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Asymmetric Mannich Reaction: Synthesis of Novel Chiral 5-(substituted aryl)-1,3,4-Thiadiazole Derivatives with Anti-Plant-Virus Potency

  • Song Bai EMAIL logo , Yunying Zhu and Qin Wu
Published/Copyright: April 3, 2019
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Heterocyclic Communications
From the journal Heterocyclic Communications Volume 25 Issue 1

Abstract

A series of novel chiral 5-(substituted aryl)-1,3,4-thiadiazole derivatives was synthesized in an enantioselective three-component Mannich reaction using cinchona alkaloid squaramide catalyst with excellent enantioselectivities (up to >99% enantiomeric excess (ee)). The bioassay results showed that these derivatives possessed good to excellent activities against tobacco mosaic virus (TMV).

Keywords: anti-plant-virus activity; asymmetric Mannich reaction; chiral 1,3,4-thiadiazole derivatives

Introduction

The design and synthesis of novel compounds that have value as agricultural therapeutic agents is one of the fundamental objectives of organic chemistry. During the past two decades, the number of non-racemic pesticides on the agrochemical market has been consistently increasing. Many novel non-racemic agrochemicals have desirable biological activity and can be used in smaller quantities because they possess low mammalian toxicity and environmental friendliness [1, 2, 3]. For example, metolachlor is a herbicide that was first used as a racemate.

The (R)-enantiomer is inactive, and modern production methods afford only (S)-metolachlor [4].

Due to their proven utility in medicinal chemistry, there has been greater interest in heterocyclic compounds [5, 6]. There are a large number of biologically active organic compounds with five-membered rings containing three heteroatoms. The 1,3,4-thiadiazole heterocycle is the most widely existing one. A survey of the available literature shows that the 1,3,4-thiadiazole heterocycle is a key structure associated with many bioactive molecules [7, 8, 9]. For example, several biologically active molecules with a 1,3,4-thiadiazole moiety are known to exhibit significant insecticidal [10], antifungal [11], and antiviral activity against TMV properties [12]. However, research on modified 1,3,4-thiadiazole derivatives has mainly focused on racemic ones. Only one work has been reported using 1,3,4-thiadiazole as a substrate in an asymmetric reaction, a study by Hu’s group. They gave the corresponding products with moderate yields (37–53%) and enantioselectivities (43–91%) [13]. In addition, our group has previously described the asymmetric addition of malonate with benzothiazolyl imine [14], and it was proven that the thiourea-cinchonine alkaloid derivatives were highly efficient catalysts in the synthesis of chiral β-amino esters bearing a benzothiazole moiety. Based on our technical competence in the field of plant virology, to exploit novel high-efficiency chiral anti-plant-virus agents, we decided to apply the cinchona alkaloid catalyst to synthesis of masked chiral 5-(substituted aryl)-1,3,4-thiadiazole derivatives. Additionally, the antiviral activity of chiral products against TMV from our asymmetric reaction was tested.

Results and Discussion

For optimization of the experimental conditions, we initially employed commercial quinine and cinchona alkaloid derivatives Q-1-Q-5 (Figure 1) in a one-pot asymmetric catalytic Mannich reaction of 5-phenyl-1,3,4-thiadiazol-2-amine, benzaldehyde, and dimethyl malonate (entry 1-6, Table 1). Quinine was a poor catalyst, whereas cinchona alkaloid-squaramide catalyst Q-5 afforded an especially promising result at 30°C for 60 h (entry 6, Table 1). Next, the influence of solvents on the model reaction was studied using the optimal catalyst Q-5 (entries 6–9, Table 1). Toluene showed higher enantioselectivity than alternative solvents. Four gradients (40 °C, 50 °C, 60 °C, and 70 °C) of reaction temperature were evaluated in this reaction (entries 10–13, Table 1). It was determined that 60 °C was suitable for obtaining high yield and excellent enantioselectivity (entry 12, Table 1). The best results were achieved at 60°C with 10 mol% catalyst loading in toluene.

