivatives (6,8) were also obtained thermally in the reaction of β‐aminovinyl phenyl thioketone (1a) and methyl propiolate and maleic anhydride.
Chemistry of the phenoxathiins and isosterically related heterocycles. IX.N‐oxidation on the 13C‐nmr chemical shifts and coupling constants of the 1‐azaphenoxathiin system
Authors: Martin Gary E.
Published: March 2009

The synthesis of 1‐azaphenoxathiin N‐oxide is described. Total assignment of the 13C‐nmr spectrum and the effects of the N‐oxide moiety on the chemical shifts and 1H‐13C spin couplings constants are described and compared to the parent 1‐azaphenoxathiin system. The potential for the use of N‐oxidation induced changes in 13C‐nmr chemical shifts and 1H‐13C coupling constants as an assignment criterion is also discussed.
Reissert compound studies. XXXIV. Base‐catalyzed reactions of the phthalazine reissert compound
Authors: Bhattacharjee D. , Popp F. D.
Published: March 2009

The phthalazine Reissert compound has been used to convert phthalazine to 1‐benzylphthalazines, bisbenzylphthalazines, 1,4‐disubstituted phthalazines, 1‐cyanophthalazine, and a number of other phthalazine derivatives including the tricyclic compound 14.
Synthesis and reactivity of a series of [14]azaannulenes
Authors: Place David A. , Ferrara Gerald P. , Harland Joseph J. , Dabrowiak James C.
Published: March 2009

Using a metal template reaction, a series of [14]azaannulenes formed from a β‐diketone and an aromatic diamine in the presence of nickel(II) have been synthesized. Attempted cyclizations with bulky β‐diketones and certain substituted diamines showed that the cyclization is sensitive to steric effects. At least one of the nickel complexes readily reacts with a series of nucleophilic reagents to give methine‐substituted products.
One‐step preparation of 3‐alkoxypyrazine‐2‐carbonitriles from pyrazine‐2,3‐dicarbonitriles and related reactions
Authors: Kojima Takakazu , Nagasaki Fumihiko , Ohtsuka Yozo
Published: March 2009

A series of 5,6‐disubstituted 3‐alkoxypyrazine‐2‐carbonitriles (2a‐i) were prepared from 5,6‐disubstituted pyrazine‐2,3‐dicarbonitriles (1a‐d) by direct substitution with alcohols. Treatment of 1 with amines gave either pyrrolopyrazines (3a,b) or substitution products (4,5). In a low temperature range, 1 afforded imidates and related compounds (6–11). The preference among these reactions depended on the 5,6‐substituents and on the reaction conditions.
Studies of spiro‐chlorin formation using porphyrin amides
Authors: Smith Kevin M. , De Almeida José A. P. Baptista , Lewis W. Michael
Published: March 2009

Syntheses of 7‐(3‐ethoxycarbonylpropyl)‐2,3,5‐triethyl‐1,4,6,8‐tetramethylporphyrin (8) (via the MacDonald dipyrrylmethane route) and 2‐(2‐chloroethyl)‐4‐ethyl‐6‐methoxycarbonyl‐7‐(3‐methoxy‐carbonylpropyl)‐1,3,5,8‐tetramethylporphyrin (22) (via the tripyrrene route) are described. The corresponding pyrrolidides of these compounds were cyclized in high yield to furnish the spiro imines (20 and 30 respectively), but attempts to hydrolyze these imines to the appropriate spiroketochlorins were largely unsuccessful. A small amount of the spiroketochlorin 9 (from 8) was obtained, and this was successfully hydrogenated to give the dihydro derivative 21. The major problem in imine hydrolysis was observed to be reversion to the parent porphyrin through simple bond migration and spiro ring cleavage. A successful transformation of protoporphyrin‐IX dimethyl ester (31) into mesoporphyrin‐IX dimethyl ester (32) using di‐imide generated from dipotassium azodicarboxylate is described.
(2‐Alkyl‐1,4‐benzodioxan‐2‐yl)carboxylic acids as potential hypolipidemic agents
Authors: Salimbeni Aldo , Manghisi Elso
Published: March 2009

