bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and cardiotonic activity of pyrimido[5,4‐b][1,4]oxazinones and 1,4‐dioxino[2,3‐d]pyrimidines
Authors: Mátyus Péter , Makk Nándor , Tegdes Anikó , Kosáry Judit , Kasztreiner Endre , Podányi Benjamin , Rabloczky György , Kiirthy Mária
Published: March 2009

The new pyrimido[5,4‐b][1,4]oxazinones 4a‐c and 6a,b, 7a,c were obtained from 6‐amino‐2,3‐dimethyl‐4(3H)‐pyrimidone (1) and 4‐substituted pyrimido[5,4–6][1,4]oxazinones 5, 7a, respectively, while derivatives 8a‐e of the novel ring system 1,4‐dioxino[2,3‐d]pyrimidine were prepared starting from 2b.

Compounds 4a, 4c and 7a showed positive inotropic effect.
Preparation of new macrocyclic polyamines containing 4‐(phenylethynyl)pyridine subunit
Authors: Takalo Harri , Kankare Jouko
Published: March 2009

Two new tetraazacycloalkane‐N‐acetic acids containing 4‐(phenylethynyl)pyridine subunit as a part of macrocycle have been prepared. Two methods for the cyclisation reaction were investigated.
Diheterocyclic compounds from dithiocarbamates and derivatives thereof. I. 2,2′‐(arylenediamino)bisbenzoazoles, 2,2′‐(arylenediamino)bis(imidazopyridines) and 8,8′‐(arylenediamino)bispurines
Authors: Garín Javier , Meléndez Enrique , Merchán Francisco L. , Merino Pedro , Orduna Jesús , Tejedor Rosa , Tejero Tomás
Published: March 2009

A general method for the synthesis of the title compounds 5, 6, 10, 14, 15 and 16 is reported. All of them were prepared in one step from readily available dimethyl N,N'‐(arylene)bisdithiocarbamates 1 and red mercury(II) oxide. The superiority of these reagents over the corresponding diisothiocyanates 7 and the synthetic utility of tetramethyl N,N'‐(arylene)bisdithiocarbonimidates 2 are also discussed.
Syntheses and conformational analyses of some 3‐amino‐2,5‐dioxo‐2,3,4,5‐tetrahydro‐1H‐1‐benzazepine derivatives: X‐ray crystal structure of 35–3‐[[(1,1‐dimethylethoxy)carbonyl]amino]‐2,5‐dioxo‐2,3,4,5‐tetrahydro‐1H‐1‐benzazepine
Authors: Ball Jonathan B. , Wong Margaret G. , Capuano Benny , Gulbis Jacqueline M. , Mackay Maureen F. , Alewood Paul F.
Published: March 2009

The constrained dipeptide mimic 1 was synthesized from 2 in three steps with 65% overall yield. Analyses of the 1H nmr data of a number of 3‐amino‐2,5‐dioxo‐2,3,4,5‐tetrahydro‐1H‐1‐benzazepine derivatives led to the conclusion that these compounds adopt a similar conformation and that this ring system is rigid. X‐ray crystallography was used to define the structure of 3, and computer‐aided energy minimization of 6 gave a preferred conformation similar to that observed in the crystal of 3.
Reaction of 2‐dimethylaminomethylene‐1,3‐diones with dinucleophiles. VIII. Synthesis of ethyl and methyl 2,4‐disubstituted 5‐pyrimidinecarboxylates
Authors: Schenone Pietro , Sansebastiano Laura , Mosti Luisa
Published: March 2009

Reaction of ethyl or methyl 2‐dimethylaminomethylene‐3‐oxoalkanoates with N‐C‐N dinucleophiles such as guanidine, acetamidine or benzamidine afforded in high yields the relative esters of 4‐substituted 2‐amino‐, 2‐methyl‐ or 2‐phenyl‐5‐pyrimidinecarboxylic acids, respectively. These esters were hydrolyzed to the corresponding carboxylic acids, which were converted by heating to 4‐substituted 2‐pyrimidinamines, 2‐methyl or 2‐phenylpyrimidines, respectively, generally in excellent yields. The 4‐unsubstituted ethyl 2‐amino‐, 2‐methyl‐ and 2‐phenyl‐5‐pyrimidinecarboxylates were obtained in moderate yields by reaction of the above dinucleophiles with ethyl 2,2‐diformylacetate. These esters were hydrolyzed and the corresponding acids (with the exception of the 2‐methyl derivative) were decarboxylated to give 2‐pyrimidinamine and 2‐phenylpyrimidine in satisfactory yields.
Theoretical reaction indices for dibenz[a,h]acridine
Authors: Soriano David S. , Draeger Jon A.
Published: March 2009

Huckel molecular orbital calculations and application of Seybold‐Smith reactivity theory suggest that the Bay‐Region diol epoxide derived from the 8,9,10,11‐benzo ring of dibenz[a,h]acridine (1) is the same in reactivity as that of the 1,2,3,4‐ring in agreement with experimental findings. The calculations dispute an earlier claim of regioselective reactivity at the 8,9,10,11‐benzo ring.
Reactivity of 4‐amino‐6,7‐diphenyl‐8H‐pyrazino[2,3‐c]‐1,2,6‐thiadiazine 2,2‐dioxide towards methylating agents
Authors: Goya Pilar , Páez Juan Antonio , Pfleiderer Wolfgang
Published: March 2009

Reaction of the title compound with different methylating agents to give mono‐, di‐ and trisubstituted derivatives has been studied.
Synthesis of isoxazolo[4,5‐d]pyridazin‐4(5H)‐ones and 4‐acyl‐5‐hydroxy‐3(2H)‐pyridazinones
Authors: Chantegrel Bernard , Deshayes Christian , Pujol Bernard , Wei Zhong Jia
Published: March 2009

The title compounds were prepared from ethyl 5‐acyl‐ or 5‐(1‐hydroxyethenyl)isoxazole‐4‐carboxylates which in turn were prepared from ethyl 3‐methylamino‐2‐butenoate or 3(2H)‐furanones.
The synthesis of benzofuroquinolines. VII. Some benzo[h]benzofuro[2,3‐b]‐ and [3,2‐c]quinoline derivatives
Authors: Yamaguchi Seiji , Yoshimoto Yoshiteru , Murai Rikuko , Ohama Eiko , Kawase Yoshiyuki
Published: March 2009

Benzo[h]benzofuro[3,2‐c]quinoline (2a) and its 6‐methyl derivative 2b were synthesized by the demethyl‐cyclization of 3‐(o‐methoxyphenyl)‐4(H)‐benzo[h]quinolinone (5a) and its 2‐methyl derivative 5b. And, two benzo[h]benzofuro[2,3‐b]‐ and [3,2‐c]quinolinones 8 and 9 were synthesized by the demethyl‐cyclization of 4‐hydroxy‐3‐(o‐methoxyphenyl)‐2(1H)‐benzo[h]quinolinone (7), and they were converted to the corresponding chloro derivatives 1c and 2c and benzo[h]benzofuro[2,3‐b]quinoline‐7‐carbonitrile (1d).
Synthetic routes to 2‐(2‐benzofuranyl)benzoic acids and their cyclization into benz[6]indeno[2,1‐d]furan‐10‐ones
Authors: Guillaumel Jean , Boccara Nicole , Demerseman Pierre
Published: March 2009

