Home An efficient, one-pot three-component synthesis of 4H-thiazolo[3,2-a][1,3,5]triazin-6-one derivatives
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An efficient, one-pot three-component synthesis of 4H-thiazolo[3,2-a][1,3,5]triazin-6-one derivatives

  • Mustafa T. Ubeid , Hamdy K. Thabet EMAIL logo and Said A. El-Feky
Published/Copyright: January 12, 2016
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Heterocyclic Communications
From the journal Heterocyclic Communications Volume 22 Issue 1

Abstract

A simple and efficient protocol was established to synthesize thiazolo[3,2-a][1,3,5]triazin-6-ones via three-component one-pot condensation reaction of readily available thioglycolic acid or ethyl thioglycolate, aldehydes or ketones and dicyandiamide in the presence of ammonium acetate. All of the newly synthesized compounds were characterized by spectroscopic analyses.

Keywords: multicomponent reaction; one-pot reaction; thiazolo[3,2-a][1,3,5]triazin-6-ones

Introduction

The design of highly efficient reaction sequences that provide the maximum structural complexity and diversity with a minimum number of synthetic steps is a great challenge for synthetic chemists [1, 2]. In this regard, the multi-component reaction (MCR) is one of the best tools available for the creation of several bonds in a single operation by virtue of efficiency and facility [3–6], because it allows more than two building blocks to be combined in a practical, time-saving, one-pot operation [7–13]. In recent years, the research on MCR has been rapidly evolved and hundreds of MCRs have been described [7–10, 14, 15]. In addition, such reactions also provide an efficient manner to discover biologically active compounds [9, 12, 16, 17]. Although impressive successes have been achieved, it is still of academic significance and application value to discover new multicomponent reactions [7, 18, 19].

The thiazolo-s-triazine moiety is found in wide range of biologically active compounds. Thiazolo-s-triazines have been found to possess antifolate activity [20, 21] and have been developed as anticancer, antibacterial, antifungal, and antiparasitic agents [22–24]. Thus, the synthesis of new compounds of this class of compounds may give a library of compounds as possible candidates for different biological activities. As a continuation to our program directed towards the synthesis of heterocyclic systems [25–31], we describe herein a powerful and highly effective synthetic route to thiazolo[3,2-a][1,3,5]triazin-6-ones via one-pot three-component reaction of thioglycolic acid/ethyl thioglycolate, aldehydes/ketones and dicyandiamide in the presence of ammonium acetate as a catalyst.

Results and discussion

The synthesis of the thiazolo[3,2-a][1,3,5]triazine skeleton has earlier been achieved by a multistep reaction. The most common synthetic methods reported for the preparation of this ring system involve annelation of the triazine ring onto a thiazole scaffold via Mannich reaction [32], multicomponent reactions of 2-aminothiazoles with heterocumulenes [33, 34], 2-aminothiazoles with C-N-C triatomic [35, 36], formal [4+2] cycloaddition [37], 1,3,5-triazine ring annelation on 2-substituted thiazoles using one-carbon inserting reagents [38] or annelation of thiazole ring into 1,3,5-triazine scaffold [39]. In the present work, it is noticed that the reaction is very much accommodative and more productive with thioglycolic ester in the place of thioglycolic acid.

The synthesis of thiazolo[3,2-a][1,3,5]triazines 5a-e (Scheme 1) was achieved by tandem cyclization of thioglycolic acid or ethyl thioglycolate (1) and dicyandiamide (2) with aromatic aldehydes 3, taken in a 1:1:1 molar ratio, in the presence of ammonium acetate. The hypothetical benzylidene derivatives 4a-e were not found in crude mixtures. When the reaction was carried out in the presence of ethyl thioglycolate instead of thioglycolic acid, the yield was improved and the reaction time was significantly reduced. Accordingly, the ester is the reagent of choice for this reaction.

Scheme 1 One-pot multicomponent synthesis of 4H-thiazolo[3,2-a] [1,3,5]triazines.
Scheme 1

One-pot multicomponent synthesis of 4H-thiazolo[3,2-a] [1,3,5]triazines.

The suggested mechanism is given in Scheme 2. The elementary step involves the formation of intermediate product A by nucleophilic addition of the sulfanyl group of thioglycolic acid or ethyl glycolate (1) to the cyano group of dicyandiamide (2). The intramolecular cyclization of A by loss of water or ethanol generates another non-isolable intermediate 4-thiazolinone product B. Then, the intermediate product B underoges a reaction with an aldehyde 3 in the presence of ammonium acetate as a catalyst to furnish Schiff base C which is a direct precursor to thiazolo[3,2-a][1,3,5]triazines 5a-e.

Scheme 2 Proposed mechanistic route to the formation of 4H-thiazolo[3,2-a][1,3,5]triazines.
Scheme 2

Proposed mechanistic route to the formation of 4H-thiazolo[3,2-a][1,3,5]triazines.

The molecular structure of 5a–e was elucidated with the help of spectral and elemental analyses. In particular, all products 5 exist in a single tautomeric form, apparently 5-B, as suggested by the experimental data (Figure 1).