Figure 1 Structure of commercial quinine and cinchona alkaloid catalysts Q-1-Q-5
Figure 1

Structure of commercial quinine and cinchona alkaloid catalysts Q-1-Q-5

Table 1

Optimization of reaction conditions using various catalysts [a]

EntryCatalyst (mol%)Temp. (°C)SolventYield[b] (%)ee[c] (%)
1Quinine (10 mol%)30PhMe3058
2Q-1 (10 mol%)30PhMe4078
3Q-2 (10 mol%)30PhMe3563
4Q-3 (10 mol%)30PhMe4372
5Q-4 (10 mol%)30PhMe4070
6Q-5 (10 mol%)30PhMe4883
7Q-5 (10 mol%)30Tetrahydrofuran3071
8Q-5 (10 mol%)30CH2Cl24078
9Q-5 (10 mol%)30Acetone3577
10Q-5 (10 mol%)40PhMe5386
11Q-5 (10 mol%)50PhMe6191
12Q-5 (10 mol%)60PhMe8493
13Q-5 (10 mol%)70PhMe8675
14Q-5 (5 mol%)60PhMe6567
15Q-5 (20 mol%)60PhMe8594

Having established the optimal reaction conditions, the substrate generality of this asymmetric Mannich reaction was investigated, and the results are summarized in Table 2. In all cases, the Mannich reaction proceed smoothly when catalyst Q-5 was used, giving the desired chiral 5-(substituted aryl)-1,3,4-thiadiazole derivatives in high isolated yields (71–90%) and excellent enantiomeric excess (up to 99% ee). Significantly, both dimethyl malonate (entries 1-3, Table 2) and diethyl malonate (entries 4-8, Table 2) proved to be good substrates with a high yield and ee values. It should be noted that the different configurations were observable using Q-5 as the catalyst.

The anti-TMV activity of the synthesized chiral compounds was tested using previously reported method [15].

Table 2

Substrate scope of the enantioselective Mannich reaction.

Entry4R1R2R3Time (h)Yieldb (%)eec (%)
14aHHMe608493
24b2, 4-di-Cl3, 4-di-ClMe608598
34c3-F3, 4-di-ClMe608187
44d2, 4-di-Cl2, 3-di-ClEt608095
54e2, 4-di-Cl2-FEt727580
64f4-Cl2, 3-di-ClEt6090>99
74g4-Cl2-FEt608290
84h3-F3, 4-di-ClEt727184

  1. a Reactions were carried out with 1.0 mmol of 1, 1.0 mmol of 2a, 1.2 mmol of 3a and 10 mol% Q-5 in 2.0 mL of toluene.

    b Isolated yield.

    c Determined by HPLC (Chiralpak IA).

As shown in Table 3. Most chiral compounds exhibited moderate to good antiviral activity against TMV in vivo, and some of them even exhibited higher antiviral activity than the commercially available plant antiviral agent ribavirin.

Table 3

EC50 values of target compounds against TMVa

CompoundEC50 for anti-TMV
Curative activityc (μg/mL)Protective activityd (μg/mL)
4b803.4±3.7361.5±4.2
4c781.2±2.6402.4±2.5
4d823.7±2.1705.6±3.2
4e813.4±3.5380.2±24
4f605.1±1.8264.2±2.0
4g465.6±1.9342.3±2.9
4h327.3±3.2254.8±4.1
Ribavirinb850.0±3.1819.5±2.4

  1. a Average of three replicates.

    b The commercial product ribavirin served as the control.

    c Curative activity refers to the therapeutic efficacy of drugs on the plant that have infected with TMV virus.

    d Protective activity refers to the ability of drugs to protect plants treated with those drugs from TMV viral infection.

Conclusions

We developed an efficient one-pot three-component selective catalytic method for the synthesis of masked chiral 5-(substituted aryl)-1,3,4-thiadiazole derivatives using chiral cinchona alkaloid-squaramide catalyst in good yields with excellent enantioselectivities (up to 99% ee). Several new chiral derivatives from our reaction showed potential anti-plant virus activities against TMV.

