Hinsberg reaction

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). 

A variety of hydroxythiophenedicarboxylic acids have been prepared via the Hinsberg reaction (Section 3.15.3.5.1), and these may be decarboxylated to hydroxythiophenes. Refluxing 3,4-dihydroxythiophene-2,5-dicarboxylic acid in pyridine led to the formation of 3,4-dihydroxythiophene in high yield (equation 63). The Dieckmann cyclization (Section 3.15.2.2.2) has been used to prepare 3-hydroxythiophene derivatives (equation 64), and again the free acid can be decarboxylated to form the 3-hydroxythiophene substituted in the 5-position. 

HINSBERG REACTION. Reaction of primary and secondary amines with sulfonyl halides to give sulfanamides because the products front 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 sepantlion and identification of amines. 

Quinoxalin-2(l//)-ones are easily prepared from benzene-1,2-diamine with a-oxo acids or esters (the Hinsberg reaction ). Thus, benzene-1,2-diamine reacts with butyl glyoxylatc to give quinoxalin-2(l//)-one. The extension of this method with phcnylglyoxylic... 

Hinsberg reaction, 412 Hoffmann, 130 Hofmann degradation, 404 elimination, 413 Huckel s rule, 193, 196 Hund s rule, 14... 

Note A number of the tests described in this experiment, such as the Hinsberg reaction, may be given as demonstrations by the instructor. 

The parent compound, the first monocyclic 1,4-thiazine to be described, was tentatively assigned the structure 6 on the basis that it failed to form a sulfonamide when subjected to the Hinsberg reaction. Although never confirmed by spectroscopic methods, this formulation is almost certainly correct since several derivatives of 1,4-thiazine have been prepared and shown to exist as the 2if-tautomers. This preference suggests that the conjugative stabilization depicted by the process 8 outweighs that illustrated by the process 9, and that the S-atom does not act as an effective electron sink. 

The Hinsberg reaction has been used in two cases to prepare tetracyclic condensed thiophenes from 1,2-diketones and thiodiglycolic esters.68 One example is shown in Scheme 7 for the synthesis of 29 (13% overall).43,69 If water is not added during the process, one isolates the half-ester (27% for methyl half-ester of 207), which undergoes decarboxylation with copper... 

Other references related to the Hinsberg reaction are cited in the literature. 

Scheme 103. The Hinsberg reaction. Alkylation at nitrogen of benzenesulfonamide with bromoethane (CHjCH2Br) produces Af-ethylbenzenesulfonaniide and, on repetition of the process, NA -diethylbenzenesulfonamide. An alternative process, the reaction of benzenesul-fonyl chloride with ethanamine (CH3CH2NH2) to produce iV-ethylbenzenesulfonamide and subsequent alkylation of the latter via formation of the sulfonamide anion and reaction of that anion with bromomethane (CHsBr) is also provided.

Scheme 44 A Hinsberg reaction using 2,2 -thiobis(acetonitrile) [73]...

Scheme 45 A Hinsberg reaction with a non-aryl substituted 1,2-diketone [74]...

Scheme 46 The Hinsberg reaction using diethyl oxalate the synthesis of 3,4-dihydroxythiophenes [75, 76]...

Scheme 48 The Hinsberg reaction using glyoxal for thiophenophane construction [78]...

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