Theoretical study on the mechanism of reaction between 3‐hydroxy‐3‐methyl‐2‐butanone and malononitrile catalyzed by magnesium ethoxide

The mechanism of reaction between 3‐hydroxy‐3‐methyl‐2‐butanone and malononitrile for the synthesis of 2‐dicyanomethylene‐4,5,5‐trimethyl‐2,5‐dihydrofuran‐3‐carbonitrile catalyzed by magnesium ethoxide was investigated by density functional theory (DFT). The geometries and the frequencies of reactants, intermediates, transition states, and products were calculated at the B3LYP/6–31G(d) level. The vibration analysis and the IRC analysis demonstrated the authenticity of transition states, and the reaction processes were confirmed by the changes of charge density at bond‐forming critical point. The results indicated that magnesium ethoxide is an effective catalyst in the synthesis of 2‐dicyanomethylene‐4,5,5‐trimethyl‐2,5‐dihydrofuran‐3‐carbonitrile from malononitrile and 3‐hydroxy‐3‐methyl‐2‐butanone. The activation energy of reaction with magnesium ethoxide decreased by 102.37 kJ mol^?1 compared with that of the reaction without it. The mechanism of reaction with catalyst magnesium ethoxide differs from that of reaction without it. © 2008 Wiley Periodicals, Inc. Int J Chem Kinet 41: 227–235, 2009     

Darstellung von Bis‐(2‐chlorethyl)amino‐substituierten Diazaphosphorinonen. Reversible oxidative Addition von Hexafluoraceton an σ3λ3‐Phosphor‐Verbindungen. Synthese von σ5λ5‐Spirophosphoranen und deren Zersetzung

Synthesis of Bis‐(2‐chloroethyl)amino‐substituted Diazaphosphorinones. Reversible Oxidative Addition of Hexafluoroacetone to σ³λ³‐Phosphorus Compounds. Synthesis of σ⁵λ⁵‐Spirophosphoranes and their Decomposition The reaction of 1‐methyl‐pyrido[3,2‐e]‐3,1‐oxazin‐2,4‐dione ( 1 ) with benzylamines led to the aminonicotinic acid amides 2 – 4 . Their reaction with phosphorus trichloride furnished the P‐chloro‐pyridodiazaphosphorinones 5 – 7 , which, upon reaction with bis‐(2‐chloroethyl) ammonium chloride/triethylamine, were converted into the P‐bis‐(2‐chloroethyl)amino‐substituted pyridodiazaphosphorinones 8 – 10 . The P‐chloro‐benzodiazaphosphorinone 11 was allowed to react with 2‐chloroethylammonium chloride/triethylamine to form the 2‐chloroethylamino‐substituted derivative 12 . The σ³‐diazaphosphorinones 8 , 9 , 12 and 13 were oxidized with the urea‐hydrogen peroxide‐(1 : 1)‐adduct to the corresponding phosphoryl derivatives 14 – 17 . The oxidative addition of hexafluoroacetone (HFA) to the σ³‐diazaphosphorinone 18 led, with abstraction of methyl chloride, to the tricyclic phosphorane 19 b . The spirophosphoranes 21 – 23 were formed by reaction of compounds 8 , 9 and 13 with HFA. NMR‐studies were made on the decomposition of the bicyclic phosphoranes 20 a , 22 and 23 . The oxidative addition of HFA to diazaphosphorinones was found to be reversible. Single crystal X‐ray determinations were conducted on compounds 17 and 19 b . They confirm the expected connectivity. Compound 17 was found to exhibit short C–H‥ O‐hydrogen bonds (H…O 234 pm). Compound 19 crystallises as two independent molecules which differ, e. g., in the orientation of the chloroethyl groups.     

Efficient Synthesis of α‐Benzylidene‐γ‐methyl‐γ‐butyrolactones

A concise synthesis of α‐benzylidene‐γ‐methyl‐γ‐butyrolactones 5a – g from substituted benzaldehydes is described. Compounds 1a – g on reaction with phosphorane 2 , provide the pentenoates 3a – g , which can be hydrolyzed to the acids 4a – g . The latter are cyclized to the corresponding butyrolactones 5a – g in excellent yields. The pentenoates 3a – g , on acid catalyzed cyclization, also provide 5a – g in very high yields.     

