Photoreduction of benzophenones by amines in room-temperature ionic liquids

[reaction: see text] The amine-mediated photoreduction of benzophenones in room temperature ionic liquids was investigated. Unlike the analogous reaction in organic solvents, the photoreduction produces mainly the corresponding benzhydrol in most cases. Because the reaction consumes only 1 equiv of amine and the solvent can be easily recycled, the photoreduction allows a very clean method for the conversion of benzophenones to benzhydrols.     

Vanadium Catalyst for C- and S-Alkylation of Benzhydrols in Water: An Experimental Study and Green Metrics Evaluation

A strategy for the vanadium-catalyzed dehydrative C- and S-alkylation by nucleophilic substitution of benzhydrols with arenes and thiols is reported. The alkylation was achieved with the divanadium oxoperoxo complex [K₃(V⁺⁵)₂(O₂²⁻⁾₄(O²⁻)₂(μ-OH)] in water under air. The newly developed transformation could accommodate a broad substrate scope, including (hetero)arenes and thiols (34 examples). Both the symmetrical and unsymmetrical benzhydrols furnished excellent yields of the alkylated product under mild reaction conditions. The scope of this strategy was further extended to synthesize bis-benzylated arenes (poly-arylated products) in high yields and regioselectivities. The green metrics determination of all the alkylated products suggests the technical and environmental benefits of the present protocol. The longevity experiment reveals the catalytic activity was maintained over seven cycles. To understand the mechanism of the present reaction, spectroscopic and kinetic studies were undertaken. This simple protocol, which affords the desired products with water as the by-product, can be achieved under mild conditions without needing a base or other additives.     

Catalytic enantioselective borohydride reduction of ortho-fluorinated benzophenones

[reaction: see text] In the presence of the optically active ketoiminatocobalt(II) complexes, the enantioselective borohydride reduction of benzophenones was successfully completed. The fluorine atom on the ortho position of the benzophenone and aryl ketones proved effective for obtaining high enantioselectivities. The combined use of modified lithium borohydride afforded the corresponding benzhydrols and arylcarbinols in high yield and high enantioselectivity (88-96% ee).     

One-pot synthesis of aryl butyl tellurides from tellurium tetrachloride and activated aromatics through a solventless step

A solventless preparation of aryl tellurium trichlorides from activated aromatic compounds avoiding the use of hazardous solvents as carbon tetrachloride and chloroform is described. The trichlorides were reduced and alkylated leading to aryl butyl tellurides in a one-pot procedure. Transmetallation of these tellurides with n-butyllithium followed by reaction with benzaldehyde gave the corresponding benzhydrols in good yields.     

Steric and electronic effects on the oxidation of ortho-substituted benzhydrols by chromic acid

A study has been made of the oxidation of a number of substituted benzhydrols by chromic acid in aqueous acetic acid. The reaction rate constants are linearly proportional to the K_R+ values of the alcohols. ortho-Substitution increases the rate of reaction and reduces the magnitude of the primary kinetic isotope effect. The major result of steric crowding appears to be an increase in the energy of the reactants, while the main electronic effect of substituents is to stabilize or destabilize the transition state.     

A very reliable method for determination of absolute configuration of chiral secondary alcohols by 1H NMR spectroscopy

Surprisingly stable synperiplanar conformers of CFTA esters have led us to develop a new and very reliable method for assigning absolute configurations of even secondary alcohols having minimal structural differences, such as chiral benzhydrols and alpha-monodeuterated benzyl alcohols.     

Contrastive photoreduction pathways of benzophenones governed by regiospecific deprotonation of imidazoline radical cations and additive effects

[Reaction: see text]. In the photoreaction of benzophenones with 1,3-dimethyl-2-phenylbenzimidazoline (DMPBI), benzhydrols were major products. Addition of H2O accelerated the reaction with no change in the product distribution, while AcOH, PhOH, and metal salts such as LiClO4 and Mg(ClO4)2 were effective additives to produce benzpinacols. In contrast, benzpinacols were exclusively formed regardless of the solvent and the additive in the reactions with 2-(o-hydroxyphenyl)-1,3-dimethylbenzimidazoline (o-HPDMBI). These observations are consistent with the hypothesis that DMPBI*+ donates a proton at the C2 position to the benzophenone ketyl radicals while o-HPDMBI*+ donates a phenol proton.     

Coupling of aromatic aldehydes with aryl halides in the presence of nickel catalysts with diazabutadiene ligands

Nickel catalysts with diazabutadiene ligands promote cross-coupling of benzaldehydes with aryl halides in the presence of zinc as reducing agent, which leads to the corresponding benzhydrols and benzophenones. The benzophenone percentage considerably increases when lithium chloride additive is used.     

