bluuebunny/crossref_metadata_2025 huggingface dataset:
Derivatives of 3,4‐dihydro‐2H‐benzo[b][1,4]dioxepin. Preparation of 7,8‐dihydro‐6H‐[1,4]dioxepino[2,3‐f]‐2,1,3‐benzoxadiazole 1‐oxide
Authors: Hadjimihalakis Phaedon M.
Published: March 2009

A novel annelated benzofuroxan 4 and a benzofurazan 4a have been prepared in good yields. Nitration of 5 afforded both trinitro derivatives 6 and 7. Low temperature nmr spectroscopy was applied on compound 4 and the value ΔG* is reported.
Ring transformations by ring‐chain‐transfer. V. Synthesis of amino‐, hydroxy‐ and mercaptoalkylpyrazoles by reaction of 3‐functionalized acrylonitriles with hydrazine hydrate
Authors: Paätzel Michael , Liebscher Jürgen
Published: March 2009

3‐Alkylamino, 3‐alkoxy or 3‐alkylthioacrylonitriles whose leaving group is incorporated in a saturated heterocyclic ring are 1,3‐bifunctional electrophiles. They react with hydrazine hydrate at the cyano group by addition as well as at position 3 by opening the saturated ring. By this ring transformation new 5‐aminopyrazoles are formed which are additionally substituted by an ω‐functionalized alkyl chain in position 3.
Transformations on 2,3,4,5‐tetrahydrobenzo[b][1,4]‐dioxocin leading to substituted ortho‐nitroaryl azides, benzofuroxans, benzofurazans and related compounds
Authors: Takakis Ioannis M. , Hadjimihalakis Phaedon M.
Published: March 2009

Nitration of the acetamido‐nitrobenzodioxocins 10, prepared from the corresponding amino derivatives 9, led to the acetamido‐dinitrobenzodioxocins 11, hydrolysis of which furnished the corresponding amines 13. Preparation of the dinitroazides 18 and acetamido‐nitroazides 21 as precursors to substituted dioxocino‐annelated benzofuroxans is described. Thermolysis of the dinitro‐azido derivatives 18a,c,e and/or direct nitration of the unsubstituted benzofuroxans 1a, 2a afforded the isomeric nitrobenzofuroxans 1b, 2b,c. Thermolysis of the acetamido‐nitroazides 21 gave the acetamidobenzofuroxans 1d, 2d,e. All benzofuroxans were deoxygenated to the corresponding benzofurazans 3b,d, 4b‐e. Some aspects of electrophilic and nucleophilic aromatic substitution are discussed.
Synthesis of benzo‐13‐crown‐4 derivatives
Authors: Czech Bronislaw P. , Zazulak Wolodymyr , Kumar Anand , Dalley N. Kent , Weiming Jiang , Bartsch Richard A.
Published: March 2009

A series of nine, new benzo‐13‐crown‐4 compounds which bear one or two substituents on the three‐carbon bridge has been prepared in good yields by cesium fluoride‐assisted cyclization reactions of catechol with ditosylates of the appropriate glycols. The solid state structure of 9,9‐dibenzyl‐2,3‐benzo‐13‐crown‐4 is determined and compared with the reported structure for the unsubstituted crown ether.
Nitrogen bridgehead compounds. Part 80 unusual reaction of ethyl 9‐bromo‐4‐oxo‐6,7,8,9‐tetr ahydro‐4h‐pyrido[1,2‐a]pyrimidine‐3‐carboxylates and N‐Methylaniline
Authors: Hermecz István , Breining Tibor , Simon Kálmán , Erös‐Takácsy Tünde , Podányi Benjamin , Sessi John
Published: March 2009

The acid‐catalysed intramolecular nucleophilic addition of the phenyl ring to the C(9a) = N(1) double bond of ethyl 9‐(N‐methyl‐N‐phenyl)‐4‐oxotetrahydro‐4H‐pyrido[1,2‐a]pyrimidine‐3‐carboxylates, formed in the reactions of ethyl 9‐bromo‐4‐oxo‐6,7,8,9‐tetrahydro‐4H‐pyrido[1,2‐a]pyrimidine‐3‐carboxylates and N‐methylaniline, gave the first examples of a new tetracyclic pyrimido[1′,2′:1,2]pyrido[3,2‐b]indole ring system (7). X‐ray diffraction analysis of 7a revealed that the annelation of the pyrimidine and piperidine rings is transoid, while that of the piperidine and pyrroline rings is cis, the piperidine ring adopts an unusual 6T8 twisted boat conformation, while the pyrroline ring has a 9T8a conformation.
Reaction of 2,3‐dichloro‐1,4‐naphthoquinone with dithiooxamide. Synthesis of dibenzo[b,i]thianthrene‐5,7,12,14‐tetrone
Authors: Matsuoka Masaru , Iwamoto Akihiro , Kitao Teijiro
Published: March 2009

The reaction of 2,3‐dihalogeno‐1,4‐naphthoquinone with dithiooxamide gave dibenzo[b,i]thianthrene‐5,7,12,14‐tetrone in high yield but not 2,2′‐bis(naphtho[2,3‐d]thiazole‐4,9‐dione) which was previously reported. A similar reaction of 3,4‐dichloro‐N‐phenylmaleimide with dithiooxamide also gave the corresponding sulfur heterocycles but not the reported bisthiazole.
A facile and practical preparation of 5,7‐dihydroxy‐3‐(4‐nitrophenyl)‐4H‐1‐benzopyran‐4‐one
Authors: Liu D. F. , Cheng C. C.
Published: March 2009

In spite of the fact that several preparative methods for the synthesis of hydroxylated isoflavones were reported during the past fifty years, none is suitable for the preparation of isoflavones containing 5,7‐dihydroxyl functions. This paper reports a simple, large scale preparation of 5,7‐dihydroxy‐3‐(4‐nitrophenyl)‐4H‐1‐benzopyran‐4‐one (2a) by the condensation of the readily available 4‐nitrobenzyl 2,4,6‐trihydroxyphenyl ketone (1a) and acetic‐formic anhydride in high yields. Similar isoflavones, such as 7‐hydroxy‐3‐(4‐nitrophenyl)‐4H‐1‐benzopyran‐4‐one (2b) can also be obtained in good yields in analogous manner.
Synthesis of 5‐(aroylamino)‐2‐methyl‐2H,‐1,2,4‐thiadiazol‐3‐ones by oxidative cyclization of 1‐aroyl‐5‐methyl‐2‐thiobiurets
Authors: Cho Nam Sook , Shon Hyun Il , Párkányi Cyril
Published: March 2009

5‐Aroylamino‐2‐methyl‐2H‐1,2,4‐thiadiazol‐3‐ones 3 have been synthesized by oxidative cyclization of 1‐aroyl‐5‐methyl‐2‐thiobiurets 2 with hydrogen peroxide in an alkaline solution. The needed 1‐aroyl‐5‐methyl‐2‐thiobiurets 2 have been obtained through the addition of methylurea to the corresponding aroyl isothiocyanates.
Synthesis and properties of a bilirubin analog with propionic acid groups replaced by carboxyl
Authors: Byun Young‐Seok , Lightner David A.
Published: March 2009