Synthesis of 3‐Ω‐amino‐2‐thiohydantoins

In the reaction of ethyl isothiocyanatoacetate with diamines, followed by cyclization of the intermediate product, 3‐monosubstituted thiohydantoins have been obtained. It was found that the reaction course depends on the purity of the isothiocyanate used and also, in the case of dialkylaminoamines, the self‐cyclization occurs. Besides the dialkylamino derivatives of 3‐monosubstituted 2‐thiohydantoins also new monoalkylamino, amino and heterocyclic derivatives were synthesized. The aryldiazonium derivative of 3‐monosubstituted 2‐thiohydantoin yielded both respective phenol derivative after hydrolysis and the product of coupling with 2‐naphthol.     

Behavior of 3(2‐pyridinylmethylene)‐5‐aryl‐2(3H)‐furanones and 3(3‐pyridinylmethylene)‐5‐aryl‐2(3H)‐furanones as alkylating agents: A comparative study

3(2‐pyridinylmethylene)‐5‐aryl‐2(3H)‐furanones and 3(3‐pyridinylmethylene)‐5‐aryl‐2(3H)‐furanones were prepared as a mixture of (E) and (Z) stereoisomers by condensing pyridine‐2‐carboxaldehyde and pyridine‐3‐carboxaldehyde with 3‐aroylpropionic acids. The reaction of the furanones 6 and 7 with anhydrous aluminium chloride in benzene led to the formation of 4,4‐diaryl‐1‐(2‐pyridinyl)but‐1,3‐diene ( 8 ) and 4,4‐diaryl‐1‐(3‐pyridinyl)but‐1,3‐diene ( 9 ) as mixtures of geometrical (E,E‐ and E,Z‐) stereoisomers via an intermolecular alkylation mode. When the reaction was carried out in tetrachloroethane as a solvent, the reaction of 6 gave 5‐arylquinoline‐7‐carboxylic acid via intramolecular alkylation mode. This may be considered as a novel method for the synthesis of quinoline derivatives. J. Heterocyclic Chem., (2011).     

Synthesis of 2‐(3‐indolyl)‐1,4‐naphthoquinones using 3‐iodoindoles

The usefulness of 3‐iodoindoles available for introduction of an indole unit is presented. The reaction of various halo‐3‐iodoindoles with 1,4‐naphthoquinone gave the corresponding 2‐(3‐indolyl)‐1‐4,naphthoquinones in moderate yields. The 3‐iodoindole was used for synthesis of a compound containing both naph‐thazarin and indole skeletons.     

Brominated Trihalomethylenones as Versatile Precursors to 3‐Ethoxy, ‐Formyl, ‐Azidomethyl, ‐Triazolyl,and 3‐Aminomethyl Pyrazoles

5‐Bromo[5,5‐dibromo]‐1,1,1‐trihalo‐4‐methoxy‐3‐penten[hexen]‐2‐ones are explored as precursors to the synthesis of 3‐ethoxymethyl‐5‐trifluoromethyl‐1H‐pyrazoles from a cyclocondensation reaction with hydrazine monohydrate in ethanol. 3‐Ethoxymethyl‐carboxyethyl ester pyrazoles were formed as a result of a substitution reaction of bromine and chlorine by ethanol. The dibrominated precursor furnished 3‐acetal‐pyrazole that was easily hydrolyzed to formyl group. In addition, brominated precursors were used in a nucleophilic substitution reaction with sodium azide to synthesize the 3‐azidomethyl‐5‐ethoxycarbonyl‐1H‐pyrazole from the reaction with hydrazine monohydrate. These products were submitted to a cycloaddition reaction with phenyl acetylene furnishing the 3‐[4(5)‐phenyl‐1,2,3‐triazolyl]5‐ ethoxycarbonyl‐1H‐pyrazoles and to reduction conditions resulting in 3‐aminomethyl‐1H‐pyrazole‐5‐carboxyethyl ester. The products were obtained by a simple methodology and in moderate to good yields.     

3‐Formylpyrroles from 3‐Furfurylamines by Bromine Oxidation Reaction

Oxidation of 3‐furfurylamines 3a‐e with bromine in acetone‐water solution gave N‐substituted 3‐formylpyrroles 4a‐e in good yields. A reaction mechanism via the Clauson‐Kaas reaction followed by the cis‐trans isomerization of the 2‐ene‐1,4‐diones 13 and 14 was proposed to account for the formation of the pyrroles 4a‐e .     

