New syntheses and spectral properties of pteridine‐related heterocycles from 2,5‐diamino‐3,6‐dicyanopyrazine

The reaction of 2,5‐diamino‐3,6‐dicyanopyrazine ( 1 ) as a new pyrazine raw material with alkyl isocyanate in the presence of sodium hydride gave novel heptahydroirnidazo[4,5‐g]pteridine‐2,6,8‐trione ( 2 ), but with tertiary butyl isocyanate gave trihydroimidazo[4,5‐b]pyrazine‐2‐ones ( 3 ). Similar reaction of 1 with alkyl thioisocyanate followed by alkyl iodide gave tetrahydropyrimido[4,5‐g]pteridines ( 4 ). The reac tion of 1 with alkylamine gave the amine‐adduct of the cyano groups which was further reacted with arylaldehyde to give the pyrimido[4,5‐g]pteridine ( 10 ). The products prepared are all of interest as potential pesticides and fluorescent chromophores.     

Synthesis and Complexing Properties of Alkyl (3-Oxo-2,3-dihydrothiophen-2-ylidene)- and (4-Oxothiazolidin-5-ylidene)acetate Derivatives

Condensation of dimethyl and diethyl acetylenedicarboxylate with thioacetamides gave the corresponding alkyl (3-oxo-2,3-dihydrothiophen-2-ylidene)- and (4-oxothiazolidin-5-ylidene)acetates. Treatment of these compounds with zinc in acetic acid resulted in reduction of the exocyclic double bonds. The products can be used in membrane processes as sodium cation carriers.     

Reduction of organic halides with lanthanum metal: a novel generation method of alkyl radicals

Results of the reaction of alkyl halides with lanthanum metal have been shown. The reduction of alkyl iodide with 1/3 equiv of lanthanum metal efficiently proceeded to give the corresponding reductive dimerized products along with the formation of reduction and dehydroiodination products. In the case of alkyl bromides and chlorides, the reaction did not proceed under the same reaction conditions as that of alkyl iodides; however, the reaction was dramatically promoted by the addition of a catalytic amount of iodine. A reaction pathway including alkyl radicals was suggested.     

Reductive Activation of Arenes: XV. Anionic Products of m-Tolynitrile Reduction with Sodium in Liquid Ammonia, and Their Alkylation

From results of oxidation, protonation, and alkylation of the products arising in one- or two- electron reduction of m-tolunitrile with sodium in liquid ammonia followed a conclusion that these products are respectively anion-radical of the compound and 3-methyl-1-cyano-2,5-cyclohexadienyl anion. The reaction of both reduction products with alkyl halides gives rise to compounds of ipso-alkylation with respect to cyano group: the corresponding alkyltoluenes and 1-alkyl-3-methyl-1-cyclohexadienes. The ratio of these products depends on the structure of alkyl halide. The possibility to prepare selectively m-alkyltoluenes by reaction of the product of two-electron reduction of m-tolunitrile with alkyl halides was demonstrated.     

Reaction of arylsulfonylhydrazones of aldehydes with alpha-magnesio sulfones. A novel olefin synthesis

Reactions of representative tosylhydrazones of aldehydes and ketones with alpha-metalated sulfones were examined in order to develop a practical olefination method. Treatment of aldehyde tosylhydrazone 2 with an excess of alpha-lithiated methyl phenyl or dimethyl sulfones yielded 3a. The reaction of 2 with sterically unhindered lithiated alkyl sulfones gave mixtures of the respective olefination products 3b-d along with the Shapiro fragmentation product 4. Sterically hindered lithiated sulfones afforded Shapiro products exclusively. In contrast, aldehyde tosylhydrazones 2 or 6 in reactions with a variety of alpha-magnesio primary or secondary alkyl sulfones gave olefination products 3a-j and 7a-c in high yields (Tables 1 and 2). beta-Branched alkyl sulfones afforded predominantly (E)-alkenes, whereas unhindered primary sulfones gave mixtures of (E)- and (Z)-alkenes with low selectivity. Reaction of the 2,4,6-triisopropylbenzenesulfonylhydrazone (trisylhydrazone) of cyclodecanone 11c with alpha-magnesio methyl phenyl sulfone afforded the methylidene derivative 12a contaminated with the Shapiro product 13. Tosylhydrazone 2 resisted reaction with i-PrMgCl and gave only a small amount of the addition product in reaction with Bu(2)Mg. Some mechanistic aspects of the reaction of tosylhydrazones with organomagnesium compounds are discussed.     

