A reaction density functional theory study of solvent effect in the nucleophilic addition reactions in aqueous solution

Whereas the proper choice of reaction solvent constitutes the cornerstone of the green solvent concept,solvent effects on chemical reactions are not mechanistically well understood due to the lack of feasible molecular models.Herein,by taking the case study of nucleophilic addition reaction in aqueous solution,we extend the proposed multiscale reaction density functional theory(RxDFT)method to investigate the intrinsic free energy profile and total free energy profile,and study the solvent effect on the activation and reaction free energy for the nucleophilic addition reactions of hydroxide anion with methanal and carbon dioxide in aqueous solution.The predictions of the free energy profile in aqueous solution for these two nucleophilic addition reactions from RxDFT have a satisfactory agreement with the results from the RISM and MD-FEP simulation.Meanwhile,the solvent effect is successfully addressed by examining the difference of the free energy profile between the gas phase and aqueous phase.In addition,we investigate the solvent effect on the reactions occurred near solid-liquid interfaces.It is shown that the activation free energy is significantly depressed when reaction takes place in the region within 10A distance to the substrate surface owing to the decrease of hydration free energy at the solid-liquid interface.

Study on Nucleophilic Additions to endo-tricyclo[5.2.1.0^(2,6)]deca-2(6),8-dien-3-one and an Unusual Payne Rearrangement of α,β-Epoxy Tricyclodecenone

Synthesis of highly strained tetracyclic ketones was achieved by cyclopropanation or epoxidation of tricyclodecenone 1. An unusual formation of α-methoxy β-hydroxy ketone from an α,β-unsaturated enone system via Payne rearrangement was reported.

Theoretical Studies on the Iodine-catalyzed Nucleophilic Addition of Acetone with Five-membered Heterocycles

The iodine-catalyzed nucleophilic addition reactions of pyrrole, furan, or thiophene with acetone were studied in gas and solvent by the density functional theory at the level of Lanl2DZ^＊. It was seen that the halogen bond between iodine and carbonyl oxygen appeared to have an important catalytic effect on such reactions, and the first iodine molecule maximally diminished the barrier height by 41 kJ/mol, while the second iodine molecule could not improve such reactions largely. It was concluded that the C2-addition was generally more favorable than the C3-addition for the three heterocycles; however, iodine considerably more effectively catalyzed the C3-addition than the C2-addition for pyrrole. It was also revealed by PCM calculation that the iodine-catalyzed nucleophilic additions occurred more easily in solvent than in gas, which explained the experiment performed by Bandgar et al..

Facial Selectivity in the Nucleophilic Additions of endo-Tricyclo[5.2.1.0^(2,6)]deca-2(6),8-dien-3-one

Nucleophilic additions to endo-tricyclo[5.2.1.0^(2,6)]deca-2(6),8-dien-3-one 4 are described. Experimental results show high preference for exo-facial attack to the enone moiety of tricyclodecadienone. Steric hindrance is the main kinetically controlling factor in the nucleophilic reaction. The shielding effect and the stabilizing effect of the norbornene double bond favor the exo-facial attack also.

Access to pyridines via cascade nucleophilic addition reaction of 1,2,3-triazines with activated ketones or acetonitriles

We studied the cascade nucleophilic addition reactions of 1,2,3-triazines with activated acetonitriles or ketones,which were used to construct highly substituted pyridines that are not easily accessed by conventional methods.The strategy addressed some structural diversity issues currently facing medicinal chemistry,and the resulting pyridines could be used as convenient precursors for the synthesis of related pharmaceuticals.In particular,our method was applied to the syntheses of the marketed drug etoricoxib and several biologically important molecules in a few steps.

