Eliminate the reaction
DBU has been used in a variety of elimination reactions to enable reagent molecules to introduce unsaturated bonds, as intermediates and raw materials for organic synthesis, and just a few examples are enough to see the application of DBU in elimination reactions.
1. Alkyl halides eliminate hydrogen halides
A typical reaction is 1, 1-diiodobutane with an equal amount of DBU heated back to a brown solid, which is distilled and separated from the reaction mixture to produce the product (E) -1-iodo-1-butene with a yield of 80%. In general, it is difficult for DBU to dehalogenate vinyl halides to form alkynes, but the special structure of (E) -vinyl bromide and DBU is reflow in benzene, almost quantitatively converted to the corresponding alkynes, while the (Z) -isomer cannot undergo such a reaction. There are many examples of using DBU to dehalogenate halocarbons, which is enough to show that DBU is a very effective reagent for dehalogenation of halogenated alkane.
2. N-halogenated amide eliminates hydrogen halide
Under the action of DBU, N-halogenated amide can be successfully dehalogenated and then rearranged into isocyanate, and N-chlorobenzamide can be rearranged into phenyl isocyanate under the action of DBU with a yield of more than 90%. However, it is difficult to obtain phenylisocyanate by replacing DBU with organic bases such as triethylamine.
Isomerization
Double bond isomerism and differential isomerism reactions are extremely useful in organic synthesis, and DBU has a good catalytic effect in these isomerism reactions.
1. Double bond isomerization reaction
The β-γ-unsaturated ester compounds can be converted into the corresponding α-β-unsaturated ester by using DBU. Under the action of DBU, the stable 2-pentenoate was formed by 60% of 3-pentenoate. Under the action of catalyst DBU, β, γ-unsaturated nitrile can also form stable α, β-unsaturated nitrile.
2. Differential isomerization reaction
The stereoisomer mixture was reacted with DBU at room temperature for 1h, and the cis-3, 4-isomer was converted into trans-3, 4-isomer with a selectivity of 96%. This provides a method for the synthesis of special configuration compounds.
Some applications of DBU
DBU is a strong alkaline reagent, but it is a weak nucleophile, easy to combine with protons and not easy to combine with carbon atoms, so the application of DBU is mainly as a strong basic reagent to transfer protons, play the role of base or catalyst. The characteristic of DBU participating in the reaction is that the amount of DBU is generally required, and the applied reactions are mainly concentrated in some reactions with proton transfer, such as elimination, isomerization, addition, esterification, etherification, amidation, diazotization and so on.
DBU as an alkaline reagent to deα-H to produce carbanion intermediate reaction
DBU is an alkaline reagent that deprotonates active α-hydrogen compounds to form carbanion, among which Michael addition reaction is the most typical one, which has mild reaction conditions and few side reactions. In the reaction of cyclohexanone formate and methyl acrylate, DBU was used as the basic reagent to obtain the product, the yield was 96%. DBU made the nitro compound and styrene ketone containing double bond Michael reaction, the yield was 95%. Compound 15 and 2-cyclopentenone undergo the Michael reaction to produce (+) -3-cyclopentenone acetic acid after water release. The total yield is 43% and the optical purity is 96%. Although the yield of the product obtained by using triphenyllithium or potassium tert-butoxy as catalyst is close, the optical purity is much lower, only 7% ~ 76%. In addition, in the Knovenagel condensation reaction of malonic acid and caproaldehyde, the selectivity of β, γ-unsaturated isomer was 94% and the yield was 56% after the reaction at 90℃ for 10h with DBU as basic reagent.
Esterification, etherification, amidation reaction
DBU can be used as catalyst for the preparation of esters and amines from carboxylic acids and halocarbons, as well as ethers, esters and carbamates from alcohols. This kind of reaction is by carboxylic acid or alcohol with alkyl halides, acylating agents or other electrophilic reagents to deprotonate, where esterification and amidation reactions can generally be carried out at room temperature, and etherification reactions are generally carried out at 60 ~ 80℃.
Cycloaddition reaction
In the synthesis of 2, 5-dimethyl-3-phenyl-2-cyclopentenone, DBU was used as catalyst, and the yield reached 70%. In the synthesis of tetrahydropyrrole derivatives, DBU is also used as a catalyst through cycloaddition to obtain, the yield is also more than 90%.
Diazotization
Recently, it has been found that DBU has a good catalytic effect in the synthesis of α-diazone and α-diazo ester. Under the catalysis of DBU, benzene sulfonyl azide compounds can diazonize the active sites of related compounds under mild conditions and with high yield.