Selective hydrogenation of benzophenones to benzhydrols. Asymmetric synthesis of unsymmetrical diarylmethanols

[reaction: see text] trans-RuCl2[P(C6H4-4-CH3)3]2(NH2CH2CH2NH2) acts as a highly effective precatalyst for the hydrogenation of a variety of benzophenone derivatives to benzhydrols that proceeds smoothly at 8 atm and 23-35 degrees C in 2-propanol containing t-C4H9OK with a substrate/catalyst ratio of 2000-20000. Use of a BINAP/chiral diamine Ru complex effects asymmetric hydrogenation of various ortho-substituted benzophenones and benzoylferrocene to chiral diarylmethanols with consistently high ee.     

A new tetrahydroisoquinoline synthesis

Cyclization of 2-vinylbenzylamines affords 1,2,3,4-tetrahydroisoquinolines. The synthesis of the vinylbenzylamines from benzhydrols or isoindolones is described.     

Structure and Substituent Effects on Retention and Chiral Resolution of Ketones and Alcohols on Microcrystalline Cellulose Triacetate Plates

This paper reports a number of original thin layer chromatography enantioseparations of closely related ketones and alcohols such as tetralones, indanones, and benzhydrols carried out by elution with aqueous-alcoholic mixtures at different ratios. In order to investigate the structural and substituent effects on chiral recognition of microcrystalline cellulose triacetate, the results were compared with those obtained in previous papers for analogous compounds in similar experimental conditions. Even though the inclusion model of retention of analytes on this chiral stationary phase is confirmed, different and unexpected results were obtained for compounds having very favourable characteristics for resolution.     

Nucleophilic additions of arylzinc compounds to aldehydes mediated by CrCl(3): efficient and facile synthesis of functionalized benzhydrols, 1(3H)-isobenzofuranones, benzyl alcohols, or diaryl ketones

In the presence of a stoichiometric amount of CrCl(3) and trimethylchlorosilane (TMSCl), nucleophilic addition of arylzinc compounds 1c-h to arylaldehydes 2a,b,g smoothly proceeded at room temperature to yield corresponding benzhydrols 4a-f in good yields. From arylzinc compounds 1a,b, 3-aryl-1(3H)-isobenzofuranones 3a-f were given by the CrCl(3)-mediated reaction with arylaldehydes 2a-f. Diaryl ketones 5a-e were obtained in good yields by the addition of excess amount of benzaldehyde as an oxidant to the resulting solution after the CrCl(3)-mediated reaction between arylzinc compounds 1c-g and arylaldehydes 2b,g was completed. In the nucleophilic additions of arylzinc compounds 1a,d,f to alkyladehydes 6b-f, the treatment of arylzinc compounds with CrCl(3) was required prior to the addition of the aldehydes in order to prevent the fast protodezincation of arylzinc compounds by the enolizable aldehydes. In these CrCl(3)-mediated nucleophilic additions of arylzinc compounds to aldehydes, arylchromium(III) species are probably reactive intermediates.     

An efficient synthesis of medicinally important indole based triarylmethanes by using propylphosphonic anhydride (T3P®)

Abstract

We have developed an economical and efficient method for the synthesis of medicinally and synthetically important indole-based triarylmethanes by using indoles and benzhydrols in the presence of propylphosphonic anhydride (T3P^®). This methodology is an alternate approach for the C–C bond formation with good to excellent yields. In this T3P-mediated dehydration approach, the by-product is highly soluble in water, so that it can be done at larger scale also. In addition to that this efficient protocol has several advantages such as mild reaction conditions, short reaction time and operational simplicity. We have successfully synthesized pyrrole, imidazothiadiazole and imidazolo pyridine based triarylmethanes also.     

Polyhydrazides. III. N-methylated polyhydrazides by ring-opening of poly-p-phenylene-1,3,4-oxadiazole

A new ring-opening reaction of 1,3,4-oxadiazole by methylating reagents was developed in fuming sulfuric acid or polyphosphoric acid and then, by applying this reaction to poly-p-phenylene-1,3,4-oxadiazole, a high molecular weight poly-N-methylterephthalylhydrazide was obtained. Various methylating reagents were investigated as ring-opening reagents. The degrees of ring-opening in polymers were estimated and related to the properties of the polymers.     