The unnatural bile pigment analog of bilirubin‐IXα, 2,3,7,13,17,18‐hexamethyl‐(10H,21H,23H,24H)‐bilin‐1,19‐dione‐8,12‐dicarboxylic acid (1), was synthesized as its diethyl ester by coupling 4,4′‐dimethyl‐3,3′‐dicarboethoxydipyrrylmethane‐5,5′‐dialdehyde with 3,4‐dimethylpyrrolin‐2‐one.
Synthesis of 2,4‐diamino‐5,10‐dideaza nonclassical antifolates
Authors: Gangjee Aleem , Devraj Rajesh , Lin Fu‐Tyan
Published: March 2009

Condensation of 2,4,6‐triaminopyrimidine (8) with bromomalonaldehyde (9) afforded, after pivaloylation, 2,4‐dipivaloyl‐6‐bromopyrido[2,3‐d]pyrimidine (11). This 6‐bromo derivative served as a key intermediate for the synthesis of 2,4‐diamino‐6‐[2‐(3′,4′‐dimethoxyphenyl)ethenyl]pyrido[2,3‐d]pyrimidine (5) via a palladium catalyzed carbon‐carbon coupling with 3,4‐dimethoxystyrene (12). Compound 5, its 9,10‐dihydro analogue 6 and the 5,6,7,8,9,10‐hexahydro analogue 7 were of interest as potential inhibitors of dihydrofolate reductase. Compounds 6 and 7 were synthesized from 5 by catalytic hydrogenation over 5% Pd‐C.
Thermolysis of hexasubstituted‐4,5‐dihydro‐3H‐pyrazoles: Synthesis of 1‐alkoxy‐ and 1‐acetoxy‐1,2,2,3,3‐pentasubstituted‐cyclopropanes
Authors: Kennedy G. Davon , Baumstark Alfons L. , Dotrong M. , Thomas Treye , Narayanan N.
Published: March 2009

A series of 5‐alkoxy‐ and 5‐acetoxy‐4,4‐dimethyl‐3,3,5‐trisubstituted‐4,5‐dihydro‐3H‐pyrazoles 2a‐f (hexasubstituted pyrazolines) was synthesized by oxidation of the corresponding 3,4‐dihydro‐2H‐pyrazoles with lead tetraacetate in the appropriate solvents. The 5‐acetoxy compounds were produced when the oxidations were carried out in methylene chloride. Oxidation with lead tetraacetate in dry alcoholic solvents resulted in the formation of the 5‐alkoxy derivatives as the major products. Thermolysis of the hexasubstituted‐4,5‐dihydro‐3H‐pyrazoles 2a‐f in cyclohexane or as the melt at high temperature yielded the 1‐alkoxy‐ and 1‐acetoxy‐1,2,2,3,3‐pentasubstituted cyclopropanes 3a‐f in good yields. Trace amounts of alkene products were formed in several reactions. No products attributable to cycloreversion pathways were detected. The product distributions were consistent with extrusion of nitrogen gas from 2a‐f to yield the singlet 1,3‐diradical, closure of which resulted in cyclopropane formation with partial retention of stereochemistry.
4,5‐Dimethylimidazole: A correction and alternative synthesis
Authors: D'Sa Albinus , Cohen Louis A.
Published: March 2009

Fractional vacuum distillation of the product obtained from thermal condensation of acetoin with formamide is a formic acid complex of 4,5‐dimethylimidazole, and not the expected free base. The 1H and 13C nmr spectra suggest that the product may be closer to a 1:1 hydrogen‐bonded adduct than to a true salt. Commercial 4‐hydroxymethyl‐5‐methylimidazole is converted quantitatively to the 4‐chloromethyl derivative with thionyl chloride; hydrogenolysis of the latter compound provides 4,5‐dimethylimidazole in an overall 80–90% yield, doubling the yield obtained by the classical method.
Acridine derivatives. IV. Synthesis, molecular structure, and antitumor activity of the novel 9‐anilino‐2,3‐methylenedioxyacridines
Authors: Kimura Michio , Kato Akira , Okabayashi Ichizo
Published: March 2009

In the biological and physical investigation of a new class of deoxyribonucleic acid (DNA)‐intercalating antitumor agents, novel 9‐anilino‐2,3‐methylenedioxyacridines (twelve compounds) have been synthesized and evaluated for the activity against L1210 leukemia in vivo. A few of them possessed the same potency of the antitumor activity as 4′‐(9‐acridinylamino)methanesulfonyl‐m‐anisidine (amsacrine, m‐AMSA), which is an important antitumor agent in clinical use. The molecular structure of a typical one, 9a in this series have been determined by the X‐ray diffraction method using a single crystal. The results of this X‐ray investigation have shown that the new class of acridine derivatives have the methylenedioxy group fused at the 2‐ and 3‐positions of the acridine ring.
Cyclocondensation of 3‐amino‐2‐iminonaphtho[1,2‐d]‐thiazole with α‐ketocarboxylic acid derivatives: Synthesis of 2‐substituted 3‐Oxo‐3H‐naphtho[1′,2′:4,5]thiazolo‐[3,2‐b][1,2,4]triazines as potential anti‐HIV agents
Authors: Liu Kang‐Chien , Shih Bi‐Jane , Lee Chuen‐Hsiang
Published: March 2009

The cyclocondensation of 3‐amino‐2‐iminonaphtho[1,2‐d]thiazole (1) with a series of α‐keto mono‐ and dicarboxylic acid derivatives 5a‐i under different conditions was investigated. When the experiments were performed by refluxing in glacial acetic acid, the corresponding cyclized products, 2‐substituted 3‐oxo‐3H‐naphtho[1′,2′:4,5]thiazolo[3,2‐b][1,2,4]triazines 4 were obtained in fair to good yields. On the other hand, when the reaction was conducted in boiling ethanol, it gave only the open chain condensates 6, or in rare cases, together with minor amount of 4. Since the intermediates 6 exist as mixture of both E‐ and Z‐isomers, cyclization through heating was found insufficient. In any event representative compounds 4b,g,i have been evaluated for anti‐HIV activity, but none of them were active.
Comparative kinetic studies on the synthesis of quinoxalinone derivatives and pyrido[2,3‐b]pyrazinone derivatives by the hinsberg reaction
Authors: Bekerman Diana G. , Abasolo Maria Inés , Fernández Beatriz M.
Published: March 2009