Alkylation of pyridine-3,5-dicarboxamide and pyridine-3,5-dicarbonitriles by radical substitution

Structural modification of NAD(P) model compounds, N,N,N',N'-tetramethylpyridine-3,5-dicarboxamide ( 1 ), pyridine-3,5-dicarbonitrile ( 2 ), and 4-methylpyridine-3,5-dicarbonitrile ( 3 ), have been explored by the reaction with alkyl radicals such as the 1-adamantyl, tert-butyl, and isopropyl radicals. The alkyl substitutions of compounds 1 , 2 , and 3 with the 1-adamantyl and the tert-butyl radical gave both 2-mono and 2,6-disubstitution products, whereas the reaction of compound 2 with the isopropyl radical gave 2-mono 6c , 2,4-di 7c, 2,6-di 8c , and 2,4,6-trisubstitution 9c products.     

Formation of 3-Bromo-1,5- and −1,7-Azulenequinones from 1-Alkyl-and 1-Phenylazulenes by Substituent Extrusion on the Bromine- Oxidation in Aqueous THF. Remarkable Substituent Effects on the Product Distribution

Oxidation of 1-ethyl-, 1-propylazulenes, and their 5-isopropyl derivatives with bromine gave 3-bromo-1,5- and 3-bromo-l,7-azulenequinones (Type A) together with 3-bromo-l-hydroxy-5-isopropyl-l-alkylazulen-7-one and its isomeric products (Type B), while the same reaction of 1-methylazulenes afforded Type B products along with many unidentified products. On the other hand, 1-phenylazulene gave 3-phenyl-1,5- and 3-phenyl-l,7-azulenequinones (Type C) and Type B products in high yie]ds. 1,2-Polymethyleneazulenes afforded a considerable amount of 3-bromo-2-(ω-formylalkyl)azulenequinones together with Type B products. Possible pathways for the extrusion of the alkyl substituent at C-l are discussed.     

New method for C-H arylation/alkylation at α-position of cyclic aliphatic ethers by iron-oxide mediated reaction

We report a new and efficient iron oxide catalyzed cross-coupling reaction between organometallic species such as alkyl/arylmagnesium halides or organolithium species and α-hydrogen bearing cyclic unbranched and branched aliphatic ethers via activation of C(sp(3))-H. In the presence of 1 mol% of iron oxide, five and six membered unbranched cyclic ethers such as tetrahydrofuran and tetrahydropyran gave good to excellent yields of cross-coupled products. Whereas, in case of branched ether such as 2-methyltetrahydrofuran, it was observed that the arylation occurred at both the sides and gave moderate yields of a mixture of regioisomers. Among the organometallic species used, alkyl organometallic reagents gave less yields as compared to aryl organometallics.     

Organocerium reagents from iodine activated cerium metal and organic iodides: Their reactions with carbonyl compounds

Cerium metal activated by a trace of iodine reacted smoothly with alkyl, allyl, and aryl iodides to give the corresponding organocerium reagents. The reaction of the organocerium reagents thus prepared in situ with carbonyl compounds gave not only Grignard-type adducts but also reduction and reductive coupling products.     

Oxidation of 3‐Furfurylcarbinols with Bromine in Acetone‐Water

Oxidation of 3‐furfurylcarbinols 3a‐e and 7 with bromine in acetone‐water solution gave the 2‐substituted‐3‐furfurals 4a‐e and 8 in good yields, respectively. Reaction of 2‐alkyl‐3‐furfurylcarbinols 9a and 9b with bromine in acetone‐water gave the bromoalkyl 3‐furfuryl ketones 10a and 10b as the major products. A reaction mechanism via the cis‐trans isomerization of the 2‐ene‐1,4‐diones 13 and 14 was proposed to account for the transposition of the alkyl group of the 3‐furfurylcarbinols 3, 7 and 9 to the 2‐position on the furan ring of the products 4, 8 and 10.     

Novel nucleophilic substitution of alkyl bromo-2(1H)-pyridones

Nucleophilic substitution of certain alkyl bromo-2(1H)-pyridones gave some unexpected products where the alkyl group is substituted and the ring bromine is replaced by hydrogen. The expected ring substituted product is also formed, but only as the minor product in most cases. Many reactions are cited with various nucleophiles, and a plausible mechanism is also presented.     

