Rapid and efficient one-pot synthesis of 1,4-dihydropyridine and polyhydroquinoline derivatives through the Hantzsch four component condensation by zinc oxide

A one-pot four-component reaction of aldehydes, ethyl acetoacetate/5,5-dimethyl-1,3-cyclohexanedione, ethyl acetoacetate and ammonium acetate in the presence of 10 mol% of ZnO as a heterogeneous catalyst for the synthesis of corresponding 1,4- dihydropyridine and polyhydroquinoline derivatives via the Hantzsch condensation is described. The present methodology offers several advantages such as simple procedure, excellent yields, and short reaction time.     

A short and efficient synthesis of (R)-(−)-sporochnol A

A short and efficient synthesis of (R)-(−)-sporochnol A in five steps and 9% overall yield has been developed. The sequence uses as starting material the easily available enantiopure monoketal derived from 1,4-cyclohexanedione and (R,R)-hydrobenzoin that serves as a chiral auxiliary.     

Uncatalysed oscillatory chemical reactions. Oxidation of 1,4-cyclohexanedione by bromate in sulfuric or nitric acid solution

Uncatalysed oxidation of 1,4-cyclohexanedione by acidic bromate has been found to generate chemical oscillations with very interesting features. Moreover this new oscillating reaction can take place in a sulfuric as well as in a nitric acid solution.     

The mechanism of 1,4 alkyl group migration in hypervalent halonium ylides: the stereochemical course

Rhodium(II)-acetate-catalyzed decomposition of either 1,3-cyclohexanedione phenyliodonium ylide or 5,5-dimethyl-1,3-cyclohexanedione phenyliodonium ylide in the presence of alkyl halides yields the corresponding 3-alkoxy-2-halocyclohex-2-enones via a 1,4 alkyl group migration shown to be concerted and intramolecular. In the case of (S)-alpha-phenethyl chloride, the rearrangement proceeds with essentially 88.6% retention of configuration. Theoretical calculations at the B3LYP/6-31G level reveal an activation energy of 5.4 kcal/mol for the process. A Claisen-like rearrangement occurs in the case where allylic halides, such as dimethylallyl or methallyl chorides, are used. The mechanistic pathway proposed for these processes involves addition of the halogen atom of the alkyl or allyl halide to the rhodium carbenoid from the iodonium ylide to yield a halonium intermediate that undergoes halogen to oxygen group migration. Aryl halides, such as chloro-, bromo-, iodo-, and fluorobenzene, behave differently under the same reaction conditions, yielding the product of electrophilic aromatic substitution, namely, the 2-(4-halophenyl) 1,3-cyclohexanedione.     

Synthesis of spiro polymers,

Synthesis of the first totally organic spiro polymer was accomplished by the reaction of 1,4-cyclohexanedione and pentaerythritol in benzene plus a trace of p-toluenesulfonic acid to produce the polyspiroketal. The polymer did not melt, but began to decompose at 350°C. Although it was insoluble in most common solvents, it was found to be soluble in hexafluoroisopropanol. The x-ray diffraction indicated the polymer was very highly crystalline. A series of lower molecular weight related polymers were prepared by carrying out a similar condensation with a mixture of 1,4-cyclohexanedione containing 5–50 mole-% of cyclohexanone. In order to prepare a material with greater solubility, a polyspiroketal was prepared from 1,10-cyclooctadecanedione plus pentaerythritol. This polymer was soluble not only in hexafluoroisopropanol, but to a limited extent in dimethyl sulfoxide.     

The 1,4-cyclohexanedione-bromate-acid oscillatory system I. Its organic chemistry

The organic chemistry of the 1,4-cyclohexanedione (CHD)-bromate-sulfuric acid oscillatory system has been revealed by following the reaction of 1,4-CHD with bromate using a GC/MS technique. We could identify 1,4-dihydroxybenzene as an intermediate, 1,4-benzoquinone as the main oxidation, and mono- and dibromocyclohexanedione as the main bromination products. Acid bromate does not cleave the alicyclic ring.     

Synthesis of a spirobenzothiazoline polymer and its thermal rearrangement to a polydihydrobenzothiazine

The reaction of 3,3′-dimercaptobenzidine with 1,4-cyclohexanedione leads to a soluble, high molecular weight, spirobenzothiazoline polymer. Above 200°C the spirolinks of this polymer rearrange into a ladder structure leading to a polydihydrobenzothiazine.     