Kinetic studies on the anelation of quinoxalinone derivatives 3a‐c and pyrido[2,3‐b]pyrazinone derivatives 5a‐c and 6a‐c synthesized by the Hinsberg reaction is reported. o‐Phenylenediamine or 2,3‐diaminopyridine were treated with bifunctional carbonyl compounds such as glyoxylic, pyruvic and benzoylformic acids under different experimental conditions. When pyridopyrazine derivatives were synthesized both position isomers were achieved applying regioselective reactions. Mixture were avoided by looking for special experimental conditions that led unambiguously to only one of the components of the classic “Hinsberg mixture”. Quinoxalinone derivatives 3a‐c were obtained at room temperature in good yields (>90%) using anhydrous methanol or ethanol as solvents. On the other hand, only pyrido[2,3‐b]pyrazin‐3(4H)‐one (5a) was regioselectively attained in aqueous buffer of pH 7 while 3‐methylpyridopyrazinone derivatives were regioselectively separated using anhydrous methanol for one isomer, 5b, and anhydrous chloroform for the other isomer, 6b, at room temperature. Yields were higher than 80%. Reactions with benzoylformic acid did not give good yields and only 2‐phenylpyrido[2,3‐b]pyrazin‐3(4H)‐one (5c) could be obtained using anhydrous chloroform (yield <30%) as the solvent. Steric hindrance exerted by the phenyl group of the benzoylformic acid is supposed to be responsible of our difficulties to obtain 2‐phenylpyrido[2,3‐b]pyrazin‐3(4H)‐one (5c) in good yields applying this technique. The other isomer, 3‐phenyl[2,3‐b]pyrazin‐2(1H)‐one (6c) was always formed together with the former isomer and could not be isolated from the mixture, when other solvents than chloroform were used as the reaction media.
Synthesis of new dibenzo nitrogen‐oxygen donor macrocycles containing two amide groups
Authors: Lindoy Leonard F. , Mahendran Sumathi , Krakowiak Krzysztof E. , An Haoyun , Bradshaw Jerald S.
Published: March 2009

Four new nitrogen‐oxygen, dibenzo macrocyclic ligands containing two amide groups have been prepared by combining a dibenzo‐containing diamidodialdehyde with an appropriate diamine followed by reduction of the intermediate bis Schiff‐base. The starting dibenzo‐containing diamidodialdehyde was prepared by treating 2 equivalents of salicylaldehyde with a bis(α‐chloroamide).
Synthesis of isomeric series of aryltetrahydrobenz‐isoxazoles and arylcyclopentisoxazoles
Authors: Fos Empar , Borràs Liset , Gasull Maria , Mauleón David , Carganico Germano
Published: March 2009

Four series of potential PAF‐antagonists in which the isoxazole nucleus is condensed with a polyhydrogenated five‐ or six‐carbon ring were prepared. The synthesis of the compounds 3‐aryl‐4,5,6,7‐tetrahydrobenz[c]isoxazoles 1, 3‐arylcyclopent[c]isoxazoles 2, 3‐aryl‐4,5,6,7‐tetrahydrobenz[d]isoxazoles 3, and 3‐arylcyclopent[d]isoxazoles 4, required an extensive optimization and comparison of the methods available in the literature.
One‐pot synthesis of novel spiro‐annelated pyrrole‐containing heterocyclic systems from suitable synthons
Authors: Artico M. , Massa S. , Mai A. , Silvestri R. , Stefancich G.
Published: March 2009

New tetracyclic systems containing a pyrrolobenzodiazepine 5 or a pyrrolobenzotriazepine 6 moiety bounded by a spiro linkage to the piperidine nucleus are described. They have been synthesized by a simple reaction involving the interaction between proper aromatic amines and 4‐oxopiperidines substituted or not at the 1‐position in the presence of maleic acid as a catalyst. The synthesis of spiropyrrolo[1,2‐a]quinoxaline‐2,4′‐piperidine 7 and its 1′‐acyl derivatives by the same procedure is also reported.
Short synthesis of tryptophane and β‐carboline derivatives by reaction of indoles with N‐(diphenylmethylene)‐α,β‐didehydroamino acid esters
Authors: Spadoni Gilberto , Balsamini Cesarino , Bedini Annalida , Duranti Ermanno , Tontini Andrea
Published: March 2009

The ethylaluminum dichloride catalyzed Michael‐type addition of indoles 1a‐h to the N‐(diphenylmethylene)‐α,β‐didehydroamino acid esters 2a‐c allows a new synthesis of β‐methyltryptophanes 41,m and a new route for 1,1‐diphenyl‐3‐carbalkoxy‐1,2,3,4‐tetrahydro‐β‐carbolines 5a‐m.
2‐Aryl‐substituted, benzo‐anellated 5‐membered heterocyclic compounds as potentially active substances for the cardiovascular system: 1,3‐Benzothiazolyl‐ and 1,3‐benzoxazolylbenzylphosphonates
Authors: Rose Ulrich
Published: March 2009

In the course of investigations on structure‐activity relationships of calcium antagonists analogous to fostedil, a series of 2‐aryl‐ and 2‐arylvinyl‐substituted 1,3‐henzothiazoles and 1,3‐benzoxazoles bearing a phosphonate group on the phenyl ring has been synthesized by cyclization, bromination, and subsequent Michaelis‐Arbuzow reaction. Pharmacological investigations on isolated organs from guinea pigs revealed both negative inotropic effects and a relaxing action on smooth musculature; these activities were particularly pronounced in the 1,3‐benzothiazole compound group.
Metalation of diazines. VI. Metalation of pivaloylaminopyrazine and N‐t‐butylpyrazinamide. Unusual regioselectivity in the metalation reaction
Authors: Turck A. , Plé N. , Trohay D. , Ndzi B. , Quéguiner G.
Published: March 2009

Metalation of pivalamidopyrazine and N‐t‐butylpyrazinamide were studied. For pivalamido pyrazine the yields were poor and some addition products were isolated. The metalation of t‐butylpyrazinamide was successful and a curious regioselectivity was highlighted.
A new synthesis of N‐substituted‐2‐alkyl(or aryl)quinazolin‐4‐amines by amide base‐mediated cyclization of carbox‐imidamides derived from 2‐(trifluoromethyl)benzenamine
Authors: Patterson Steven E. , Janda Lubomir , Strekowski Lucjan
Published: March 2009

A one‐pot preparation of carboximidamides (amidines) 11–14 involves treatment of amides 2–5 with phosphorus pentachloride followed by the treatment of the resultant crude imidoyl chlorides 7–10 with ammonia. Amidines 11–14 are cyclized to quinazolines 20–26 in lithium alkylamide‐or dialkylamide‐mediated reactions.
Thermolysis of 3‐methyl‐3‐(o‐aryl)‐1,2‐dioxetanes: Activation parameters and chemiexcitation yields
Authors: Baumstark Alfons L. , Parker Alesia N.
Published: March 2009

3‐Methyl‐3‐(o‐tolyl)‐1,2‐dioxetane 1 and 3‐methyl‐4‐(o‐bromophenyl)‐1,2‐dioxetane 2 were synthesized in low yield by the β‐bromo hydroperoxide method. The activation parameters were determined by the chemilumin‐escence method (for 1 ΔG‡ = 24.7 ± 0.3 kcal/mol, ΔH‡ = 25.4, ΔS‡ = + 1.9 e.u., k60 = 3.4 × 10−4s−1; for 2 ΔG‡ = 24.7 ± 0.4 kcal/mol, ΔH‡ = 24.7, ΔS‡ = 0.0 e.u., k60 = 4.1 × 10−4s−1). Thermolysis of 1–2 directly produced high yields of excited triplets as expected for this type of dioxetane [triplet chemiexcitation yields (ϕ7) for 1 0.03; for 2 0.02; the ϕT/ϕS ratios were estimated to be approximately 200 for both compounds]. The effect of ortho‐aryl substituents was inconsistent with electronic effects. The ortho substitution in 1–2 resulted in a marked increase in stability of the dioxetanes. The results are discussed in relation to a diradical‐like mechanism.
Properties and cage lactone synthesis of diels‐alder adducts from 2‐pyrones
Authors: Shimo Tetsuro , Nagahama Hideki , Yorozu Kiyotaka , Somekawa Kenichi
Published: March 2009