Double Nucleophilic Addition of Ketene Silyl (THIO)Acetals and Trimethylsilyl Cyanide to N-Allylideneamine

1 Results We have already published a double nucleophilic addition reaction of α,β-unsaturated imines with several nucleophiles such as ketene silyl acetals, trimethylsilyl cyanides, trimethylsilyl azides and thiols[1]. However, it was not easy to use N-allylideneamine 2 derived from acrolein for such reactions. Since there is no substituent at the β-position, imine 2 has high reactivity and are prone to be polymerization. We report the first synthesis of N-allylideneamines 2 using the isomerization of ...

Effect of solid particle loading on nucleophilic addition of epoxy-resin to isophorone diisocyanate

In the preparation of surface coatings made of conductive composites consisting of conductive particulate fillers in a soft matrix, cracks will develop with increase of the particulate loading, which is believed to be related to the nucleophilic addition reaction between glycidyl end-capped poly （bisphenol A-co-epichlorohydrin） and isophorone diisocyanate molecules. This curing reaction is responsible for the generation of crosslinking network throughout the coatings. The influence of solid particle loading on the chemical reaction may be described as a volume-excluded effect, that is, the high solid particle loading will occupy the space between the functional groups thus preventing the chemical reaction to take place. As a direct consequence, the cross-linking network cannot develop properly due to the insufficiency of curing reaction. This will lead to the generation of cracks, as was supported by FT-IR analysis in this work.

Asymmetric Synthesis of Fluorinated Vicinal Diamines from Fluoromethyl Sulfinyl Imines and Diphenylmethylene-Benzylamines

A novel strategy was developed for the asymmetric synthesis of fluorinated vicinal diamines.Deprotonation of N-(diphenylmethylene)-benzylamines under base,followed by asymmetric nucleophilic addition to N-tert-butanesulfinylfluoroacetaldimines,a pair of diastereomeric isomers were afforded.The diastereomeric isomers can be easily separated from each other by silica gel column chromatography.The absolute steric configuration of two isomers was confirmed by single crystal X-ray diffraction analyses.The proposed mechanism revealed that the configuration of the carbon next to tert-butanesulfinyl was well controlled to be R by the chiral auxiliary.

Synthesis and Determination of Absolute Configuration of a Divergent Polyhydroxy Enyne Compound

Polyhydroxy enyne compound （＋）-（1＇S, 2R, 3S, 5S, 6S）-5,6-dimethoxy-5, 6-dimethyl- 2-（1＇-hydroxylpropyl-2-ne）-3-vinyl-l,4-dioxane has been synthesized from D-（-）-tartaric acid. A new chiral center was established by nucleophilic addition with 87% de. The modified Mosher＇s method was employed to confirm the absolute configuration of 17, which assigned the S-configuration at the new chiral center.

Construction of a Metallacyclopentadiene Ring through the Attack of Carbanions to M≡C Bond Followed by C—H Activation

Metallacyclopentadienes are important metallacycles and regarded as intermediates in many reactions,therefore,new methods to achieve them are anticipated.In this study,a formal[3+2]method,through the reactions of an osmapentalyne with benzyl carbanions,was developed.The reactions underwent a nucleophilic attack of carbanions to the Os≡C bond,followed by C—H activation to form the five-membered osmacyclopentadiene ring.Most of the reactions were carried out at room temperature,the substituents on the aromatic rings of benzyl carbanions are diverse,and the resulting products contain an Os—H bond,representing a novel type of 10C-carbolong complexes.This work provides a new convenient route to construct metallacyclopentadienes,which is expected to further promote the development of such a type of substances.

Atroposelective Construction of Axially Chiral Alkene-lndole Scaffolds via Catalytic Enantioselective Addition Reaction of 3-Alkynyl-2-indolylinethanols

Atroposelective construction of axially chiral alkene-heteroaryl scaffolds is highly desired but challenging.In this work,we established an atroposelective construction of axially chiral alkene-indole scaffolds via the strategy of catalytic enantioselective addition reaction of 3-alkynyl-2-indolylmethanols with bulky nucleophiles.

