Neue Wege zu 1H- und 2H-Pyrrolen

New Routes to 1H- and 2H-Pyrroles A synthesis of 1H-pyrroles is described starting with pyridine analogues of chalcones and involving the reaction of acetic anhydride with 1-pyrroline-1-oxides. Another route leads from 1-pyrrolines to 2 H-pyrroles via bromination with N-bromosuccinimide and subsequent dehydrobromination in dimethylformamide.     

Reaction of 2-dimethylaminomethylene-1,3-diones with dinucleophiles. VI. Synthesis of ethyl or methyl 1,5-disubstituted 1H-pyrazole-4-carboxylates

Reaction of ethyl or methyl 3-oxoalkanoates with N,N-dimethylformamide dimethyl acetal gave, generally in excellent yields, a series of ethyl or methyl 2-dimethylaminomethylene-3-oxoalkanoates II which reacted with phenylhydrazine to afford the esters of 5-substituted 1-phenyl-1H-pyrazole-4-carboxylic acids III in high yields. Esters III were hydrolyzed to the relative 5-substituted 1-phenyl-1H-pyrazole-4-carboxylic acids which were converted by heating to 5-substituted 1-phenyl-1H-pyrazoles in excellent yields. Reaction of II with methylhydrazine afforded in general a mixture of 3- and 5-substituted ethyl 1-methyl-1H-pyrazole-4-carboxylates with the exception of IIg , which gave in high yield methyl 5-benzyl-1-methyl-1H-pyrazole-4-carboxylate, which was hydrolyzed to the relative pyrazolecarboxylic acid. This afforded by heating 5-benzyl-1-methyl-1H-pyrazole in quantitative yield.     

Cyclopropanation of N-Substituted 2-Oxochromene- and 6-Bromo-2-oxochromene-3-carboxamides with Zinc Enolates Derived from 1-Aryl-2,2-dibromoalkanones

Zinc enolates derived from 1-aryl-2,2-dibromoalkanones react with N-cyclohexyl-2-oxochromene-3-carboxamides to give N-cyclohexyl-1-alkyl-1-aroyl-2-oxo-1a,7b-dihydrocyclopropa[c]chromene-1a-carboxamides mainly as cis isomers with respect to the substituents in positions 1 and 1a. Reactions of the same zinc enolates with N-benzyl-2-oxochromene-3-carboxamide and N-benzyl-6-bromo-2-oxochromene-3-carboxamide lead to formation of 1-aryl-2-benzyl- and 1-aryl-2-benzyl-6-bromo-1-hydroxy-9c-alkyl-1,2,9b,9c-tetrahydro-5-oxa-2-azacyclopenta[2,3]cyclopropa[1,2-a]naphthalene-3,4-diones. The reaction of zinc enolates with N-aryl-2-oxochromene-3-carboxamides in a weakly polar solvent (diethyl ether or ethyl acetate) affords mixtures of cis-N-aryl-1-aroyl-1-alkyl-2-oxo-1a,7b-dihydrocyclopropa[c]chromene-1a-carboxamides and their cyclic isomers, 9c-alkyl-1,2-diaryl-1-hydroxy-1,2,9b,9c-tetrahydro-5-oxa-2-azacyclopenta[2,3]cyclopropa[1,2-a]naphthalene-3,4-diones, the latter prevailing. N-Substituted 1-alkyl-1-aroyl-2-oxo-1a,7b-dihydrocyclopropa[c]chromene-1a-carboxamides in which the aroyl group on C¹ and the carboxamide group on C^1a are arranged trans are formed by reactions of zinc enolates with the corresponding 2-oxochromene-3-carboxamides in the presence of hexamethylphosphoric triamide.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 4, 2005, pp. 539–546.Original Russian Text Copyright © 2005 by V. Shchepin, Silaichev, R. Shchepin, Ezhikova, Kodess.     

