Preparation and application of DBU

DBU: 1,8-diazabicyclo-bicyclo(5,4,0)-7-undecene, is a bicyclic amidine compound with strong basicity. a paper published in nature in 2005 said that DBU as a convertible polar solvent, and can be used as an extractant in the extraction operation of oil and grease, the extraction rate is high, in the process of separation only need to pass CO2 to make the conversion to ionic DBU, as a kind of organic strong base with unique structure, has been applied in many synthetic reactions, showing the catalytic effect which is difficult to be played by other strong bases, with the characteristics of mild reaction conditions, simplified synthesis steps, specific product selectivity and high yield. It can be predicted that with the deepening of the understanding of DBU, DBU will have a wide range of uses in the research of improving the existing synthesis process, developing new organic synthesis methods and synthesizing new products.

The general method of synthesizing DBU is the nucleophilic addition of caprolactam and acrylonitrile to form N-(2-cyanoethyl)caprolactam, catalytic hydrogenation to obtain N-(3-aminopropyl)caprolactam, and dehydration cyclization to obtain DBU, in the synthesis of N-(3-aminopropyl)caprolactam, generally no solvent is used, the operation is simple, but it is not easy to control the reaction temperature, and a large amount of polymer is often produced. In the synthesis of DBU, catalytic hydrogenation under pressure is usually required, which requires high requirements for the reaction equipment.

DBU is a strong basic reagent, but it is a weak nucleophilic reagent, easy to combine with protons but not easy to combine with carbon atoms, so the application of DBU is mainly as a strong basic reagent to transfer protons and play the role of base or catalyst. the characteristics of DBU participation in the reaction is that generally need equal amounts of DBU, the application of the reaction is also mainly focused on some reactions with proton transfer, such as elimination, isomerization, addition, esterification, etherification, addition, esterification, etherification, amidation, diazotization, etc.

1. Elimination reactions

DBU has been applied to a variety of elimination reactions to introduce unsaturated bonds to reagent molecules as intermediates and raw materials for organic synthesis, just a few examples are enough to see the application of DBU in elimination reactions.

1) Elimination of hydrogen halides by haloalkanes

Typical reaction is 1,1-diiodobutane with equal amount of DBU is heated and refluxed until a brown solid appears, and the product (E)-1-iodo-1-butene is obtained by distillation separation from the reaction mixture in 80% yield. Usually DBU is difficult to make vinyl halides dehalogenate to produce alkynes, but the special structure of (E)-vinyl bromide and DBU refluxed in benzene, almost quantitatively converted to the corresponding alkynes, while the (Z)-form isomers can not undergo such reaction. There are many examples of dehalogenation of haloalkanes with DBU, which is enough to show that DBU is a very effective reagent for dehalogenation of haloalkanes.

2) Elimination of hydrogen halide by N-halogenated amide

Under the action of DBU, N-halogenated amide can remove hydrogen halide smoothly, and then rearrange into isocyanate, N-chlorobenzamide under the action of DBU, rearrange to get benzene isocyanate, the yield reaches more than 90%. And it is difficult to get benzene isocyanate by replacing DBU with organic base like triethylamine.

2. Isomerization reaction

Double bond isomerization and differential isomerization reaction are extremely useful in organic synthesis, DBU has good catalytic effect in this kind of isomerization reaction.

1) Double bond isomerization reaction

DBU can be used to convert β,γ-unsaturated esters into corresponding α,β-unsaturated esters. Under the action of DBU, 60% of 3-pentenoate isomerizes into stable 2-pentenoate; under the action of catalyst DBU, β,γ-unsaturated nitrile can also isomerize into stable α,β-unsaturated nitrile.

2) Differential isomerization reaction

The stereoisomeric mixture and DBU reacted at room temperature for 1h, and its cis-3,4-isomer was converted to trans-3,4-isomer with 96% selectivity. This provides a method for the synthesis of special conformation compounds.

3.DBU as a basic reagent to deα-H to produce carbon-negative ion intermediate reaction

DBU is a basic reagent to make active α-hydrogen compounds deprotonate to form carbon negative ions, of which the Michael addition reaction is typical, with mild reaction conditions and few side reactions. In the reaction of cyclohexanone formate and methyl acrylate, DBU was used as a basic reagent to obtain the product in 96% yield:

 

 

DBU caused the Michael reaction of the nitro compound with styryl ketone containing a double bond in 95% yield; the Michael reaction of compound 15 and 2-cyclopentenone, after hydrolysis and decarboxylation to form (+)-3-cyclopentane