Synthesis of derivatives of ketocarboxylic acids by the decomposition of 1,4-cyclohexanedione monoethyleneketal hydroperoxide

The decomposition of 1,4-dihydroxy-1,4-dihydroperoxycyclohexane under the action of FeSO₄ and the decomposition of 1,4-cyclohexanedione monoethyleneketal hydroperoxide under the action of Fe^II salts in the presence of various ligands or under the action of Cu^II sulfate have been studied. A preparative method for the synthesis of derivatives of diketodicarboxylic or -functionally substituted ketocarboxylic acids from 1,4-cyclohexanedione monoethyleneketal has been developed.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1231–1235, July, 1993.     

Kinetic parameters of radical reactions of 2-mercaptobenzothiazole with quinone imines

The chain reaction of N,N′-diphenyl-1,4-benzoquinone diimine with 2-mercaptobenzothiazole was studied by two methods developed earlier for the nonchain reaction of N-phenyl-1,4-benzoquinone monoimine with 2-mercaptobenzothiazole. In the methods used, the kinetic scheme of the reaction is simplified by creating conditions under which the rates of all stages except radical generation and decay can be neglected. One of the methods was updated. For the nonchain reaction of N-phenyl-1,4-benzoquinone monoimine with 2-mercaptobenzothiazole, both methods gave close results; for the chain reaction of N,N′-diphenyl-1,4-phenylenediamine with 2-mercaptobenzothiazole, the results differed by approximately one order of magnitude.     

Silica-supported perchloric acid (HClO4–SiO2): a mild, reusable and highly efficient heterogeneous catalyst for multicomponent synthesis of 1,4-dihydropyridines via unsymmetrical Hantzsch reaction

Facile synthesis of some 1,4-dihydropyridine derivatives via Hantzsch reaction of 5,5-dimethyl-1,3-cyclohexanedione (dimedone), 1,3-diphenyl-2-propen-1-one derivatives and ammonium acetate under solvent-free condition in the presence of silica-supported perchloric acid (HClO₄–SiO₂) is described. The catalyst is easily prepared, stable, reusable and efficient under the reaction conditions.     

对苯二甲醛或间苯二甲醛与5，5-二甲基-1，3-环己二酮的反应：含有双4（日）-吡喃、1，4-二氢吡啶结构单元的杂环化合物的合成

用对苯二甲醛或间苯二甲醛与5，5-二甲基-1，3-环己二酮反应，在不同条件下得到了含有双4(H）-吡喃、1，4_二氢吡啶结构单元的双一氧杂蒽衍生物、双-吖啶衍生物、以及双-AL羟基吖啶衍生物．     

Stereoselective cascade reactions for construction of polyfunctionalised octahydroquinolines via [2C+2C+1C,1N] cyclisation

A conceptually unifying approach for a highly enantio- and diastereoselective synthesis of polyfunctionalised octrahydroquinolines incorporating three contiguous chiral centres is reported. The synthesis involves diphenylprolinol silyl ether-catalysed Michael addition of 1,3-cyclohexanedione to nitroalkenes followed by potassium carbonate-promoted aza-Henry reaction with N-tosyl aldimines, intramolecular hemiaminalisation and dehydration reaction cascade in a one-pot operation.     

Polyethylene glycol (PEG-400): an efficient and recyclable reaction medium for the synthesis of pyrazolo[3,4-b]quinoline derivatives

A simple, efficient, and eco-friendly synthetic protocol has been developed via one pot three-component reaction between aldehyde, amino pyrazole, and 1,3-cyclohexanedione by using recyclable polyethylene glycol (PEG)-400 as a reaction medium. Utilizing this protocol a variety of pyrazolo[3,4-b]quinoline derivatives were synthesized in excellent yields.     

Synthesis of zwitterionic salts via three component reactions of nitrogen-containing heterocycles, acetylenedicarboxylate and cyclic 1,3-dicarbonyl compounds

A practical synthetic procedure for the preparation of the charge-separated pyridinium-Meldrum acid zwitterionic salts was developed through a unique one-pot three component reaction of pyridine, acetylenedicarboxylate and Meldrum acid. Other nitrogen-containing heterocycles such as N-methylimidazole, 2-picoline, quinoline, isoquinoline and other cyclic 1,3-dicarbonyl compounds such as 1,3-cyclopentanedione, 1,3-cyclohexanedione, barbituric acid also took part in the reaction to give corresponding zwitterionic salts in moderate yields, respectively. In one case an unusual isoquinolinium 1,3-cyclopentanedionate was obtained. A feasible explanation is given for this novel one-pot tandem reaction and the formation of different kinds of products.     

