Hinsberg

Separation of a Mixture of Aniline, Monomethyianiline, and Dimethylaniline.f Hinsberg s Method. 

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

There are complications in applying the Hinsberg test to certain amines containing hydroxyl, nitro and carboxyl groups, e.g., p-N-methylamiiiobenzoic acid CHjNHC.HjCOOH (I 4) may behave in this test as a primary amine (soluble in alkali) so that it is essential to consider the properties of the original compound in conjunction with the results of the test. 

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

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. 

Feebly basic amines, e.g., the nitroanilines, generally react so slowly with benzenesulphonyl chloride that most of the acid chloride is hydrolysed by the aqueous alkali before a reasonable yield of the sulphonamide is produced indeed, o-nitroaniline gives little or no sulphonamide under the conditions of the Hinsberg test. Excellent results are obtained by carrying out the reaction in pyridine solution ... 

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. ... 

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). 

R. Aden, G. Wadraff, W. Hinsberg, L. Simpson, and R. Kunz, in Polymers for Microelectronics, MCS Symposium Series 537, American Chemical Society, Washington, D.C., 1994, p. 165. 

HINSBERG - STOLLS Indoie-OxindoiaSynthesis indoie synthesis Irom anilines and glyoxal (Hinsberg), oxindola synthesis from anilines and a haloacyi hafides (Stolie). 

The Hinsberg synthesis of thiophene derivatives describes the original condensation of diethyl thiodiglycolate and a-diketones under basic conditions which provides 3,4-disubstituted-thiophene-2,5-dicarboxylic acids upon hydrolysis of the crude ester product with aqueous acid. ... 

In 1910, Hinsberg described the reaction between benzil and diethylthiodiacetate, resulting in the preparation of the thiophene ring system. The reaction was run under Claisen condensation conditions, and after hydrolysis with aqueous acid at reflux, the free dicarboxylic acid 1 was produced. 

The Hinsberg thiophene synthesis has seen limited use owing to the potential for regioisomeric mixtures when unsymmetrical 1,2-dicarbonyls are condensed with unsymmetrical thiodiacetates. Thus, symmetrically substituted thiophenes are generally prepared in this manner. 

A notable utilization of the Hinsberg procedure was executed in the synthesis of a thiophene analogue of porphyrin. A previous synthesis of the tetrathioporphyrin dication of 7 found this material to be unsuitable for chemical exploration as a result of its limited accessibility and solubility. Efforts by Vogel et al. were then directed toward... 

In addition to thiodiglycolic acid esters, the use of bis(cyanomethyl)sulfide in the Hinsberg reaction has facilitated the preparation of 5-cyano-thiophene-2-carboxamides. Thus, the condensation of biacetyl with bis(cyanomethyl)sulfide resulted in the efficient preparation of 10 (94% yield). 

Another significant advance of the Hinsberg thiophene synthesis has explored the reactivity of diketosulfides in place of the use of diethylthiodiglycolate. This process has been extensively utilized for the preparation of novel thiophene containing systems. With glyoxal as condensation partner, the utility of this method has been pioneered Miyahara et al. in the synthesis of novel thiophenophanes 19, 20, and 21. 

Finally, the Hinsberg synthesis has been extended to the use of a-aryl-a-carboethoxydimethyl sulfide in conjunction with a series of 1,2-dicarbonyl compounds. Specifically, the 4-nitroaryl substituent provides for sufficient activation of the a-proton to allow condensation and ring closure. These examples appear general and suggest future opportunities for the Hinsberg thiophene protocol. 

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