Experimental

IR spectra were recorded on a Bruker Vector 22 spectrometer. NMR spectra were recorded at 500 MHz (1H) and 125 MHz (13H) on a JEOL-ECX 500 NMR spectrometer using TMS as an internal standard and DMSO-d6 or CDCl3 as a solvent. Mass spectral studies were conducted on an Agilent 5973 organic mass spectrometer. Elemental analysis was performed on an Elementar Vario-III CHN analyzer. High-performance liquid chromatography (HPLC) analysis was performed on an Agilent 1100/1200 Series system using a Daicel Chiralcel IA Column (250 mm × 4.6 mm). HPLC analysis: Hexane/IPA = 70/30, 1.0 mL⋅min-1. Analytical TLC was performed on silica gel GF254. Except where otherwise stated, all reagents were purchased from Aladdin-reagent Inc. and Sigma-Aldrich Inc., and all the commercial reagents were used as received.

General experimental procedure to prepare 4a-4h Diethyl malonate or dimethyl malonate (1.20 mmol) in toluene (2.0 mL) was added all at once to a mixture of 5-(substituted aryl)-1,3,4-thiadiazole-2-amine (1.0 mmol), aldehyde (1.0 mmol), and chiral catalyst Q-5 (10 mol%) at 60 °C and stirred for 60–72 h. After completion of the reaction, the reaction mixture was directly purified by preparative TLC hexane/ethyl ether = 3/1 afforded the desired compounds 4a-4h.

(+)-Dimethyl 2-(phenyl((5-phenyl-1,3,4-thiadiazol-2-yl)amino)methyl)malonate (+)-4a, yield 84%; white solid; 93% ee as determined by HPLC [λ = 210 nm, tr (major) = 9.07 min, tr (minor) = 9.86 min]; [α]D25 = +76.2 (c = 0.95, CHCl3); mp 128–129 °C; IR (KBr, cm-1) ν:3311, 3080, 2953, 2920, 1620, 1558, 1506, 1458, 1375, 1259, 1072, 975, 758 cm-1; 1H NMR (DMSO-d6): δ (ppm) 7.74-7.72 (m, 2H), 7.46–7.28 (m, 8H), 5.45–5.41 (m, 1H), 4.14-4.12 (m, 1H), 3.68 (s, 3H), 3.45 (s, 3H); 13C NMR (DMSO-d6): δ (ppm) 167.9, 167.4, 166.8, 157.4, 139.2, 130.4, 130.3, 129.6, 129.0, 128.9, 127.9, 126.9, 58.6, 57.7, 56.2, 53.3, 52.0; MS(ESI): m/z = 398([M+H]+), 420([M+Na]+), 436([M+K]+). Anal. Calcd for C20H19N3O4S: C, 60.44; H, 4.82; N, 10.57; Found: C, 60.58; H, 4.95; N, 10.46.

(-)-Dimethyl 2-((3,4-dichlorophenyl)((5-(2,4-dichl orophenyl)-1,3,4-thiadiazol-2-yl)amino)methyl) malonate (-)-4b, yield 85%; white solid; 98% ee as determined by HPLC [λ = 210 nm, tr (major) = 7.16 min, tr (minor) = 7.73 min]; [α]D25 = -81.6 (c = 0.95, CHCl3); mp 177-179 °C; IR (KBr, cm-1) ν: 3201, 3003, 2951, 2916, 1661, 1550, 1435, 1280, 1232, 1168, 1062, 979, 823 cm-1; 1H NMR (CDCl3): δ (ppm) 8.13 (d, J = 8.6 Hz, 1H), 7.51 (d, J = 1.7 Hz, 1H), 7.47 (d, J = 1.75 Hz, 1H), 7.42-7.31 (m, 2H), 7.27-7.25 (m, 1H), 5.63(d, J = 4.5 Hz, 1H), 3.96(d, J = 4.6 Hz, 1H), 3.76(s, 3H), 3.72(s, 3H); 13C NMR (CDCl3): δ (ppm) 169.3, 168.3, 166.8, 153.5, 138.5, 136.2, 133.2, 132.6, 132.0, 131.3, 130.9, 130.1, 128.8, 128.1, 127.7, 126.1, 57.9, 56.4, 53.4, 53.1; MS(ESI): m/z =536 ([M+H]+), 558([M+Na]+). Anal. Calcd for C20H15Cl4N3O4S: C, 44.88; H, 2.82; N, 7.85; Found: C, 44.79; H, 2.95; N, 7.90.