1,2‐Diphenols reacted with 2‐alkyl‐3‐chloro‐1,2‐epoxypropane to give a mixture of 1,4‐benzodioxane, V, and 1,5‐benzodioxepine, VII, alcohols. From potassium permanganate oxidation of benzodioxane compounds V the corresponding (2‐alkyl‐1,4‐benzodioxan‐2‐yl)carboxylic acids II were obtained. In a preliminary pharmacological evaluation benzodioxane acids II did not show any effect on plasma cholesterol, while producing a moderate lowering of triglycerides.
Synthesis of 6‐(arylthio)‐ and 6‐[(arylmethyl)thio] ‐1,2,4,5‐tetrazin‐3‐amines and n‐phenyl‐ and n‐(phenylmethyl)‐1,2,4,5‐tetrazine‐3,6‐diamines as potential antimalarial agents
Authors: Johnson Judith L. , Whitney Barbara , Werbel Leslie M.
Published: March 2009

Alkylation of tetrahydro‐1,2,4,5‐tetrazine‐3,6‐dithione with iodomethane and 1,2‐dichloro‐4‐(chloromethyl)benzene, respectively (Scheme 1, 4) followed by oxidation afforded 3,6‐bis(methylthio)‐ and 3,6‐bis[[(3,4‐dichlorophenyl)methyl]thio]‐1,2,4,5‐tetrazines (6, 15). The reaction of 15 with amines provided the 6‐[(arylmethyl)thio]‐1,2,4,5‐tetrazin‐3‐amines (16) while sequential displacement of both methylthio groups in 6 afforded the tetrazine‐diamines 8 and 10. Hydrolysis of N,N‐dimethyl‐6‐(methylthio)‐1,2,4,5‐tetrazin‐3‐amine (11) with potassium hydroxide afforded the tetrazin‐3‐ol (12) which was chlorinated and then treated with 4‐chlorobenzenethiol to provide 13. The target 6‐substituted‐1,2,4,5‐tetrazin‐3‐amines displayed negligible antimalarial activity.
Reaction of ketenes with N,N‐disubstituted α‐aminomethyleneketones. X. Synthesis of N,N‐disubstituted 6‐alkyl‐4‐amino‐3,3‐dichloro‐3,4‐dihydro‐2H‐pyran‐2‐ones and of 6‐alkyl‐4‐amino‐3‐chloro‐2H‐pyran‐2‐ones
Authors: Bargagna Alberto , Cafaggi Sergio , Schenone Pietro
Published: March 2009

Cycloaddition of dichloroketene to N,N‐disubstituted 1‐amino‐4‐methyl‐1‐penten‐3‐ones and 1‐amino‐4,4‐dimethyl‐1‐penten‐3‐ones occurred in moderate to fair yield only in the case of aromatic N‐substitution to give N,N‐disubstituted 6‐alkyl‐4‐amino‐3,3‐dichloro‐3,4‐dihydro‐2H‐pyran‐2‐ones, which were dehydrochlorinated with DBN to afford in good yield N,N‐disubstituted 6‐alkyl‐4‐amino‐3‐chloro‐2H‐pyran‐2‐ones. In the case of aliphatic N,N‐disubstitution, cyclo‐addition led directly to 6‐alkyl‐4‐dialkylamino‐3‐chloro‐2H‐pyran‐2‐ones only for N,N‐disubstituted 1‐amino‐4,4‐dimethyl‐1‐penten‐3‐ones. The reaction between 1‐dimethylamino‐4‐methyl‐1‐penten‐3‐one and dichloroketene gave 3‐chloro‐4‐dimethylamino‐3,6‐dihydro‐6‐isopropylidene‐2H‐pyran‐2‐one in low yield.
The synthesis of polycyclic benz‐fused pyrroles
Authors: Anderson Wayne K. , Mcpherson Howard L. , New James S.
Published: March 2009