New cage lactones were synthesized by the photocyclization of the tricyclodienolactones 1a, 1b, 2 which were available from the Diels‐Alder reactions of 2‐pyrones with p‐benzoquinones or norbornadiene. Retro‐Diels‐Alder reactions of cross‐adducts between 2‐pyrone‐mono‐adducts and p‐benzoquinone were also described.
Heterocyclic intermediates for the synthesis of disperse and cationic dyes
Authors: Viscardi Guido , Savarino Piero , Barni Ermanno , Carpignano Rosarina , Montoneri Enzo , Quagliotto Pierluigi
Published: March 2009

Nitro derivatives and amines containing X‐azolo[4,5‐c]pyridine moieties were prepared choosing more favourable synthetic pathways. Their physical and spectroscopic data were discussed in correlation with those of previously studied systems. The heteroaromatic amines were shown to be suitable precursors for the synthesis of disperse dyes and of their cationic counterparts.
Synthesis of indoles via amidoselenation
Authors: Izumi Taeko , Sugano Miwa , Konno Touru
Published: March 2009

The reaction of 2‐styrylacetanilides (2) with N‐phenylselenosuccinimide affords 1‐N‐acetyl‐2‐phenyl‐3‐phenylselenoindoles (3) and 1‐N‐acetyl‐2‐phenylindoles (4). The reaction of 2‐vinylacetanilides (5) with phenylselenenyl bromide proceeds to form indoles via an intramolecular amidoselenation.
A regioselective route to 3‐alkyl‐1‐aryl‐1H‐pyrazole‐5‐carboxylates: Synthetic studies and structural assignments
Authors: Ashton Wallace T. , Doss George A.
Published: March 2009

Ethyl 2,4‐dioxooctanoate (1) was selectively protected as the 2‐(methoxyimino) derivative 2. When 2 was reacted with phenylhydrazine hydrochloride, ethyl 3‐butyl‐1‐phenyl‐1H‐pyrazole‐5‐carboxylate (4) was favored over the corresponding 5‐butyl‐1‐phenyl‐1H‐pyrazole‐3‐carboxylate product 5 by a ratio of at least 6:1, a complete reversal of the regioselectivity observed for 1. The structures of 4 and 5 were assigned definitively by NOE difference experiments. Regiochemical and configurational assignments of the mono‐ and bis(methoxyimino) derivatives of 1 were also achieved by ID and 2D 1H and 13C nmr methods.
Retro‐ene reaction I: Reaction of N‐hydroxymethylsaccharin with benzoyl chlorides and alkyl halides
Authors: Kim Sung‐Kyu , Moon Jung‐Gyen , Lee Sang‐Gyeong , Choi Sam‐Young , Cho Su‐Dong , Choi Woo‐Yong , Yoon Yong‐Jin
Published: March 2009

N‐Benzoylsaccharins, N‐(saccharinylmethyl) benzoates and N‐alkylsaccharins were synthesized from N‐hydroxymethylsaccharin and the corresponding benzoyl chlorides or alkyl halides under different conditions. The reaction mechanisms are also discussed.
Site‐selective photocycloadditions of 2‐pyrones with electron‐poor olefins and the derivation from the cycloadducts
Authors: Shimo Tetsuro , Yamasaki Shinichi , Date Kenichi , Uemura Hisako , Somekawa Kenichi
Published: March 2009

Photosensitized cycloaddition of 4,6‐dimethyl‐2‐pyrone (1) with methacrylonitrile (3b) afforded two types of [2 + 2]cycloadducts, 4b and 6b, across the C5‐C6 and C3‐C4 double bonds in 1, respectively. Photosensitized reactions of 1 with dimethyl maleate and dimethyl cyclobutene‐1,2‐dicarboxylate gave [2 + 2]cycload‐ducts 4d, 4e across the C5‐C6 double bond, in addition to [4 + 2]cycloadduct 9d or bicyclo[4.2.0]octadiene 10e. The photoreactions of methyl 2‐pyrone‐5‐carboxylate (2) with 3b and 2‐chloroacrylonitrile (3c) gave [4 + 2]cycloadducts 5b, 5c in addition to [2 + 2]cycloadducts 11b and 11c across the C5‐C6 double bond in 2. The photocycloaddition mechanism was explained from results calculated by means of PM3‐CI method. Namely, the site‐ and/or regio‐selective products, 4, 5, 8, 9 and 10 were thought to come from the same site‐selective radical intermediates in the case of electron‐poor olefins. Pyrolysis and/or hydrolysis of the cycload‐ducts 4e, 5b, 5c gave 5,6‐dihydro‐2‐pyrone 12 or benzene derivatives.
Reaction of 3‐benzylidene‐2,4‐pentanedione and 3‐methoxymethylene‐2,4‐pentanedione with aroylhydrazines
Authors: Mitkidou Sophia , Stephanidou‐Stephanatou Julia , Stephopoulou Helen
Published: March 2009

Aroylhydrazines 2 reacted with 3‐benzylidene‐2,4‐pentanedione (1) to give 1‐aroyl‐3,5‐dimethyl‐1H‐pyrazoles 5 and benzaldehyde aroylhydrazones 6. From the reaction of 3‐methoxymethylene‐2,4‐pentanedione (7) with aroylhydrazines 2 the unknown N‐aroyl‐4‐acetyl‐1H‐pyrazoles 9 were exclusively isolated in good yields.
Porphyrins with exocyclic rings. Part 4. An improved one step synthesis of cyclopenta[b]pyrroles
Authors: Quizon‐Colquitt Desiree M. , Lash Timothy D.
Published: March 2009

Cyclopentanone condensed with phenylhydrazones 5, or oximes 6, in the presence of zinc dust, sodium propionate and propionic acid at 150° to give cyclopenta[b]pyrroles 7 in good yields. This chemistry was extended to the synthesis of pyrrolic products from 1‐indanone, 2‐indanone and 2‐methylcyclopentanone. Benzyl 3‐methylcyclopenta[b]pyrrole‐2‐carboxylate was found to react regioselectively with lead tetraacetate to give the corresponding 6‐acetoxy derivative and subsequent acid‐catalyzed condensations with 5‐unsubsti‐tuted pyrrole‐2‐carboxylates afforded a series of synthetically valuable dipyrroles 18a‐c.
Reactions of amidoximes with orthoacetates
Authors: Kaugars Girts , Watt William
Published: March 2009

The reaction of two amidoximes 4 with ethyl orthoacetate in the presence of an acid catalyst gave triazine N‐oxides 7. A mechanism via a Beckmann rearrangement to a carbodiimide, followed by reaction with amidoxime and the ortho ester, is proposed.
4‐benzoyl‐5‐phenyl‐1,3‐oxathiol‐2‐one. Synthesis and reaction with N‐nucleophiles
Authors: He‐Xi Chang , Kollenz Gert
Published: March 2009

The synthesis of 4‐benzoyl‐5‐phenyl‐1,3‐oxathiol‐2‐ones 1 and the behaviour of 1a against several amines were investigated to afford aminomercaptoethenes 2 or thiocarbamates 3, as well as complete cleavage to sulfur, dibenzoylmethane and the corresponding urea, depending on the nature of the N‐nucleophile used.
The chloromethylation of codeine. Isolation of a quaternary iodide
Authors: Grant Andrew D. , Zacharias David E. , Mascavage Linda M. , Kemmerer George E. , Dalton David R.
Published: March 2009