Figure 1 Possible tautomeric forms of thiazolo[3,2-a][1,3,5]triazin-6(7H)-ones 5a-e.
Figure 1

Possible tautomeric forms of thiazolo[3,2-a][1,3,5]triazin-6(7H)-ones 5a-e.

We also studied the participation of ketones 6 as one-carbon inserting reagents. Thus, spiro- products 7a-c were readily obtained by one-pot three-component reaction of thioglycolic acid or ethyl thioglycolate, a ketone including barbituric acid and dicyandiamide in a 1:1:1 molar ratio in the presence of ammonium acetate as a catalyst. The spectral characteristics and analytical data of the products were in full agreement with the given structures 7a-c (Scheme 3). In a similar manner, dispiro compounds 8a-d were obtained as major products using thioglycolic acid or ethyl thioglycolate, ketone 6 and dicyandiamide in a 1:2:1 molar ratio.

Scheme 3 One-pot multicomponent synthesis of spiro-4H-thiazolo[3,2-a][1,3,5]triazines.
Scheme 3

One-pot multicomponent synthesis of spiro-4H-thiazolo[3,2-a][1,3,5]triazines.

Conclusions

An efficient procedure for the synthesis of thiazolo[3,2-a][1,3,5]triazin-6-ones (5a-e, 7a-c, 8a-d) using one-pot three-component condensation reaction of ethyl thioglycolate, an aldehydes or a ketone, and dicyandiamide in the presence of ammonium acetate as a inexpensive catalyst is reported. The major advantages are simplicity, high yields of products and ease of the work-up including isolation of the products without chromatography.

Experimental

All chemicals were purchased from Aldrich or Merck and used without further purification. Melting points are uncorrected. IR spectra were taken in KBr pellets on Shimadzu 440 spectrometer, 1H NMR (400 MHz) spectra and 13C NMR (100 MHz) spectra were obtained in DMSO-d6 on a Varian Gemini 400 spectrometer using TMS as internal standard. The elemental analyses were carried out at the Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo.

General procedure for synthesis of 4H-thiazolo[3,2-a][1,3,5]triazin-6(7H)-ones 5a-e and spiro-4H-thiazolo[3,2-a][1,3,5]triazin-6(7H)-ones 7a-c

A mixture of the aldehyde 3 or ketone 6 (0.01 mol), ethyl thioglycolate (1, 0.01 mol), dicyandiamide (2, 0.01 mol) in acetic acid (30–50 mL) in the presence of ammonium acetate (3 g) was heated under reflux for a period of time indicated below. The reaction progress was monitored monitored by TLC. The resultant solid product was filtered off, washed with ethanol, dried and crystallized to give 5a-e or 7a-c.

2-Amino-4-phenyl-4H-thiazolo[3,2-a][1,3,5]triazin-6(7H)-one (5a)

This compound was obtained from benzaldehyde in 91% yield as yellow crystals (from dioxane); reaction time 3 h; mp 291–292°C; IR: 3404, 3121 (NH2), 3050 (CH-arom.), 2914 (CH-aliph.), 1690 (C=O), 1647, 1604 cm-1 (C=N); 1H NMR: δ 7.40 (s, 1H, H-7), 7.21 (d, 2H, H-2′ and H-6′), 7.43–7.53 (m, 3H, H-3′, H-4′, and H-5′), 7.55 (s, 1H, H-4), 8.35 (s, 2H, NH2, exchangeable with D2O), 9.19 (s, 1H, OH, exchangeable with D2O); 13C NMR: 69.7 (C-4), 74.4 (C-7), 128.6 (C-4′), 127.5 (C-2′ and C-6′), 128.4 (C-3′ and C-5′), 143.6 (C-1′), 154.6 (C-2), 159.2 (C-8a), 179.6 (C-6). Anal. Calcd for C11H10N4OS: C, 53.64, H, 4.09, N, 22.75. Found: C, 53.52, H, 3.94, N, 22.59.

2-Amino-4-(p-tolyl)-4H-thiazolo[3,2-a][1,3,5]triazin-6(7H)-one (5b)

This compound was obtained from 4-methylbenzaldehyde in 88% yield as yellow crystals (from EtOH/dioxane); reaction time 2 h; mp 268–269°C; IR: 3329, 3135 (NH2), 3088 (CH-arom.), 2940 (CH-aliph.), 1675 (C=O), 1648, 1610 cm-1 (C=N); 1H NMR: δ 2.35 (s, 3H, CH3), 7.30 (s, 1H, H-7), 7.32 (d, 2H, H-3′ and H-5′), 7.41 (d, 2H, H-2′ and H-6′), 7.57 (s, 1H, H-4), 8.34 (s, 2H, NH2, exchangeable with D2O), 9.41 (s, 1H, OH, exchangeable with D2O); 13C NMR: δ 20.5 (4′-Me), 69.5 (C-4), 75.5 (C-7), 137.2 (C-4′), 125.6 (C-2′ and C-6′), 128.8 (C-3′ and C-5′), 142.4 (C-1′), 154.5 (C-2), 159.2 (C-8a), 179.2 (C-6). Anal. Calcd for C12H12N4OS: C, 55.37, H, 4.65, N, 21.52. Found: C, 55.24, H, 4.49, N, 21.34.