The reactions of 4-dicyanomethylene-2-phenyl-4H-1-benzopyran and some benzologs with nucleophiles

4-Dicyanomethylene-2-phenyl-4H-1-benzopyran (1) reacts with primary amines under mild conditions to give 4-imino-3-alkyl-5-alkylimino-2-phenyl-3,4-dihydro-5H-[1]benzopyrano[3,4-c]-pyridine derivatives which, in turn, are hydrolyzed with acid to 4-imino-3-alkyl-2-phenyl-3,4-dihydro-5H-[1]benzopyrano[3,4-c]pyridin-5-ones. When more vigorous conditions are employed for the reactions of 1 with primary amines, Dimroth rearrangements take place and the products are derivatives of 4-alkyl- (or aryl)amino-5-alkyl- (or aryl)imino-2-phenyl-5H-[1]benzopyrano-[3,4-c]pyridine. The latter compounds are hydrolyzed by acid to the corresponding 5-pyridone derivatives. The reaction of 1 with piperidine gives 2-phenyl-4-piperidyl-5H-[1]benzopyrano-[3,4-c]pyridin-5-one. Sodium methoxide reacts with 1 to give 3-cyano-2-methoxy-4-(2-hydroxyphenyl)-6-phenylpyridine. Two benzologs of 1 have been allowed to react with primary and secondary amines and the products are analogous to those obtained from 1 .     

A comparison of nucleophilic reactions of 3-benzenesulfonyloxyalloxazine and its 1-methyl analog

Reactions of 3-benzenesulfonyloxyalloxazine ( 1a ) and its 1-methyl analog 1b with a number of nucleophilic reagents are reported. Relatively small nucleophiles, such as hydroxide ion, methanol, ethanol, methylamine, hydrazine and hydroxylamine converted 1a to 4-carboxy-s-triazolo[4,3-a]quinoxalin-1(2H)-ones and the corresponding esters or amides. As the size of the amine increased from methylamine to ethylamine, dimethylamine, propylamine and isopropylamine, there were obtained 4-(carboxamido)-s-triazolo[4,3-a]quin-oxalin-1(2H)-ones, (1-carboxamido)imidazolo[4,5-b]quinoxalines and 2,3-bis(ureido)quinoxalines. Sodium hydride or potassium cyanide in hot DMF degraded 1a to imidazolo[4,5-b]quinoxaline. However, methylmer-captide and benzylmercaptide ions attacked the sulfonate group of 1a to form 3-hydroxyalloxazine. 1-Methyl-3-benzenesulfonyloxyalloxazine ( 1b ) reacted with methanol, ethanol, 1-propanol, and to some degree 2-propanol, in the presence of triethylamine to furnish anhydro-1-hydroxy-3-methyl-4-(alkoxycarbonyl)-s-triazolo[4,3-a]quinoxalinium hydroxides. However, sodium methoxide in methanol converted this starting material to a mixture of anhydro-1-hydroxy-3-methyl-s-triazolo[4,3-a]quinoxalinium hydroxide and 1-methyl-3-hydroxyflavazole. A saturated aqueous solution of triethylamine transformed 1b to anhydro-1-hydroxy-3-methyl-s-triazolo[4,3-a]quinoxalinium hydroxide, apparently via the corresponding unstable 4-carboxylic acid. The reactions of 1b with a number of aliphatic amines yielded either amides based on the above mesoionic system or on the 3-carboxamido-2-quinoxalyl semicarbazide structure. The reaction of 1b with potassium cyanide furnished 1-methylimidazolo[4,5-b]quinoxaline. Mechanisms to explain all of the degradations are advanced.     

Electrophilic Reactivities of 1,2‐Diaza‐1,3‐dienes

The kinetics of the reactions of 1,2‐diaza‐1,3‐dienes 1 with acceptor‐substituted carbanions 2 have been studied at 20 °C. The reactions follow a second‐order rate law, and can be described by the linear free energy relationship log k(20 °C)=s(N+E) [Eq. (1)]. With Equation (1) and the known nucleophile‐specific parameters N and s for the carbanions, the electrophilicity parameters E of the 1,2‐diaza‐1,3‐dienes 1 were determined. With E parameters in the range of ?13.3 to ?15.4, the electrophilic reactivities of 1 a–d are comparable to those of benzylidenemalononitriles, 2‐benzylideneindan‐1,3‐diones, and benzylidenebarbituric acids. The experimental second‐order rate constants for the reactions of 1 a – d with amines 3 and triarylphosphines 4 agreed with those calculated from E, N, and s, indicating the applicability of the linear free energy relationship [Eq. (1)] for predicting potential nucleophilic reaction partners of 1,2‐diaza‐1,3‐dienes 1 . Enamines 5 react up to 10² to 10³ times faster with compounds 1 than predicted by Equation (1), indicating a change of mechanism, which becomes obvious in the reactions of 1 with enol ethers.     