A single N‐chloromethylcodinium iodide has been isolated from the reaction of chloroiodomethane with codeine. Complete proton and carbon nmr and X‐ray analyses dictate that this stable material bears the chloromethyl group axial. It is identical (except for the anion) to one of the salts obtained on long term storage of codeine in dichloromethane.
A new method for the synthesis of 6H,11H‐indolo[3,2‐c]‐isoquinolin‐5‐ones/thiones and their reactions
Authors: Hiremath Shivayogi P. , Saundane Ananda R. , Mruthyunjayaswamy B. H. M.
Published: March 2009

The synthesis of 8‐substituted and unsubstituted 6H,11H‐indolo[3,2‐c]isoquinolin‐5‐ones/thiones 3a‐c and 4a‐c and their derivatives viz, ethyl (8‐substituted‐6H,11H‐indolo[3,2‐c]isoquinolin‐5‐on‐6‐yl)acetates 5a‐c, (8‐substituted‐6H,11H‐indolo[3,2‐c]isoquinolin‐5‐on‐6‐yl)acetyl hydrazides 6a‐c, 3,5‐disubstituted‐pyrazoles 7a‐c and 8a‐c, 3‐substituted‐pyrazol‐5‐ones 9a‐c and 5‐(8‐substituted‐6H,11H‐indolo[3,2‐c]isoquinolin‐5‐on‐6‐yl)methyl‐1,3,4‐oxadiazole‐2‐thiones 10a‐c, also ethyl (8‐substituted‐11H‐indolo[3,2‐c]isoquinolin‐5‐ylthio)ace‐tates 11a‐c, (8‐substituted‐11Hindolo[3,2‐c]isoquinolin‐5‐ylthio)acetyl hydrazides 12a‐c, 3,5‐disubstituted‐pyrazoles 13a‐c and 14a‐c, 3‐substituted‐pyrazol‐5‐ones 15a‐c and 5‐(8‐substituted‐11H‐indolo[3,2‐c]isoquin‐olin‐5‐yl)thiomethyl‐1,3,4‐oxadiazole‐2‐thiones 16a‐c is described.
Unusual reaction of 1,8‐diazabicyelo‐[5.4.0]undec‐7‐ene with diethyl maleate
Authors: Perbost Michel , Lucas Marc , Chavis Claude , Imbach Jean‐Louis
Published: March 2009

Michael addition of DBU on diethyl maleate and subsequent cyclization of the adduct afforded a tricyclic derivative which was susceptible to react further with a second molecule of unsaturated diester.
Synthesis of novel 2‐substituted‐5‐oxycoumarans via A direct route to 2,3‐dihydro‐5‐hydroxy‐2‐benzofuranacetic acids
Authors: Ceccarelli Stefano , De Vellis Patrizia , Scuri Romolo , Zanarella Sergio , Brufani Mario
Published: March 2009

A number of novel 2‐substituted 2,3‐dihydro‐5‐benzofuranols optionally protected on 5‐OH group have been prepared via a simple two step route to racemic 2,3‐dihydro‐5‐hydroxy‐2‐benzofuranacetic acids from hydroquinones and 4‐bromocrotonates.
Research on nitrogen containing heterocyclic compounds. XX. Synthesis of 8H‐Imidazo[5,1‐c]pyrrolo[1,2‐a][1,4]benzodiazepine and its 6‐derivatives
Authors: Massa Silvio , Di Santo Roberto , Costi Roberta , Artico Marino
Published: March 2009

Starting from 1H‐1‐(2‐aminomethylphenyl)pyrrole the synthesis of 8H‐imidazo[5,1‐c]pyrrolo[1,2‐a][1,4]ben‐zodiazepine, a novel nitrogen containing tetracyclic ring, has been performed by two routes involving a three‐step and a six‐step sequence, respectively. The more complex sequence offers the advantage to obtain also 3‐alkyl and 3‐aryl derivatives of the parent nucleus. The three step sequence involves the use of toluene‐4‐sulfonylmethylisocyanide (TosMIC) as a synthon.
The synthesis of electron donor‐acceptor substituted pyrazoles
Authors: Miller R. D. , Reiser O.
Published: March 2009

A variety of 1,3‐ and 1,5‐donor‐acceptor substituted pyrazole derivatives have been synthesized by the cyclocondensation of α,β‐ethynyl ketones with substituted phenyl hydrazines. The regioselectivity of the cyclization depends on the reaction conditions in a manner consistent with competitive 1,2‐ and 1,4‐addition followed by ring closure. 1,4‐Disubstituted derivatives can be prepared from the corresponding 4‐iodopyrazole using palladium catalyzed carbon‐carbon bond forming reactions. The pyrazole chromophores are expected to show interesting nonlinear optical properties.
Novel synthesis modes and properties of [1,4]benzodioxinopyridazines
Authors: Chupp John P. , Jones Claude R. , Dahl Maria L.
Published: March 2009

A simple synthesis involving fusion of catechol and derivatives with 3,4,5‐trichloropyridazine has furnished 4‐chloro[1,4]benzodioxino[2,3‐c]pyridazines 5 for the first time. This new method complements the previously reported base promoted procedure for preparing 4‐chloro[1,4]benzodioxino‐[2,3‐d]pyridazines 3. Employing both methods, 4‐(trifluoromethyl)catechol was converted to the four regio isomers 3b,c and 5c,d. Structure assignment of these four was aided by the remarkably consistent influence of the pyridazine 4‐chlorine substituent and diazo‐linkage in inducing 1H nmr downfield shifts of their nearest neighbor phenyl ring protons. Finally, contrary to what might be expected from previously reported results, reaction of methoxide with either 3 or 5, gave chlorine substitution with formation of methoxybenzodioxinopyridazines 6 and 7 respectively. However, these reactions both give what appears to be an unprecedented rearrangement, with conversion of [2,3‐c]‐pyridazine to [2,3‐d]pyridazine, and vice versa.
Synthesis and selective reactions of v‐triazolo‐[1,5‐b]pyridazinium salts with nucleophiles. A facile access to functionalized ethenyl‐1,2,3‐triazoles
Authors: Riedl Zsuzsanna , Hajós György , Messmer András , Kollenz Gert
Published: March 2009

v‐Triazolo[1,5‐b]pyridazinium salts 5a‐c synthesized from α‐pyridazinyl ketone arylhydrazones and 2,4,4,6‐tetrabromocyclohexa‐2,5‐dien‐1‐one (TBB) reacted selectively with nucleophiles to yield ‐ besides substituted derivatives 6 ‐ ring‐opened cyano compound 9 and/or v‐triazoles containing olefinic side chain 10–12. Mechanistic considerations reveal that cation 5 reacts with nucleophiles predominantly at C‐7 unless other positions are especially activated. This selectivity proved to be in good agreement with results of semiempirical quantum chemical calculations.
Synthesis of naproxen via regioselective ring opening of (2S,3S)‐epoxy‐1‐butanol
Authors: Ahn Kyo Han , Jin Chang Soo , Ho Kang Dong , Shin Yong Soon , Kim Jeong Sook , Han Do Soon , Kim Dong H.
Published: March 2009