C(arenium)-C(alkyl) bond making and breaking: key process in the platinum-mediated C(aryl)-C(alkyl) bond formation. Analogies to organic electrophilic aromatic substitution

The reaction of cationic platinum aqua complexes 2 [Pt(C(6)H(2)[CH(2)NMe(2)](2)-E-4)(OH(2))](X') (X' = SO(3)CF(3), BF(4)) with alkyl halides RX gave various air-stable arenium complexes 3-5 containing a new C-C bond (R = Me, 3; Et, 4; Bn, 5). Electron-releasing oxo-substituents on the aromatic ligand (E = e.g., OH, b; OMe, c) enhance the reactivity of the aqua complex 2 and were essential for arenium formation from alkyl halides different from MeX. This process is initiated by oxidative addition of alkyl halides to the platinum(II) center of 2, which affords (alkyl)(aryl) platinum(IV) complexes (e.g., 9, alkyl = benzyl) as intermediates. Spectroscopic analyses provided direct evidence for a subsequent reversible 1,2-sigmatropic shift of the alkyl group along the Pt-C(aryl) bond, which is identical to repetitive C(arenium)-C(alkyl) bond making and breaking and concerted metal reduction and oxidation. Temperature-dependent NMR spectroscopy revealed DeltaH degrees = -1.3 (+/- 0.1) kJ mol(-1), DeltaS degrees = +3.8 (+/- 0.2) J mol(-1) K(-1), and DeltaG degrees (298) = -2.4 (+/- 0.1) kJ mol(-1) for the formation of the arenium complex 5b from 9 involving the migration of a benzyl group. The arenium complexes were transformed to cyclohexadiene-type addition products 7 or to demetalated alkyl-substituted arenes, 8, thus completing the platinum-mediated formation of a sp(2)-sp(3) C-C bond which is analogous to the aromatic substitution of a [PtX](+) unit by an alkyl cation R(+). The formation of related trimethylsilyl arenium complexes 6 suggests arenium complexes as key intermediates, not only in (metal-mediated) sp(2)-sp(3) C-C bond making and breaking but also in silyl-directed cyclometalation.     

Combinatorial liquid-phase synthesis of structurally diverse benzimidazole libraries

An expedient liquid-phase synthesis for construction of the diverse benzimidazole libraries is described. Nucleophilic aryl substitution of poly(ethylene glycol)-supported 4-fluoro-3-nitrobenzoic acid 3 with several primary amines under basic conditions, followed by Zn/NH(4)Cl mediated nitro group reduction, gave the PEG bound diamines 5. Subsequent cyclization of immobilized o-phenylenediamine 5 using thiocarbonyldiimidazole (TCD) or thiophosgene in dichloromethane furnished benzimidazole-2-thiones 6. Treatment of 6 with alkyl halides and benzylic halides in the presence of triethylamine provided 1-substituted-2-alkylthio-5-carbamoylbenzimidazoles on the support. The desired products 8 were severed from the PEG under mild conditions in high yield and high purity.     

双环戊二烯基二氯化钛催化下格氏试剂与偕二卤代烷的反应

近年来,双环戊二烯基二氯化钛在有机合成中的应用得到迅速发展,从而开发了多种新型反应。其中双环成二烯基二氯化钛催化下,Grignard试剂的还原反应是研究得极为广泛的一类新反应。Cp_2Ticl_2/RMgX体系可以还     

Synthesis of α‐alkylidene‐γ‐butyrolactones via Ring‐cleavage/recyclization of 2‐Amino‐4,5‐dihydro‐3‐furancarboxamides

The reactions of 2‐amino‐4,5‐dihydro‐3‐furancarboxarnides 1a,b with cyanomethylene compounds (such as alkyl cyanoacetates and malononitrile) gave the corresponding ring‐opened products 2a‐f. Compounds 2a‐d reacted with methanesulfonic acid to give the corresponding α‐alkylidene‐γ‐butyrolactones 3a‐d. On the other hand, treatment of 2e,f with methanesulfonic acid yielded 3‐pyridinecarbonitrile derivatives 4a,b.     