A convenient and mild synthesis of new 2-aryl-3-hydroxy-6,7-dihydro-1H-indol-4(5H)-ones via a one-pot,three-component reaction in water

A simple and convenient synthesis of 2-aryl-3-hydroxy-6,7-dihydro-1H-indol-4(5H)-ones is achieved in high yields via the one-pot, three-component reaction of arylglyoxals, 1,3-cyclohexanedione, and ammonium acetate in water under reflux conditions.     

Microwave-enhanced Pd(0)/acetic acid catalyzed allylation reactions of C, N, and O-pronucleophiles with alkynes

An efficient method for the allylation of C, N, and O-nucleophiles with alkynes under solvent-free conditions and by microwave activation is established. The process can be termed as a real eco-chemical process since no waste elements are produced in the reaction, moreover it is solvent free. This technique can also be used for the allylation of dimethyl methylmalonate, which proves inert under the previously reported reaction conditions (refluxing in 1,4-dioxane).     

A novel enzymatic tandem process: utilization of biocatalytic promiscuity for high stereoselective synthesis of 5-hydroxyimino-4,5-dihydrofurans

A lipase-catalyzed protocol for the synthesis of 5-hydroxyimino-4,5-dihydrofurans via tandem coupling between β-nitrostyrenes and 1,3-dicarbonyl compounds was developed in a ‘one-pot’ strategy. A series of β-nitrostyrenes were employed to expand the scope of this new biocatalytic promiscuity with high stereoselectivity (Z/E up to 99:1) and moderate to good yields. The reaction activity of 1,3-cyclohexanedione was found to be better than linear 2,4-pentanedione, while ethyl acetoacetate and diethylmalonate were not suitable for this reaction under the same conditions. Single-crystal X-ray diffraction analysis indicated that the reaction was stereoselective and Z-stereomer was found to be the major product. A reaction mechanism was supposed to elucidate the biocatalytic process.     

Direct asymmetric Michael reactions of cyclic 1,3-dicarbonyl compounds and enamines catalyzed by chiral bisoxazoline-copper(II) complexes

The catalytic direct Michael addition of cyclic 1,3-dicarbonyl compounds and enamines to unsaturated 2-ketoesters is presented. A series of different 4-hydroxycoumarins, 4-hydroxy-6-methyl-2-pyrone, 3-hydroxy-1H-phenalene-1-one, 2-hydroxy-1,4-naphthoquinone, 5,5-dimethyl-1,3-cyclohexanedione, and various enamines of cyclic 1,3-diketones all add to unsaturated 4-substituted 2-ketoesters in an enantioselective manner. The reaction is catalyzed by chiral bisoxazoline-copper(II) complexes and proceeds in the absence of base to afford Michael adducts in good to high yields and with up to 98% ee. The products formed are substructures found in skeletons of important biological and pharmaceutical molecules. The scope and potential of the new reaction are discussed as well as the mechanism for the catalytic enantioselective reaction.     

Synthesis of polyhydroxylated bicyclic tetrahydrofurans and tetrahydropyrans via a stereoselective domino cyclization/reduction reaction

A novel reaction cascade involving a Lewis acid-induced migration of an isopropylidene protecting group followed by the formation of a pyranose or furanose ring and subsequent reduction of the hemiacetal is described. Depending on the reaction conditions, as well as, the stereochemistry of the substrate, polyhydroxylated tetrahydrofurans or tetrahydropyrans can be obtained in reasonable yields. The synthons used in this transformation were prepared via a highly stereoselective one-pot tandem reaction, consisting of a 1,4-Michael addition of vinylmagnesium bromide to d-glucose-derived cyclohexenone followed by aldol reaction with 2,3-O-isopropylidene-d-glyceraldehyde.     

Collective reaction behavior of an oscillating system coupled with an excitable reaction

The collective reaction behavior of limit cycles coupled to a nonoscillatory forcing is investigated experimentally and computationally. The coupled chemical system is constructed by adding 1,4-cyclohexanedione (CHD), a species which is capable of forming an oscillator with acidic bromate, into the cerium-catalyzed Belousov-Zhabotinsky reaction. Two levels of coupling exist in the system: (1) through autocatalytic reactions with bromine dioxide radicals and (2) via reactions with oxidized metal catalysts. Experiments illustrate that there is an optimum [1,4-CHD]/[cerium] ratio for inducing complex oscillations, whereas in the 1,4-CHD and malonic acid concentration phase plane two resonant ratios are observed for the onset of complex behavior. In addition, bromate, the oxidant for both suboscillators, also exhibits subtle influences on the complexity of the collective reaction behavior. The experimental observations are qualitatively reproduced with the Field-Koros-Noyes mechanism, modified to account for the coupling reactions with the 1,4-CHD-bromate system.