Reaktionen von 3-Dimethylamino-2,2-dimethyl-2H-azirin mit Phenolen und Halogenaromaten

Reactions of 3-dimethylamino-2,2-dimethyl-2H-azirine with phenols and aryl halides The reactions of 3-dimethylamino-2,2-dimethyl-2H-azirine ( 1 ) with phenols are described in chap. 1. The azirine 1 reacts with the 2-formyl- and 2-acetylphenols 5 – 8 to yield the N′-methylidene derivatives of 2-amino-N,N-dimethyl-isobutyramide 9 - 12 (Scheme 2, tautomeric form b ). These products are in equilibrium with the tautomeric quinoide forms 9a-12a . Under similar conditions 4-hydroxybenzaldehyde did not react with 1 . Reaction of 1 with 4-hydroxycoumarine ( 13 ) gives the 4-amino-coumarine 14 (Scheme 2). The mechanism of these reactions is analogous to the previously reported one for the reaction of 1 with cyclic enolisable 1,3-diketones [2] [3]. Activated phenols with pK_a-values < 8, e.g. 2- and 4-nitrophenol, 2,4-dinitrophenol and pentachlorophenol, undergo addition reactions with 1 in boiling benzene solution to give the aniline derivatives 15 - 18 (Scheme 3). A reaction mechanism is given in Scheme 3: after protonation of the azirine 1 followed by attack of the phenolate ion at the amidinium-C-atom, the intermediate of type e undergoes a rearrangement to the spiro-Meisenheimer complexes of type f . Ring opening leads to 15 – 18 . A similar reaction is observed for 2,4-dinitro-thiophenol and 1 , giving 2-(N′-(2,4-dinitrophenyl)amino)-N,N-dimethyl-isobutyrothioamide ( 19 ). The azirine 1 reacts with the more acidic 2,4,6-trinitrophenol (picric acid) to yield 3,3,6,6-tetramethylpiperazine-2,5-bis(N,N-dimethyliminium) dipicrate ( 21 , Scheme 4). The methacrylamidinium salt 22 is the only product (97% yield) in the reaction of 8-hydroxy-5,7-dinitroquinoline and 1 in acetonitrile solution. The reaction of 1 with picric acid can be explained in a similar way as the previously reported one with strong acids (cf. Scheme 1, [1] [3] [5]). An alternative mechanism without formation of the 1-aza-allylcation c is postulated in Scheme 5, together with a mechanism which could explain the exclusive formation of 22 in the reaction of 1 with 8-hydroxy-5,7-dinitroquinoline. In chap. 2 a few reactions of the azirine 1 with aryl halides are reported. In the reaction with 2,4-dinitrofluorobenzene it is shown by UV. and NMR., that m , n and o are intermediates (Scheme 6). Working up the reaction mixture with water, hydrogen sulfide or benzylamine leads to the aniline derivatives 17 , 19 and 26 , respectively. With picryl chloride and 8-hydroxy-5,7-dinitroquinoline the azirine 1 undergoes a nucleophilic aromatic substitution to afford the intermediates p and q , which via deprotonation and ring opening give acrylamidine derivatives ( 27 and 29 , Scheme 7 and 8). The steric hindrance in p and q between the aziridine ring and the two groups in o-position could be the reason for the different behaviour of the intermediates n and p or q (cf. Schemes 6 and 8).     

Reactions of <Emphasis Type="Italic">N</Emphasis>-and <Emphasis Type="Italic">C</Emphasis>-Alkenylanilines: VII. Synthesis of Indole Heterocycles from Products of Reaction between <Emphasis Type="Italic">N</Emphasis>-Mesyl-2-(1-alken-1-yl)anilines and Halogens