2-Amino-4-(2-hydroxyphenyl)-4H-thiazolo[3,2-a][1,3,5]triazin-6(7H)-one (5c)

This compound was obtained from 2-hydroxybenzaldehyde in 93% yield as yellow crystals (from dioxane); reaction time 2 h; mp 280–282°C; IR: 3332, 3276, 3133 (NH2/OH), 3040 (CH-arom.), 2920 (CH-aliph.), 1674 (C=O), 1633, 1587 cm-1 (C=N); 1H NMR: δ: 6.90 (s, 1H, H-7), 6.93 (d, 1H, H-3′), 7.21 (dd, 1H, H-5′), 7.24 (dd, 1H, H-4′), 7.34 (d, 1H, H-6′), 7.54 (s, 1H, H-4), 7.92 (s, 2H, NH2, exchangeable with D2O), 8.31 (s, 1H, OH, exchangeable with D2O), 9.07 (hump, 1H, OH, exchangeable with D2O); 13C NMR: 66.5 (C-4), 75.4 (C-7), 116.2 (C-3′), 122.6 (C-5′), 127.6 (C-4′), 128.0 (C-6′), 134.2 (C-1′), 154.7 (C-2), 156.2 (C-2′), 157.6 (C-8a), 180.1 (C-6). Anal. Calcd for C11H10N4O2S: C, 50.37, H, 3.84, N, 21.36. Found: C, 50.19, H, 3.90, N, 21.28.

2-Amino-4-(4-methoxyphenyl)-4H-thiazolo[3,2-a][1,3,5]triazin-6(7H)-one (5d)

This compound was obtained from 4-methoxybenzaldehyde in 94% yield as yellow crystals (from dioxane); reaction time 3 h; mp 295–296°C; IR: 3330, 3177 (NH2), 2920, 2833 (CH-aliph.), 1682 (C=O), 1645, 1589 cm-1 (C=N); 1H NMR: δ: 3.82 (s, 3H, OCH3), 7.06 (s, 1H, H-7), 7.40 (d, 2H, H-3′ and H-5′), 7.53 (d, 2H, H-2′ and H-6′), 7.56 (s, 1H, H-4), 8.33 (s, 2H, NH2, exchangeable with D2O), 11.98 (hump, 1H, OH, exchangeable with D2O); 13C NMR: 55.4 (OMe), 69.6 (C-4), 76.3 (C-7), 113.3 (C-3′ and C-5′), 126.4 (C-2′ and C-6′), 140.3 (C-1′), 154.4 (C-2), 158.1 (C-8a), 159.8 (C-4′), 180.4 (C-6). Anal. Calcd for C12H12N4O2S: C, 52.16, H, 4.38, N, 20.28. Found: C, 52.04, H, 4.25, N, 20.32.

2-Amino-4-(furan-2-yl)-4H-thiazolo[3,2-a][1,3,5]triazin-6(7H)-one (5e)

This compound was obtained from furan-2-carbaldehyde in 87% yield as green crystals (from dioxane); reaction time 4 h; mp 284–286°C; IR: 3305, 3115 (NH2), 2930 (CH-aliph.), 1688 (C=O), 1651, 1612 cm-1 (C=N), 1H NMR: δ: 6.69 (s, 1H, H-7), 6.89 (d, 1H, H-3′), 7.25 (dd, 1H, H-4′), 7.38 (d, 1H, H-5′), 7.51 (s, 1H, H-4), 8.34 (s, 2H, NH2, exchangeable with D2O), 11.96 (hump, 1H, OH, exchangeable with D2O); 13C NMR: 69.5 (C-4), 74.6 (C-7), 106.8 (C-3′), 110.3 (C-4′), 142.7 (C-5′), 152.4 (C-2′), 154.6 (C-2), 158.6 (C-8a), 179.2 (C-6). Anal. Calcd for C9H8N4O2S: C, 45.76, H, 3.41, N, 23.72. Found: C, 45.59, H, 3.34, N, 23.61.

2′-Aminospiro[indene-2,4′-thiazolo[3,2-a][1,3,5]triazine]-1,3,6′ (7′H)-trione (7a)

This compound was obtained from ninhydrin in 89% yield as brown crystals (from dioxane); reaction time 4 h; mp 298–300°C; IR: 3380, 3163 (NH2), 2920, 2838 (CH-aliph.), 1710, 1660 (C=O), 1636, 1605 cm-1 (C=N), 1H NMR: δ 6.95 (s, 1H, H-7), 7.70 (d, 2H, Ar-H), 7.84 (dd, 2H, Ar-H), 8.39 (s, 2H, NH2, exchangeable with D2O), 9.49 (s, 1H, OH, exchangeable with D2O); 13C NMR: 76.5 (C-7), 108.4 (C-4), 126.7 (2Ar-C), 134.6 (2Ar-C), 142.6 (2Ar-C), 155.2 (C-2), 157.8 (C-8a), 180.5 (C-6), 194.8 (2CO). Anal. Calcd for C13H8N4O3S: C, 52.00, H, 2.69, N, 18.66. Found: C, 51.83, H, 2.56, N, 18.49.