The benz[6]indeno[2,1‐d]furan‐10‐ones 1 were prepared by the intramolecular cyclization of the 2‐(2‐benzofuranyl)benzoic acids, 2, the unequivocal routes to which are described herein. Various synthetic methods to these acids were tested, as well as the methods to cyclize them.
N‐Amination of 3‐amino‐1,2,4‐triazole with hydroxylamine‐O‐sulfonic acid: Synthesis of 1,5‐diamino‐1,2,4‐triazole
Authors: Salazar Loreto , Espada Modesta , Avendaño Carmen , Elguero José
Published: March 2009

N‐Amination of the 3(5)‐amino‐1,2,4‐triazolide anion with hydroxylamine‐O‐sulfonic acid is studied. This method provided an access to the previously unknown 1,5‐diamino‐1,2,4‐triazole.
Carbazoledioxazines having long alkyl groups 1. Synthesis of carbazoledioxazines with linear type structure
Authors: Ikeda Masaaki , Kitahara Kiyoshi , Nishi Hisao , Kozawa Kozo , Uchida Tokiko
Published: March 2009

Carbazoledioxazines with linear type structure (5,15‐dialkyl‐8,18‐dichloro‐5,15‐dihydrodiindolo[3,2‐b:‐3′,2′‐m]triphenodioxazine) were selectively synthesized by demethanolation ring closure of 2,5‐bis(2‐methoxy‐9‐alkyl‐3‐carbazolylamino)‐3,6‐dichloro‐1,4‐benzoquinone in a high boiling solvent. The structure has been confirmed by 1H‐nmr and X‐ray crystallography.
Amine‐induced rearrangements of 2‐bromo‐1‐(1H‐indol‐3‐yl)‐2‐methyl‐1‐propanones: A new route to α‐substituted indole‐3‐acetamides, β‐substituted tryptamines, α‐substituted indole‐3‐acetic acids and indole β‐aminoketones
Authors: Sanchez Joseph P. , Parcell Robert F.
Published: March 2009

The reaction of 2‐bromo‐1‐(1H‐indol‐3‐yl)‐2‐methyl‐1‐propanone (1) and 2‐bromo‐1‐(1‐methyl‐1H‐indol‐3‐yl)‐2‐methyl‐1‐propanone (2) with primary amines proceeds in good yields to produce rearranged amides by a proposed pseudo‐Favorskii mechanism. These amides in turn can either be reduced to produce β‐substituted tryptamines or hydrolyzed to produce substituted indole‐3‐acetic acids. When the reaction is carried out using bulky primary or secondary amines, β‐aminoketones are produced by elimination of hydrogen bromide followed by Michael addition. When hindered secondary amines or tertiary amines are used, elimination to the α,β‐unsaturated ketones occurs.
Synthesis of 5‐methyl‐4‐oxo‐quinolinecarboxylic acids
Authors: Hagen Susan E. , Domagala John M.
Published: March 2009

A series of 5‐methyl‐4‐oxo‐3‐quinolinecarboxylic acids was prepared in which the eight‐position was substituted with fluorine, chlorine, methyl, or hydrogen. These quinolones were synthesized from the appropriate 2‐methyl‐3,4,6‐trifluorobenzoic acids which were derived from oxazolines 8 and 16. The oxazoline moiety served as both an ortho‐director (where feasible) and a protecting group; a trimethylsilyl moiety was used to block the most acidic site in the molecule.
An improved synthesis of 5,15‐diaryloctaalkylporphyrins
Authors: Osuka Atsuhiro , Nagata Toshi , Kobayashi Fumikazu , Maruyama Kazuhiro
Published: March 2009

The title compounds were prepared from an aromatic aldehyde and bis(3‐ethyl‐4‐methyl‐2‐pyrrolyl)‐methane in acetonitrile in the presence of catalytic amount of trichloroacetic acid, followed by p‐chloranil oxidation. The reaction conditions employed here are milder than those previously reported, allowing efficient preparation of porphyrins with acid‐labile groups such as cyclic acetals, for which the previous method provided no direct synthetic access. Using the new method, aromatic aldehydes with acid‐labile groups, as well as sterically hindered aldehydes, gave the corresponding porphyrins in satisfactory yields (50–90%). This method therefore can be widely utilized for synthesis of 5,15‐diaryloctaalkylporphyrins.
Synthesis, stereochemistry and conformational properties of diastereomeric cyclic dipeptides containing tetrahydro‐1,4‐thiazine‐3,5‐dicarboxylic acid
Authors: Paradisi Mario Paglialunga , Zecchini Giampiero Pagani , Torrini Ines , Lucente Gino
Published: March 2009

The synthesis of linear dipeptides containing N‐protected L‐phenylalanine and (3R‐cis)‐tetrahydro‐1,4‐thiazine‐3,5‐dicarboxylic acid dialkyl diester residues is described. N‐Deprotection of these dipeptides by hydrogenolysis on palladium afforded directly a mixture of cis and trans dioxopiperazines. The stereochemistry and the solution conformational properties of the cyclic dipeptides are determined.
Preparation of pyrazolo[5,1‐c][1,4]benzoxazines by intramolecular [3+ + 2] cycloaddition reaction of hydrazonium chlorides with alkenes
Authors: Shimizu Tomio , Hayashi Yoshiyuki , Miki Masayuki , Teramura Kazuhiro
Published: March 2009

Pyrazolo[5,1‐c][1,4]benzoxazines were prepared by the reaction of 2‐(allyloxy)phenylhydrazine with arylaldehydes in the presence of hydrochloric acid. The formation of the fused heterocycles can be explained by intramolecular 1,3‐dipolar cycloaddition reaction of cationic dipole, i.e‥, hydrazonium chlorides.
Derivation of fluorine‐containing pyridine dicarboxylates IV. N‐substituted dihydropyridine derivatives
Authors: Chupp John P.
Published: March 2009

The bio‐activity observed for certain Hantzsch derived fluorine‐containing dihydropyridinecarboxylates 6, 11 and 12 and pyridinecarboxylates 10 prompted the preparation of a number of related N‐substituted dihydropyridines for the first time. One method involved a mixed Hantzsch sequence to give 2 from which unexpected side products 3–5 were also isolated and identified. A second preparative method relied on lithiobase deprotonation of 6, 11 and 12 followed by alkylation or acylation to give products 7–9 and 13–15. Structure determination and stereo‐assignments are discussed in terms of their spectral properties, and reaction mode.
Synthesis and single‐crystal X‐ray diffraction analysis of 2‐sulfamoyladenosine (6‐amino‐9‐β‐D‐ribofuranosylpurine‐2‐sulfonamide)
Authors: Hanna Naeem B. , Larson Steven B. , Robins Roland K. , Revankar Ganapathi R.
Published: March 2009