Pyrrolo[1,2‐f]phenanthridine (2), benzo[f]pyrrolo[2,1‐a]isoquinoline (3), 5,6,7,8,9,10,11‐hexahydrobenzo[g]pyrrolo[2,1‐a]isoquinoline (5), and pyrrolo[2,1‐a]isoquinoline (6) dicarboxylic acid diesters were prepared in 1,3‐dipolar cycloaddition reactions between dimethyl acetylenedicarboxylate and the hydrofluoroborate salt of the appropriate Reissert compound. Several of the different methods to prepare Reissert compounds are compared and the carbon‐13 nmr spectra for the Reissert compounds are reported. Carbon‐13 nmr was used to assign the structures of isomers 10 and 11; the latter compounds arose from a prior reaction in which the cyclization of β‐(5,6,7,8‐tetrahydro‐2‐naphthyl)ethylamine N‐formate which gave a mixture of hexahydroisoquinolines, 8a and 9a. Pyrrolo[1,2‐b]isoquinoline (12) and pyrrolo[2,1‐a]isoquinoline dicarboxylic acid diesters were made in münchnone cycloaddition reactions. The latter compound was made from tetrahydroisoquinoline‐1‐carboxylic acid which was readily prepared from isoquinaldic acid by catalytic reduction. The dehydrogenation of several of the partially saturated compounds is also discussed.
Hydrazinolysis of 4‐acyl and 4‐ethoxycarbonyl‐3H‐imidazo[1,5‐b]‐pyridazine‐5,7‐(6H)diones: 8‐Oxo‐1,4,7,8‐tetrahydropyridazino‐[4,5‐c]pyridazine, 8‐oxo‐7,8‐dihydropyridazino[4,5‐c]pyridazine and 5,8‐dioxo‐1,4,5,6,7,8‐hexahydropyridazino[4,5‐c]pyridazine derivatives
Authors: Migliara Onofrio , Petruso Salvatore , Sprio Vincenzo
Published: March 2009

Reaction of 4‐acyl‐3H‐imidazo[1,5‐b]pyridazine‐5,7‐(6H)diones with hydrazine hydrate gave 3R‐5R′‐8‐oxo‐1,4,7,8‐tetrahydropyridazino[4,5‐c]pyridazine together with 3R‐5R′‐8‐oxo‐7,8‐dihydropyridazino[4,5‐c]pyridazine derivatives. Their structures were assigned by means of elemental analyses and spectroscopic data (ir, uv, nmr and ms). The conclusive structural elucidation involved the fact that 2R‐4‐ethoxycarbonyl‐3H‐imidazo[1,5‐b]pyridazine‐5,7‐(6H)‐diones treated with hydrazine hydrate afforded 3R‐5,8‐dioxo‐1,4,5,6,7,8‐hexahydropyridazino‐[4,5‐c]pyridazine which, upon dehydrogenation, gave products previously reported in the literature.
Benzo[c]fused isothiazoles. I. synthesis of the angular benzo[c]bisisothiazoles and of the symmetrical benzo[c]trisisothiazole
Authors: Danylec Basil , Davis Michael
Published: March 2009

The synthesis of all the possible angular benzo[c]bisisothiazoles (1, 2 and 3), and of the symmetrical benzo[c]trisisothiazole (4) are described. The pmr properties of these compounds are compared with analogous thiophenes and thiadiazoles
Benzo[c]fused isothiazoles. II. Synthesis of some angular isothiazolo[c]benzothiadiazoles. An anomalous amination reaction
Authors: Danylec Basil , Davis Michael
Published: March 2009

The syntheses and pmr properties of the angular isothiazolo[c]‐2,1,3‐benzothiadiazoles (1 and 2) are described. An unusual electrophilic amination reaction with N‐sulfinylmethanesulfonamide is discussed.
Selenium heterocycles. XXX. Synthesis of 4‐substituted vinyl 2‐thioxo‐1,3‐dithioles and 5‐substituted vinyl 2‐thioxo‐1,3‐thiaselenoles
Authors: Shafiee A. , Vosooghi M. , Lalezari I.
Published: March 2009

4‐Substituted vinyl and 4‐(4‐phenyl‐1,3‐butadienyl)‐1,2,3‐thiadiazoles were prepared through the reaction of 4‐aryl‐3‐buten‐2‐one semicarbazone and 6‐phenyl‐3,5‐hexadien‐2‐one semicarbazone with thionyl chloride, respectively. Decomposition of these 1,2,3‐thiadiazoles as well as the corresponding 1,2,3‐selenadiazoles with base and subsequent addition of carbon disulfide afforded 4‐substituted vinyl 2‐thioxo‐1,3‐dithioles and 5‐substituted vinyl 2‐thioxo‐1,3‐thiaselenoles.