2′-Aminospiro[indoline-3,4′-thiazolo[3,2-a][1,3,5]triazine]-2,6′ (7′H)-dione (7b)

This compound was obtained from isatin in 87% yield as red solid (from dioxane); reaction time 3 h; mp 269–271°C; IR: 3463, 3276, 3118 (NH2/NH), 1695 (C=O), 1649, 1614 (C=N), 1H NMR: δ 6.91 (s, 1H, H-7), 7.02 (dd, 1H, Ar-H), 7.16 (dd, 1H, Ar-H), 7.47 (d, 1H, Ar-H), 7.52 (d, 1H, Ar-H), 8.42 (s, 2H, NH2, exchangeable with D2O), 9.02 (s, 1H, OH, exchangeable with D2O), 11.10 (s, 1H, NH, exchangeable with D2O)); 13C NMR: 76.9 (C-7), 98.4 (C-4), 117.6, 125.6, 128.9, 129.6, 142.6 (Ar-C), 156.4 (C-2), 158.8 (C-8a), 174.6 (CO), 181.4 (C-6). Anal. Calcd for C12H9N5O2S: C, 50.17, H, 3.16, N, 24.38. Found: C, 50.10, H, 3.20, N, 24.25.

2′-Amino-1H-spiro[pyrimidine-2,4′-thiazolo[3,2-a][1,3,5]triazine]-4,6,6′ (3H,5H,7′H)-trione (7c)

This compound was obtained from barbituric acid in 84% yield as brown crystals (from dioxane); reaction time 4 h; mp 275–276°C; IR: (potassium bromide, cm-1): 3400, 3214, 3130 (NH2/NH), 2935 (CH-aliph.), 1690, 1655 (C=O), 1619 (C=N), 1H NMR (400 MHz, DMSO-d6 ): δ: 3.12 (s, 2H, CH2), 6.91 (s, 1H, H-7), 8.42 (s, 2H, NH2, exchangeable with D2O), 8.76 (s, 1H, NH, exchangeable with D2O), 9.15 (s, 1H, OH, exchangeable with D2O), 10.02 (s, 1H, NH, exchangeable with D2O); 13C NMR: 44.7 (methylene), 77.4 (C-7), 114.1 (C-4), 156.7 (C-2), 158.7 (C-8a), 171.2 (2CO), 180.3 (C-6). Anal. Calcd. for C8H8N6O3S: C, 35.82, H, 3.01, N, 31.33. Found: C, 35.74, H, 2.88, N, 31.26.

General procedure for synthesis of 4,7-dispiro-4H-thiazolo[3,2-a][1,3,5]triazin-6(7H)-ones 8a-d

A mixture of ketone 6 (0.02 mol), ethyl thioglycolate (1, 0.01 mol), dicyandiamide (2, 0.01 mol) in acetic acid (30–50 mL) in the presence of ammonium acetate (3 g) was heated under reflux for a period of time indicated below. The reaction progress was monitored by TLC. The resultant solid product was filtered off, washed with ethanol, dried and crystallized from a mixture of dioxane and N,N-dimethylformamide.

2′-Amino-7′-(1,3-dioxo-1,3-dihydro-2H-inden-2-ylidene)spiro[indene-2,4′-thiazolo[3,2-a][1,3,5]triazine]-1,3,6′ (7′H)-trione (8a)

This compound was obtained from ninhydrin in 92% yield as grey solid; reaction time 4 h; mp 309–311°C; IR: 3390, 3314 (NH2), 3070 (CH-arom.), 1671 (C=O), 1649, 1599 (C=N); 1H NMR: δ 7.16-8.28 (m, 8H, Ar-H), 9.44, 10.74 (2s, 2H, 2NH, exchangeable with D2O. Anal. Calcd for C22H10N4O5S: C, 59.73; H, 2.28; N, 12.66. Found: C, 59.58, H, 2.29, N, 12.92.

2′-Amino-7′-(2-oxoindolin-3-ylidene)spiro[indoline-3,4′-thiazolo[3,2-a]-[1,3,5]triazine]-2,6′ (7′H)-dione (8b)

This compound was obtained from isatin in 94% yield as red solid; reaction time 4 h; mp 289–291°C; IR: 3459, 3326, 3241 (NH2/NH), 1716, 1680 (C=O), 1618 cm-1 (C=N); 1H NMR: δ: 7.33–8.05 (m, 8H, Ar-H), 8.17 (s, 2H, NH2, exchangeable with D2O), 9.92, 10.66 (2s, 2H, 2NH, exchangeable with D2O); 13C NMR: δ 97.5 (C-4), 114.3, 115.6, 124.5, 125.4, 125.6, 127.1, 127.8, 128.4, 128.5 (Ar-C), 128.9 (C-7), 130.2, 141.8, 142.6 (Ar-C), 151.3 (indole-C-3′), 156.4 (C-2), 158.8 (C-8a), 168.2, 169.6, 174.6 (3CO). Anal. Calcd for C20H12N6O3S: C, 57.69, H, 2.90, N, 20.18. Found: C, 57.74, H, 2.76, N, 20.09.

