What is the alkylation of amines?

The reaction in which hydrogen atoms on carbon, oxygen and nitrogen in organic compounds are replaced by alkyl groups.

Alkylation on carbon atom ① Alkylation of hydrogen on carbon a of carbonyl group. The hydrogen on the A carbon of carbonyl group is weakly acidic, and the A carbon of carbonyl group can be alkylated with alkyl halide under the action of strong base (such as sodium amino acid and sodium hydride) to generate the A carbon alkylation product;

Direct alkylation of ketones and esters will produce self-condensation; Polyalkylation can also occur. In order to obtain monoalkylation products of α-carbon, enamines can be prepared from secondary amines such as tetrahydropyrrole and morpholine, and then reacted with active alkyl halides (methyl iodide, benzyl halide, etc.). ) to produce substituted enamines, and alkylated carbonyl compounds can be obtained by hydrolysis;

② Alkylation of active methylene. The methylene group between two active groups is active and can be easily alkylated under the action of sodium alkoxide. The active group can be nitro, carbonyl, ester or cyano, etc. For example, the synthesis methods of substituted malonates and acetoacetates: H2C (CocoC2H5) 2+C2H5O-Na+CH (CocoC2H5) 2-Na+C2H5Ohch (CocoC2H5) 2-Na+RXCH (Co2H5) 2+Naxch3CocH2H5+C2H5O-. X is halogen. Substituted malonates and acetoacetates are easily decarboxylated and decomposed into substituted acetic acids or ketones after hydrolysis, which are widely used in organic synthesis. These alkylation reactions are carried out under anhydrous conditions.

③ Phase transfer catalytic alkylation. Reactants in two immiscible liquid phase systems react by using phase transfer catalysts. There is no need to operate under anhydrous conditions, and concentrated sodium hydroxide aqueous solution can be used instead of anhydrous sodium alkoxide. The reaction conditions are mild and the operation is simple. Commonly used catalysts are quaternary ammonium salt (Q+X-), such as (n-c4h9) 4n+hso4-, quaternary phosphonium salt [(C2H5)3P+CH2C6H5]Cl- or crown ether. The reactant reacts with alkali at the interface to generate negative carbon ions. The latter forms ion pairs with quaternary ammonium cations, which are transferred to the organic phase and alkylated with haloalkanes. For example:

It is an important method to synthesize asymmetric ether by the reaction of sodium alkoxide alkylated on oxygen atom with alkyl halide.

Rona+r ′ xror ′+nax phenol is more acidic than alcohol, and can generate aromatic oxygen negative ions by sodium hydroxide, which can be alkylated. For example:

Diethyl sulfate is also a commonly used alkylation reagent, which has higher activity than alkyl halides and mild reaction conditions. Usually, only one alkyl group participates in the reaction.

Alkylated alkyl halides on nitrogen atoms can be heated with ammonia or amine under a certain pressure to form a mixture of primary, secondary, tertiary and even quaternary ammonium salts. Primary amine, secondary amine and tertiary amine can be separated one by one by fractionation. By controlling the ratio and conditions of reactants, one of the amines can become the main product.

N3H+RXH3R+X-

H3R+NH3RNH2+H4

RNH2+RXR2N2+X-

R2H2+NH3R2NH+H4

R2NH+RXR3H+X-

R3H+NH3R3N+H

R3N+rxr 4+X- When alkylation is carried out with diester sulfate, strongly basic nitrogen atoms are preferred for the reaction.