2‐Amino‐9‐β‐D‐ribofuranosylpurine‐2‐sulfonamide (2‐sulfamoyladenosine, 4), a congener of sulfonosine (3), was synthesized by four different routes. Acid catalyzed fusion of 6‐chloropurine‐2‐sulfonyl fluoride (5) with 1,2,3,5‐tetra‐O‐acetyl‐β‐D‐ribofuranose (8) gave a good yield of 6‐chloro‐9‐(2,3,5‐tri‐O‐acetyl‐β‐D‐ribofuranosyl)purine‐2‐sulfonyl fluoride (9). Ammonolysis of 9 furnished 4. Lewis acid catalyzed glycosylation of the trimethylsilyl derivative of either 6‐chloropurine‐2‐sulfonamide (6) or 6‐aminopurine‐2‐sulfonamide (7) with 8 gave the corresponding N9‐glycosylated products, 10 and 11, respectively, which on ammonolysis gave 4. Amination of 2‐thioadenosine (12) with chloramine solution gave the sulfenamide derivative 13, which on subsequent oxidation with m‐chloroperoxybenzoic acid furnished an alternate route to 4. The structure of 4 was established by single‐crystal X‐ray diffraction studies. 2‐Sulfamoyladenosine (4) is devoid of significant inhibitory activity against L1210 leukemia in mice.
The reaction of amines with isoflavones. 2.. Formation of phenolic sulphonamidopyrimidines
Authors: Olugbade T. A. , Usifoh C. O. , Oluwadiya J. O. , Reisch J.
Published: March 2009

Isoflavones in alkaline dimethylsulphoxide at 100° under a nitrogen atmosphere reacted with sulphaguanidine to give phenolic sulphonamidopyrimidines.
Synthesis of the penta‐glutamyl derivative of N‐[4‐[N‐[3‐(2,4‐diamino‐1,6‐dihydro‐6‐oxo‐5‐pyrimidinyl)‐propyl]amino]benzoyl]‐L‐glutamic acid (5‐DACTHF). An acyclic analogue of tetrahydrofolic acid
Authors: Styles Virgil L. , Kelley James L.
Published: March 2009

The penta‐glutamyl derivative of N‐[4‐[N‐[3‐(2,4‐diamino‐1,6‐dihydro‐6‐oxo‐5‐pyrimidinyl)propyl]amino]‐benzoyl)‐L‐glutamic acid (1, 5‐DACTHF, 543U76) was synthesized by a convergent route. L‐γ‐Glutamyl‐L‐γ‐glutamyl‐L‐γ‐glutamyl‐L‐γ‐glutamyl‐L‐γ‐glutamyl‐L‐glutamic acid heptakis t‐butyl ester (20) was prepared in ten steps from L‐glutamic acid di‐t‐butyl ester and N‐(benzyloxycarbonyl)‐L‐glutamic acid α‐t‐butyl ester. 4‐[N‐[3‐(2,4‐Diamino‐1,6‐dihydro‐6‐oxo‐5‐pyrimidinyl)propyl]trifluoroacetamido]benzoic acid (6), which was synthesized from pyrimidinylpropionaldehyde 3 in three steps, was condensed with 20, followed by deprotection to provide N‐[4‐[N‐[3‐(2,4‐diamino‐1,6‐dihydro‐6‐oxo‐5‐pyrimidinyl)propyl]amino]benzoyl]‐L‐γ‐glutamyl‐L‐γ‐glutamyl‐L‐γ‐glutamyl‐L‐γ‐glutamyl‐L‐γ‐glutamyl‐L‐glutamic acid (2). Hexaglutamate 2 is a potent inhibitor of glycinamide ribonucleotide transformylase.
Synthesis of 6‐[[(hydroxyimino)phenyl]methyl]‐1‐[(1‐methylethyl)sulfonyl]‐1H‐imidazo[4,5‐b]pyridin‐2‐amine. An aza analogue of enviroxime
Authors: Kelley James L. , Mclean Ed W. , Davis Ronda G. , Crouch Ronald
Published: March 2009

6‐[[(Hydroxyimino)phenyl]methyl]‐1‐[(1‐methylethyl)sulfonyl]‐1H‐imidazo[4,5‐b]pyridin‐2‐amine (1), an aza analogue of enviroxime, was synthesized in eight steps from 6‐hydroxynicotinic acid (2). Acid 2 was nitrated, chlorinated with phosphorus pentachloride, and subjected to Friedel‐Crafts aroylation to give 6‐chloro‐5‐nitro‐3‐pyridyl phenyl ketone (5). Amination of 5 was followed by reduction of the nitro group and condensation with ethoxycarbonylisothiocyanate to give 6‐benzyl‐2‐ethoxycarbonylamino‐1H‐imidazo[4,5‐d]pyridine (8). The ethoxycarbonyl moiety of 8 was cleaved, N‐1 was isopropylsulfonylated, and the carbonyl moiety was condensed with hydroxylamine to give 1. Compound 1 was inactive against rhinovirus 1B and poliovirus type 1.
Synthesis of 7‐alkyl‐2,4‐dimethoxy‐5‐oxo‐5H‐pyrano[4,3‐d]pyrimidines
Authors: Wada Akimori , Kanatomo Shōchi
Published: March 2009

A convenient synthesis of 7‐alkyl‐2,4‐dimethoxy‐5‐oxo‐5H‐pyrano[4,3‐d]pyrimidines from methyl 2,4‐dimethoxy‐6‐phenylselenylmethyl (or 6‐phenylthiomethyl)‐5‐pyrimidinecarboxylate with alkylaldehydes is described.
Régiospécificit de l'action des arylnitriloxydes sur la 4‐cyano 1‐methyl 1,4‐dihydro quinoline
Authors: Soufiaoui M. , Jazouli H.
Published: March 2009

Les réactions de cycloaddition dipolaires‐1,3 des arylnitriloxydes sur la 4‐cyano 1‐méthyl 1,2‐dihydro quinoline sont régiospécifiques. La structure des cycloadduits est démontrée par rmn du proton et du carbone‐13.
Synthesis of 3‐(1,5‐diphenyl‐3‐pyrazolyl)aryl propanoates
Authors: Murray William V. , Hadden Susan K. , Wachter Michael P.
Published: March 2009

New procedures for the synthesis of 3‐(1,5‐diphenyl‐3‐pyrazolyl)aryl propanoates and related 2‐(1,5‐diphenyl‐3‐pyrazolyl)aryl propanoates from a common 3‐hydroxymethylpyrazole intermediate are described. These new procedures include an improved method for carrying out pyridinium chlorochromate oxidations under ultrasonic conditions. These syntheses also utilize lithium triethylphosphonoacetate formed from n‐butyllithium and triethylphosphonoacetate as a Wittig‐Horner reagent to improve olefination yields.
Etude des conditions D'accés aux 6,11‐dihydro‐5H‐pyrimidino[4,5‐a]carbazoles
Authors: Gazengel Jean‐Marie , Lancelot Jean‐Charles , Rault Sylvain , Robba Max
Published: March 2009

Les tétrahydrocarbazolones 15‐27 sont obtenues par cyclisation des phénylhydrazones 2‐14. La cyclisation de ces carbazolones 15‐27 qui est opérée au moyen du triformarnidométhane dans le formamide fournit les dihydropyrimidinocarbazoles 28‐40. Les spectres de rmn enregistrés dans le DMSO‐d6 confirment la structure des dérivés obtenus.
Chemistry of condensed thiophenes. IV. Acetylation of phenanthro[4,5‐bcd]thiophene
Authors: Klemm L. H. , Lam Lee , Severns Bryon , Sur Sandip K.
Published: March 2009