1‐Methyl‐3‐phenyl‐3‐thiocyanato‐1H,3H‐quinoline‐2,4‐dione: A novel thiocyanating agent

Under mild reaction conditions, the thiocyanato group is selectively transferred from 1‐methyl‐3‐phenyl‐3‐thiocyanato‐1H,3H‐quinoline‐2,4‐dione ( 3 ) to some nucleophiles. Aliphatic primary and secondary amines are converted to S‐cyanothiohydroxylamines, anilines afford p‐thiocyanatoanilines, Wittig reagent is thiocyanated in α‐position, and thiols are oxidized to disulfides.     

Synthesis of Bis‐Heterocyclic 1H‐Imidazole 3‐Oxides from 3‐Oxido‐1H‐imidazole‐4‐carbohydrazides

The reaction of 1H‐imidazole‐4‐carbohydrazides 1 , which are conveniently accessible by treatment of the corresponding esters with NH₂NH₂?H₂O, with isothiocyanates in refluxing EtOH led to thiosemicarbazides (=hydrazinecarbothioamides) 4 in high yields (Scheme 2). Whereas 4 in boiling aqueous NaOH yielded 2,4‐dihydro‐3H‐1,2,4‐triazole‐3‐thiones 5 , the reaction in concentrated H₂SO₄ at room temperature gave 1,3,4‐thiadiazol‐2‐amines 6 . Similarly, the reaction of 1 with butyl isocyanate led to semicarbazides 7 , which, under basic conditions, undergo cyclization to give 2,4‐dihydro‐3H‐1,2,4‐triazol‐3‐ones 8 (Scheme 3). Treatment of 1 with Ac₂O yielded the diacylhydrazine derivatives 9 exclusively, and the alternative isomerization of 1 to imidazol‐2‐ones was not observed (Scheme 4). It is important to note that, in all these transformations, the imidazole N‐oxide residue is retained. Furthermore, it was shown that imidazole N‐oxides bearing a 1,2,4‐triazole‐3‐thione or 1,3,4‐thiadiazol‐2‐amine moiety undergo the S‐transfer reaction to give bis‐heterocyclic 1H‐imidazole‐2‐thiones 11 by treatment with 2,2,4,4‐tetramethylcyclobutane‐1,3‐dithione (Scheme 5).     

Synthesis of (−)‐3‐Carene‐2,5‐dione via Allylic Oxidation of (+)‐3‐Carene

Activated carbon‐supported CuCl₂ (CuCl₂/AC) is a heterogeneous catalyst for the liquid‐phase selective allylic oxidation of (+)‐3‐carene with tert‐butyl hydroperoxide (TBHP) and O₂ to produce (?)‐3‐carene‐2,5‐dione. The possible reaction mechanism and the effects of different factors on the allylic oxidation were investigated. The optimal conditions are as follows: reaction temperature, 45 °C; molar ratio of CuCl₂ to (+)‐3‐carene, 1%; volume ratio of (+)‐3‐carene to TBHP, 1:3; and reaction time, 12 h. Under the optimal conditions, the conversion of (+)‐3‐carene reached 100%, whereas the selectivity for (?)‐3‐carene‐2,5‐dione reached 78%. The CuCl₂/AC catalyst was characterized via X‐ray diffraction, and the chemical structure of the target compound was identified via infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, mass spectrometry, and optical analysis.     

Kristallstrukturen und spektroskopische Eigenschaften von 2λ3‐Phospha‐1, 3‐dionaten und 1, 3‐Dionaten des Calciums ‐ ein Vergleich am Beispiel der 1, 3‐Diphenyl‐ und 1, 3‐Di(tert‐butyl)‐Derivate