(S)‐Naproxen was synthesized by the regioselective and stereospecific epoxide ring opening of (2S,3S)‐epoxy‐1‐butanol (2) with diethyl‐2‐(6‐methoxynaphthyl)aluminium (5) as the key step. Thus, treatment of di‐ethylaluminate of 2 with 5 at 0° afforded (2S,3S)‐3‐(6‐methoxy‐2‐naphthyl)butan‐1,2‐diol (6), which was oxidized by sequential treatment with sodium periodate and potassium permanganate in a mixture of tert‐butyl‐alcohol and phosphate buffer (pH 7.0) to give naproxen in high enantiomeric purity.
Formation and catalytic hydrogenation of the dimer of 1,2,3,4,5,7a‐hexahydroimidazo[1,2‐a]pyrazine
Authors: Mirkin Chad A. , Premecz Joan E. , Ford Michael E. , Johnson Thomas A.
Published: March 2009

Reaction of diethylenetriamine with glyoxal or N,N'‐dicyclohexylethylenediimine forms the novel heterocycle 1,2,3,4,5,7a‐hexahydroimidazo[1,2‐a]pyrazine 1 (R1 = R2 = H) which is isolated as its dimer. Catalytic hydrogenation converts 1 into N(2‐aminoethyl)piperazine in high yield.
Introduction of a triflate group into sterically‐hindered positions in 1‐aryl‐4,6‐diamino‐1,3,5‐triazines and their dimroth rearrangement products
Authors: Stevens M. F. G. , Chui Wai Keung , Castro M. A.
Published: March 2009

Decomposition of 1‐(azidophenyl)‐4,6‐diamino‐1,3,5‐triazines 11–13 and their 4‐amino‐6‐(azidoanilino)‐1,3,5‐triazine isomers 31–33 in trifluoromethanesulphonic acid at 0° led to the introduction of the triflate group (OSO2CF3) into the aryl group. This method can be employed to introduce a bulky substituent into the hindered position ortho to the triazinyl substituent. Dimroth rearrangement of 1‐(aryl)‐4,6‐diamino‐1,3,5‐triazines is best effected in refluxing ethanolic pyridine.
Acetylene chemistry. Part 25. Reactions of ethyl 4‐hydroxy‐3‐quinolin‐2(1H)‐onecarboxylates with 3‐bromoprop‐1‐yne
Authors: Reisch Johannes , Iding Marlies , Schönweiler (The Late) Dörte
Published: March 2009

Ethyl 4‐hydroxyquinolin‐2(1H)‐onecarboxylates 1a and 1b which are obtained conveniently by the condensation of isatoic anhydride and diethylmalonate [4], were reacted with 3‐bromoprop‐1‐yne (2) to obtain monoand dialkylated derivatives.
The lead tetraacetate oxidation of bisacylhydrazones of α‐diketones: A scope re‐assesment
Authors: Maroulis A. J. , Akrivos P. D. , Hadjiantoniou‐Maroulis C. P.
Published: March 2009

Oxidation of the title compounds yields, besides the reported isoimides 3 and/or the amides 4, also the imides 5. The observed product dichotomy is considered as the result of an intramolecular nucleophilic attack on the aroyl group, of the pressumed zwitterionic intermediate 2, by O or N present in the ambident N‐aroylimine site of 2. The results of AM1 calculations agree with the product studies and both permit the formulation of a set of rules correlating structure and selectivity.
Polycyclic N‐heterocyclic compounds. XLIV. Synthesis of the novel B,D‐Dihomo‐11,13,15‐triazasteroidal skeleton and their effect on reserpine‐induced hypothermia and inhibitory activity on platelet aggregation
Authors: Sasaki Kenji , Arimoto Yuichi , Ohtomo Hiromi , Nakayama Taiji , Hirota Takashi
Published: March 2009

Synthesis of benzo[3,4]cyclohepta[1,2‐e]pyrimido[1,2‐c]pyrimidines, corresponding to the B,D‐dihomo‐11,13,15‐triazasteroidal skeleton as a novel ring system is described. Their effects on reserpine‐induced hypothermia in mice and inhibitory activity against collagen‐induced platelet aggregation were also investigated.
On triazoles XXXI. The reaction of 1,2,4‐triazolylcarbothiohydrazides with homo‐ and heterocyclic ketones. An unexpected reaction leading to 4,5‐polyalkylene thiazoles
Authors: Barkóczy József , Szabó éva , Reiter József
Published: March 2009

The reaction of 1,2,4‐triazolylcarbothiohydrazides with homo‐ and heterocyclic ketones to yield 8‐spiro‐[1,2,4]triazolo[1,5‐d][1,2,4,6]tetrazepine‐5‐thiones 7 (n = 4, 5, 6, 7 and 11), 8 and 9, respectively, all representing novel ring systems was studied. Providing the reaction at higher temperature a novel reaction was observed to yield 4,5‐polyalkylene thiazoles for which a mechanism is proposed.
Furopyridines. XIV. Synthesis of 2‐aminoalkyl derivatives of furo[2,3‐b]‐, furo[3,2‐b], furo[2,3‐c]‐ and furo[3,2‐c]pyridine
Authors: Shiotani Shunsaku
Published: March 2009

The preparation of 2‐aminomethyl‐ 3a‐d, 2‐acetamidomethyl‐ 4a‐d, 2‐N,N‐dimethylaminomethyl‐ 5a‐d, 2‐(1‐hydroxy‐2‐nitroethyl)‐ 6a‐d, 2‐(1‐hydroxyl‐2‐aminoethyl)‐ 7a‐d and 2‐(1‐hydroxy‐2‐N,N‐dimethylaminoethyl)‐8b‐d derivatives of furo[2,3‐b]‐, furo[3,2‐b]‐, furo[2,3‐c]‐ and furo[3,2‐c]pyridine is described.
Synthesis and transformations of 1‐(1,3‐butadien‐1‐yl)benzotriazoles
Authors: Katritzky Alan R. , Gupta Vandana , Gordeev Mikhail
Published: March 2009

1‐[α‐(Phenylthio)alkyl]benzotriazoles were converted into the corresponding 1‐(1,3‐butadien‐1‐yl)benzotriazoles in good yields by one‐pot sequential reactions with (i) lithium diisopropylamide, (ii) allyl bromide or cinnamyl chloride, and (iii) potassium t‐butoxide. Diels‐Alder and hetero [4 + 2] cycloadditions of 1‐(1,3‐butadien‐1‐yl)benzotriazoles and some transformations of their α‐lithio derivatives were studied.
Ring closure of 1‐[4‐(imidazol‐1‐yl)phenyl]‐3‐phenyl‐2‐propen‐1‐one derivatives to potential biologically active compounds
Authors: Coudert P. , Couquelet J. , Tronche P. , Leal F.
Published: March 2009

