Hinsberg separation of amines

The following experimental details will illustrate how the Hinsberg separation of amines may be carried out in practice. 

Sulfonamides of type RS02NH2 or RS02NHR containing the S02NH moiety are weakly acidic and form water soluble sodium salts (see the Hinsberg separation of amines, p. 105). In such cases, removal of the acidic proton allows alkylation or acylation at nitrogen (Scheme 49). 

Benzenesulphonyl chloride reacts with primary and secondary, but not with tertiary, amines to yield substituted sulphonamides (for full discussion, see Section IV,100,3). The substituted sulphonamide formed from a primary amine dissolves in the alkaline medium, whilst that produced from a secondary amine is insoluble in alkali tertiary amines do not react. Upon acidifying the solution produced with a primary amine, the substituted sulphonamide is precipitated. The reactions form the basis of the Hinsberg procedure for the separation of amines see Section IV,100,(viii) for details. Feebly basic amines, such as o-nitroaniline, react slowly in the presence of allcali in such cases it is best to carry out the reaction in pyridine solution see Section IV,100,3. ... 

In the preparation of 1-n-butyIpyrrolidine (3) from di-n-butylamine (1) by the Hofmann-LofHer reaction, benzenesulfonyl chloride is used for Hinsberg separation of the product (3) from starting material (1). The /-amine (3) is separated by steam... 

The three classes of amines also react differently with organic sulfonyl chlorides this is exploited in the Hinsberg separation of primary, secondary and tertiary amines. ... 

Hinsberg s separation of amines. A mixture of primary, secondary and tertiary amines may be separated by treatment with p-toluene-sulphonyl chloride, which reacts with primary amines to give mono-sulphonyl derivatives soluble in alkali, and converts secondary amines to alkali-insoluble sulphonyl derivatives, but does not react with tertiary amines. 

Among chemical methods for the separation of amines, those of Hinsberg (reaction with / -toluenesulfonyl chloride) and of Alexander (94) (reaction with 3-nitrophthalic anhydride) are most commonly used. Tertiary amines do not react with the reagents mentioned and they can be separated after the reaction — for example, by extraction. Derivatives of primary amines with p-toluenesulfonyl chloride are soluble in alkali hydroxide solutions, in contrast to sulfonamides of secondary amines this is utilized for their separation. When primary and secondary amines are separated by reacting them with 3-nitrophthalic anhydride, use is made of the fact that only phthal-imine acids derived from primary amines can be cyclized. Practical utilization of both procedures is demonstrated by the separated of a mixture of aniline, ethylaniline, and diethylaniline. However, it should be mentioned that in a number of cases the procedures fail or do not lead to a sufficiently sharp separation. Negatively substituted amines which do not react with / -toluenesulfonyl chloride can be separated with 3-nitrophthalic anhydride. Some p-toluenesulfonamides of primary amines are poorly soluble in alkali. The derivative of primary amine with 3-nitrophthalic anhydride is cyclized merely by boiling in benzene, and the phthalimide formed is soluble in benzene and can be isolated together with the tertiary amine. 

Hinsberg procedure for the separation of primary, secondary and tertiary amines is given under (viii) above, and this method may be used. The following experimental details may, however, be found useful for the preparation of derivatives of primary and secondary amines. 

The separation of a mixture of amines by means of benzenesulphonyl chloride or p-toluenesulphonyl chloride (Hinsberg s procedure) is described in Section IV,100,(viii). 

For the separation of mixtures of primary, secondary and tertiary amines using benzenesulphonyl or toluene-p-sulphonyl chloride (Hinsberg s method), see p. 1288. 

Benzenesulfonyl chloride (66) is used in organic qualitative analysis for the separation of primary (67), secondary (68) and tertiary (69) amines by the Hinsberg method (Scheme 39). The alkaline reaction mixture is first filtered, which removes the precipitate of the... 

Hinsberg reaction. Reaction of primary and secondary amines with sulfonyl halides to give sulfonamides because the products from primary amines are soluble in alkali and those from secondary amines are not, and since tertiary amines do not react, this method is useful for the separation and identification of amines. 

Special methods are available for particular classes of compounds, Hinsberg s method of separating primary, secondary and tertiary amines (p. 249)-... 

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