Polymeric oxidizing reagents based on polyacrylamides: Effect of the nature and extent of crosslinking on reactivity

Acrylamide was copolymerized with N,N′-methylene-bis-acrylamide (NNMBA), tetraethyl-eneglycol diacrylate (TEGDA), and divinyl benzene (DVB) in different proportions to afford crosslinked polyacrylamides with varying nature and extent of crosslinking. These insoluble polymers were functionalized with the N-bromoamide function and the reactivity of the resulting polymeric N-bromoamide was investigated under different conditions. The capacities of the reagents varied from 6.7 mequiv / g for the linear polymeric reagent to 1.1 mequiv / g for the 15% DVB-crosslinked reagent. Oxidation of benzoin to benzil was used as the model reaction. Investigation of the reaction under different conditions of solvent and varying molar excess revealed a significant influence of the nature and extent of crosslinking in deciding the extent of reaction. In the case of NNMBA-crosslinked reagents, the reactivity increased up to 10% crosslinking and then decreased. The reactivity of the reagents increased up to 15% crosslinking in the case of TEGDA-crosslinked ones and for DVB-crosslinked reagents the reactivity decreased with crosslinking. The polarity of the crosslinking agent and its molar percentage on the polymeric reagent (crosslink density) are factors affecting the solvent compatibility, which in turn, is decisive in the facilitation of the reactions.     

几种新重氮氨基试剂的合成及其分析性能

合成了 6种新的重氮氨基新试剂。研究了试剂亚氨基质子的离解常数p Ka及试剂与 Cd( )的显色反应。结果表明 ,随着试剂 1位苯环上的对、间位取代基的取代基常数 σ值的增大 ,试剂亚氨基的质子离解常数 Ka也增大 ( p Ka值减小 ) ,与 Cd2 +反应的显色酸度也越高 ;反应的最佳操作酸度 p H操作 与试剂p Ka存在如下关系 :p Ka=p H操作 - ( 1 .4± 0 .2 )     

High‐Throughput Reaction Screening with Nanomoles of Solid Reagents Coated on Glass Beads

Technologies that enable rapid screening of diverse reaction conditions are of critical importance to methodology development and reaction optimization, especially when molecules of high complexity and scarcity are involved. The lack of a general solid dispensing method for chemical reagents on micro‐ and nanomole scale prevents the full utilization of reaction screening technologies. We herein report the development of a technology in which glass beads coated with solid chemical reagents (ChemBeads) enable the delivery of nanomole quantities of solid chemical reagents efficiently. By exploring the concept of preferred screening sets, the flexibility and generality of this technology for high‐throughput reaction screening was validated.     

Fe(OTf)3‐Catalyzed α‐Benzylation of Aryl Methyl Ketones with Electrophilic Secondary and Aryl Alcohols

Acid‐catalyzed Friedel–Crafts alkylation of 1,3‐dicarbonyl compounds with electrophilic alcohols, is known to be an effective C? C bond forming reaction. However, until now, this reaction has not been amenable for α‐alkylation of aryl methyl ketones because of the notoriously low nucleophilicities of these compounds. Therefore, α‐alkylation of aryl methyl ketone relies on precious metal catalysts and also, the use of primary alcohols is mandatory. In this study, we found that a system composed of a Fe(OTf)₃ catalyst and chlorobenzene solvent is sufficient to promote the title Friedel–Crafts reaction by using benzhydrols as electrophiles. 3,4‐Dihydro‐9‐(2‐hydroxy‐4,4‐dimethyl‐6‐oxo‐1‐cyclohexen‐1‐yl)‐3,3‐dimethyl‐xanthen‐1(2 H)‐one was also applicable as an electrophile in this type of benzylation reaction. On the basis of this result, a three‐component reaction of salicylaldehyde, dimedone, and aryl methyl ketone was also developed, and this provided an efficient way for the synthesis of densely substituted 4H‐chromene derivatives.     

Tandem addition beta-lithiation-alkylation sequence on alpha,beta-unsaturated aldehydes

A tandem reaction between (E)-cinnamaldehyde, 1a, and phenyllithium affording beta-substituted dihydrochalcones was recently reported. NMR spectroscopic studies on the reaction mixture, as well as isotopic exchange reactions and trapping of two intermediates, provide clues on the several mechanistic steps of this new reaction. Extended studies revealed that beta-alkyl-substituted alpha,beta-unsaturated aldehydes and aliphatic lithium reagents did not afford good yields of the tandem reaction products, while aromatic lithium reagents gave good results. The aggregation features of the aryllithium reagents and the extended charged delocalization effects are considered to promote beta-selectivity. This approach provides a convenient route for the synthesis of a wide variety of beta-alkyl-substituted dihydrochalcones.     

Impact of reaction products on the Grignard reaction with silanes and ketones

Grignard reactions with alkoxysilanes or carbonyl compounds produce alkoxymagnesium halides as by-products. Kinetic measurements for reactions of silanes and of a ketone were performed with Grignard reagents, enriched in alkoxymagnesium halides and taken in a great excess.The alkoxide-type reaction products complex tightly with Grignard reagents and enhance in this way their nucleophilicity, thus accelerating the reaction. However, alkoxides branched at α-C atom exert an unfavorable steric hindrance to reaction resulting in a decrease in the reaction rate.