(+)-Dimethyl 2-((3,4-dichlorophenyl)((5-(3-fluoro phenyl)-1,3,4-thiadiazol-2-yl)amino) methyl) malonate (+)-4c, yield 81%; white solid; 87.7% ee as determined by HPLC [λ = 270 nm, tr (major) = 14.36 min, tr (minor) = 10.17 min]; [α]D25 = +79.3 (c = 0.81, CHCl3); mp 151–152 °C; IR (KBr, cm-1) ν: 3385, 3053, 2953, 2918, 1622, 1583, 1506, 1471, 1394, 1240, 1197, 980, 783; 1H NMR (DMSO-d6): δ (ppm) 8.77 (d, J = 9.1 Hz, 1H), 7.61 (d, J = 8.5 Hz, 1H), 7.54–7.39 (m, 5H), 7.27 (t, J = 8.0 Hz), 5.47 (t, J = 9.2 Hz, 1H), 4.22 (d, J = 9.7 Hz, 1H), 3.64 (s, 3H), 3.49 (s, 3H); 13C NMR (DMSO-d6): δ (ppm) 167.9, 167.3, 166.8, 163.7, 161.8, 156.7, 140.5, 133.0, 131.9, 131.5, 131.1, 129.9, 128.7, 123.3, 117.3, 113.4, 57.1, 56.9, 53.3, 53.2; 19FNMR (200 MHz, DMSO-d6 ) δ: -112.0; MS (ESI): m/z = 484 ([M+H]+), 506 ([M+Na]+), 522([M+K]+). Anal. Calcd for C20H16Cl2FN3O4S: C, 49.60; H, 3.33; N, 8.68; Found: C, 49.45; H, 3.31; N, 8.64.

(-)-Diethyl 2-((2,3-dichlorophenyl)((5-(2,4-dichloro phenyl)-1,3,4-thiadiazol-2-yl)amino)methyl) malonate (-)-4d, yield 80%; white solid; 95% ee as determined by HPLC [λ = 210 nm, tr (major) = 12.48 min, tr (minor) = 13.71 min] ; [α]D25 =-78.6 (c = 0.94, CHCl3); mp 156-158 °C; IR (KBr, cm-1) ν: 3225, 3076, 2954, 2916, 1679, 1587, 1496, 1375, 1244, 1160, 1035, 980, 833; 1H NMR (CDCl3): δ (ppm) 8.12 (d, J = 8.6 Hz, 1H), 7.46 (d, J = 1.7 Hz, 1H), 7.43 (d, J = 8.0 Hz, 1H),7.39-7.36 (m, 2H), 7.31 (dd, J = 2.3, 2.2 Hz, 1H), 7.20-7.16 (t, J = 8.0 Hz, 1H), 5.97 (dd, J = 4.0, 4.0 Hz, 1H), 4.28-4.13 (m, 5H), 1.26-1.16 (m, 6H); 13C NMR (CDCl3): δ (ppm) 169.4, 168.3, 166.6, 153.4, 137.7, 136.1, 133.8, 132.0, 131.2, 130.4, 130.1, 128.2, 127.7, 127.6, 126.3, 62.6, 62.2, 57.1, 53.7, 14.1, 13.9; MS(ESI): m/z = 564 ([M+H]+), 586 ([M+Na]+), 602 ([M+K]+). Anal. Calcd for C22H19Cl4N3O4S: C, 46.91; H, 3.40; N, 7.46; Found: C, 46.87; H, 3.33; N, 7.56.