Crystal Structures and Spectroscopic Properties of 2λ³‐Phospha‐1, 3‐dionates and 1, 3‐Dionates of Calcium ‐ Comparative Studies on the 1, 3‐Diphenyl and 1, 3‐Di(tert‐butyl) Derivatives A hydrogen‐metal exchange between dibenzoylphosphane and calcium carbide in tetrahydrofuran (THF) followed by addition of the ligand 1, 3, 5‐trimethyl‐1, 3, 5‐triazinane (TMTA) furnishes the binuclear complex bis[(tmta‐N, N′, N″)calcium bis(dibenzoylphosphanide)] ( 1a ) co‐crystallizing with benzene. Similarly, reaction of bis(2, 2‐dimethylpropionyl)phosphane with bis(thf‐O)calcium bis[bis(trimethylsilyl)amide] in 1, 2‐dimethoxyethane (DME) gives bis(dme‐O, O′)calcium bis[bis(2, 2‐dimethylpropionyl)phosphanide] ( 1b ) in high yield. The carbon analogues 1, 3‐diphenylpropane‐1, 3‐dione (dibenzoylmethane) or 2, 2, 6, 6‐tetramethylheptane‐3, 5‐dione (dipivaloylmethane) and bis(thf‐O)calcium bis[tris(trimethylsilylmethyl)zincate] in DME afford bis(dme‐O, O′)calcium bis(dibenzoylmethanide) ( 2a ) and the binuclear complex (μ‐dme‐O, O′)bis[(dme‐O, O′)calcium bis(dipivaloylmethanide)] ( 2b ), respectively. Dialkylzinc formed during the metalation reaction shows no reactivity towards the 1, 3‐dionates 2a and 2b . Finally, from the reaction of the unsymmetrically substituted ligand 2‐(methoxycarbonyl)cyclopentanone and bis(thf‐O)calcium bis[bis(trimethylsilyl)amide] in toluene, the trinuclear complex 3 is obtained, co‐crystallizing with THF. The β‐ketoester anion bridges solely via the cyclopentanone unit.     

Synthesis of 3‐phenyl‐5‐(trifluoromethyl)isoxazole and 5‐phenyl‐3‐(trifluoromethyl)isoxazole

Reaction of 4,4,4‐trifluoro‐1‐phenyl‐1,3‐butanedione with hydroxylamine led to the formation of 5‐hydroxy‐3‐phenyl‐5‐(trifluoromethyl)‐4,5‐dihydroisoxazole which was dehydrated to 3‐phenyl‐5‐(trifluoro‐methyl)isoxazole. This isomer can also be synthesized by reaction of 4‐chloro‐4‐phenyl‐1,1,1‐trifluoro‐3‐buten‐2‐one with sodium azide. The regioisomer, 5‐phenyl‐3‐(trifluoromethyl)isoxazole was synthesized by reaction of 1,1,1‐trifluoro‐4‐phenylbut‐3‐yn‐2‐one with hydroxylamine and by the reaction of 3‐chloro‐1‐phenyl‐4,4,4‐trifluorobut‐2‐en‐1‐one with sodium azide. Both isomers were characterized by mass and NMR spectroscopy.     

A Green Synthesis of 2‐Amino‐4‐(9H‐carbazole‐3‐yl)thiophene‐3‐carbonitriles by a Step‐wise and One‐pot Three‐component Gewald Reaction

An eco‐friendly method has been developed for the synthesis of 2‐amino‐4‐(9H‐carbazole‐3‐yl)thiophene‐3‐carbonitriles from preliminary carbazole ( 1 ) through an intermediate of 2‐(1‐(9H‐carbazole‐3‐yl)ethylidene)malononitriles using the Knoevenagel condensation followed by the Gewald reaction. On the other hand, the target compounds could also be prepared in a one‐pot three‐component manner by treating equimolar quantities of 1‐(9H‐carbazole‐3‐yl)ethanone ( 3 ), malononitrile, and elemental sulfur. The merits of this preparation are mild reaction conditions. The Gewald reaction is executed with inorganic base NaHCO₃ (H₂O) in tetrahydrofuran, easy work‐up procedure with good yields.     

Synthesis of 1‐substituted 5‐aryl‐3‐(3‐coumarinyl)‐2‐pyrazolines by the reaction of 3‐aryl‐1‐(3‐coumarinyl)propen‐1‐ones with hydrazines

1‐Acetyl‐ and 1‐propionyl‐2‐pyrazolines 11‐27 have been synthesized by the reaction of (3‐coumarinyl)chalcones 1‐10 with hydrazine in hot acetic acid or propionic acid. While 5‐aryl‐3‐(3‐coumarinyl)‐1‐phenyl‐2‐pyrazolines 28‐35 have been prepared by the reaction of (3‐coumarinyl)chalcones 1,3,5‐10 with phenylhydrazine in hot pyridine. Structures of all new compounds have been elucidated by microanalyses, ¹H and ¹³C nmr spectroscopies.     