2′-Amino-7′-(4,6-dioxotetrahydropyrimidin-2(1H)-ylidene)-1H-spiro[pyrimidine-2,4′-thiazolo[3,2-a][1,3,5]triazine]-4,6,6′ (3H,5H,7′H)-trione (8c)

This compound was obtained in 89% yield from barbituric acid as brown solid; reaction time 3 h; mp 301–302°C; IR: 3362, 3271, 3123 (NH2/NH), 2945 (CH-aliph.), 1670, 1652 (C=O), 1610 cm-1 (C=N); 1H NMR: δ 3.18 (s, 2H, CH2), 3.24 (s, 2H, CH2), 6.90 (s, 2H, NH2, exchangeable with D2O), 11.47, 12.30 (2s, 4H, 4NHCO, exchangeable with D2O. Anal. Calcd for C12H10N8O5S: C, 38.10; H, 2.66; N, 29.62. Found: C, 37.88; H, 2.45; N, 29.44.

2-Amino-4,4-dimethyl-7-(propan-2-ylidene)-4H-thiazolo[3,2-a][1,3,5]triazin-6(7H)-one (8d)

This compound was obtained from acetone in 93% yield as white solid; reaction time 4 h; mp 263–265°C; IR: 3389, 3210 (NH2), 2920 (CH-aliph.), 1733 (C=O), 1615 (C=N), 1H NMR (400 MHz, DMSO-d6 ); δ: 1.94 (s, 6H, 2Me), 2.31 (s, 6H, 2Me), 7.20 (s, 1H, NH, exchangeable with D2O), 8.21 (s, 1H, NH, exchangeable with D2O); 13C NMR: δ 18.4 (2CH3), 31.2 (2CH3), 76.4 (C-4), 122.2 (C-7), 146.7 (C=C), 155.7 (C-2), 159.2 (C-8a), 166.6 (CO). Anal. Calcd for C10H14N4OS: C, 50.40, H, 5.92, N, 23.51. Found: C, 50.43, H, 5.77, N, 23.46.

Corresponding author: Hamdy K. Thabet, Faculty of Arts and Science, Department of Chemistry, Northern Border University, Rafha, 91911, P.O. 840, Saudi Arabia; and Faculty of Science, Department of Chemistry, Al-Azhar University, 11284, Nasr City, Cairo, Egypt, e-mail:

Acknowledgments

The authors extend their appreciation to the Deanship of Scientific Research, Northern Border University, Kingdom of Saudi Arabia for funding this research work through the research group project No. (435-082-8).

References

[1] Schreiber, S. L. Target-oriented and diversity-oriented organic synthesis in drug discovery. Science 2000, 287, 1964–9.10.1126/science.287.5460.1964Search in Google Scholar

[2] Wen, L. R.; Li, Z. R.; Li M.; Cao, H. Solvent-free and efficient synthesis of imidazo[1,2-a]pyridine derivatives via a one-pot three-component reaction. Green Chem. 2012, 14, 707–716.10.1039/c2gc16388hSearch in Google Scholar

[3] Jiang, B.; Rajale, T.; Wever, W.; Tu S. J.; Li, G. G. Multicomponent reactions for the synthesis of heterocycles. Chem. Asian J. 2010, 5, 2318–2335.10.1002/asia.201000310Search in Google Scholar

[4] Lin, X. F.; Mao, Z. J.; Dai, X. X.; Lu P.; Wang, Y. G. A straightforward one-pot multicomponent synthesis of polysubstituted pyrroles. Chem. Commun. 2011, 47, 6620–6622.10.1039/c1cc11363aSearch in Google Scholar

[5] Hong, D.; Zhu, Y. X.; Li, Y.; Lin, X. F.; Lu P.; Wang, Y. G. Three-component synthesis of polysubstituted pyrroles from α-diazoketones, nitroalkenes, and amines. Org. Lett. 2011, 13, 4668–4671.10.1021/ol201891rSearch in Google Scholar

[6] Ghahremanzadeh, R.; Rashid, Z.; Zarnani A. H.; Naeimi, H. A facile one-pot ultrasound assisted for an efficient synthesis of 1H-spiro[furo[3,4-b]pyridine-4,3′-indoline]-3-carbonitriles. Ultrason. Sonochem. 2014, 21, 1451–1460.10.1016/j.ultsonch.2014.02.014Search in Google Scholar