Treatment of phenanthro[4,5‐bcd]thiophene (2) with acetyl chloride and aluminum chloride in nitrobenzene gives acetylation of positions ortho and para to the heteroatomic sulfur atom. In separate experiments, mixtures of 1‐ and 3‐acetyl (50% yield, ratio 1.9:1) or of 1,5‐, 1,7‐, and 3,5‐diacetyl (79% yield, ratio 3:1:1) derivatives were obtained. Isolated as isomerically pure products were the 1‐acetyl and the 1,5‐diacetyl compounds, as well as the oximes of the 1‐ and 3‐acetyl derivatives. Comparison of these results is made with those reported for nitration of 2, which also occurs ortho and para to the sulfur atom, and with nitration and acetylation of pyrene (the benzolog of 2) which substitutes in the corresponding positions.
1,3‐Dipolar cycloaddition reactions of 1,4‐benzoquinones with nitrilimines
Authors: Argyropoulos N. G. , Mentzafos D. , Terzis A.
Published: March 2009

The cycloaddition reactions of some aryl conjugated p‐benzoquinones with nitrilimines were studied. Depending upon the reaction conditions mono‐ and/or bis‐ adducts were isolated only from carbon‐carbon double bond. The structure determination was unequivocally established by an X‐ray analysis carried out on a bis‐adduct. The observed regio‐, as well as site‐selectivity, was qualitatively correlated with frontier molecular orbitals of the reacting species.
Heterocycles. XXV Sodium borohydride reduction of flavanonols
Authors: Li Shaoshun , Onda Masayuki , Kagawa Hitoshi , Kawase Hiromi , Iguchi Mieko , Harigaya Yoshihiro
Published: March 2009

Solvent effects on the stereochemistry in the sodium borohydride reduction of (±)‐flavanonols have been examined. The effects observed for the (±)‐flavanonols with 5‐OMe in 2‐propanol, dioxane and methanol are explainable by the differences between the steric interactions inherent in the product‐like transition states A and B. It has been also found that 5‐OAc peculiarly affects the stereochemistry in the reduction to produce the (±)‐catechin‐type compounds in a one‐pot process. The solvent and temperature effects are examined using a model analogous to the above.
Cyclopropyl‐substituted pyrylium salts
Authors: Fǎrcaşiu Dan , Kizirian Mark
Published: March 2009

The previously unknown 2,4,6‐trisubstituted pyrylium salts 1‐4, carrying cyclopropyl and methyl or phenyl substituents in the same molecule, and 5‐8, substituted with isopropyl groups instead of cyclopropyl, were synthesized as perchlorates. The electronic spectra and the C‐13 nmr spectra of the two groups of compounds were compared. A cyclopropyl group has a batochromic effect on the electronic spectrum roughly half that exerted by a phenyl; replacement of an alkyl by a cyclopropyl shifts the highest wavelength absorption band by about 20 nm. Presence of phenyl substituents reduces the batochromic effects of cyclopropyl substituents. The effects of both cyclopropyl and phenyl substituents on the electronic spectra are smaller for pyrylium than for tropylium. The nmr signals for all the ring carbons are shifted upfield upon replacement of isopropyl by cyclopropyl; in particular, the effect of substituents in position 2 upon the chemical shift of C(4) indicates that the electron‐releasing effect varies in the series alkyl < phenyl < cyclopropyl, in agreement with the findings for 2,6‐disubstituted pyrylium salts. The difference between the chemical shifts for the methine and methylene carbons of the three‐membered ring is a function of the electron demand of the cationic heterocycle.
The synthesis of difluoro[1]benzothieno[2,3‐c]quinolines and their N‐methyl quaternary salts
Authors: Luo Jiann‐Kuan , Castle Steven L. , Castle Raymond N.
Published: March 2009

A series of difluoro[1]benzothieno[2,3‐c]quinolines has been prepared by photocyclization of the appropriate carboxamides. The lactams obtained were converted into the corresponding chloro derivatives which were catalytically dechlorinated into the difluoro[1] benzothieno[2,3‐c]quinolines. The latter compounds were transformed into the N‐methyl quaternary salts.
Synthesis and In vitro biological activity of some 7‐(5‐aminomethyl‐2‐isoxazolidinyl)quinolone‐3‐carboxylic acids
Authors: Ziegler Carl B. , Kuck Nydia A. , Strohmeyer Timothy W. , Lin Yang‐I
Published: March 2009

The synthesis of the title compounds via nitrone cycloaddition is described. The in vitro antibacterial activity of these compounds is compared against 1‐ethyl‐6,8‐difluoro‐7‐[3‐[(ethylamino)methyl]‐1‐pyrrolidinyl]‐1,4‐dihydro‐4‐oxoquinoline‐3‐carboxylic acid (CI‐934).
Synthetic route to 4‐(2‐aminoethyl)‐5‐hydroxyindole derivatives
Authors: Cannon Joseph G. , Roufos Ioannis
Published: March 2009

In synthetic studies leading to the title compounds, application of the Claisen rearrangement of 5‐allyloxyindole was investigated. Almost quantitative yields of Claisen rearrangement product were realized, and a strategy for oxidative cleavage of the allyl double bond to an indole‐4‐acetaldehyde derivative was developed. A new method for conversion of 2,3‐dihydroindoles into indoles was utilized: air oxidation in a strongly basic environment. The Claisen rearrangement of allyloxyindoles is presented as a method having considerable potential utility in synthesis of a variety of polysubstituted indoles.
1,3‐Dipolar cycloaddition reactions of 4‐arylidene‐2‐phenyl‐1,4‐dihydroimidazol‐5‐ones with nitrile oxides
Authors: Argyropoulos N. G. , Coutouli‐Argyropoulou E. , Siacavara C.
Published: March 2009

Stable nitrile oxides add regioselectively to the carbon‐carbon double bond of 4‐arylidene‐2‐phenyl‐1,4‐dihydroimidazol‐5‐ones to afford spiro isoxazolines 3. Compounds 3 are further hydrolysed to isoxazole derivatives.
Reaction of reissert anion with aldimines: A new approach to the imidazo[5,1‐α]isoquinoline ring system
Authors: Kant Joydeep
Published: March 2009

The carbanion derived from N‐alkoxycarbonyl Reissert compound readily undergoes addition‐cyclization reaction with aldimines to give imidazo[5,1‐a]isoquinolines. A detailed study of this new ring annelation chemistry is described.
Synthetic entries to 6‐fluoro‐7‐substituted indole derivatives
Authors: Mckittrick Brian , Failli Amedeo , Steffan Robert J. , Soll Richard M. , Hughes Philip , Schmid Jean , Asselin Andre A. , Shaw C. C. , Noureldin R. , Gavin G.
Published: March 2009

Three practical synthetic entries of functionalized 6‐fluoro‐7‐substituted indole derivatives were developed in connection with the preparation of 7‐fluoro‐8‐substituted‐1,3,4,9‐tetrahydropyrano[3,4‐b]indole‐1‐acetic acid derivatives 11. The first route, which permits group modification about position 8 of the pyranoindole skeleton, employs 2‐bromo‐3‐fluoroaniline (18) as a key intermediate, the preparation of which was achieved by either a novel ortho metalation of 15 or via the intermediacy of 22. The second route utilizes 32 to append a terminally functionalized three carbon side chain onto the indole template and in addition leads to 43 from 40. The third route to the 7‐fluoro‐8‐substituted‐pyranoindole skeleton complements route two in that the synthetic pathway exploits 32 in a nucleophilic fashion to construct a terminally functionalized two carbon appendage onto the indole nucleus.
Synthesis and stereochemistry of the (9S,13S,14S)‐3‐hydroxy‐17‐methylmorphinan‐10‐ols
Authors: Mohacsi Erno , O'Brien Jay P.
Published: March 2009

