Isatin

Isatin
Names
IUPAC name
1H-indole-2,3-dione
Identifiers
91-56-5 YesY
ChEBI CHEBI:27539 YesY
ChEMBL ChEMBL326294 YesY
ChemSpider 6787 YesY
DrugBank DB02095 YesY
Jmol 3D model Interactive image
KEGG C11129 YesY
PubChem 7054
Properties
C8H5NO2
Molar mass 147.1308 g/mol
Appearance Orange-red solid
Melting point 200 °C (392 °F; 473 K)
Hazards
Harmful (Xn)
R-phrases R22 R36 R37 R38
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YesYN ?)
Infobox references

Isatin or 1H-indole-2,3-dione is an indole derivative. The compound was first obtained by Erdmann[1] and Laurent[2] in 1841 as a product from the oxidation of indigo dye by nitric acid and chromic acids. The compound is found in many plants, such as Isatis tinctoria, Calanthe discolor and in Couroupita guianensis.[3]

Schiff bases of isatin are investigated for their pharmaceutical properties.[4]

Isatin forms a blue dye (indophenin) if it is mixed with sulfuric acid and crude benzene. The formation of the indophenin was long believed to be a reaction with benzene. Victor Meyer was able to isolate the substance responsible for this reaction from crude benzene. This new heterocyclic compound was thiophene.[5]

Synthesis

The classical methods for the synthesis of isatins are Sandmeyer’s method, the Stolle procedure, and Gassman procedure, all using aniline as substrate.[6]

Chloral hydrate reacts with aniline and hydroxylamine to give a condensation product which cyclicizes in sulfuric acid to give the target compound:[7]

Drugs

Isatin is a precursor used in the syntheses of pirquinozol, talnetant, tacrine, dibucaine, ciclazindol, and methisazone, and also for Oxyphenisatin.

A variety of tryptamine derivatives, including many substituted with alkyl or aryl groups in the α-position, have been prepared from isatin intermediates.

Tryptamine Derivative Synthesis:[8][9][10][11][12][13]


Addition of methylketones to isatin or substituted isatins in the presence of diethylamine and dehydration of the resulting aldol with hydrochloric acid affords the corresponding 3-oxindolidene derivative. Oximination of the ketone, followed by catalytic reduction. The corresponding α-substituted tryptamine results from reduction of the oximiooxindole with sodium and IPA or with NaBH4-AlCl3.[14]

7-Trifluoromethyl-isatin is used as a precursor in the synthesis of mefloquine.

6-Chloro-isatin is for the drug Ziprasidone, respectively.

N-dichlorophenyl-isatin is for diclofenac. N-phenyl-isatin is for Linopirdine.

Reactions

Isatoic anhydride synthesis:[15]

Oxidation of isatin using either hydrogen peroxide or chromic anhydride yields isatoic anhydride (used for tranilast, cloperidone, molinazone, tioperidone, ketanserin, and Belaperidone. In the oxidation of isatin to isatoic anhydride, the oxidizing agent selected should be able to introduce an oxygen atom between the two adjacent carbonyl groups without substantial decomposition of the ring system. A mixture of aqueous hydrogen peroxide in acetic or formic acid in the presence of catalytic amount of sulfuric acid is also used for the oxidation of isatin to isatoic anhydride. Another economic and environment-friendly procedure for the oxidation of isatins is through the use of the urea–hydrogen peroxide complex (percarbamide, H2NCONH2 · H2O2).

Note: Isatoic anhydride is made from anthranilic acid also.

See also

References

  1. ↑ Erdmann, O. L. (1840). "Untersuchungen über den Indigo". Journal für Praktische Chemie 19 (1): 321–362. doi:10.1002/prac.18400190161.
  2. ↑ Laurent, A. (1840). "Recherches sur l'indigo". Annales de Chimie et de Physique 3 (3): 393–434.
  3. ↑ da Silva, J. F. M.; Garden, S. J.; Pinto, A. C. (2001). "The Chemistry of Isatins: a Review from 1975 to 1999" (pdf). Journal of the Brazilian Chemical Society 12 (3): 273–324. doi:10.1590/S0103-50532001000300002.
  4. ↑ Jarrahpour, A. A.; Khalili, D. (2005). "Synthesis of 3,3´-[methylenebis(3,1-phenylenenitrilo)]bis[1,3-dihydro]-2H-indol-2-one as a Novel bis-Schiff Base" (pdf). Molbank 2005 (4): M437. doi:10.3390/M437.
  5. ↑ Sumpter, W. C. (1944). "The Chemistry of Isatin". Chemical Reviews 34 (3): 393–434. doi:10.1021/cr60109a003.
  6. ↑ Hewawasam, P.; Meanwell, N. A. (1994). "A General Method for the Synthesis of Isatins". Tetrahedron Letters 35 (40): 7303–7306. doi:10.1016/0040-4039(94)85299-5.
  7. ↑ C. S. Marvel and G. S. Hiers (1941). "Isatin". Org. Synth.; Coll. Vol. 1, p. 327
  8. ↑ S. Pietra, Farmaco, Ed. Sci., 12, 946 (1957).
  9. ↑ S. Pietra, Farmaco, Ed. Sci., 13, 75 (1958).
  10. ↑ Pietra, S; Tacconi, G (1958). "Indole derivatives. III. The preparation of alpha-alkyl and of alpha-aryltryptamines". Il Farmaco; edizione scientifica 13 (12): 893–910. PMID 13619730.
  11. ↑ Pietra, S; Tacconi, G (1959). "Indole derivatives. Note IV. Preparation of alpha-alkyl- and alpha-aryl-N-methyltryptamines". Il Farmaco; edizione scientifica 14: 854–66. PMID 13854355.
  12. ↑ Pietra, S; Tacconi, G (1960). "Indole derivatives. Note 5. Synthesis of alpha-phenyl-beta-methyltryptamine". Il Farmaco; edizione scientifica 15: 451–67. PMID 13854354.
  13. ↑ S. Pietra, G. Tacconi, Farmaco, Ed. Sci., 16, 483 (1961).
  14. ↑ Franklin (1963). "A Novel Preparation of α-Substituted Tryptamines from Isatins.". J. Chem. Soc. 0 (0): 1318–1343. doi:10.1039/JR9630001318. ISSN 0368-1769.
  15. ↑ Deligeorgiev, Todor; Vasilev, Aleksey; Vaquero, Juan J.; Alvarez-Builla, Julio (2007). "A green synthesis of isatoic anhydrides from isatins with urea–hydrogen peroxide complex and ultrasound". Ultrasonics Sonochemistry 14 (5): 497. doi:10.1016/j.ultsonch.2006.12.003. PMID 17258493.

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