Theoretical Investigation On Mechanisms Of Several Typical Cyanosilylation Reactions Of Imines And Carbonyl Compounds

It is an important focus to investigate reaction mechanism by combining quantum chemistry method with chemical knowledge, which is helpful to understand the nature of chemical reaction and the design of further new synthesis pathways and catalysts. In this work, theoretical investigation on the activation of C=N and C=O double bonds and the reaction mechanism of cyanosilylation of imine and ketone in gas phase has been performed. The information on the energetics, geometry and IR frequency of intermediates and transition states involved in the reactions has been obtained. In order to take into account the solvent effect, the self-consistent reaction field (SCRF) method based on the polarized continuum model (PCM) for the Strecker reaction of imine and cyanosilylation of ketone is also performed. The main results are as the following:1. Theoretical investigation on the Strecker reaction catalyzed by chiral N-oxideIn the present work, model molecules are employed to model the mechanism for the Strecker reaction of benzaldehyde N-benzhydrylimine (PhCH=NCHPh₂) and trimethylsilyl cyanide (TMSCN) catalyzed by chiral N-oxide, in which silyl cyanide (H₃SiCN) and 3, 3'-dimethyl-2, 2'-bipyridine N, N'-dioxide (B) are used, respectively, to substitute for TMSCN and 3, 3'-dimethyl-2, 2'-biquinoline-N, N'-dioxide (A), and benzaldehyde N-methylimine (PhCH=NCH₃) (D) is used to substitute for benzaldehyde N-benzhydrylimine (PhCH)NCHPh₂) (C). The mechanism of the reaction between PhCH=NCH₃ and H₃SiCN has been studied at the B3LYP/6-31G* level. The calculations indicate that the reaction involved two reaction pathways in the absence of N-oxide catalyst, that is, isomerization followed by addition (a) or addition followed by isomerization (b).In pathway a, H₃SiCN isomerizes to H₃SiNC firstly, followed by the addition of H₃SiNC to PhCH=NCH₃ to produce targetα-amino nitrile. In pathway (b), the addition of H₃SiCN to PhCH=NCH₃ occurres firstly to produceα-amino isonitrile, which isomerizes to targetα-amino nitrile in the following step. The calculations indicate that the two pathways are competitive with comparable energy maxium. The energy barriers for the addition reactions are high for both the pathways in the absence of N-oxide catalyst.It is similar to the background reaction, the Strecker reaction proceeds along two different pathways (c and d), respectively, when catalyzed by 3, 3'-dimethyl-2, 2'-bipyridine N, N'-dioxide, in which the Si-C bond of H₃SiCN is weakened by coordinating O atom of N-oxide to Si atom of H₃SiCN. In the pathway c, the binary molecular complex forms by N-oxide and H₃SiCN interacts with imine to form hexacoordinate hypervalent silicate intermediate. Next, the addition reaction proceeds by the attack of-CN to the C=N double to produceα-imime isonitrile. In the final step, theα-amino isonitrile isomerizes to targetα-amino nitrile, which is the same as that in the pathway b. In the pathway d, H₃SiCN isomerizes to H₃SiCN catalyzed by N-oxide firstly to increase the nucleophilicity of-NC. Next, hexacoordinate hypervalent silicate intermediate is formed, in which C=N double bond has been activated. In the following step, the targetα-amino nitrile has been produced by the attack of the high reactive -NC to C=N double bond via a five-membered rings transitinate state.The calculations indicate that the step corresponding to the formation of hexacoordinate silicate is the rate-determining-step (RDS) in pathway c, in which the energy barrier of RDS is 24.7 kcal/mol. In pathway d, the reaction step correspondeding to the isomeration of H₃SiCN to H₃SiNC catalyzed by chiral N-oxide is predicted to be the rate-determiningstep (RDS) in CH₂Cl₂, in which the energy barrier of RDS is 28.7 kcal/mol. Although the energy barrier of RDS for pathway c is lower than that in the pathway d, the energy maximum along the reaction pathway d (22.1 kcal/mol for TSld) is lower than the energy maximum along the reaction pathway c (34.3 kcal/mol for TS2b). Thus, the