[7] Toure, B. B.; Hall, D. G. Natural product synthesis using multicomponent reaction strategies. Chem. Rev. 2009, 109, 4439–4486.10.1021/cr800296pSearch in Google Scholar

[8] Candeias, N. R.; Montalbano, F.; Cal P. M.; Gois, P. M. P. Boronic acids and esters in the Petasis-borono Mannich multicomponent reaction. Chem. Rev. 2010, 110, 6169–6193.10.1021/cr100108kSearch in Google Scholar

[9] Ramachary, D. B.; Jain, S. Sequential one-pot combination of multi-component and multi-catalysis cascade reactions: an emerging technology in organic synthesis. Org. Biomol. Chem. 2011, 9, 1277–1300.10.1039/C0OB00611DSearch in Google Scholar

[10] Bonfield, E. R.; Li, C. J. Efficient preparation of the isoindoline framework via a six component, tandem double A3-coupling and [2+2+2] cycloaddition reaction. Adv. Synth. Catal. 2008, 350, 370–374.10.1002/adsc.200700500Search in Google Scholar

[11] Elders, N.; Vander Born, D.; Hendrickx, L. J. D.; Timmer, B. J. J.; Krause, A.; Janssen, E.; de Kanter, F. J. J.; Ruijter E.; Orru, R. V. A. The efficient one-pot reaction of up to eight components by the union of multicomponent reactions. Angew. Chem. Int. Ed. 2009, 48, 5856–5859.10.1002/anie.200902683Search in Google Scholar

[12] Brahmachari, G.; Das, S. Bismuth nitrate-catalyzed multicomponent reaction for efficient and one-pot synthesis of densely functionalized piperidine scaffolds at room temperature. Tetrahedron Lett. 2012, 53, 1479–1484.10.1016/j.tetlet.2012.01.042Search in Google Scholar

[13] H. Deng, Z. Li, F. Ke and X. Zhou, Cu-catalyzed three-component synthesis of substituted benzothiazoles in water. Chem. Eur. J. 2012, 18, 4840–4843.10.1002/chem.201103525Search in Google Scholar

[14] Sunderhaus, J. D.; Dockendorff, C.; Martin, S. F. synthesis of diverse heterocyclic scaffolds via tandem additions to imine derivatives and ring-forming reactions. Tetrahedron 2009, 65, 6454–6469.10.1016/j.tet.2009.05.009Search in Google Scholar

[15] Tu, X. C.; Feng, H.; Tu, M. S.; Jiang, B.; Wang S. L.; Tu, S. J. Multicomponent domino reactions of acetylenedicarboxylates: divergent synthesis of multi-functionalized pyrazolones and C-tethered bispyrazol-5-ols. Tetrahedron Lett. 2012, 53, 3169–3172.10.1016/j.tetlet.2012.04.051Search in Google Scholar

[16] Yu, J.; Shi F.; Gong, L. Z. Brønsted-acid-catalyzed asymmetric multicomponent reactions for the facile synthesis of highly enantioenriched structurally diverse nitrogenous heterocycles. Acc. Chem. Res. 2011, 44, 1156–1171.10.1021/ar2000343Search in Google Scholar

[17] Dömling, A.; Wang W.; Wang, K. Chemistry and biology of multicomponent reactions. Chem. Rev. 2012, 112, 3083–3135.10.1021/cr100233rSearch in Google Scholar

[18] Hajipour, A. R.; Ghayeb Y.; Sheikhan, N. Brønsted acidic ionic liquid as an efficient and reusable catalyst for one-pot synthesis of 1-amidoalkyl 2-naphthols under solvent-free conditions. Tetrahedron Lett. 2009, 50, 5649–5651.10.1016/j.tetlet.2009.07.116Search in Google Scholar

[19] Jiang, B.; Xue, L. Y.; Wang, X. H.; Tu, M. S.; Liu Y. P.; Tu, S. J. Microwave-assisted multicomponent reaction of aryl amidines: regiospecific synthesis of new polysubstituted thiopyrano-, and pyrano[4,3-d]pyrimidines. Tetrahedron Lett. 2012, 53, 1261–1264.10.1016/j.tetlet.2011.12.128Search in Google Scholar

[20] Dolzhenko A. V.; Chui, W-K. Synthesis of 2-amino-s-triazino[1,2-a]benzimidazoles as potential antifolates from 2-guanidino- and 2-guanidino-5-methylbenzimidazoles. J. Heterocycl. Chem. 2006, 43, 95–100.10.1002/jhet.5570430115Search in Google Scholar

[21] Toyoda, T.; Brobey, R. K.; Sano, G.; Horii, T.; Tomioka N.; Itai, A. Lead discovery of inhibitors of the dihydrofolate reductase domain of Plasmodium falciparum dihydrofolate reductase-thymidylate synthase. Biochem. Biophys. Res. Commun. 1997, 235, 515–519.10.1006/bbrc.1997.6814Search in Google Scholar