A Highly Efficient Friedel–Crafts Reaction of 3‐Hydroxyoxindoles and Aromatic Compounds to 3,3‐Diaryl and 3‐Alkyl‐3‐aryloxindoles Catalyzed by Hg(ClO4)2⋅3 H2O

We report a highly efficient Friedel–Crafts reaction of 3‐alkyl or 3‐aryl 3‐hydroxyoxindoles with a variety of aromatic and heteroaromatic compounds to unsymmetrical 3,3‐diaryloxindoles or 3‐alkyl‐3‐aryloxindoles, which are interesting medicinal targets and useful building blocks for the synthesis of natural products. Hg(ClO₄)₂ ? 3 H₂O was identified as a powerful catalyst for this reaction, and is significantly more efficient than other screened metal perchlorate hydrates and Brønsted acids such as HOTf and HClO₄. The high catalytic property of Hg(ClO₄)₂ ? 3 H₂O originates from the unprecedented dual activation effects of aromatic mercuration, which could generate a strong protic acid to facilitate the generation of a carbocation at the C3‐position of oxindoles and simultaneously form the more reactive nucleophilic reaction partner.     

Phosphine‐Catalyzed Enantioselective γ‐Addition of 3‐Substituted Oxindoles to 2,3‐Butadienoates and 2‐Butynoates: Use of Prochiral Nucleophiles

The first phosphine‐catalyzed enantioselective γ‐addition with prochiral nucleophiles and 2,3‐butadienoates as the reaction partners has been developed. Both 3‐alkyl‐ and 3‐aryl‐substituted oxindoles could be employed in this process, which is catalyzed by a chiral phosphine that is derived from an amino acid, thus affording oxindoles that bear an all‐carbon quaternary center at the 3‐position in high yields and excellent enantioselectivity. The synthetic value of these γ‐addition products was demonstrated by the formal total synthesis of two natural products and by the preparation of biologically relevant molecules and structural scaffolds.     

An Efficient Synthesis of N‐Substituted‐3‐aryl‐3‐(4‐hydroxy‐6‐methyl‐2‐oxo‐2H‐pyran‐3‐yl)propanamides by Four‐Component Reaction in Aqueous Medium

A mild and efficient synthesis of N‐substituted‐3‐aryl‐3‐(4‐hydroxy‐6‐methyl‐2‐oxo‐2H‐pyran‐3‐yl)propanamides via four‐component reaction of an aldehyde, amine, Meldrum's acid, and 4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one in the presence of benzyltriethylammonium chloride (TEBAC) in aqueous medium is described. This method has the advantages of accessible starting materials, good yields, mild reaction conditions, and begin environmentally friendly.     

Ligand‐Controlled Direct γ‐C−H Arylation of Aldehydes

The first example of Pd^II‐catalyzed γ‐C(sp³)?H functionalization of aliphatic and benzoheteroaryl aldehydes has been developed using a transient ligand and an external ligand, concurrently. A wide array of γ‐arylated aldehydes were readily accessed without preinstalling internal directing groups. The catalytic mechanism was studied by performing deuterium‐labelling experiments, which indicated that the γ‐C(sp³)?H bond cleavage is the rate‐limiting step during the reaction process. This reaction could be performed on a gram scale, and also demonstrated its potential application in the synthesis of new mechanofluorochromic materials with blue‐shifted mechanochromic properties.     

Photoinduced and thermal reactions of α‐cyano‐β‐bromomethylcinnamide with 1‐benzyl‐1,4‐dihydronicotinamide

The photoinduced reaction of a mixture of (Z)‐α‐cyano‐β‐bromomethylcinnamide (1) and (E)‐α‐cyano‐β‐bromomethylcinnamide (2) with 1‐benzyl‐1, 4‐dihydronicotinamide produces a mixture of the (E)‐ and (Z)‐ isomers of α‐cyano‐β‐methylcinnamide (3 and 4). Using spin‐trapping technique for monitoring reactive intermediate, it is shown that the reaction proceeds via electron transfer‐debromination‐H abstraction mechanism. The thermal reaction of the same substrate with BNAH at 60°C in the dark gives three products: the (E)‐ and (Z)‐isomers of α‐cyano‐β‐methylcinnamide and a dehydrodimeric product; 2, 7‐dicyano‐3, 6‐diphenylocta‐2, 4, 6‐trien‐1, 8‐dioic amide (7). Based on product analysis, scavenger experiment and cyclic voltammetry, an electron transfer‐debromination‐disproportionation mechanism is proposed.