two reaction pathways are also competitive in the viewpoint of energetics.In the Strecker reaction catalyzed by N-oxide, the strong electron donor (N-O) of chiral N-oxide B plays an important role in enhancing the reactivity and nucleophilicity of H₃SiCN. The hexacoordinate hypervalent silicate is a stable intermediate. The formation of such hexacoordinate hypervalent silicate intermediate could enhance intensively the nucleophilicity of -NC or -CN group and lower the energy barriers of addition reaction (The energy barrier of addition step is lowered by 20.9 and 27.4 kcal/mol for pathway c and d, respectively). As a consequence, it facilitates the production of the targetα-aminonitrile. Thus, chiral N-oxide could be used as a good catalyst for the reaction, which is in agreement with the experimental observations.2. Cyanosilylation reaction of ketone catalyzed by N-oxidesIn this work, the model molecule H3SiCN is employed to substitute for TMSCN in the investigation of the reaction mechanisms of cyanosilylation of acetone and acetophenone at B3P86/6-31G* level. For the background reaction in the absence of N-oxides catalysts, the reaction proceeds concertedly via a four-membered-ring transition state. The energy barrier for the addition step (33.3 kcal/mol) is so high that the reaction is hardly to occur in the absence of N-oxides.For the cyanosilylation reactions of acetone catalyzed by N-oxide 1 (aliphatic-type N-oxide), N-oxide 2 (aromatic-type N-oxide) and N-oxide 3 (pyridine-type N-oxide), the reaction proceeds along with two pathways (a and b), involving the formation of pentacoordinate silicate. For the pathways a and b, the reaction starts from the activation of H3SiCN by coordinating O atom of N-oxide to the Si atom of H3SiCN with the formation of two different binary complexes. In the view of geometry, the two binary complexes can be considered as pentacoordinate species, in which the -CN groups are in the horizontal position or perpendicular position. In the following step, acetone attacks pentacoordinate silicate in the perpendicular direction (pathway a) or horizontal direction (pathway b), respectively, leading to the production of target cyanohydrinsilyl ethers via two four-membered ring transition states. For the reaction catalyzed by 1, 2 and 3, the energy barriers along with pathway a are all lower than those along with the corresponding pathway b. Hence, the reaction may take place preferably along the energetically favorable pathway a, where acetone attacks the pentacoordinate silicon compound perpendicularly to form four-membered rings transition state. The calculations indicate that the strong donor (N-O) of N-oxides could play important role in enhancing the reactivity and nucleophilicity of H₃SiCN by coordinating O atom to Si atom of H₃SiCN. As a consequence, it facilitates the production of the target cyanohydrinsilylethers.For the cyanosilylation reactions of acetone catalyzed by phenolic N-oxide 2, the reaction proceeds along with two reaction pathways (c and d). In the pathway c, the reaction carries out stepwisely, in which the formation of three-membered complex has been involved. In the following step, the final intermidiate is formed by -CN attacking the C=O double bond. In the pathway .d, the binary complex is formed firstly. Next, intramolecular hydrogen bond has been broken assisted by H₃SiCN. In the following step, the H atom in the phenolic N-oxide interacts with N atom of -CN, leading to the further activation of Si-C bond in H₃SiCN. Then, the cyanohydrinsilyl ethers would be produced by acetone attacking the pentacoordinate silicon compound perpendicularly to form four-membered rings transition state. Therefore, the coordination of O atom of N-oxide 2 to Si atom, combining with the hydrogen bond between the hydroxyl group of phenol and N atom of -CN group, makes the Si-C bond weakened remarkably. The calculations indicate that the energy barriers of RDS in the pathway e and d are 13.5 and 22.8 kcal/mol, respectively. Thus, the cyanosilylation reactions catalyzed by phenolic N-oxide 2 may take place preferably along the