(+)-Diethyl 2-(((5-(2,4-dichlorophenyl)-1,3,4-thiadiazol-2-yl)amino)(2-fluorophenyl) methyl) malonate (+)-4e, yield 75%; white solid; 80.0% ee as determined by HPLC [λ = 210 nm, tr (major) = 6.17 min, tr (minor) = 6.83 min]; [α]D25 = +81.2 (c = 0.66, CHCl3); mp 147–149 °C; IR (KBr, cm-1) ν: 3361, 3228, 2953, 2916, 1663, 1548, 1456, 1292, 1236, 1166, 1037, 979, 802; 1H NMR (DMSO-d6): δ (ppm) 8.85 (d, J = 8.6 Hz, 1H), 8.00 (d, J = 8.6 Hz, 1H), 7.80 (S, 1H), 7.55 (d, J = 7.4 Hz, 2H), 7.35 (s, 1H), 7.22–7.19 (m, 2H), 5.78 (t, J = 9.7 Hz, 1H), 4.16–4.13 (m, 3H), 3.92–3.91 (m, 2H), 1.13–1.12 (m, 3H), 0.91–0.90 (m, 3H); 13C NMR (DMSO-d6): δ (ppm) 169.3, 166.8, 166.1, 161.5, 151.9, 135.4, 131.9, 131.8, 130.7, 130.4, 130.0, 128.7, 128.5, 126.1, 125.0, 115.8, 62.0, 61.8, 56.9, 52.3, 14.3, 13.9; 19FNMR(200 MHz, DMSO-d6) δ: -116.8; MS(ESI): m/z = 512([M+H]+), 534([M+Na]+), 550([M+K]+). Anal. Calcd for C22H20Cl2FN3O4S: C, 51.57; H, 3.93; N, 8.20;Found: C, 51.43; H, 3.79; N, 8.08.

(-)-Diethyl 2-(((5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl)amino)(2,3-dichlorophenyl) methyl) malonate (-)-4f, yield 90%; white solid; >99% ee as determined by HPLC [λ = 210 nm, tr (major) = 22.78 min, tr (minor) = 26.87 min]; [α]D25 = -63.8 (c = 0.11, CHCl3); mp 142–144 °C; IR (KBr, cm-1) ν: 3421, 3226, 2976, 2918, 1653, 1521, 1477, 1273, 1226, 1159, 1033, 981, 829; 1H NMR (CDCl3): δ (ppm) 7.70 (d, J = 8.0 Hz, 2H), 7.44–7.36 (m, 3H), 7.21 (t, J = 8.0 Hz, 1H), 5.87 (s, 1H), 4.25–4.11 (m, 5H), 1.26 (t, J = 8.0 Hz, 3H), 1.19 (t, J = 6.9 Hz, 3H); 13C NMR (CDCl3): δ (ppm) 168.1, 168.0, 166.5, 157.7, 137.5, 136.1, 133.8, 131.2, 130.5, 129.2, 129.1, 128.1, 127.7, 126.3, 62.6, 62.2, 57.6, 53.8, 14.1, 13.9; MS (ESI): m/z = 530([M+H]+),552 ([M+Na]+). Anal. Calcd for C22H20Cl3N3O4S: C, 49.97; H, 3.81; N, 7.95; Found: C, 49.67; H, 3.61; N, 7.55.

(+)-Diethyl 2-(((5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl)amino)(2-fluorophenyl)methyl) malonate (+)-4g, yield 82%; white solid; 90% ee as determined by HPLC [λ = 210 nm, tr (major) = 7.37 min, tr (minor) = 6.80 min]; [α]D25 = +99.1 (c = 1.15, CHCl3); mp 163–165 °C; IR (KBr, cm-1) ν3444, 3365, 3209, 2918, 1653, 1521, 1489, 1290, 1232, 1136, 1035, 981, 831 cm-1; 1H NMR (DMSO-d6): δ (ppm) 7.76 (d, J = 8.6 Hz, 2H), 7.53–7.51 (m, 3H), 7.35–7.34 (m, 1H), 7.22–7.17 (m, 2H), 5.74–5.70 (s, 1H), 4.14–3.91 (m, 5H), 1.28 (t, J = 6.8 Hz, 3H), 0.91 (t, J = 6.9 Hz, 3H); 13C NMR (DMSO-d6): δ (ppm) 167.8, 166.8, 166.1, 156.3, 134.8, 129.9, 129.7, 128.5, 126.2, 125.0, 120.0, 62.0, 61.8, 56.2, 14.3, 14.0; 19FNMR (200 MHz, DMSO-d6 ) δ: -116.8; MS(ESI): m/z = 478 ([M+H]+), 500 ([M+Na]+), 516([M+K]+). Anal. Calcd for C22H21ClFN3O4S: C, 55.29; H, 4.43; N, 8.79; Found: C, 55.40; H, 4.57; N, 8.67.