O‐Demethylation of (9S,13S,14S)‐3‐methoxy‐17‐methylmorphinan‐10‐one (2) to (9S,13S,14S)‐3‐hydroxy‐17‐methylmorphinan‐10‐one (3) and reduction of 3 to 10α‐ and 10β‐hydroxylated morphinans 4 and 5, are described. The stereochemistry of these epimeric alcohols was established on the bases of 1H nmr data.
The synthesis of two benzo[c:d′]diisothiazoles
Authors: Mckinnon David M. , Abouzeid Azza
Published: March 2009

Two benzo[c:d']diisothiazoles, 8‐methylbenzo[1,2‐c:5,6‐d']diisothiazole and 3‐methylbenzo[1,2‐c:6,5‐d']diisothiazole, have been made by reaction of appropriate aminomethyl‐1,2‐benzisothiazoles with N‐sulfinylmeth‐anesulfonamide.
Synthesis of a proposed isomer of F420 having α‐glutamyl bonding
Authors: Kimachi Tetsutaro , Tanaka Kiyoshi , Yoneda Fumio
Published: March 2009

A proposed isomer of redox coenzyme F420, having αglutamyl bonding, has been synthesized from 8‐benzyloxy‐10‐D‐ribityl‐5‐deazaflavin and α‐L‐glutamyl‐L‐glutamic acid moiety, by the phosphite triester approach followed by deprotection procedures.
Regio‐ and stereochemistry of the photo‐ring contraction of 4‐pyrones
Authors: Pavlik James W. , Kirincich Steven J. , Pires Richard M.
Published: March 2009

Irradiation of 2‐ethyl‐3‐methyl‐4‐pyrone 3 in aqueous solution led to the formation of trans‐4‐ethyl‐5‐methy‐4,5‐dihydroxycyclopent‐2‐enone 4 and trans‐2‐methyl‐3‐ethyl‐4,5‐dihydroxycyclopent‐2‐enone 5. In the latter case 1H nmr analysis confirmed the trans‐configuration at C4 and C5. These results are consistent with trapping of a photochemically generated oxabicyclohexenyl zwitterion by nucleophilic attack of both sides of the oxyally system along a path anti to the epoxide ring.
A novel synthesis of 2‐arylaminothiazolo[4,5‐d]pyridazinones
Authors: Yamasaki Tetsuo , Kawaminami Eiji , Uchimura Fumi , Okawara Tadashi , Furukawa Mitsuru
Published: March 2009

The reaction of 5(4)‐amino‐4(5)‐chloropyridazin‐3(2H)‐ones 1 (9) with methyl dithiocarbamates 2 gave 2‐arylaminothiazolo[4,5‐d]pyridazinones 3 (10). Treatment of 5(4)‐alkylamino‐4(5)‐chloropyridazin‐3(2H)‐ones 5 (12) with 2 afforded the corresponding 2‐aryliminothiazolo[4,5‐d]pyridazinones 6 (13). Cyclization of 1a with phenylisothiocyanate produced 2‐amino‐ and 2‐iminothiazolo[4,5‐d]pyridazinones 3a and 16.
Diels‐alder reactions of methyl‐ and π‐acceptor‐substituted 2‐vinylindoles with dimethyl acetylenedicarboxylate and tetracyanoethylene: Novel functionalized carbazoles
Authors: Pindur Ulf , Eitel Manfred
Published: March 2009

The Diels‐Alder reactions of the 2‐vinylindoles 1a‐1d, which are now readily accessible, with dimethyl acetylenedicarboxylate and tetracyanoethylene give rise to the novel 1,2‐dihydro‐ and 1,2,3,4‐tetrahydrocarbazoles 2, 4, and 5 as well as the fully aromatized carbazoles 3. With regard to the product spectrum, the mechanistic rationale comprises a Diels‐Alder step, formal 1,3‐hydrogen shift, ene reaction, and dehydrogenation. Conformational aspects of the 1,2‐dihydrocarbazoles 2b and 2c are also discussed.
Synthesis of 10‐thia‐5‐deazafolic acid and 2‐desamino‐2‐oxo‐10‐thia‐5‐deazafolic acid
Authors: Singh Shyam K. , Hynes John B.
Published: March 2009

The folate analogue, 10‐thia‐5‐deazafolic acid, was obtained via a multistep synthetic sequence beginning with the known intermediate, 2,4‐diaminopyrido[2,3‐d]pyrirnidine‐6‐carboxaldehyde. Reduction of this aldehyde with sodium borohydride gave 2,4‐diamino‐6‐(hydroxymethyl)pyrido[2,3‐d]pyrimidine, which when heated in base gave 2‐amino‐3,4‐dihydro‐6‐(hydroxymethyl)‐4‐oxopyrido[2,3‐d]pyrimidine. Treatment of the latter compound with phosphorus tribromide in tetrahydrofuran afforded 2‐amino‐6‐(bromomethyl)‐3,4‐dihydro‐4‐oxopyrido[2,3‐d]pyrimidine, thus constituting the first successful synthesis of this elusive intermediate. The aforementioned bromomethyl compound reacted smoothly with the sodium salt of ethyl 4‐mercaptobenzoate, and the resulting ester was saponified to give 10‐thia‐5‐deazapteroic acid. Conventional peptide bond coupling to di‐tert‐butyl L‐glutamate followed by treatment with trifluoroacetic acid afforded the target compound in respectable yield. Attempts to prepare its 5,6,7,8‐tetrahydro derivative by catalytic hydrogenation were unsuccessful.
Synthesis of 4‐phenyl‐2h‐benzopyrans
Authors: Jurd Leonard
Published: March 2009

Sesamol and other phenols react with equimolar quantities of cinnamaldehyde and morpholine in methanol to yield epimeric 2‐morpholinyl‐4‐phenylbenzopyran derivatives, which are useful intermediates for the synthesis of alcoholic neoflavanoid (4‐phenylbenzopyran) compounds.
Benzimidazole condensed ring systems. 7. An entry to substituted 1h,6h‐2,6a,10b‐triazafluoranthene‐1,3,6‐(2h)‐triones and related systems as possible chemotherapeutic agents
Authors: Badawey El‐Sayed A. M. , Kappe Thomas
Published: March 2009

The syntheses of some derivatives of three new benzimidazole condensed ring systems; namely, 1H,6H‐2,6a,10b‐triazafluoranthene‐1,3,6(2H)‐trione (3), 1H,8H,11H‐12‐oxa‐2,3a,7b‐triazabenz[e]acephenanthrylene‐1,3,8,11(2H)‐tetrone (4) and 1H,4H‐2,5,6a,10b‐tetrazafluoranthene‐1,3,4,6(2H,5H)‐tetrone (10) are described. Two compounds exhibited in vitro antibacterial activity. Four compounds were screened for in vitro anti‐HIV activity and three compounds were evaluated for antileukemic potency but were inactive.
An unusual labilization of a 4‐(trifluoromethyl)thiazole
Authors: South Michael S.
Published: March 2009

