ⓘ Isatin, also known as tribulin, is an organic compound derived from indole with formula C 8 H 5 NO 2. The compound was first obtained by Otto Linne Erdman and A ..

                                     

ⓘ Isatin

Isatin, also known as tribulin, is an organic compound derived from indole with formula C 8 H 5 NO 2. The compound was first obtained by Otto Linne Erdman and Auguste Laurent in 1840 as a product from the oxidation of indigo dye by nitric acid and chromic acids.

Isatin is a well-known natural product which can be found in plants of Genus Isatis and Couroupita Guianensis, and also in humans, as a metabolic derivative of adrenaline.

It looks like an red-orange powder, and it is usually employed as building block for the synthesis of a wide variety of biologically active compounds including antitumorals, antivirals, anti-HIVs, and antituberculars.

The isatin core is also responsible for the color of" Maya blue” and" Maya yellow” dyes.

                                     

1.1. Synthesis Sandmeyer methodology

The Sandmeyer methodology is the oldest and straightforward way for the synthesis of isatin. The method involves the condensation between chloral hydrate and a primary arylamine e.g. aniline, in the presence of hydroxylamine hydrochloride, in aqueous sodium sulfate to form an α‐isonitrosoacetanilide. Isolation of this intermediate and subsequent electrophilic cyclization promoted by strong acids e.g. sulfuric acid furnishes isatin in > 75% yield.

                                     

1.2. Synthesis Stolle methodology

The Stolle procedure is considered the best alternative to Sandmeyer methodology for the synthesis of both substituted and unsubstituted isatins. In this case primary or secondary arylamines are condensed with oxalyl chloride to form a chlorooxalylanilide intermediate which can then cyclize in the presence of a Lewis acid.

                                     

1.3. Synthesis Other procedures

More recent approaches to the synthesis of N-substituted isatins involves the direct oxidation of commercially available, substituted indoles or oxindoles with different oxidizing agents such as TBHP, IBX-SO3K, tBuONO etc.

                                     

2. Reactivity

The presence of an aromatic ring, a ketone and a γ-lactam moiety, gives to isatin the rare potential to be used as both an electrophile and a nucleophile: indeed, it undergoes an enormous number of reactions, such as N-substitutions, electrophilic aromatic substitution at positions C-5 and C-7 of the phenyl ring, nucleophilic additions onto the C-3 carbonyl group, chemoselective reductions, oxidations, ring-expansions and spiro-annulations. Because of this unique reactivity, isatin is considered one of the most valuable building blocks in organic synthesis.

                                     

2.1. Reactivity N-Substitution

The N-functionalization of the isatin core can be readily obtained by the deprotonation of the amino moiety, forming the corresponding sodium or potassium salt, and subsequent addition of an electrophile e.g. alkyl or acyl halides.

On the other hand, N-arylation is usually achieved by cross-coupling reactions with aryl halides using copper al palladium catalysts.

                                     

2.2. Reactivity C-2 / C-3 nucleophilic addition

Isatin suffers nucleophilic addition on carbonyls at C-2 and C-3 positions. The regioselectivity of the process strongly depends both on the substrate properties of the substituents on the isatin core, especially those bonded to the nitrogen atom and the reaction conditions solvent, temperature etc. In some cases the nucleophilic addition could be followed by secondary reactions



                                     

2.3. Reactivity Oxidation

The oxidation of isatin using hydrogen peroxide or chromic anhydride yields isatoic anhydride, a compound widely used either in herbicide products and in medicinal chemistry.

                                     

2.4. Reactivity Dimerization

Dimerization of isatin with KBH 4 in methanol yield Indirubin. This represent the indigo pigments red component and a highly effective cytotoxic compound.

                                     

2.5. Reactivity Reduction

Reduction of the non-amide carbonyl group obviously occurs to give oxindole, respectively.

                                     

3. Reviews

  • Popp, Prank D. 1975. "The Chemistry of Isatin". Advances in Heterocyclic Chemistry Volume 18. Advances in Heterocyclic Chemistry. 18. pp. 1–58. doi:10.1016/S0065-27250860127-0. ISBN 9780120206186.
  • Silva, Joaquim F. M. da; Garden, Simon J.; Pinto, Angelo C. June 2001. "The chemistry of isatins: a review from 1975 to 1999". Journal of the Brazilian Chemical Society. 12 3: 273–324. doi: 10.1590/S0103-50532001000300002.
  • Mesropyan, E. G.; Avetisyan, A. A. 2009. "New isatin derivatives". Russian Journal of Organic Chemistry. 45 11: 1583. doi:10.1134/S1070428009110013.
  • Varun, Varun; Sonam, Sonam; Kakkar, Rita 2019. "Isatin and its derivatives: a survey of recent syntheses, reactions, and applications". MedChemComm. 10 3: 351–368. doi:10.1039/C8MD00585K. PMC 6438150. PMID 30996856.
Free and no ads
no need to download or install

Pino - logical board game which is based on tactics and strategy. In general this is a remix of chess, checkers and corners. The game develops imagination, concentration, teaches how to solve tasks, plan their own actions and of course to think logically. It does not matter how much pieces you have, the main thing is how they are placement!

online intellectual game →