1‐[4‐(Imidazol‐1‐yl)phenyl]‐3‐phenyl‐2‐propen‐1‐one 1 reacted with acetone cyanohydrin, ethyl phenylacetate and cyanoacetamide to give the adducts 2, 8 and 10 respectively. Action of hydrazine hydrate on both the γ‐ketonitrile 2 and the corresponding γ‐ketoacid 4 led to pyridazine derivatives 3 and 5. 4,5‐Dihydropyridazinone 5 was dehydrogenated by the action of bromine in acetic acid to give pyridazinone 6. Cyclization of acid 8 in acetic medium resulted in α‐pyrone 9. Cyanopentanamide 10 was converted with hydrochloric acid into δ‐ketoacid 13 which led to α‐pyrone 14 via an intramolecular dehydration. Refluxing 10 in the presence of acetic acid and ammonium acetate gave 3,4‐dihydropyridone 11 which was dehydrogenated to produce pyridone 12.
N‐Alkylation of pyrazolones with OH‐protection
Authors: Hichour M. , Mary F. , Marzin C. , Naji M. , Tarrago G.
Published: March 2009

The synthesis of a biheterocyclic compound containing two pyrazolone sub‐units, precursor of a new macrocyclic family, is described. It is shown that it is necessary to protect first the pyrazol‐5‐one oxygen site before condensing it with a bifunctional compound in order to obtain a selective alkylation on the heterocyclic nitrogen atom.
1,2,3‐triazol‐1‐imines. 2. Electric dipole moments and semiempirical studies of some 2‐aryl‐N‐benzoyl‐4,5‐dimethyl‐1,2,3‐triazol‐1‐imines
Authors: Hadjiantoniou‐Maroulis C. P. , Akrivos P. D. , Maroulis A. J.
Published: March 2009

Electric dipole moments of some 2‐aryl‐N‐benzoyl‐4,5‐dimethyl‐1,2,3‐triazol‐1‐imines were measured in carbon tetrachloride solution and the results compared with those derived computationally using MNDO, AM1 and PM3. Good correlation of the dipole moments with σ+ substituent constants was obtained.
Preparation of 3(5)‐phenyl‐1‐hydroxypyrazole 2‐oxide and 4‐methyl‐3(5)‐phenyl‐1‐hydroxypyrazole 2‐oxide
Authors: Hansen John F. , Luther Matthew L.
Published: March 2009

Nitrosation of acrylophenone oxime or of methacrylophenone oxime with n‐butyl nitrite in the presence of pyridine and copper(II) sulfate gives the copper complexes of the title compounds. The free 1‐hydroxypyrazole 2‐oxides are isolated by treating the copper complexes with dilute sodium hydroxide, filtration, and acidification of the basic filtrates. The title compounds are the first examples of 1‐hydroxypyrazole 2‐oxides in which the C3(5) ring position is unsubstituted.
Synthesis of thieno[3,4‐c] and thieno[3,2‐c][2,1]benzothiazepines
Authors: Vega Salvador , Diaz Juan A.
Published: March 2009

Starting from [4,3‐c] and [3,2‐c] methyl chlorosulfonylthiophenecarboxylates the synthesis of ketones 7 and 8 is described. These compounds are the first two representatives of the new thieno[3,4‐c] and thieno‐[3,2‐c][2,1]benzothiazepine ring systems. The formation of methyl 3‐chlorosulfonylthiophene‐2‐carboxy‐late is also revised.
Tetrazole compounds. 8. Synthesis of tetrazolylpyrimidines from tetrazolyl‐substituted enamino ketones
Authors: Fischer Gerhard W.
Published: March 2009

Tetrazolyl‐substituted enamino ketones 1 react with various amidines 2 to give 5‐(1‐phenyl‐1H‐tetrazol‐5‐yl)pyrimidines 3. In the case of the chloroacetyl enamine 4 4‐(N,N‐dimethylaminomethyl)‐substituted tetra‐zolylpyrimidines 5 were obtained. Subsequent hydrolysis of the 4‐trifluoromethyl derivatives 3b, 3d and 3g afforded the corresponding 5‐(1‐phenyl‐1H‐tetrazol‐5‐yl)pyrimidine‐4‐carboxylic acids 6.
A mass spectrometric investigation on some 4,7‐dioxo‐4,5,6,7‐tetrahydroindole derivatives
Authors: Bertazzo A. , Ferlin M. G. , Chiarelotto G. , Catinella S. , Traldi P.
Published: March 2009

The mass spectrometric behaviour of a series of 2‐aryl substituted 4,7‐dioxo‐4,5,6,7‐tetrahydroindoles has been studied in different ionization conditions (Electron Ionization and Fast Atom Bombardment), with the aid of the metastable ion studies. In electron ionization conditions all the compounds exhibit a highly favoured, primary H2 loss giving rise to the corresponding indole‐4,7‐diones; in the usual spectra no evidence for the molecular ions in the enolic form was found, while the OH* loss observed in the MIKE (mass analyzed ion kinetic energy) spectra of molecular ions suggests that species at low internal energy content isomerize to the corresponding tautomeric enolic form. FAB mass spectra show easy formation of an unusual [M + 2H]+ species, together with abundant [M + H]+ and M+ cations.
Synthesis and stereochemistry of new trihydrodiazabicyclo‐[3.m.n]alkano[4′,5′:1,2]pyrido[3,4‐b]indole ring system
Authors: Misztal Stanislaw , Paluchowska Maria H. , Mokrosz Maria J. , Bartyzel Piotr , Mokrosz Jerzy L.
Published: March 2009

The classical Pictet‐Spengler reaction of tryptamine with the isomeric N‐benzylpiperidones 3a, 3b and N‐benzylpyrrolidone 3c yielded the spiro derivatives of 1,2,3,4‐tetrahydro‐β‐carboline 5a, 5b and 5c. Cyclocon‐densation of the spirotetrahydrocarboline with chloroacetic chloride and the subsequent reductive debenzylation afforded the new ring systems of trihydrodiazabicyclo[3.m.n]alkano[4′,5′:1,2]pyrido[3,4‐b]indoles 8a, 8b, and 8c. The structures of the bicyclic systems 8a, 8b, and 8c were determined by using both, high‐resolution 1H and 13C nmr techniques and force field and MNDO calculations.
Thiazolidine‐2,4‐dicarboxylic acid and its esters: Synthesis, in solution behaviour and regioselective cyclocondensation
Authors: Refouvelet Bernard , Robert Jean‐FranÇOis , Couquelet Jacques , Tronche Pierre
Published: March 2009

Thiazolidine‐2,4‐dicarboxylic acid 2 was obtained as a diastereoisomeric mixture from the condensation of glyoxylic acid with L(‐)R‐cysteine 1. In solution behaviour studies suggested that the reaction proceeded through an acid catalyzed epimerization mechanism. The methyl esterification of 2 was stereoselective, which can be explained by an interconversion of 2a via a ring seco intermediate. Condensation of the dimethyl ester 3 or the dissymmetric diester 4 with phenyl isocyanate gave rise to the same hydantoin 5. N‐acylation of diesters 3 or 4 followed by the reaction with benzylamine was regioselective leading to bicyclic derivatives 8‐10.
Synthesis of 1H‐ and 2H‐pyrazolo[3,4‐c][2,1]benzothiazepines
Authors: Diaz Juan A. , Vega Salvador
Published: March 2009

Starting from ethyl chlorosulfonylpyrazole‐4‐carboxylates we have carried out the synthesis of ketones 3 and 4 which are the first two structures of the novel 1H‐ and 2H‐pyrazolo[3,4‐c][2,1]benzothiazepine ring systems.
Synthesis and anti‐hiv‐1 activities of 6‐arylthio and 6‐arylselenoacyclonucleosides
Authors: Pan Bai‐Chuan , Chen Zhi‐Hao , Piras Giovanna , Dutschman Ginger E. , Rowe Elizabeth C. , Cheng Yung‐Chi , Chu Shih‐Hsi
Published: March 2009