N-Mesyl-2-(1-methyl-1-butenyl)-6-methylaniline reacted with Br₂ to afford N-mesyl-2-(3-bromo-1-penten-2-yl)aniline that under treatment with NH₃ or amines underwent cyclization into N-mesyl-7-methyl-3-methylene-2-ethylindoline. The reaction of N-mesyl-2-(1-methyl-1-buten-1-yl)-4-methyl- and 2-(1-methyl-1-buten-1-yl)aniline with Br₂ gave rise to the corresponding N-mesyl-2-(2-bromo-1-methyl-1-buten-1-yl)anilines. Under the similar conditions N-tosyl-2-(1-cyclohexen-1-yl)aniline was converted into N-tosyl-2-(6-bromo-1-cyclohexen-1-yl)aniline that under treatment with NH₃ furnished N-tosyl-1,2,3,9a-tetrahydrocarbazole. The reaction of N-mesyl-1,2,3,9a-tetrahydrocarbazole with CuBr₂ in MeOH afforded N-mesyl-4-methoxy-1,2,3,4-tetrahydrocarbazole. N-Mesyl-6-methyl-2-(1-cyclopenten-1-yl)aniline in reaction with Br₂ in the presence of NaHCO₃ was oxidized into the corresponding cyclopentenone, and with NBS it gave N-mesyl-2-(2-bromo-1-cyclopenten-1-yl)aniline.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 5, 2005, pp. 730–737.Original Russian Text Copyright © 2005 by Gataullin, Sotnikov, Spirikhin, Abdrakhmanov.     

Bortrifluorid-katalysierte Umsetzungen von 3-Amino-2H-azirinen mit Aminosäure-estern und Aminen

Boron-Trifluoride-Catalyzed Reactions of 3-Amino-2H-azirines with Amino-acid Esters and Amines After activation by protonation or complexation with BF₃, 3-amino-2H-azirines 1 react with the amino group of α-amino-acid esters 3 to give 3,6-dihydro-5-aminopyrazin-2(1H)-ones 4 by ring enlargement (Scheme 2, Table 1). The configuration of 3 is retained in the products 4 . With unsymmetrically substituted 1 (R¹ ≠ R²), two diastereoisomers of 4 (cis and trans) are formed in a ratio of 1:1 to 2:1. With β-amino-acid esters 5 and 7 , only openchain α-amino-imidamides 6 and 8 , respectively, are formed, but none of the seven-membered heterocycle (Scheme 3). Primary amines also react with BF₃-complexed 1 to yield α-amino-imidamides of type 9 (Scheme 4, Table 2). Compound 9b is characterized chemically by its transformation into crystalline derivatives 10 and 12 with 4-nitrobenzoyl chloride and phenyl isothiocyanate, respectively (Scheme 5). The structure of 12 is established by X-ray crystallography. Mechanisms for the reaction of activated 1 with amino groups are proposed in Schemes 6 and 7.     

Ring-opening reaction of 1,3,4-oxadiazolone and 1,3,4-oxadiazolinethione: Reaction of 2-phenyl-1,3,4-oxadiazolin-5-one and 2-phenyl-1,3,4-oxadiazoline-5-thione with amines

The ring-opening abilities of amines toward 1,3,4-oxadiazolines, 2-phenyl-1,3,4-oxadiazolin-5-one ( 1a ) and 2-phenyl-1,3,4-oxadiazoline-5-thione ( 1b ), were investigated with relation to their basicities or pK_b values. Oxadiazolines 1a and 1b were easily reacted with amines such as benzylamine and aniline, but not with p-nitroaniline, to form the corresponding ring-opening adducts. The reactions of both 1a and 1b with o-phenylenediamine produced benzodiazoles with the liberation of benzoylhydrazide, whereas the reactions with o-aminobenzamide furnished quinazolines with the liberation of ammonia. o-Aminophenol and o-aminothiophenol were also reacted with 1a and 1b both of them giving 1,5-dibenzoylcarbohydrazide from 1a and 1,2-dibenzoylhydrazine from 1b. From the conditions affording the corresponding ring-opening adducts or reaction products, the ring-opening abilities of the amines toward 1a and 1b are in good correlation with the strength of their basicities or pK_b values. The ring-opening of oxadiazolines were proved to occur with anilines. Therefore, the other reactions are also supposed to proceed via the ring-opening steps.     