N‐Chloro‐4‐(trifluoromethyl)‐5‐thiazolyl‐N',N'‐diethylurea 5 has been found to undergo a facile labilization of the trifluoromethyl group under mild conditions. The reaction relies on the assistance of the nitrogen substitution at the 4‐position of the thiazole ring. Treatment of 5 with triethylamine and either methanol or methanethiol replaced the trifluoromethyl group with a methyl ester or a trimethylorthothio ester respectively at room temperature. Combination of 5 with diethylamine led to an unusual thiazolidine with two exocyclic double bonds, 8.
α‐Hydroxyacylation of pyridine
Authors: Sliwa Henri , Randria‐Raharimanana Clarisse , Cordonnier Guy
Published: March 2009

Efficient synthesis of 2‐α‐hydroxyacylpyridines 10 starting from pyridine N‐oxide and 2‐bromoaldehydes via base‐induced rearrangement of the resulting N‐alkoxypyridinium salts 6 is described.
“Azaphilic addition” of methyl lithium to 3,6‐bisalkylthio‐1,2,4,5‐tetrazines: A remarkable dichotomy
Authors: Wilkes Marty C.
Published: March 2009

A new type of “azaphilic addition” reaction of methyl lithium to 3,6‐bisalkylthio‐1,2,4,5‐tetrazines has been discovered. Methyl lithium adds at the tetrazine nitrogen of 1 affording 4 while nitrogen nucleophiles displace tetrazine alkylthio groups at carbon affording 3. The structures of the N‐alkyl products were determined by 1H‐ and 13C‐nmr and uv experiments. Reversing the order of methyl lithium addition caused the formation of a bicyclic tetrazine 6. Grignard reagents add in the same fashion as methyl lithium.
Protonation studies on the oximes of some 7‐acetyl‐1,2‐benzisothiazoles
Authors: Mckinnon David M. , Abouzeid Azza A.
Published: March 2009

Three 7‐acetyl‐1,2‐benzisothiazoles have been made by cyclisation of the monooximes of 2‐methylthio‐1,3‐diacetylbenzenes. The oximes of these ketones dissolved in acidic media give only protonated forms, and no indication of the formation of stable bridged sulfonium ions.
Carbamoylation of B6 vitamins
Authors: Ponticelli Fabio , Marinello Enrico , Pagani Roberto , Terzuoli Lucia
Published: March 2009

The reaction of B6 vitamins 1–3 with cyanate, in the presence of equivalent amounts of hydrochloric acid, yields different adducts according to the structure of the starting material. Regiospecific attack on the amino group or the phenolic hydroxy group was found for 2a,b and 3a,b, respectively. From the aldehydes 1a,b, the 2H‐pyrido[3,4‐e]‐1,3‐oxazin‐2‐ones 7a,b were obtained through an attack on both the phenolic and aldehyde group.
The synthesis of substituted [1]benzothieno[2,3‐c]quinolines and their N‐methyl quaternary salts
Authors: Luo Jiann‐Kuan , Musmar M. J. , Castle Raymond N.
Published: March 2009

Four substituted [1]benzothieno[2,3‐c]quinolines 14a‐14d were prepared by photocyclization of the appropriate carboxamides 8a‐8d to the corresponding [1]benzothieno[2,3‐c]quinolin‐6(5H)‐ones 12a‐12d followed by chlorination to 6‐chloro[1]benzothieno[2,3‐c]quinolines 13a‐13d and dechlorination resulting in the title compounds. Treatment of 14a‐14d with iodomethane furnished the corresponding N‐methyl quaternary salts 5a‐5d.
Aziridination of the uracil 5,6‐olefinic bond of 3‐N‐3′,5′‐Di‐O‐tribenzoyl‐5‐vinyl‐2′‐deoxyuridine
Authors: Kumar Rakesh , Wiebe Leonard I. , Knaus Edward E. , Nakashima Thomas T.
Published: March 2009

Oxidation of N‐aminophthalimide with lead tetra‐acetate at ‐50° gives N‐acetoxyaminophthalimide (3) which selectively aziridinates the 5,6‐double bond present in 3‐N‐3′,5′‐di‐O‐tribenzoyl‐5‐vinyl‐2′‐deoxyuridine (1a) to yield 2‐[1′‐(2′‐deoxy‐β‐D‐ribofuranosyl)]‐7‐(1‐phthalimido)‐4‐N‐3′,5′‐di‐O‐tribenzoyl‐6‐vinyl‐2,4,7‐triazabicyclo[4.1.0]heptan‐3,5‐dione (5).
Formation of a 1,4,2,3‐dithiadiazine via dimerization of a transient thione‐S‐imide (thiocarbonyl imine dipole)
Authors: Potts Kevin T. , Baum Jonathan S.
Published: March 2009

N‐(p‐Tolyl)trichloromethane sulfenamide when treated with potassium hydroxide in an ether‐alcohol mixture resulted in the formation in solution of a red, transient thione‐S‐imide which underwent a head‐to‐head dimerization to 2,3‐di(p‐tolyl)‐5,5,6,6‐tetrachloro‐1,4,2,3‐dithiadiazine whose structure was established by a single crystal X‐ray determination. A variety of sulfenamides derived from aryl‐substituted primary aromatic amines and alcoholic potassium hydroxide undergo this reaction with the formation of analogous structures. This thiocarbonyl imine dipole could not be trapped with alkenic or alkynic dipolarophiles.
Synthesis of 4,8‐disubstituted 4H,8H‐bis[1,2,5]oxadiazolo[3,4–6:3′,4′‐e]pyrazines
Authors: Fischer John W. , Nissan Robin A. , Lowe‐Ma Charlotte K.
Published: March 2009

The dilithio anion of 3,4‐N,N′‐disubstituted diamino[1,2,5]oxadiazole (4a R = benzyl, 4b R = p‐methoxybenzyl, 4c R = isopropyl) and cyanogen oxide gave 4,7‐disubstituted 5,6‐dioximino[1,2,5]oxadiazolo[3,4‐b]‐pyrazines 5a,b,c. Ring closure to the title compound 1 was accomplished upon heating 5 with sodium hydroxide in ethylene glycol at 150°.
Transformations of 2,2,6‐trimethyl‐1,3‐dioxen‐4‐one with heterocyclic amines and other amino compounds
Authors: Zupet Rok , Tišler Miha , Golič Ljubo
Published: March 2009

Heterocyclic amines were acetoacetylated with 2,2,6‐trimethyl‐1,3‐dioxen‐4‐one and the obtained compounds reacted on the reactive methylene group to give C‐substituted products. Nitrosation, followed by reduction afforded a pyrazine derivative. Azido‐ or chloroacetamide were also acetoacetylated, with heterocyclic amines, the corresponding enamines were prepared and reduction of the azido group of 15 afforded compounds 22 and/or amides of substituted 3‐oxobutanoic acid 23. An X‐ray structural determination of compound 23a revealed that the orientation about the double bond is Z.
Alkylation of N‐boc‐1,2,3,4‐tetrahydroisoquinolines in the 1‐position and its application to the synthesis of isoquinoline alkaloids
Authors: Coppola Gary M.
Published: March 2009