Structural requirements in chiral diphosphine-rhodium complexes—XIII: Steric and electronic factors in the asymmetric homogeneous hydrogenation of Z-α-acylaminocinnamic acids and esters catalyzed by rhodium(I) complexes

Z-α-acylaminocinnamic acids and esters were hydrogenated with rhodium(I) complexes containing (4R,5R) - trans - 4,5 - bis(diphenylphosphinomethyl) - 2,2 - dimethyl - 1,3 - dioxolan (DIOP). Increasing the steric bulk of the acyl function (NHCOR, where R is an alkyl moiety) resulted in a lowered reduction of the si-re prochiral face to yield a decreasing excess of the (R)-amino acid derivatives. In the series of N-acylphenylalanine free acids (resulting from hydrogenation of Z-α-acylaminocinnamic acids) the optical purity decreased from 82% ee-(R) [Me]; 57% ee-(R) [i-Pr]; 52% ee-(R) [t-Bu]; to 46% ee-(R) [1-adamantyl]. Theα-benzamido, α-formamido and α-trifluoroacetamido substrates gave hydrogenation products having 68% ee-(R) [Ph]; 60% ee-(R) [H]; and 16% ee-(R)[CF₃]. In the corresponding methyl esters, increasing the steric bulk of the acyl function (NHCOR) resulted in a markedly greater decrease in enantioface differentiation. In the series of N-acylphenylalanine methyl ester products (resulting from hydrogenation of Z-methyl α-acylaminocinnamates) the optical purity decreased from 69% ee-(R)[Me]; 15% ee-(R) [i-Pr]; to 0% ee[t-Bu and 1-adamantyl]. The α-benzamido, α-formamido, and α-trifluoroacetamido substrates gave hydrogenation products having 36% ee-(R) [Ph]; 58% ee-(R) [H]; and 22% ee-(S) [CF₃]In the series of N-acetylphenylalanine alkyl ester products (resulting from hydrogenation of Z-alkyl α-acetamidocinnamate esters) trifluoro substitution in the alkyl alcohol moiety resulted in a decrease in optical purity to 52% ee-(R) [CH₂CF₃] compared to 72, 76 and 77% ee-(R) [Et, i-Pr and t-Bu, respectively].     

Synthesis of and tautomerism in 3-acyltetramic acids

The synthesis of 3-acyltetramic acids, the substructure of bioactive natural products, via O-acylation of tetramic acids with carboxylic acids followed by acyl migration, has been investigated. This acylation sequence is mediated by N,N'-dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) and is very sensitive to the nature of the nitrogen substituent (R(1)), the nature of the carboxylic acid (R(2)CO(2)H), and the amount of DMAP. Acylation of N-acyl tetramic acids with an alkyl carboxylic acid using 1.3 equiv of DMAP (with 1.1 equiv of DCC) unexpectedly gave the 3-acyltetramic acid directly as a result of acyl migration induced by excess amounts of DMAP. On the other hand, N-unsubstituted, N-alkyl, and N-acyl tetramic acids with alkyl and aromatic carboxylic acids gave the O-acyl tetramic acids by using only 0.1 equiv of DMAP (with 1.1 equiv of DCC); these could be further rearranged to the acyl product by treatment with excess DMAP. The tautomeric equilibrium of these 3-acyltetramic acids in solution was found to strongly depend on the nitrogen substituent group (R(1)) rather than the 3-acyl group.     

Reactions of piroxicam with alkyl iodides

Alkylation of piroxicam with a homologous series of alkyl iodides gave reversibly formed O-alkyl products 1 as well as unexpected, irreversibly formed zwitterionic compounds 2 , alkylated on the pyridine nitrogen, and O,N-bis-alkyl products 3 . Proof of structure was accomplished by nmr and X-ray crystal analysis. Product distribution ratios were determined by hplc and are explained by the Hard-Soft Acid-Base principle.     

A green and highly efficient alkylation of thiols in water

An environmentally benign and efficient process for the preparation of thioethers was developed by simple and practical reactions of alkyl halides and thiols in water in the presence of K₂CO₃ or Et₃N in very high yields. The reaction of aryl, alkyl, aliphatic and hindered thiols with various alkyl halides gave the corresponding products with significant advantages such as high conversions, short reaction time, mild reaction conditions, and low cost, simple workup with good to quantitative yields.     

Synthetic Applications of 3‐(Phenylsulfinyl)‐3‐sulfolene

The title compound 2 was readily prepared by MCPBA oxidation of the sulfide 1. Thermal desulfonylation of 2 gave the sulfoxide‐substituted diene 3. The Diels‐Alder reactions of 3 with various dienophiles gave the cyclized products 4‐9 in good yields. The regiochemistry was found to be dominated by the phenylsulfinyl group, but could be reversed by the presence of a Lewis acid. Deprotonation of 2 by BuLi, followed by the reaction with alkyl halides, gave the substituted 2‐sulfolenes 10. A synthetic application of 10 was demonstrated by converting 10e to the bicyclic product 11.