3-Hydrazino-1,2,4-triazin-5(2H)-ones in Reactions with Compounds Containing Carbonyl and Active Methylene Groups

Boiling of ethyl cyanoacetate with 6-tert-butyl-3-hydrazino-1'2'4-triazin-5(2H)-one in alkalinemedium yielded 6-tert-butyl-3-(5-hydroxy-3-oxo-2'3-dihydro-1H-pyrazol-1-yl)-1'2'4-triazin-5(2H)-one.Acylation of 6-tert-butyl-3-hydrazino-1'2'4-triazin-5(2H)-one with benzoyl chloride furnished 3-benzoyl-hydrazido-1'2'4-triazine that cyclized when treated with POCl₃ providing a derivative of[1'2'4]triazolo[4'3-b][1'2'4]triazine. Boiling of 6-tert-butyl-3-hydrazino-1'2'4-triazin-5(2H)-one in glacialacetic acid gave rise to diacetylated derivative whereas the boiling with acetic anhydride in an inert solventafforded monoacetylated product.     

Stereoselective reductive tetraallylation of pyridinecarboxylic acids with triallylborane

Reductive tetraallylation of pyridine-3-and pyridine-4-carboxylic acids with triallylborane in the presence of propan-2-ol proceeded stereoselectively to yieldtrans-2,6-diallyl-3- andtrans-2,6-diallyl-4-(1-allyl-1-hydroxybut-3-en-1-yl)-1,2,5,6-tetrahydropyridines, respectively. Under the same conditions, the reaction with pyridine-2-carboxylic acid gave a mixture oftrans- andcis-2,6-diallyl-2-(1-allyl-1-hydroxybut-3-en-1-yl)-1,2,5,6-tetrahydropyridines in a ratio of 57:43. When 2,6-diphenylpyridine-4-carboxylic acid reacted with triallylborane, only the carboxylic group underwent reductive diallylation. When heated with triallylborane ino-xylene (130–133°C, 7 h),trans-2,6-diallyl-4-(1-allyl-1-hydroxybut-3-en-1-yl)-1,2,3,6-tetrahydropyridine was converted to the correspondingcis-isomer. The stereochemistry oftrans-2,6-diallyl-3-(1-allyl-1-hydroxybut-3-en-1-yl)-1,2,5,6,-tetrahydropyridine was confirmed by X-ray diffraction analysis. Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 11, pp. 2320–2326, November, 1998.     

Bestimmung des Chiralitätssinns der enantiomeren 2,6-Adamantandiole

Determination of the Chirality Sense of the Enantiomeric 2,6-Adamantanediols The enantiomers of 2,6-adamantanediol ( 1 ) are resolved via the diastereoisomeric camphanoates. The (2R,6R)-chirality sense for (?)- 1 and (2S,6S) for (+)- 1 was determined by chemical correlation with (?)-(1R,5R)-bicyclo[3.3.1]nonan-2,6-dion ((1R,5R)- 3 ) of known absolute configuration in the following way: alkylation of the bis(pyrrolidine enamine) of (?)-(1R,5R)- 3 with CD₂I₂ and hydrolysis of the product gives the enantiomer 4 of (4,4-D₂)-2,6-adamantanedione. Reduction of 4 with LiAlH₄ leads to one enantiomer (Scheme 2) of each of the three diols 5 – 7 of known absolute configuration. The three diols are themselves configurational isomers due to the presence of the CD₂ group, but correspond otherwise entirely to the enantiomeric diols 1 . Accordingly, they can also be separated by means of their diastereoisomeric camphanoates to give the diols 5 / 6 and 7 . These samples are easily distinguished and identified by their characteristic ¹H-NMR spectra (cf. Fig. 2). This allows to identify the (2R,6R)- and (2S,6S)-enantiomer of 1 on the basis of their behavior in the resolution experiment analogous to that of the diols 5 / 6 and 7 , respectively. The diol (?)- 1 must have the (2R,6R)-configuration because it forms, like the diols 5 / 6 , with (?)-camphanic acid the diastereoisomeric ester less soluble in benzene. The diol (+)- 1 has (2S,6S)-configuration, because it forms, like 7 , with (+)-camphanic acid the diastereoisomeric ester less soluble in benzene. The bis(4-methoxybenzoate) of (?)-(2R,6R)- 1 shows chiroptical properties which are in accordance with Nakanishi's rule for two chromophores having coupled electric dipol transition moments arranged with a left-handed torsion angle.     

