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DOI: 10.1055/s-2004-825608
Phenyl Isothiocyanate: A Very Useful Reagent in Heterocyclic Synthesis
Publication History
Publication Date:
19 May 2004 (online)
Biographical Sketches
Introduction
Naturally occurring isothiocyanates are limited in number. There is, however, a large number of synthetic isothiocyanates which constitute an important class of compounds. Thus, it is apparent that the chemistry of and from isothiocyanates has burgeoned over the years, [1] and it continues to be a blossoming field. The attraction of isothiocyanates as synthons is due to their ready availability. The most important isothiocyanate which is easily synthesized from aniline and carbon disulfide is phenyl isothiocyanate. Several heterocycles, such as thiophenes, pyrroles, pyrimidines [2] or imidazoles, [3] can be constructed from this starting material.
Figure 1
Abstracts
(A) Phenyl isothiocyanate can be condensed with a 1,3-dicarbonyl compound (or its equivalent) in basic media, followed by the addition of an activated methylene compound to synthesize 5-phenylamino-thiophenes. [4] Another equivalent of an activated methylene compound can react with the amine to build the pyrrole fused ring. [5] |
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(B) When benzothiazolyl-2-guanidine reacts with phenyl isothiocyanate, instead of the expected addition products, 2-imino-3,4-dihydro-2H-benz[1,3]thiozolo[3,2-a]-1,3,5-triazin-4-ones are obtained. [6] The thioureas are formed as intermediates in the first step and then undergo ring closure to the triazinthiones with elimination of aniline. |
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(C) Cyclohexylidenemalononitrile was allowed to react with phenyl isothiocyanate under phase-transfer catalysis to give the following bicyclic fused compounds: 3-amino-4-cyano-1-phenylimino-5,6,7,8-tetrahydroisothiachromene, 3-amino-4-cyano-2-phenyl-1-thioxo-5,6,7,8-tetrahy-droisoquinoline and 3-amino-4-cyano-2-phenyl-5,6,7,8-tetrahydroisoquinolin-1-one. [7] |
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(D) 1-Methylsulfanyl-1,3-butadiene is metalated by n-BuLi followed by the addition of phenyl isothiocyanate to give an intermediate thioamide. The latter undergoes electrocyclization to provide imino-thiopyran. [8] |
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(E) The reaction of ketene-N,N-acetals and phenyl isothiocyanate at room temperature in acetonitrile afforded a thioamide intermediate. The propenamide was converted into 6-thioxopyrimidine upon treatment with excess DMF-DMA in toluene. [9] |
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(F) Photocondensation of the unstable azirene with phenyl isothiocyanate leads to the 2,4-diarylthiazole. [10] |
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(G) 1-Allylbenzotriazole was functionalized by the sequential addition of n-BuLi and quenching of the resulting anion with phenyl isothiocyanate followed by an S-methylation. Cyclization readily occurred with a Lewis acid in dry methylene chloride to give the corresponding 2-methylsulfanylpyrrole. [11] |
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1a
Sharma S. Sulfur Reports 1989, 8: 327 -
1b
Mukerjee AK.Ashare R. Chem. Rev. 1991, 91: 1 - 2
Srirastava SK.Haq W.Chauhan PMS. Bioorg. Med. Chem. Lett. 1999, 9: 965 - 3
Boeijen A.Likamp MJ. Tetrahedron Lett. 1998, 39: 3589 -
4a
Sommen G.Comel A.Kirsch G. Tetrahederon Lett. 2002, 43: 257 -
4b
Lozinskii MO.Shelyakin VV. Chem. Heterocycl. Cmpd. 2002, 38: 1077 -
5a
Sommen G.Comel A.Kirsch G. Synlett 2001, 1731 -
5b
Sommen G.Comel A.Kirsch G. Tetrahedron 2003, 59: 1557 - 6
Krylsky DV.Shikhaliev KS.Solovyev AS. Chem. Heterocycl. Cmpd. 2001, 37: 524 - 7
El-Sayed AM.Abdel-Ghany H. J. Heterocycl. Chem. 2000, 37: 1233 -
8a
Nedolya NA.Brandsma L.Verkruijsse HD.Van der Kerk A.Trofimov BA. Tetrahedron Lett. 1998, 39: 2631 -
8b
Brandsma L.Nedolya NA.Tarasova OA.Trofimov BA. Chem. Heterocycl. Cmpd. 2000, 36: 1241 - 9 Cocco M. T., Congiu C., Onnis V., Piras R.; Il Farmaco; 2001, 56: 741
-
10a
Katritzky AR.Wang X.Maimait R. J. Org. Chem. 2000, 65: 8077 -
10b
Jackson B.Gakis N.Marky M.Hansen H.-J.von Philipsborn W.Schmid H. Helv. Chim. Acta 1972, 55: 916 - 11
Katritzky AR.Wang X.Denisenko A. J. Org. Chem. 2001, 66: 2850
References
-
1a
Sharma S. Sulfur Reports 1989, 8: 327 -
1b
Mukerjee AK.Ashare R. Chem. Rev. 1991, 91: 1 - 2
Srirastava SK.Haq W.Chauhan PMS. Bioorg. Med. Chem. Lett. 1999, 9: 965 - 3
Boeijen A.Likamp MJ. Tetrahedron Lett. 1998, 39: 3589 -
4a
Sommen G.Comel A.Kirsch G. Tetrahederon Lett. 2002, 43: 257 -
4b
Lozinskii MO.Shelyakin VV. Chem. Heterocycl. Cmpd. 2002, 38: 1077 -
5a
Sommen G.Comel A.Kirsch G. Synlett 2001, 1731 -
5b
Sommen G.Comel A.Kirsch G. Tetrahedron 2003, 59: 1557 - 6
Krylsky DV.Shikhaliev KS.Solovyev AS. Chem. Heterocycl. Cmpd. 2001, 37: 524 - 7
El-Sayed AM.Abdel-Ghany H. J. Heterocycl. Chem. 2000, 37: 1233 -
8a
Nedolya NA.Brandsma L.Verkruijsse HD.Van der Kerk A.Trofimov BA. Tetrahedron Lett. 1998, 39: 2631 -
8b
Brandsma L.Nedolya NA.Tarasova OA.Trofimov BA. Chem. Heterocycl. Cmpd. 2000, 36: 1241 - 9 Cocco M. T., Congiu C., Onnis V., Piras R.; Il Farmaco; 2001, 56: 741
-
10a
Katritzky AR.Wang X.Maimait R. J. Org. Chem. 2000, 65: 8077 -
10b
Jackson B.Gakis N.Marky M.Hansen H.-J.von Philipsborn W.Schmid H. Helv. Chim. Acta 1972, 55: 916 - 11
Katritzky AR.Wang X.Denisenko A. J. Org. Chem. 2001, 66: 2850
References
Figure 1