Studies On The Product Selectivity Of The β-Alkylation Of Secondary Alcohols Through The Activation Of Primary Alcohols Catalyzed By Fe（acac）₂

The seeking for high selectivity, high yield, environment-friendly, efficient method of organic synthesis has become a huge challenge to contemporary chemists. Construction of new C-C bond is a very important method to complete the challenge. Building a new C-C bond for the construction of new molecular and improving molecular complexity are very powerful. Alkylation is very convenient, simple method to building a new C-C bond. Alkylation reagents commonly used, such as alkyl halides usually produce some salts by-products. In line with green chemistry and sustainable development requirements, improvement of the traditional method is imminent. This requires the general chemists and organic synthesis experts more "green", and further explore efficient new alkylation reagents, atomic conversion rate is higher.to further explore the more "green", efficient, high atomic conversion of alkylation reagent. Alcohols as electrophilic reagents used in alkylation will be a very substancial and " Green " type of reaction. The byproduct of the reaction will be only tiny molecular weight of water- the innoxious substances. This prompts us to look for one-step reaction direct using alcohols as alkylating reagent, to fit the requirements of the green chemistry and sustainable development.Summarizing the reaction conditions of catalyzing alcohols as alkylating reagents, we found that methods used in the study still exist many problems still : 1) the catalyst for reactions with Ru, Ir, Pd etc, not only expensive, but most are not commercially available, part of the catalyst used in the N, P ligand; 2) part of the reactions primary alcohols dosage is significantly higher than that of secondary alcohols, atoms have low efficiency; 3) some reactions need additional hydrogen receptor or hydrogen donor, such as 1-dodecene, it not only produces unwanted by-products, but also reduces the atom utilization rate; 4) alkali dosage of this reactions is stoichiometric which produces a lot of salt waste, and post-processing process requires many complex acidification and alkalization, therefore they seriously violate the standard of the "green". The study of the direct oxidative alkylation of secondary alcohols with the activated primary alcohols is very little, only the two precious metal catalyst: Pd and Ag. Pd as catalyst, the reactions are joined in large amounts of hydrogen receptor, e.g.1-decene, and the amount of alkali is stoichiometric; Ag catalysts is not commercially available and need complex pretreatment process. Therefore, development of new effective catalytic system for the direct alkylation and oxidative alkylation reaction is a big problem contemporary chemical workers need to face.The early stage of our laboratory with ferrocenealdehyde as catalyst. The laboratory was first the direct β-alkylation of secondary alcohols with the activated primary alcohols. Relative to the catalytic system has been reported, the catalytic system has the following advantages: 1) iron elements are widely distributed, which provides adequate resources for iron catalyst; 2) The solvent used for the reaction is p-xylene, furthermore, alkali dosage is catalytic, so it produces little environmental hazards; 3) Reaction does not require inert gas protection, reduce the risk of operation. On the basis of the above catalytic system, the laboratory further found that: ferroacetylacetonate can be used to the direct β-alkylation of secondary alcohols with the activated primary alcohols. 1-phenyl ethanol and benzyl alcohol as the substrate, we established the model reaction and the optimum reaction conditions were determined, then we conducted a preliminary study of the suitability of the substrate. In addition, the laboratory also surprised to find that, the catalyst can be used for the direct oxidative β-alkylation of secondary alcohols through the activation of primary alcohols. Similarly, with 1-phenyl ethanol and benzyl alcohol as the substrate, established the model reaction and the optimum reaction conditions were determined, then we conducted a preliminary study of the suitability of the substrate.First of all, with 1-phenyl ethanol and n-butyl alcohol direct alkylation reaction for the model, we screened the conditions of fatty alcohol as alkylating agents of the direct β-alkylation of secondary alcohols with the activated primary alcohols, the optimal reaction conditions were obtained. On the basis of the reaction conditions of the two models: The 1-phenyl ethyl alcohol alkylated by benzyl alcohol and 1- phenyl ethanol alkylated by n-butanol, application of other substrates applied to ferrocene formaldehyde in this catalytic system was studied, we got nine senior alcohol product, which production rate is in similar with ferrocene formaldehyde or even better.Secondly, on the basis of preliminary work, by direct alkylation of 1-phenyl ethanol with butanol as a model, the reaction conditions of the direct oxidative β-alkylation of the secondary alcohols with the fatty alcohols were also screened and the optimum reaction conditions were obtained. Based on the model reaction, we got the product of direct oxidative β-alkylation reaction, namely eight ketone type products.Through this study and previous work in our laboratory we proves that:Ferroacetylacetonate catalytic system is a new generation of iron catalysts which is suitable for the type of reaction wider than the previously developed catalyst ferrocenecarbaldehyde, which is not only suitable for the direct β-alkylation of secondary alcohols with the activated primary alcohols but also suitable for the direct oxidative β-alkylation of secondary alcohols with the activated primary alcohols. Further, ferroacetylacetonate catalytic system has the following advantages: 1) ferrous acetylacetonate is very stable and easy to store; 2) ferroacetylacetonate is cheaper relative to ferrocene formaldehyde(ferrocene formaldehyde ￥ 1880/25 g, ferroacetylacetonate￥282/25g), and easily available; 3) The reaction system can be smoothly carried out under atmospheric conditions without adding inert gas;4) The reaction requires only catalytic amount of alkali and mild reaction conditions which is more environmentally friendly, it produces no by-products except water, which reduces reaction difficulty and get high atom utilization with small environmental hazards. So it is more in line with the requirements of green chemistry and sustainable development. On the other hand, we found a new product selectivity regulatory pathway- solvent dosage adjustment, which is suitable for the alkylation of secondary alcohols with the activated primary alcohols. This way only need to adjust the amount of the solvent to obtain a high yield ketones and alcohols respectively. This is the first time we prove that the regulation of solvent dosage can be used to adjust the product selectivity of this kind of reaction. This study makes we have a further understanding of iron catalysts and opens up a new direction for the application of iron catalysts in organic synthesis.