HMBC‐1,1‐ADEQUATE via generalized indirect covariance: a high sensitivity alternative to n,1‐ADEQUATE

1,1‐ADEQUATE and the related long‐range 1,n‐ and n,1‐ADEQUATE variants were developed to provide an unequivocal means of establishing ²J_CH and the equivalent of ⁿJ_CH correlations where n = 3,4. Whereas the 1,1‐ and 1,n‐ADEQUATE experiments have two simultaneous evolution periods that refocus the chemical shift and afford net single quantum evolution for the carbon spins, the n,1‐variant has a single evolution period that leaves the carbon spin to be observed at the double quantum frequency. The n,1‐ADEQUATE experiment begins with an HMBC‐type ⁿJ_CH magnetization transfer, which leads to inherently lower sensitivity than the 1,1‐ and 1,n‐ADEQUATE experiments that begin with a ¹J_CH transfer. These attributes, in tandem, serve to render the n,1‐ADEQUATE experiment less generally applicable and more difficult to interpret than the 1,n‐ADEQUATE experiment, which can in principle afford the same structural information. Unsymmetrical and generalized indirect covariance processing methods can complement and enhance the structural information encoded in combinations of experiments e.g. HSQC‐1,1‐ or ?1,n‐ADEQUATE. Another benefit is that covariance processing methods offer the possibility of mathematically combining a higher sensitivity 2D NMR spectrum with for example 1,1‐ or 1,n‐ADEQUATE to improve access to the information content of lower sensitivity congeners. The covariance spectrum also provides a significant enhancement in the F₁ digital resolution. The combination of HMBC and 1,1‐ADEQUATE spectra is shown here using strychnine as a model compound to derive structural information inherent to an n,1‐ADEQUATE spectrum with higher sensitivity and in a more convenient to interpret single quantum presentation. Copyright © 2012 John Wiley & Sons, Ltd.     

Cycloaddition of Dialkylalumanyl Anion toward Unsaturated Hydrocarbons in (1+2) and (1+4) Modes

The reactivity of dialkylalumanyl anion ( 1 ) towards naphthalene, anthracene, diphenylacetylene, and (E)/(Z)-stilbenes was investigated. The compound 1 reacts with naphthalene and anthracene through (1+4) cyclization, giving Al-containing norbornadiene derivatives. In the reaction of 1 with diphenylacetylene and (E)/(Z)-stilbenes, (1+2) cyclization proceeded to form Al-C-C three-membered rings. Cyclization toward (E)- or (Z)-stilbenes solely gave a trans-cycloadduct. DFT calculations revealed that the cycloaddition of 1 with (Z)-stilbene proceeds via a single transition state with a carbanion character, which results in the selectivity towards the trans-cycloadduct.     

Synthesis of 1,2,4-triazole, 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole and 1,2,4-triazolo[3,4-b][1,3,4]thiadiazine derivatives of benzotriazole

A novel series of 1-(1-carbonylmethyl-1H-benzotriazole) thiosemicarbazides 3a-e was synthesized and then cyclized with sodium hydroxide to afford 1-(4-substituted-4H-1,2,4-triazole-3-thion-5-yl)methyl-1H-benzotriazoles 4a-e , which were alkylated with ethyl iodide to l-(3-ethylthio-4-substituted-4H-1,2,4-triazol-5-yl)-methyl-1H-benzotriazoles 5b-e . The reaction of 1H-benzotriazol-1-acetic acid hydrazide ( 2 ) with carbon disulphide and potassium hydroxide followed by hydrazine hydrate gave 1-(4-amino-4H-1,2,4-triazole-3-thion-5-yl)methyl-1H-benzotriazole ( 6 ). Its subsequent condensation with carboxylic acids in the presence of phosphorus oxychloride or with phenacyl bromides afforded two series of fused heterocycles namely; 6-substituted-3-[1-(1H-benzotriazole)methyl]-1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles 7a-e and 6-substituted phenyl-3-[1-(1H-benzotriazole)methyl]-7H-1,2,4-triazolo[3,4-b][1,3,4]thiadiazines 8a-e respectively. The structure of the newly synthesized compounds was elucidated by elemental analyses, ir and nmr spectra.     

