Background and Overview

DBU: 1,8-diazabicyclo-bicyclo(5,4,0)-7-undecene, is a bicyclic amidine compound with strong basicity. an article published in nature in 2005 indicated that DBU is used as a convertible polar solvent and can be applied as an extractant in the extraction operation of oil and grease with high extraction rate, and only CO2 needs to be passed in the process of separation 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.
Preparation [2]
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 and the operation is simple, but it is not easy to control the reaction temperature and often produces a large amount of polymer. In the synthesis of DBU, catalytic hydrogenation under pressure is usually required, and the requirements for the reaction equipment are high.
Applications [2]
DBU is a strong basic reagent, but it is a weak nucleophilic reagent, easy to bind with proton but not easy to bind with carbon atom, so the application of DBU is mainly as a strong basic reagent to transfer proton and play the role of base or catalyst.The characteristics of DBU participation in reactions are that generally equal amount of DBU is needed, and the applied reactions are also mainly focused on some reactions with proton transfer, such as elimination, isomerization, 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 the 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 Michael addition reaction is the most 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.
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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, which was hydrolyzed and decarboxylated to yield (+)-3-cyclopentanone acetic acid in 43% overall yield and 96% optical purity. In contrast, the yields of the products obtained with triphenyl lithium or potassium tert-butoxide as catalysts were close but the optical purity was much lower, only 7%-76%. In addition, in the Knovenagel condensation reaction occurring between malonic acid and adipaldehyde, DBU was used as the basic reagent and the reaction was carried out at 90°C for 10h to obtain β,γ-unsaturated isomers with a selectivity of 94% and a yield of 56%.
4. Esterification, etherification and amidation reactions
DBU can be used as a catalyst for the preparation of esters and amides from carboxylic acids and halogenated hydrocarbons and for the preparation of ethers, esters and carbamates from alcohols. These reactions are carried out by deprotonation of carboxylic acids or alcohols with alkyl halides, acyl agents or other electrophilic reagents, where esterification and amidation reactions can generally be carried out at room temperature, while etherification reactions are generally carried out at 60 to 80°C.
5. Cycloaddition reaction
In the synthesis of 2,5-dimethyl-3-phenyl-2-cyclopentenone, DBU was utilized as a catalyst and the yield reached 70%. In the synthesis of tetrahydropyrrole derivatives, DBU is also used as a catalyst to obtain through cycloaddition, and the yield also reaches more than 90%.
6. Diazotization reaction
Recently, it was found that DBU has good catalytic effect in the synthesis of α-diazo ketone and α-diazo ester reaction. Under the catalysis of DBU, benzenesulfonyl azide reacts with diazotization of the active site of the compound concerned under mild conditions and in high yield.

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