(+)-Diethyl 2-((3,4-dichlorophenyl)((5-(3-fluoro phenyl)-1,3,4-thiadiazol-2-yl)amino) methyl) malonate (+)-4h, yield 71%; White solid; 84.6% ee as determined by HPLC [λ = 210 nm, tr (major) = 16.62 min, tr (minor) = 11.44 min]; [α]D25 = +131.2 (c = 0.69, CHCl3); mp 138-140 °C; IR (KBr, cm-1) ν: 3442, 3040, 2958, 2920, 1620, 1540, 1506, 1471, 1380, 1260, 1228, 1031, 779; 1H NMR (DMSO-d6): δ (ppm) 8.82 (d, J = 8.6 Hz, 1H), 7.73 (d, J = 1.7 Hz, 1H), 7.65 (d, J = 8.0 Hz, 1H), 7.59–7.45 (m, 4H), 7.32 (t, J = 8.0 Hz, 1H), 5.51 (t, J = 9.15 Hz, 1H), 4.20–3.98 (m, 5H), 1.13 (t, J = 6.8 Hz, 3H), 0.98 (t, J = 6.8 Hz, 3H); 13C NMR (DMSO-d6): δ (ppm) 168.0, 166.7, 166.3, 163.8, 161.8, 156.5, 140.5, 133.1, 131.9, 131.5, 131.1, 130.0, 123.3, 117.1, 113.4, 62.0, 61.9, 57.3, 57.1, 14.3, 14.1; 19F NMR (200 MHz, DMSO-d6) δ: -112.0; MS(ESI): m/z = 512([M+H]+), 534([M+Na]+), 550 ([M+K]+). Anal. Calcd for C22H20Cl2FN3O4S: C, 51.57; H, 3.93; N, 8.20; Found: C, 51.46; H, 3.87; N, 8.15.

Acknowledgements

We are grateful for financial support from the National Natural Science Foundation of China (Grant No. 21602039), the Natural Science Foundation of Guizhou Province (Grant No. Qian Ke He Ji Chu[2017]1066), and the Opening Foundation of the Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University (Grant No. 2018GDGP0102), Science and Technology Program of Guizhou Province (Grant NO. Qian Ke He Ping Tai Ren Cai [2017]5789).

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Received: 2018-06-20
Accepted: 2018-10-26
Published Online: 2019-04-03

© 2019 Song Bai et al., published by De Gruyter.

This work is licensed under the Creative Commons Attribution 4.0 Public License.

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  9. Synthesis and antitubercular activity of new N-[5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl]-(nitroheteroaryl)carboxamides
  10. Remarkable electronic effect on the total stereoselectivity of the cycloaddition reaction of arylnitrile oxides with pyrrol-2-one derivatives
  11. Preliminary Communications
  12. Crystal structure and molecular docking studies of new pyrazole-4-carboxamides
  13. Research Article
  14. Synthesis of polycyclic phosphonates via an intramolecular Diels-Alder reaction of 2-benzoylbenzalaldehyde and alkenyl phosphites
  15. Asymmetric total synthesis of filamentous fungi related resorcylic acid lactones 7-epi-zeaenol and zeaenol
  16. The first in situ synthesis of 1,3-dioxan-5-one derivatives and their direct use in Claisen-Schmidt reactions
  17. Synthesis and fungicidal activities of perfluoropropan-2-yl-based novel quinoline derivatives
  18. Combined XRD-paramagnetic 13C NMR spectroscopy of 1,2,3-triazoles for revealing copper traces in a Huisgen click-chemistry cycloaddition. A model case
  19. Cytotoxic and antimicrobial activities of some novel heterocycles employing 6-(1,3-diphenyl-1H-pyrazol-4-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile
  20. Substrate-controlled Diastereoselective Michael Addition of Alkylidene Malonates by Grignard Reagents
  21. Synthesis of 1,2,3 triazole-linked benzimidazole through a copper-catalyzed click reaction
  22. Synthesis and spectral characteristics of N-(1-([1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-ylamino)-2,2,2-trichloroethyl)carboxamides
  23. Facile One-pot Protocol of Derivatization Nitropyridines: Access to 3-Acetamidopyridin-2-yl 4-methylbenzenesulfonate Derivatives
  24. Naphthalene substituted benzo[c]coumarins: Synthesis, characterization and evaluation of antibacterial activity and cytotoxicity
  25. A Green Synthesis and Antibacterial Activity of N-Arylsulfonylhydrazone Compounds
  26. Preliminary Communications
  27. Facile Synthesis of Spiro[cyclohexane-1,3’-indoline]-2,2’-diones
  28. Research Article
  29. Synthesis and AChE inhibitory activity of N-glycosyl benzofuran derivatives
  30. [DMImd-DMP]: A highly efficient and reusable catalyst for the synthesis of 4H-benzo[b]pyran derivatives
https://doi.org/10.1515/hc-2019-0005
Keywords for this article
anti-plant-virus activity; asymmetric Mannich reaction; chiral 1,3,4-thiadiazole derivatives
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Articles in the same Issue

