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Synthesis 2025; 57(03): 616-628
DOI: 10.1055/a-2434-9481
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A Reactivity Study of 4-Hydroxy-2H-chromene-2-thione and 4-Hydroxy-2H-thiochromene-2-thione with tert-Butyl Nitrite and Aromatic Amines: An Environmentally Benign Synthesis of New Hydrazone Derivatives

Anjela Xalxo
a   Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati, 781039, Assam, India
,
Ujjwal Jyoti Goswami 
a   Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati, 781039, Assam, India
,
Chiranjit Das
b   Department of Chemistry, Indian Institute of Technology Palakkad, Palakkad, 678623, Kerala, India
,
Kriti Mehta
c   National Institute of Pharmaceutical Education and Research, S. A. S. Nagar, Mohali, 160062, Punjab, India
,
Prasad V. Bharatam
c   National Institute of Pharmaceutical Education and Research, S. A. S. Nagar, Mohali, 160062, Punjab, India
,
Abu T. Khan  ∗
a   Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati, 781039, Assam, India
b   Department of Chemistry, Indian Institute of Technology Palakkad, Palakkad, 678623, Kerala, India
› Author AffiliationsWe are grateful to the Department of Science and Technology, Ministry of Science and Technology, India for financial support to A.T.K. (Grant No. CRG/2022/00751/OC). A.X. and U.J.G. thank the Indian Institute of Technology Guwahati for their research fellowships. We acknowledge the North East Centre for Biological Sciences and Healthcare Engineering (NECBH), IIT Guwahati, Department of Biotechnology (DBT), Govt. of India for the NMR instrumentation facility (Project No. BT/NER/143/SP44675/2023). We also acknowledge the Department of Science and Technology, New Delhi, India for providing XRD facilities to the Department of Chemistry under the FIST programme (Grant No. SR/FST/CS-II/2017/23C).
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Abstract

The synthesis of biologically active coumarin-based hydrazone derivatives is achieved through a one-pot, three-component reaction of 4-hydroxy-2H-chromene-2-thiones with aniline derivatives and tert-butyl nitrite under solvent- and catalyst-free conditions in yields of 76–86%. Similarly, the reactions of 4-hydroxydithiocoumarins with aniline derivatives and tert-butyl nitrite under identical conditions provided the corresponding hydrazone products in 79–85% yield through a four-component reaction. It is observed in both cases that the C=S group at the C2 position is converted into a C=O moiety. However, the intermediate products derived from 4-hydroxydithiocoumarin react further with another aniline molecule leading to thioesters. 4-Hydroxy-2H-chromene-2-thione and 4-hydroxydithiocoumarin exhibit distinct reactivity pathways, resulting in the formation of two different types of product. In addition, quantum chemical analysis of the mechanistic steps show that this reaction is exergonic. This protocol offers broad substrate scope and tolerates various functional groups, leading to high product yields in short reaction times.

Key words

4-hydroxy-2H-chromene-2-thione - 4-hydroxydithiocoumarin - anilines - hydrazones - exergonic reaction

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2434-9481.
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Publication History

Received: 06 August 2024

Accepted after revision: 04 October 2024

Accepted Manuscript online:
04 October 2024

Article published online:
29 October 2024

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