Isatins synthesis

Sandmeyer s valuable isatin synthesis involves the removal of sulphur from diphenylthiourea (I) (p. 169) with basic lead carbonate. Hydrogen cyanide is combined with the reactive diphenylcarbodiimide (II) so obtained, and the nitrile (III) produced is converted by means of hydrogen sulphide into tbe thioamide (IV). Concentrated sulphuric acid brings about ring closure and the product is the a-anil of isatin (V). Then, by hydrolysis with dilute sulphuric acid, aniline is removed ... 

Treatment of anilines with oxalyl chloride followed by cyclization of the intermediate 15 is a useful isatin synthesis. Generally a Lewis acid... 

A de novo isatin synthesis based upon a palladium catalysed double carbonylation of 0/7/20-haloacetanilides in the presence of Et2NH to yield the corresponding glyoxylic acid amide was reported by Yamamoto and co-workers63. Hydrolysis of this amide yielded the respective isatin (Scheme 20). 

Sandmeyer isonitrosoacetanilide isatin synthesis. Formation of isonitrosoacetodi-phenylamidine by condensation of chloral hydrate, hydroxylamine, and aniline cyclization with concentrated sulfuric acid and quantitative hydrolysis to isatin on dilution. 

Methoxatin is an enzyme cofactor of bacteria which metabolises methanol and latterly was recognized, 55 years after the 13th, to be a 14th vitamin, also now referred to as pyrroloquinoline qninone (PQQ)- This total synthesis is a particnlarly instrnctive one since it inclndes an isatin synthesis (20.16.4), a quinoline synthesis and an indole synthesis. 

SANDMEYER Isatin Synthesis Isatin synthesis from anilines (see 1st edition). 

Other references related to the Sandmeyer isatin synthesis are cited in the literature. ... 

Adolf von Baeyer s first synthetic efforts on the preparation of indigo - for which the question of its correct structure remained unanswered - were not exploitable on an industrial scale due to the inaccessibility of the starting materials. Already in 1870, following his seven-stage isatin synthesis, Baeyer (Fig. 2.11) had succeeded in converting this material with phosphorus pentachloride into isatin chloride reductive dehalogenation of the latter with zinc yielded indigo directly. 

The Sandmeyer diphenylurea isatin synthesis uses symmetrical diphenylthiourea 1 as a substrate for generation of cyanoformamidine 2, via treatment of 1 with potassium cyanide in the presence of lead carbonate. Reaction of formamidine 2 with ammonium sulfide leads to thioamide 3, which can undergo acid-induced cyclization and hydrolysis to produce isatin (4). Examples of the diphenylurea isatin synthesis in the literature are scarce. This is due to Sandmeyer developing the more practical isonitrosoacetanilide isatin synthesis 16 years later. 

There has been limited mechanistic work regarding the two steps of the Sandmeyer isatin synthesis, although Wang offered a proposal in an earlier summary of the reaction. ... 

Although many of the anilines used in the Sandmeyer isatin synthesis have minimal functionality, examples exist where potentially sensitive motifs can survive the harsh reaction conditions. The 6-azauracil substituted aniline 39 could be converted to isatin 40 en route to the polyheterocyclic compound 41. A trifluoroacetyl protected amine could also be carried through the two-step Sandmeyer sequence to yield the isatin of interest. ... 

To study the conformational changes of tryptophan synthase by N-NMR, indole enriched in A-15 was required. Phillips used a Sandmeyer isatin synthesis starting with A-15-labeled aniline (45) to prepare 46 in good yield... 

Wang, Z. Sandmeyer Isatin Synthesis In Comprehensive Organic Name Reactions and Reagents, 3 V set, Wiley Hoboken, NJ, pp. 2467-2470,2009. 

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