  1. Research Article
  2. Magnesium porphyrazine with peripheral methyl (3,5-dibromophenylmethyl)amino groups – synthesis and optical properties
  3. Synthesis and fungicidal activity of novel imidazo[4, 5-b]pyridine derivatives
  4. Synthesis of indazolo[5,4-b][1,6]naphthyridine and indazolo[6,7-b][1,6]naphthyridine derivatives
  5. Zinc Chloride Catalyzed Amino Claisen Rearrangement of 1-N-Allylindolines: An Expedient Protocol for the Synthesis of Functionalized 7-Allylindolines
  6. Synthesis and Biological Evaluation of (E)-N’-Benzylidene-7-methyl-2-propyl-1H-benzo[d] imidazole-5-carbohydrazides as Antioxidant, Anti-inflammatory and Analgesic agents
  7. Efficient synthesis, reactions and spectral characterization of pyrazolo[4’,3’:4,5]thieno[3,2-d] pyrimidines and related heterocycles
  8. Asymmetric Mannich Reaction: Synthesis of Novel Chiral 5-(substituted aryl)-1,3,4-Thiadiazole Derivatives with Anti-Plant-Virus Potency
  9. Synthesis and antitubercular activity of new N-[5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl]-(nitroheteroaryl)carboxamides
  10. Remarkable electronic effect on the total stereoselectivity of the cycloaddition reaction of arylnitrile oxides with pyrrol-2-one derivatives
  11. Preliminary Communications
  12. Crystal structure and molecular docking studies of new pyrazole-4-carboxamides
  13. Research Article
  14. Synthesis of polycyclic phosphonates via an intramolecular Diels-Alder reaction of 2-benzoylbenzalaldehyde and alkenyl phosphites
  15. Asymmetric total synthesis of filamentous fungi related resorcylic acid lactones 7-epi-zeaenol and zeaenol
  16. The first in situ synthesis of 1,3-dioxan-5-one derivatives and their direct use in Claisen-Schmidt reactions
  17. Synthesis and fungicidal activities of perfluoropropan-2-yl-based novel quinoline derivatives
  18. Combined XRD-paramagnetic 13C NMR spectroscopy of 1,2,3-triazoles for revealing copper traces in a Huisgen click-chemistry cycloaddition. A model case
  19. Cytotoxic and antimicrobial activities of some novel heterocycles employing 6-(1,3-diphenyl-1H-pyrazol-4-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile
  20. Substrate-controlled Diastereoselective Michael Addition of Alkylidene Malonates by Grignard Reagents
  21. Synthesis of 1,2,3 triazole-linked benzimidazole through a copper-catalyzed click reaction
  22. Synthesis and spectral characteristics of N-(1-([1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-ylamino)-2,2,2-trichloroethyl)carboxamides
  23. Facile One-pot Protocol of Derivatization Nitropyridines: Access to 3-Acetamidopyridin-2-yl 4-methylbenzenesulfonate Derivatives
  24. Naphthalene substituted benzo[c]coumarins: Synthesis, characterization and evaluation of antibacterial activity and cytotoxicity
  25. A Green Synthesis and Antibacterial Activity of N-Arylsulfonylhydrazone Compounds
  26. Preliminary Communications
  27. Facile Synthesis of Spiro[cyclohexane-1,3’-indoline]-2,2’-diones
  28. Research Article
  29. Synthesis and AChE inhibitory activity of N-glycosyl benzofuran derivatives
  30. [DMImd-DMP]: A highly efficient and reusable catalyst for the synthesis of 4H-benzo[b]pyran derivatives
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