energetically favorable pathway c.Comparing the energy barriers for four N-oxides 1-4 catalyzed reactions, it is found that they decrease in the following order: 4_a＞3_a＞1_a＞2_d, that is, the catalytic activity order for the four N-oxides should be as the following: aliphatic-type N-oxide＞aromatic-type N-oxide＞pydrine-type N-oxide, which is in agreement with the experimental results. In addition, some structural parameters of N-oxides, such as the charge accumulated on O atom, N-O bond length and intensity, and the geometry, may be related to the catalytic activity of N-oxides in the cyanosilylation reactions of acetone.3. The cyanosilylation reaction of aldehyde catalyzed by several inorganic and organic saltsIn this work, the model molecule H3SiCN and CH₃CHO are employed to substitute for TMSCN and PhCHO in the investigation of the reaction mechanisms of cyanosilylation of aldehyde at B3P86/6-31G* level. For the background reaction in the absence of N-oxides catalysts, the reaction proceeds concertedly via a four-membered-ring transition state. The energy barrier for the addition step (38.0 kcal/mol) is so high that the reaction is hardly to occur in the absence of catalyst.The calculations indicate that the reactions are all stepwisely catalyzed by inorganic salts LiHCO₃, NaHCO₃ and KHCO₃, in which the binary complexes have been formed by O atom of carboxylic salts coordinating to Si atom of H₃SiCN. In the following step, the carbonyl compounds get close to Si atom perpendicularly to form three-membered complex. Then, the transfer of-CN from Si atom to H atom of carboxylic salts takes place in the reaction catalyzed by LiHCO₃ and NaHCO₃. Next, the target product has been formed by attacking of-CN to C=O double bond. However, the addition reaction takes place directly by-CN attacking to C=O double bond after the formation of three-membered complex in the reaction catalyzed by KHCO₃.The catalytic activity of the three inorganic salts in the cyanosilylation reaction of carbonyl compound may be related to the basicity of them. The calculations indicate that the energy barrier changed in the following order:â–³E LiHCO3 (12.7 kcal/mol)＞△E NaHCO3 (8.7 kcal/mol)＞AE KHco3 (7.4 kcal/mol). The basicity of KHCO3 is strongest among three carboxylic salts, in which HCO₃ moiety is with more negative charge. As a result, the nucleophilicity of O atom is stronger in KHCO3, which is feasible to interact with Si atom of H₃SiCN.For organic sodium salt with carboxyl, the Si-C bond can be activated by O atom of carboxyl coordinating to Si atom of H₃SiCN. In addition, the organic sodium salt with -NH₂ or -OH can activate the aldehyde simultaneously by the hydrogen bond between H atom of-NH₂ or -OH and O atom of aldehyde. In the following step, the cyanohydrinsilyl ethers can be produced by four-rnembered rings transition state.3. Other workTheoretical study on the reaction of ZnO + CH₄ has been performed at the CCSD(T)//B3LYP/6-311++G(2d,2p) levels. At the initial step of the overall reaction, two models concerning the initial interaction between CH₄ and ZnO are considered: (i) two hydrogen atoms of the methane point to the Zn end of the ZnO (COM1) and (ii) a collinear C-H approaches to the O end of the ZnO (COM2). COM1 is an important intermediate, which may be the most feasible complex in the ZnO + CH4 reaction when the frequencies analysis and stabilization energies are considered. Furthermore, three reactions involved in the present investigations all start from COM1. From this complex, the insertion of ZnO into the C-H bond of CH₄ proceeds through two concerted manners along with charge transfer.The calculations show that the entire reaction contains three main reaction pathways, leading to the formation of syngas, CH₃OH and HCHO, respectively. The calculations predict that the energy barriers for the three reaction pathways are 45.4, 60.3 and 55.8 kcal/mol, respectively. In the view of energetics, the production of synthesis gas and HCHO are more possible for the reaction of ZnO+CH₄, and the formation of CH₃OH is highly unlikely when the rather high barrier is considered.