Nucleophilic imidoesterification of dicarbonyl compounds with cyanatobenzenes through C-C bond formation

Under neat conditions,an efficient method for synthesis of imidoesters has been developed using cyanatobenzenes and dicarbonyl compounds.Nucleophilic addition spontaneously occurred between the two kinds of materials at room temperature with yields of up to 90%.A mechanism directed towards to the imidoester formation has been proposed.

Construction of Chiral All-Carbon Quaternary Stereocenters by Asymmetric Friedel-Crafts Reaction of Isatin Derivatives

Un der the catalysis of chiral Cu(ll)complex,C2 and C3 alkylati on of pyrrole and C3 alkylation of in dole were realized simulta neously.The chiral oxindole skeleton with an all-carb on quater nary stereogenic cen ter at the C3-position could be obtai ned exclusively with high yields(up to 95%)and excellent enantioselectivities(up to>99%).

Highly Stereoselective Synthesis of 1,2-Diorganothio-l-alkenes via Hydrothiolation of Alkynyl Sulfides Catalyzed by Cesium Hydroxide

In the presence of catalytic amount of cesium hydroxide, the hydrothiolation of alkynyl sulfides occurred at room temperature in DMF under nitrogen atmosphere to afford exclusive （Z）-1,2-diorganothio-1-alkene in excellent yields. It could provide a new and expedient way for the preparation of symmetrical and unsymmetrical （Z）-1,2-diorganolthiol-1-alkenes.

Highly Stereoselective and One-Pot Synthesis of Tetra-substituted Monofluoroalkenes with Aldehydes and Fluorobis（phenylsulfonyl）methane

A highly stereoselective synthesis of tetrasubstituted monofluoroalkenes with aldehydes and fluorobis（phenyl- sulfonyl）methane （FBSM） in one pot has been developed. The reaction was amenable topara- and meta-substituted aryl aldehydes, 2-naphthaldehyde, and cinnamaldehyde, giving phenylsulfonyl-substituted monofluoroalkenes in 40%--86% yields with 98/2- 99/1 Z/E ratios. The presence of the sulfonyl group enables the further transformation of the products into more useful monofluoroalkenes.

A Novel Ratiometric Fluorescent Probe for Cyanide Anion with High Selectivity and Its Application in Cell Imaging

A novel hybrid acenaphthene-hemicyanine dye（Acc） was designed and synthesized as a colorimetric and ratiometric fluorescent sensor for cyanide detection. The nucleophilic addition of cyanide anion resulted in the blocking of the intramolecular charge transfer（ICT）. Thus, the sensor exhibited high sensitivity and selectivity to- wards cyanide anion among many anions in dimethylsulphoxide（DMSO）-water media, with the emission wavelength displaying a very large shift（186 nm）. Moreover, the color changes of the solution could be observed by the naked eyes and it had a short response time. Under optimized conditions, the detection limit for cyanide was calculated to be 1.3μmol/L（R2=0.9958）. In addition, the probe had excellent biocompatibility and could be utilized to monitor cyanide in living cells.

MgCl2/Et3N Base System as a New Catalyst for the Synthesis of a-Hydroxyphosphonate

An efficient and simple synthesis of a-hydroxyphosphonates via reaction of aldehydes and ketones with di- methylphosphite in the presence of MgCI2/Et3N base system is reported. The use of readily available and easy to handle reagent MgCI2/Et3N makes this method simple, convenient, and practical.

Hydrocyanation of Unsaturated Imines Using Potassium Hexacyanoferrate(Ⅱ) as a Cyanide Source

An efficient method for the hydrocyanation of unsaturated imines to synthesizeβ,γ-unsaturatedα-aminonitriles by a one-pot two-step procedure using potassium hexacyanoferrate(Ⅱ)as a cyanide source and benzoyl chloride as a promoter under catalyst-free condition is described.The advantages of this protocol are the use of a nontoxic,nonvolatile and inexpensive cyanating agent,no use of transition metal catalysts,high yield and simple work-up procedure.