Benzimidazole condensed ring systems. 2. New synthesis of substituted 1-oxo-1H,5H-pyrido[1,2-a]benzimidazole-4-carbonitriles and related derivatives

The synthesis of some 3-substituted and 2,3-disubstituted-1-oxo-1H,5H-pyrido[1,2-a]benzimidazole-4-carbo-nitriles 5,6 by fusing 1H-benzimidazole-2-acetonitrile 1 with some β-keto esters 2,4 in the presence of ammonium acetate or with ethyl β-aminocrotonate 3 is described. The tricyclic compounds were converted to their N-5 methyl of N-5 ethyl derivatives 8,9. Vilsmeir-Haack formylation of 3-methyl-1-oxo-1H,5H-pyrido[1,2-a]-benzimidazole-4-carbonitrile 5a afforded its 2-formyl derivative 10. Chlorination of 5 and 6 with phosphorus oxychloride yielded the respective 1-chloropyrido[1,2-a]benzimidazole-4-carbonitriles 11,12 which were utilized to prepare the 1-azido, 1-amino, 1-piperidino and 1-methoxy derivatives of the ring system. Compound 11a exhibited strong in vitro activity against S. aureus. Four compounds were screened against P-388 lymphocytic leukemia in mice but were inactive.     

Naphtho[1′,2′:5,6] pyrano[2,3-c] pyrazole derivatives

Reaction of 1-oxo-3-dialkylamino-1 H-naphtho[2,1-b]pyrans with N,N-dimethylformamide in the presence of phosphorus oxychloride afforded the corresponding 1-oxo-2-formyl-3-dialkyl-amino-1H-naphtho[2,1-b]pyrans. Condensation of 1-oxo-2-formyl-3-dimethylamino-1H-naphtho[2,1-b]pyran with hydrazine or monosubstituted hydrazines was found to lead to the formation of 8-alkyl(aryl)-1 1-oxo-8H,1 1H-naplitho[1′,2′:5,6] pyrano[2,3-c]pyrazoles through the intermediate hydrazones and subsequent cyclization. The same result was achieved starting from other 3-dialkylamino derivatives but in a lower yield.     

Asymmetric synthesis of tertiary alcohols from α-halo boronic esters

Reaction of pinanediol boronates with (1,1-dichloroethyl)lithium generated in situ at −78°C followed by rearrangement of the resulting borate complex 2S in the presence of zinc chloride at 25°C has resulted in chirally biased insertion of the 1-chloroethyl group into the carbon–boron bond. (s)-Pinanediol phenylboronate ( 7 ) produced (s)-pinanediol (1S)-(1-chloro-1-phenylethyl)boronate ( 8S ) in 92% DE. Nonstererospecific reaction with ethylmagnesium bromide to form (s)-pinanediol (1S)-(1-phenyl-1-methylpropyl)boronate ( 5S ) reduced the DE to 88%. Peroxidic deboronation yielded (R)-(+)-2-phenyl-2-butanol ( 6R ) (84% EE). (s)-Pinanediol ethylboronate ( 4 ) with (1,1-dichloroethyl)lithium showed the opposite chiral preference, yielding (s)-pinanediol (1R)-(1-chloro-1-methylpropyl)boronate ( 3R ) (89% DE), which was converted by phenylmagnesium bromide followed by hydrogen peroxide to 6R (76% EE). Diastereoselections were small in reactions of (1,1-dichloroethyl)-lithium with n-alkylboronates 9a and 13 and with cyclohexylboronate 9c . The 13 was converted to the enantiomer of the insect pheromone frontalin ( 17 ) (21% EE). Good diastereoselections were found with α-substituted alkylboronates 9b and 18 , but the configurations of the products could not be determined. (s)-Pinanediol (1,1-dichloroethyl)boronate ( 1 ) reacts with Grignard reagents via an intermediate borate 2R with negligible diastereoselection.     

Isolation and Characterization of a Novel Plasma Membrane Intrinsic Protein Gene, <Emphasis Type="Italic">LcPIP1</Emphasis>, in <Emphasis Type="Italic">Leymus chinensis</Emphasis> that Enhances Salt Stress Tolerance in <Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis>

A novel plasma membrane intrinsic, LcPIP1, was isolated from Leymus chinensis using RACE method. The LcPIP1 has 288 amino acids with an estimated molecular mass of 30.6 kDa. Semi RT-PCR analysis indicated that the expression level of LcPIP1 was obviously higher in leaf than root. The LcPIP1 was also found to be induced by salt stress. In addition, transformed with the LcPIP1, Saccharomyces cerevisiae could increase tolerance to salt stress. These results indicate that the LcPIP1 gene seems to play a role in resistance against salt stress.