Boc‐protected 1,2,3,4‐tetrahydroisoquinolines 2 can be lithiated with t‐butyllithium in the presence of N,N,N',N',‐tetramethylethylenediamine. Reaction of the anion with alkyl halides provides 1‐alkyl N‐Boc‐1,2,3,4‐tetrahydroisoquinolines in 67–71% yield. The protecting group is easily removed in high yield with trifluoroacetic acid. The alkaloids salsolidine (8) and laudanosine (11) were synthesized in racemic form using this method.
Reissert compound studies. LXIV. Reissert compound and other products from an isolated N‐benzoylisoquinolinium triflate salt
Authors: Duarte F. F. , Popp F. D.
Published: March 2009

In the presence of trimethylsilyl trifluoromethanesulfonate, a methylene chloride solution of isoquinoline and benzoyl chloride gave N‐benzoylisoquinolinium triflate (3) and N‐H‐isoquinolinium triflate (4). Depending on the reaction conditions, reaction of 3 may occur on the isoquinoline ring yielding a Reissert compound and 1,2‐dihydroisoquinoline species. Otherwise, reactions transpire on the carbonyl of 3 to give an amide, an ester, and an anhydride.
The synthesis and biological activity of new 7‐[2‐(cyanomethyl)piperazinyl]‐ and 7‐[3‐(cyanomethyl)piperazinyl]quinolone antibacterials
Authors: Gubert S. , Braojos C. , Anglada L. , Bolós J. , Palacin C.
Published: March 2009

Some novel 7‐[2‐ or 3‐(cyanomethyl)piperazinyl]quinolones have been prepared. Most notable, 2‐cyanomethyl‐piperazine 5 and 1‐methyl‐2‐cyanomethylpiperazine 8 at the quinolone C‐7 position produce products with good in vitro antibacterial activity. The key step in the synthesis of these products involves the regioselective deprotection of the benzyl group in function of the time reaction.
Multiple reactivity of freund's “methyl isothiocyanate sulfide” in cycloaddition‐elimination reactions
Authors: L'Abbé Gerrit , Sannen Ingrid , Vandendriessche Ann
Published: March 2009

4‐Methyl‐5‐methylimino‐1,2,4‐dithiazolidine‐3‐thione (l)and 2,4‐dimethyl‐1,2,4‐thiadiazolidine‐3,5‐dithione (2) are interconvertible in acetone at 50°. They react with ketenes and electrophilic acetylenes to give the thiazole derivatives 6 and 7 after elimination of methyl isothiocyanate or carbon disulfide. Electrophilic isothiocyanates and phenylsulfonyl isocyanate transform the C = S function of 1 in an imine function (8), and a similar transformation of the thiourea C = S function of 2 is observed on reaction with phenylsulfonyl isocyanate, giving 9.
Substituted 1,4‐diazepino[5,6,7‐kl]acridines as unexpected side products in reaction of 2‐(dialkylamino)ethylamine with 1‐chloro‐7‐methyoxy‐4‐nitro‐9‐phenoxyacridine
Authors: Cholody Wieslaw M. , Martelli Sante , Gariboldi Pierluigi V.
Published: March 2009

Substituted 1,4‐diazepino[5,6,7‐kl]acridines were obtained in reaction of 2‐(dialkylamino)ethylamine with 1‐chloro‐7‐methoxy‐4‐nitro‐9‐phenoxyacridine. The mechanism of their formation was studied. The correct structure of these compounds was established on the basis of their 1H nmr studies.
N‐1 and C‐2 substituted tryptophans as potential inhibitors of sickle cell hemoglobin gelation
Authors: Prasitpan Noojaree , Patel Jayeshkumar N. , De Croos Philomen Z. , Stockwell Brenda L. , Manavalan Parthasarathy , Kar Leela , Johnson Michael E. , Currie Bruce L.
Published: March 2009

A series of N‐1 or C‐2 phenylalkyl substituted tryptophans and C‐1 phenylalkyl substituted 3,4‐dihydro‐β‐carbolines were prepared from the apropriate aniline, 1b or 1e, or tryptophan, 8 or 11, by ring closure methods. None of the compounds prepared were more potent than 5‐bromotryptophan (11) as inhibitors of sickle cell hemoglobin gelation.
Novel transformations of two kinds of chlorinated photo [2 + 2] cycloadducts of 2‐pyrone‐5‐carboxylate
Authors: Shimo Tetsuro , Date Kenichi , Somekawa Kenichi
Published: March 2009

Novel reactions of 7,7‐dichloro‐ and 7,7,8‐trichloro‐3‐oxo‐2‐oxabicyclo[4.2.0]oct‐4‐ene‐6‐carboxylates 5 with 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) in alcohol gave pyrano[4,3‐b]pyran‐2,5‐diones 8 via (Z)‐(2H‐pyran‐2‐on‐3‐yl)butenoates 7. On the other hand, the same treatment of 7,7,8‐trichloro‐2‐oxo‐3‐oxabicyclo‐[4.2.0]oct‐4‐ene‐5‐carboxylate 6b afforded 2‐oxo‐3‐oxabicyclo[4.2.0]oct‐4,7‐diene‐5‐carboxylate 14 via cyclobutene formation and SN2′ displacement by attack of the alkoxy anion.
The molecular structure of 2‐methylbenzotriazole (2MeBzTr) in connection with the x‐ray structure of 2MeBzTr.HBF4.H2O
Authors: Angeles Monge María , Gutiérrez Puebla Enrique , Ramos Gallego María Del Mar , Pardo Carmen , Elguero José
Published: March 2009

The fluoroborate of 1H‐2‐methylbenzotriazolium monohydrate crystallizes in the Pbca space group [Z = 8, a = 16.734(3), b = 19.153(9), c = 6.937(1) Å], The hydrogen bond network between the three molecules, 2MeBzTr, HBF4 and H2O, corresponds to a situation intermediate between the fluoroborate of a protonated benzotriazole (BF4−.2MeBzTrH+) and a neutral benzotriazole hydrogen‐bonded to fluoroboric acid (HBF4,2MeBzTr). The behaviour of the title compound in solution is also intermediate between these two extreme situations. Thus, the present compound is one of the rare examples of a proton solvated only by very weak hydrogen bond acceptors.
Synthesis of 3‐(6‐alkylaminopurin‐9‐yl)‐2,3‐dideoxy‐D‐thero‐pentopyranoses and their reduction to 3‐(6‐alkylaminopurin‐9‐yl)‐2,3‐dideoxy‐D‐thero‐pentitols
Authors: Hjuler‐Nielsen Hans Peter , Pedersen Hans , Hansen Henning Bue , Pedersen Erik B. , Nielsen Claus
Published: March 2009

3‐(6‐Alkylaminopurin‐9‐yl)‐2,3‐dideoxy‐D‐threo‐pentopyranoses 3 were prepared by condensation of unprotected 2‐deoxy‐D‐ribose (2) with N6‐alkyladenines 1 in a phosphorus pentoxide reagent mixture. Reduction of the pentoses 3 gave the corresponding 3‐(6‐alkylaminopurin‐9‐yl)‐2,3‐dideoxy‐D‐threo‐pentitols 4. The structures of 3 and 4 were determined by 13C nmr, 1H nmr and 2D 1H nmr (COSY).
Synthesis of 6R(β)‐tritylaminopenicillanic‐3R(β)‐alcohol, a versatile stereoisomer of natural β‐lactams
Authors: De Meester F. , Frère J. M. , Piette J. L. , Jacquemin P. , Grooters L. , Llabres G. , Defays S.
Published: March 2009