[22] Chan, D.; Anderson, A. Towards species-specific antifolates. Curr. Med. Chem. 2006, 13, 377–398.10.1016/j.annemergmed.2006.07.457Search in Google Scholar

[23] Kompis, I. M.; Islam K.; Then, R. L. DNA and RNA synthesis: antifolates. Chem. Rev. 2005, 105, 593–620.10.1021/cr0301144Search in Google Scholar

[24] Gangjee, A.; Jain H. D.; Kurup, S. Recent advances in classical and non-classical antifolates as antitumor and antiopportunistic infection agents: part I. Anticaner Agents Med. Chem. 2007, 7, 524–542.10.2174/187152007781668724Search in Google Scholar

[25] Ammar, Y. A.; Al-Sehemi, A. G.; Ali, M. M.; Mohamed, Y. A.; Thabet H. Kh.; El-Gaby, M. S. A. Cyanoacetanilide intermediate in heterocyclic synthesis, part 8: preparation of thiazolidine, benzo[d][1,3]oxazine,4-aminothiophene and 4-aminothiazole derivatives strating from 2-(2-cyanoacetamido)-benzoate. Heterocycl. Lett. 2015, 5, 157–167.Search in Google Scholar

[26] Ammar, Y. A.; Ali, M. M.; Mohamed, Y. A.; Thabet H. Kh.; El-Gaby, M. S. A. Cyanoacetanilide intermediates in heterocyclic synthesis. Part 7: preparation of some spiro[indoline-3,4′-pyridine] and chromeno[3,4-c]pyridine derivatives. Heterocycl. Commun. 2013, 19, 195–200.10.1515/hc-2013-0032Search in Google Scholar

[27] El-Feky, S. A.; Thabet H. Kh.; Ubied, M. T. Synthesis, molecular modeling and anti-inflammatory screening of novel fluorinated quinoline incorporated benzimidazole derivatives using the Pfitzinger reaction. J. Fluorine Chem. 2014, 161, 87–94.10.1016/j.jfluchem.2014.02.012Search in Google Scholar

[28] El-Feky, S. A.; Abd El-Samii, Z. K.; Osman, N. A.; Lashine, J.; Kamel M. A.; Thabet, H. Kh. Synthesis, molecular docking and anti-inflammatory screening of novel quinoline incorporated pyrazole derivatives using the Pfitzinger reaction II. Bioorg. Chem. 2015, 58, 104–116.10.1016/j.bioorg.2014.12.003Search in Google Scholar

[29] Farrag, A. A.; Ammar, Y. A.; El-Sehemi, A. G.; Thabet, H. Kh.; Hassan N. A.; Samy, A. Kh. Synthesis, and pharmacological screening of novel sulfamoylphenylcarbamoyl-quinoxaline derivatives as anti-inflammatory, analgesic and antitumour agents. J. Chem. Res. 2011, 35, 163–166.10.3184/174751911X12983997221326Search in Google Scholar

[30] Elzahabi, H. S. A.; Salem, M. A.; Thabet, H. Kh. Synthesis and Anticancer activity of some novel diphenic acid derivatives. Der Pharma Chemica 2011, 3, 48–58.Search in Google Scholar

[31] Ammar, Y. A.; Thabet, H. Kh.; Ali, M. M.; Mohamed Y. A.; Ismail, M. A.; Salem, M. A. Cyanothioacetanilide Intermediates in Heterocyclic Synthesis, Part 1: Synthesis and Biological Evaluation of Some Novel Thiazole, Thiophene, Pyrazole, and Pyrazolo[1,5-a]Pyrimidine Derivatives. Phosphorus, Sulfur Silicon Relat. Elem. 2010, 185, 743–53.10.1080/10426500902953938Search in Google Scholar

[32] Hamama, W. S.; Ismail, M. A.; Shaaban S.; Zoorob, H. H. Synthesis and biological evaluation of some new Thiazolo[3,2-a][1,3,5]triazine derivatives. Med. Chem. Res. 2012, 21, 2615–2623.10.1007/s00044-011-9783-1Search in Google Scholar

[33] Bödeker, J.; Courault, K.; Köckritz A.; Köckritz, P. Reaktionen von Heteroaryliminotriphenylphosphoranen mit Heterokumulenen: Synthese und Cycloadditionen α-N-Heteroaryl-substituierter Carbodiimide. J. Prakt. Chem. 1983, 325, 463–474.10.1002/prac.19833250316Search in Google Scholar

[34] Klayman, D. L.; Milne, G. W. 2-Amino-2-thiazoline – VI: The formation of a thiazolo-s-triazine from 2-amino-2-thiazoline. Tetrahedron 1969, 25, 19198.10.1016/S0040-4020(01)99471-2Search in Google Scholar

[35] Saeed, S.; Rashid, N.; Jones P. G.; Yunas, U. 2-substituted 4H-[1,3]thiazolo[3,2-a][1,3,5]triazine-4-thiones: synthesis, crystal structure, and antifungal activity. J. Heterocycl. Chem. 2010, 47, 908–912.10.1002/jhet.439Search in Google Scholar