6‐Arylthio and 6‐arylselenoacyclonucleosides was synthesized and tested for the ability to inhibit replication of HIV‐1. Lithiation of acyclonucleosides with LDA followed by reaction with the electrophiles phenyl disulfide, diphenyl diselenide, 2,2′‐dipyrdyl disulfide or 2,2′‐dipyridyl diselenide afforded 6‐(arylthio or arylseleno)acyclonucleosides 5a‐c, 6, 7, 9, 15a‐c, 17a‐c. Compounds 19a‐c and 20a‐c were obtained by deprotection of corresponding TBDMS derivatives. Dehydrated products 16a, and 18a‐c were also formed during the reactions. 5‐Ethyl‐6‐(α‐pyridylthio or α‐pyridylseleno) disubstituted acyclouracils 6 and 7 were more active against HIV‐1 in both MT‐2 and CEM‐IW cell lines than AZT, DDC, DDI or D4T. The EC50 of 6 against HIV‐1 in CEM‐IW cell was in the nanomolar range with a therapeutic index of 1100.
A novel rearrangement of 1‐(2‐aminoaryl)imidazoles
Authors: Lampe John W. , Di Meo Susan V. , Traina Joseph A.
Published: March 2009

6‐Ethyl‐2,4‐bis(1H‐imidazol‐1‐yl)pyrimidin‐5‐amine was found to undergo a novel rearrangement in the presence of acetic anhydride. The structure of the rearrangement product was deduced using a combination of one‐ and two‐dimensional nmr methods. Confirmation of the structure was obtained by unambiguous synthesis of a reduced analog and establishment of the identity of this material with material prepared by reduction of the rearrangement product. Examination of three related cases indicated that the rearrangement process is significant only when both positions adjacent to the aryl amino group are substituted.
Reaction of 5‐acetyl‐10,11‐didehydro‐5H‐dibenz[b, f]azepine with pyrrole, N‐methylpyrrole, imidazole and N‐methylimidazole: Cycloaddition versus michael addition
Authors: Bennett Robert A. , Cann Michael C.
Published: March 2009

Reaction of 5‐acetyl‐10‐bromo‐5H‐dibenz[b, f]azepine 1 with potassium t‐butoxide results in the reactive intermediate 5‐acetyl‐10,11‐didehydro‐5H‐dibenz[b, f]azepine (2). The intermediate 2 reacts with N‐methylpyrrole to give a mixture of the Michael addition adduct 10‐(2‐N‐methylpyrrolyl)‐5H‐dibenz[b, f]azepine (9) and the Diels‐Alder/retro Diels Alder adduct 8H‐(N‐methylpyrrolo[3,4‐d]dibenz[b, f]azepine (8a). Reaction of 2 with pyrrole gives a mixture of two Michael addition adducts 10‐(1‐pyrrolyl)‐5H‐dibenz[b, f]azepine (16) and 10‐(2‐pyrrolyl)‐5H‐dibenz[b, f]azepine (18). Reaction of 2 with imidazole results in the Michael addition adduct 10‐(1‐imidazolyl)‐5H‐dibenz[b, f]azepine (21).
Enzymatic resolution of 4‐methyl‐, 4‐phenyl‐ and 6‐phenyltetrahydro‐2H‐pyran‐2‐one using esterases
Authors: Izumi Taeko , Tamura Futoshi , Akutsu Mitsuyo
Published: March 2009

Enantioselective hydrolysis of racemic tetrahydro‐2H‐pyran‐2‐ones (δ‐valerolactones) using esterase resulted in the formation of optically active (R)‐4‐methyl‐, (R)‐4‐phenyl‐ or (R)‐6‐phenyltetrahydro‐2H‐pyran‐2‐ones and the corresponding (S)‐8‐hydroxypentanoic acid derivatives.
Synthesis of imidazo[4,5‐c]pyridines with a trifluoromethyl group at C‐4 and/or C‐6
Authors: Gautam Rakesh K. , Fujii Shozo , Nishida Masakazu , Kimoto Hiroshi , Cohen Louis A.
Published: March 2009

Thermal condensation of histamine with trifluoroacetaldehyde gives 4‐(trifluoromethyl)spinacamine and subsequent dehydrogenation with selenium dioxide leads to 4‐(trifluoromethyl)‐1H‐imidazo[4,5‐c]pyridine (42%). Fluorination with sulfur tetrafluoride of L‐spinacine, obtained from the condensation of L‐histidine with formaldehyde, affords 6‐(trifluoromethyl)spinacamine, which can be converted to 6‐(trifluoromethyl)‐1H‐imidazo[4,5‐c]pyridine with selenium dioxide (49%). Application of the sequential reactions to 4‐(trifluoro‐methyl)‐L‐spinacine gives 4,6‐bis(trifluoromethyl)‐1H‐imidazo[4,5‐c]pyridine. Dehydrogenation of the tetrahydropyridine ring also occurred during the fluorination with sulfur tetrafluoride.
The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 14. 14‐methylbenzo[h]naphtho‐[1′2′:4,5]thieno[2,3‐c][1,6]naphthyridine
Authors: Musmar M. J. , Castle Raymond N.
Published: March 2009

Benzo[h]naphtho[1′2′:4,5]thieno[2,3‐c][1,6]naphthyridine, a novel polycyclic heterocyclic ring system, has been synthesized as the 14‐methyl derivative 8 in four steps from known intermediates. The structure of 8 is supported by assignment of the proton and the protonated carbon atoms by 2D‐nmr techniques (COSY and a carbon‐hydrogen one‐bond coupling experiment).
Synthesis and prototropic tautomerism of 1‐n‐alkyl‐3‐methyl‐4‐nitroso‐5‐pyrazolones
Authors: Bartulín I. , Belmar I. , Gallardo H. , León G.
Published: March 2009

Nitrosation at C‐4 of 1‐n‐alkyl‐3‐methyl‐5‐pyrazolones is achieved in about 50% yield with sodium nitrite in hydrochloric acid medium. A tautomeric equilibrium in solution with a proton moving from the OH at C‐5 to N‐2 in the nitrosated pyrazolones is proposed.
Heterocyclic compounds studies. Dynamic 13C NMR investigation and crystal structure of 3‐hydroxy‐1,5‐benzoxathiepine
Authors: Cerioni Giovanni , Floris Costantino , Marongiu Giaime , Navarra Gabriele , Sotgiu Francesca
Published: March 2009

1‐5‐benzoxathiepine compounds are a novel class of heterocyclic rings that present interesting properties as central nervous system depressants. With the aim to contribute to the elucidation of the structure‐activity relationship of this class of compounds we report a structural study of the 3‐hydroxy‐1,5‐benzoxathiepine both in solution and in the solid state. Studies by dynamic 13C‐nmr in solution show that three conformations are possible for the oxathiepin ring. A unique chair conformation characterizes the atoms in the oxathiepine ring of the crystallized molecule. The crystal structure was solved by direct methods. Values of bond distances and angles are within the expected range.