In an attempt to rationalize a synthesis of penicillin analogs modified at C(3), we have isolated the 3R(β)‐carbinolamide derivative 4a. The trityl substituent on N(6′) seems to be responsible for the inversion of configuration which occurs at C(3) during the acid hydrolysis of the isocyanate intermediate. An hydrogen bond is formed on the β‐face of the bell‐shaped bicyclic skeleton between the N(6′)‐nitrogen lone pair and the C(3) hydroxyl group. On standing, the carbinolamide analog slowly isomerizes to its expanded bicyclic isomer 4b, but the starting material may be easily recovered by treatment with acid. The postulated intermediate during isomerization, i.e., the open aldehyde form, does not accumulate. Substitutions of the hydroxyl group at C(3) lead to a variety of compounds with the biologically active 3S(α) configuration. These may be used to study the importance of the carboxyl group of penicillins in their interaction with β‐lactamases at the molecular level.
Nitrogen bridgehead compounds. Part 83. Synthesis and ring transformation of 6‐methyl‐4‐oxo‐4H‐pyrido[1,2‐a]pyrimidine‐3‐acrylates
Authors: Hermecz István , Horváth Agnes
Published: March 2009

The thermal ring transformation of 2‐substituted 4‐oxo‐4H‐pyrido[1,2‐a]pyrimidine‐3‐acrylates gave 2‐substituted 1,8‐naphthyridine‐3‐acrylates, pyrano‐1,8‐naphthyridines and anthyridine, depending upon the nature of the 2‐substituent. A longer reaction period and a higher reaction temperature favored the formation of tricyclic products from 1,8‐naphthyridine‐3‐acrylate after isomerization of the side‐chain at position 3. The products were characterized by means of uv, ir and 1H nmr spectroscopy.
On the synthesis of 3,4‐dihydro‐2H‐1,2‐benzothiazine 1,1‐dioxides
Authors: Camoutsis Charalambos , Catsoulacos Panayotis
Published: March 2009

The 3,4‐dihydro‐2H‐1,2‐benzothiazine 1,1‐dioxides were prepared by reduction of the corresponding 1,2‐benzothiazin‐2‐ones with diborane. The latter were obtained by the action of primary amines on 4,5‐dimethoxy‐2‐carbomethoxymethylbenzenesulfonyl chloride followed by basic hydrolysis and cyclization of the formed 4,5‐dimethoxy‐2‐carbomethoxymethylbenezenesulfonamides.
Photochemistry of azole N‐oxides. Facile photoisomerisation of 2H‐imidazole N‐oxides to 1,3‐diaza‐6‐oxabicyclo[3.1.0]hex‐3‐enes and synthesis of a 1,3‐diaza‐4,7‐dioxatricyclo[4.1.0.1,603,5]heptane
Authors: Gainsford Graeme J. , Woolhouse Anthony D.
Published: March 2009

Ultraviolet irradiation of a series of 2H‐imidazole N‐oxides 2 has been shown to effect a clean isomerisation to derivatives of the new ring system, 1,3‐diaza‐6‐oxabicyclo[3.1.0]hex‐3‐ene, 7. Epoxidation of a representative 7 has given access to the hitherto inaccessible trans‐fused 1,3‐diaza‐4,7‐dioxatricyclo[4.1.0. 1,603,5]‐heptane ring system 9.
Diels‐alder reactions of 2‐pyrones with acyclic dienophiles and hydrolyses of the mono‐adducts
Authors: Shimo Tetsuro , Kataoka Katsuyuki , Maeda Ayumi , Somekawa Kenichi
Published: March 2009

Diels‐Alder reactions of 2‐pyrone (1) with fumaronitrile and maleonitrile afforded regio‐ and stereo‐specific mono‐adducts 3a and 3b, respectively. The reaction of 1 with acrylonitrile gave a bis‐adduct. The reaction of 4,6‐dimethyl‐2‐pyrone (7) with dimethyl fumarate and dimethyl maleate at higher temperature gave benzene derivatives. The low reactivity of 7 and the instability of the mono‐adducts with 7 were considered from the existence of back reaction and easy elimination of methyl formate, respectively. Hydrolyses of the mono‐adducts of 2‐pyrones gave polyfunctionalized cyclohexenes and elimination products generated from the preferencial trans‐elimination of the leaving groups.
Preparation of bis(heteroaryl)iodonium salts via an iodonium transfer reaction between di(cyano)iodonium triflate and organostannes
Authors: Stang Peter J. , Tykwinski Rik , Zhdankin Viktor V.
Published: March 2009

Di(cyano)iodonium triflate 5 generated in situ from iodosyl triflate (0 = I‐OTf) and cyanotrimethylsilane is a preferred reagent for the preparation of various bis(heteroaryl)iodonium triflate salts 11–15 via an iodonium transfer reaction with the corresponding tributyltin substituted heterocycles 6–10. Novel heteroaromatic iodonium salts 3, 11–15 were isolated in good yields as relatively stable microcrystalline solids and characterized by multinuclear nmr, ir and hrms data.
Study of the reactivity of ketone enolates with 3‐halo‐2‐amino derivatives of benzo[b]thiophene under photostimulated sRN1 reaction conditions
Authors: Beltran Lluís , Gálvez Carmen , Prats Montserrat , Salgado Juan
Published: March 2009

Reactivity of the 3‐halo‐2‐amino derivatives of benzo[6]thiophene 1a‐c and 2 with several ketone enolates 3–5 have been studied under photostimulated SRN1 reaction conditions. The normal substitution product 6 only was obtained in low yields using potassioacetophenone 3 as the enolate ion and 2‐(tert‐butoxycarbonylamino)‐3‐chlorobenzo[b]thiophene (1a) and 2‐(tert‐butoxycarbonylamino)‐3‐iodobenzo[b]thiophene (1c) as substrates. In all reactions the main product was the corresponding dehalogenated substrate 7a‐b, thus indicating that reduction of the substrate strongly competes with the desired substitution reaction.
Preparation of 6‐(nitron‐c‐yl)‐ and 6‐(1,3‐butadienyl)‐2‐pyrones and their cycloaddition reactions
Authors: Shimo Tetsuro , Somekawa Kenichi , Tsuge Otohiko
Published: March 2009

6‐(N‐Substituted nitron‐C‐yl)‐2‐pyrones 1 and 6‐(4‐substituted 1,3‐butadienyl)‐2‐pyrone 2 were prepared and their cycloaddition reactions with three kinds of diene systems were investigated. Namely, the reactions of 1 with methyl acrylate, vinyl crotonate and divinylsulfone took place at the nitrone moiety to afford 3‐substituted isoxazolidines 9–14, and that of 2 with maleimide took place at the 2‐pyrone moiety to give a bis‐adduct 17 via elimination of carbon dioxide.
A facile synthesis of 3‐substituted indoles
Authors: Nagarathnam Dhanapalan
Published: March 2009

1‐Benzoyl‐3‐bromomethylindole (2a) or 1‐benzenesulfonyl‐3‐bromomethylindole (2b) reacts with C, N, O, and P‐containing nucleophiles to give potential intermediates for the synthesis of a wide range of indole alkaloids and pharmacologically important substances, in good to excellent yields.