[36] Sokolov, V. B.; Aksinenko, A. Y.; Epishina, T. A.; Goreva, T. V.; Pushin A. N.; Martynov, I. V. Acylimines of hexafluoroacetone and methyl trifluoropyruvate in cyclocondensation with 2-aminothiazolines. Russ. Chem. Bull. 2005, 54, 1667–1671.10.1007/s11172-006-0019-3Search in Google Scholar

[37] Abdel-Hafez, S. H. Synthesis, Antimicrobial Activity of Some New 2-Amino-4-(4′-phenylsulfanyl-phenyl)-thiazole Derivatives and Theoretical Studies of Their Schiff’s Base. Phosphorus, Sulfur Silicon Relat. Elem. 2003, 178, 2563–2579.10.1080/714040970Search in Google Scholar

[38] Dolzhenko, A. V.; Chui, W. K.; Dolzhenko, A. V. Microwave-assisted synthesis of s-triazino[2,1-b][1,3]-benzoxazoles, s-triazino[2,1-b][1,3]benzothiazoles and s-triazino[1,2-a]benzimidazoles. Synthesis 2006, 4, 597–602.10.1055/s-2006-926290Search in Google Scholar

[39] Mirzoyan, R. G.; Saakyan, S. M.; Demirchyan, M. P.; Terent’ev, P. B.; Dovlatyan V. V.; Dovlatyan, A. V. Mass-spectral investigation of some alkyl- and dialkylaminosubstituted oxazolino- and thiazolino-sym-triazines. Khim. Geterotsikl. Soedin. 1982, 124–128 (Chem. Heterocycl. Compd. 1982, 18, 106–109).10.1007/BF00513301Search in Google Scholar

Received: 2015-6-28
Accepted: 2015-9-1
Published Online: 2016-1-12
Published in Print: 2016-2-1

©2016 Walter de Gruyter GmbH, Berlin/Boston

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Articles in the same Issue

  1. Frontmatter
  2. Preliminary Communication
  3. Design, synthesis, and anticancer activity of novel aryl/heteroaryl chalcone derivatives
  4. Research Articles
  5. A simple and convenient method for the synthesis of 1,3,5-triazine-nitrolic acids. The first X-ray investigation of Z-isomeric nitrolic acid
  6. Pot, atom and step-economic (PASE) synthesis of medicinally relevant spiro[oxindole-3,4′-pyrano[4,3-b]pyran] scaffold
  7. An efficient asymmetric approach to the R-enantiomer impurity of esomeprazole
  8. Synthesis, optical and electrochemical properties of 2-[(9H-fluoren-2-yl)aryl]-1H-benz[d]imidazole and 2,7-bis[(1H-benz[d]imidazol-2-yl)aryl]- 9H-fluorene derivatives
  9. Synthesis and fluorescence of pyrazolines substituted with pyrimidine and ferrocene subunits
  10. Design and synthesis of a novel rhodamine-based chemosensor and recognition study to Fe3+
  11. An efficient, one-pot three-component synthesis of 4H-thiazolo[3,2-a][1,3,5]triazin-6-one derivatives
  12. Microwave-assisted synthesis and antibacterial evaluation of new derivatives of 1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one
  13. Efficient assembly of quinoxaline derivatives from benzene-1,2-diamines, dialkyl acetylenedicarboxylates and ninhydrin
https://doi.org/10.1515/hc-2015-0135
Keywords for this article
multicomponent reaction; one-pot reaction; thiazolo[3,2-a][1,3,5]triazin-6-ones
Creative Commons
BY-NC-ND 3.0

Articles in the same Issue

  1. Frontmatter
  2. Preliminary Communication
  3. Design, synthesis, and anticancer activity of novel aryl/heteroaryl chalcone derivatives
  4. Research Articles
  5. A simple and convenient method for the synthesis of 1,3,5-triazine-nitrolic acids. The first X-ray investigation of Z-isomeric nitrolic acid
  6. Pot, atom and step-economic (PASE) synthesis of medicinally relevant spiro[oxindole-3,4′-pyrano[4,3-b]pyran] scaffold
  7. An efficient asymmetric approach to the R-enantiomer impurity of esomeprazole
  8. Synthesis, optical and electrochemical properties of 2-[(9H-fluoren-2-yl)aryl]-1H-benz[d]imidazole and 2,7-bis[(1H-benz[d]imidazol-2-yl)aryl]- 9H-fluorene derivatives
  9. Synthesis and fluorescence of pyrazolines substituted with pyrimidine and ferrocene subunits
  10. Design and synthesis of a novel rhodamine-based chemosensor and recognition study to Fe3+
  11. An efficient, one-pot three-component synthesis of 4H-thiazolo[3,2-a][1,3,5]triazin-6-one derivatives
  12. Microwave-assisted synthesis and antibacterial evaluation of new derivatives of 1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one
  13. Efficient assembly of quinoxaline derivatives from benzene-1,2-diamines, dialkyl acetylenedicarboxylates and ninhydrin
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