A sustainable strategy for the synthesis of bis-2-iminothiazolidin-4-ones utilizing novel series of asymmetrically substituted bis-thioureas as viable precursors
Abstract:A series of bis-thioureas was synthesized as viable precursors for the design of bis-2-iminothiazolidin-4-ones utilizing the ultrasonic irradiation as a sustainable energy source.
“…The genesis of this work has commenced with one of our recent papers on a green synthetic procedure for the synthesis of asymmetrically substituted bis-thioureas (scheme 1) [39]. The bis-thioureas ( 3a – d ) were obtained in excellent yields by the reaction of isothiocyanates ( 1a, b ) with diamines ( 2a, b ) in CH 3 CN by using ultrasound irradiation as a sustainable energy source (scheme 1).…”
Section: Resultsmentioning
confidence: 99%
“…The bis-thioureas ( 3a – d ) were obtained in excellent yields by the reaction of isothiocyanates ( 1a, b ) with diamines ( 2a, b ) in CH 3 CN by using ultrasound irradiation as a sustainable energy source (scheme 1). Scheme 1.An ultrasound-assisted methodology for the preparation of unsymmetrically substituted bis-thioureas 3a–d [39]. …”
Section: Resultsmentioning
confidence: 99%
“…In comparison with traditional procedures, decreased reaction times, improved yields and diminished energy used are significant merits of ultrasound methodology. As a part of our ongoing research plan on the preparation of diversified biologically active bis-heterocyclic compounds and on interesting new and eco-friendly green synthetic protocols [36][37][38][39][40][41], a straightforward synthetic procedure for the synthesis of novel series of bisheterocycles can be effectively accomplished under ultrasound irradiation as a viable greener technique. Furthermore, the electronic impact of the 1,3-substituents on the bis-thiourea performs an essential role on the regioselectivity of the cyclization and product distribution.…”
An expedient and tandem regioselective one-pot protocol for the sono-synthesis of bis-[1,2,4]-triazol-3-yl amines and bis-2-iminothiazolines from corresponding bis-1,3-disubstituted thioureas has been developed. The products' regioselectivity correlate well with the p
K
a
s of the parent amines, in which the amine possessing higher p
K
a
goes to the ring nitrogen, whereas the other nitrogen remains flanked as an exocyclic nitrogen of the bis-triazole or bis-thiazole moieties. Further, the sonochemical preparation of both bis-5-(2-nitrobenzylidene) thiobarbiturates and bis-2-thioxoimidazolidine-4,5-diones from bis-1,3-disubstituted thioureas has also been achieved. The obtained bis-5-(2-nitrobenzylidene)thiobarbiturates easily underwent reductive cyclization to afford the corresponding bis-5-benzo[
c
]isoxazol-3-ylidenethiobarbiturates. The scope and limitations of these strategies have been studied. Moreover, the suggested methodologies have advantages such as broad functional group tolerance, mild conditions, operational simplicity and applicability on a gram scale. Furthermore, the protocols scored well in a number of green metrics, subsequently showing these approaches to be environmentally benign and sustainable processes.
“…The genesis of this work has commenced with one of our recent papers on a green synthetic procedure for the synthesis of asymmetrically substituted bis-thioureas (scheme 1) [39]. The bis-thioureas ( 3a – d ) were obtained in excellent yields by the reaction of isothiocyanates ( 1a, b ) with diamines ( 2a, b ) in CH 3 CN by using ultrasound irradiation as a sustainable energy source (scheme 1).…”
Section: Resultsmentioning
confidence: 99%
“…The bis-thioureas ( 3a – d ) were obtained in excellent yields by the reaction of isothiocyanates ( 1a, b ) with diamines ( 2a, b ) in CH 3 CN by using ultrasound irradiation as a sustainable energy source (scheme 1). Scheme 1.An ultrasound-assisted methodology for the preparation of unsymmetrically substituted bis-thioureas 3a–d [39]. …”
Section: Resultsmentioning
confidence: 99%
“…In comparison with traditional procedures, decreased reaction times, improved yields and diminished energy used are significant merits of ultrasound methodology. As a part of our ongoing research plan on the preparation of diversified biologically active bis-heterocyclic compounds and on interesting new and eco-friendly green synthetic protocols [36][37][38][39][40][41], a straightforward synthetic procedure for the synthesis of novel series of bisheterocycles can be effectively accomplished under ultrasound irradiation as a viable greener technique. Furthermore, the electronic impact of the 1,3-substituents on the bis-thiourea performs an essential role on the regioselectivity of the cyclization and product distribution.…”
An expedient and tandem regioselective one-pot protocol for the sono-synthesis of bis-[1,2,4]-triazol-3-yl amines and bis-2-iminothiazolines from corresponding bis-1,3-disubstituted thioureas has been developed. The products' regioselectivity correlate well with the p
K
a
s of the parent amines, in which the amine possessing higher p
K
a
goes to the ring nitrogen, whereas the other nitrogen remains flanked as an exocyclic nitrogen of the bis-triazole or bis-thiazole moieties. Further, the sonochemical preparation of both bis-5-(2-nitrobenzylidene) thiobarbiturates and bis-2-thioxoimidazolidine-4,5-diones from bis-1,3-disubstituted thioureas has also been achieved. The obtained bis-5-(2-nitrobenzylidene)thiobarbiturates easily underwent reductive cyclization to afford the corresponding bis-5-benzo[
c
]isoxazol-3-ylidenethiobarbiturates. The scope and limitations of these strategies have been studied. Moreover, the suggested methodologies have advantages such as broad functional group tolerance, mild conditions, operational simplicity and applicability on a gram scale. Furthermore, the protocols scored well in a number of green metrics, subsequently showing these approaches to be environmentally benign and sustainable processes.
“…In spite of that, to the best of our knowledge there have been no reports to date on the preparation of bisquinazolinones using deep eutectic solvents under ultrasonic irradiation. In continuation to our ongoing efforts to develop greener synthetic pathways for organic conversions [43][44][45][46], herein I wish to report a DES-mediated protocol for greener and atom-economical preparation of novel series of bis-quinazolinones by using commercially available and inexpensive materials under appropriate catalyst-free and ultrasonic conditions.…”
To produce a new category of anti-cancer compounds, a facile and environmentally sustainable method for preparing diversified
bis
-quinazolinones was demonstrated using recyclable deep eutectic solvent (DES) under ultrasonic irradiation. The reactions were performed smoothly with a wide scope of substrates affording the desired derivatives in good-to-excellent yields under an atom-economical pathway. Particularly, halogen substituents that are amenable for further synthetic elaborations are well tolerated. Furthermore, the ‘greenness’ of the protocol was assessed within the scope of several green metrics and found to display an excellent score in the specified parameters. Cytotoxic activity of all novel
bis
-quinazolinones was investigated utilizing two cancer cell lines: breast (MCF-7) and lung (A549) cell lines and their IC
50
values were determined. Most of the prepared derivatives displayed fascinating inhibitory activity with IC
50
values in a low micromolar range. Remarkably, the derivative
7e
[3,3'-(sulfonyl
bis
(4,1-phenylene))
bis
(2-methyl-6-nitroquinazolin-4(3
H
)-one)] showed superior potency against MCF-7 and A549 cancer cell lines, with IC
50
values of 1.26 µM and 2.75 µM, respectively. Moreover, this derivative was found to have low toxicity to the normal breast cell line (MCF-10A) and could serve as a promising lead candidate for further development.
“…Accordingly, development of an effective protocol for the preparation of thiazol-4(5 H )-one cores sounds interesting from the medicinal and chemical standpoint. As a part of our interest in developing novel strategies for heterocycles assembly [28,29,35–37], herein we present the synthesis of a broad scope of mono- and bis-2-amino-5-arylidenethiazol-4-ones using new DABCO-based ILs under sustainable reaction conditions. In this context, recyclability and recoverability of the IL as well as the reaction mechanism were also investigated.…”
Herein, a novel DABCO-based dicationic ionic liquid (bis-DIL) was easily prepared from the sonication of DABCO with 1,3-dichloro-2-propanol and then characterized by several techniques. Thereafter, under the ultimate green conditions, the performance of the bis-DIL was examined for the sono-synthesis of a new library of bis-2-amino-5-arylidenethiazol-4-ones via one-pot pseudo-five-component Knoevenagel condensation reaction of appropriate dialdehydes, rhodanine and amines. This protocol is tolerant towards several mono- and dialdehydes, excellently high yielding and affording access to the desired products in a single step within a short reaction time. Compared with the conventional methodologies, the proposed method displayed several remarkable merits such as milder reaction conditions without any side product, green solvent media, recording well in a variety of green metrics and applicability in gram-scale production. The recyclability of the bis-DIL was also investigated with an average recovered yield of 97% for six sequential cycles without any significant loss of the activity.
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