CC BY-NC-ND 4.0 · SynOpen 2021; 05(02): 108-113
DOI: 10.1055/a-1492-9229
paper
Virtual Collection in Honor of Prof. Issa Yavari

Synthesis of Functionalized Bicyclic Pyridones Containing the Dithiocarbamate Group Using Thioazlactones, Diamines, and Nitroketene Dithioacetal

Marziyeh Saeedi
a   Chemistry & Chemical Engineering Research Center of Iran, P.O. Box 14335-186, Tehran, Iran
,
Maryam Khoshdoun
a   Chemistry & Chemical Engineering Research Center of Iran, P.O. Box 14335-186, Tehran, Iran
,
Salman Taheri
a   Chemistry & Chemical Engineering Research Center of Iran, P.O. Box 14335-186, Tehran, Iran
,
b   Faculty of Chemistry, Kharazmi University, P. O. Box 15719-14911, 49 Mofateh Street, Tehran, Iran
c   Institut für Organische Chemie, Albert-Ludwigs-Universität Freiburg, Albertstraße 21, 79104 Freiburg im Breisgau, Germany
,
Aliasghar Mohammadi
a   Chemistry & Chemical Engineering Research Center of Iran, P.O. Box 14335-186, Tehran, Iran
,
Mohammad Reza Halvagar
a   Chemistry & Chemical Engineering Research Center of Iran, P.O. Box 14335-186, Tehran, Iran
,
Vahid Amani
d   Department of Chemistry, Farhangian University, Tehran, Iran
› Author Affiliations
We thank the Research Council of the Chemistry and Chemical Engineering Research Center of Iran (CCERCI) and the Faculty of Chemistry of Kharazmi University for supporting this work. A.Z.H. thanks the Alexander von Humboldt-Stiftung for supporting his research in the Albert-Ludwigs-Universität Freiburg.
 


Abstract

An efficient method for the synthesis of highly substituted bicyclic pyridone derivatives containing the dithiocarbamate group is reported via a one-pot three-component reaction of 2-(alkylthio)thio­azlactones, diamines, and nitroketene dithioacetal in EtOH under catalyst-free conditions. The reaction proceeds via a domino amidation–­intramolecular 1,4-addition-type Friedel–Crafts alkylation reaction to afford the corresponding fused bicyclic pyridones with high yields and diastereoselectivity.


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Among the various types of fused heterocyclic compounds, bicyclic pyridone scaffolds are present in the structure of many biologically active compounds and natural products.[1] Compounds containing these motifs show various properties including anticancer,[2] antianxiety,[3] antileishmanial, [4] antibacterial,[5] antifungal,[6] anti-HIV,[7] and anti-inflammatory[8] activities. Various methods for the synthesis of substituted bicyclic pyridones have been reported.[9] Among them, the cyclocondensation of ketenaminals with dielectrophiles such as propiolic esters,[10] diethyl but-2-ynedioate,[11] β-ketoesterenol tosylates,[12] α-bromoenals,[13] azlactones,[14] itaconic anhydride,[15] and other compounds[16] are extensively utilized for the synthesis of libraries of bicyclic pyridones.

Dithiocarbamates are well known for their applications as herbicides, fungicides, and pesticides in agriculture.[17] The dithiocarbamate group is also a valuable pharmaco­phore that induces diverse biological activities when incorporated in a particular structure.[18] Therefore, finding novel methods for the synthesis of various heterocycles containing a dithiocarbamate group is interesting for biological studies.

Heterocyclic ketene aminals are useful dinucleophiles for the construction of fused heterocyclic compounds and have been extensively applied in cascade reactions with dielectrophiles for the synthesis of condensed nitrogen-containing heterocycles.[19]

Although there are many reports on the utilization of azlactones in organic transformations,[20] the use of thioazlactones with similar active sites has received less attention.[21] Lin and co-workers reported the synthesis of bicyclic pyridone derivatives using ketene aminals and azlactones in the presence of acetic acid.[14] Recently, our group has reported a domino reaction for the diastereoselective synthesis of novel alkyl 2,3-dihydro-3-oxo-1-aryl-1H-benzo[f]chromen-2-ylcarbamodithioates and alkyl 3,4-dihydro-2-oxo-4-aryl-2H-chromen-3-ylcarbamodithioates via the reaction of naphthols and phenols with thioazlactones (Scheme [1], reaction 1).[22] In continuation of our research toward the synthesis of novel dithiocarbamates and their applications as intermediates in organic chemistry,[23] we wish to report herein the synthesis of novel bicyclic pyridone derivatives containing a dithiocarbamate group from 2-alkylthio-thioazlactones, diamines, and nitroketene dithioacetal (Scheme [1], reaction 2).[24] The presence of the dithiocarbamate and pyridone motifs in a single skeleton may have a synergic effect to provide a new class of heterocyclic compounds with interesting biological activities.

Zoom Image
Scheme 1 Synthesis of novel dithiocarbamates and bicyclic pyridones containing a dithiocarbamate group

A model reaction between thioazlactone 1a (1 equiv), 1,3-diaminopropane 2a (1 equiv), and nitroketene dithio­acetal 3 (1 equiv) was examined to optimize the reaction conditions. No reaction occurred at room temperature in water, EtOH, and CHCl3 under catalyst-free conditions (Table [1], entries 1–3), nor was there any reaction in refluxing water (Table [1], entry 4). In refluxing EtOH for 3 h (Table [1], entry 5), a high yield (88%) of the desired product 4a was obtained. Using an acid such as p-toluenesulfonic acid (Table [1], entry 6) or a base such as triethylamine (Table [1], entry 7) as possible catalysts for this reaction in ethanol showed no improvement of the reaction yield. In addition, varying other reaction conditions such as temperature, ratio of the starting materials, and reaction time did not improve the reaction yield.

Table 1 Optimization of the Reaction Conditions for the Synthesis of Bicyclic Pyridones 4a a

Entry

Catalyst (mol%)

Solvent

Temp (°C)

Yield (%)b

1

EtOH

r.t.

NR

2

CHCl3

r.t.

NR

3

H2O

r.t.

NR

4

H2O

reflux

NR

5

EtOH

reflux

88

6

PTSA (30)

EtOH

reflux

64

7

Et3N (30)

EtOH

reflux

45

a Reaction conditions: 1a (1 mmol), 2a (1 mmol), 3 (1 mmol), and solvent (5 mL), 3 h.

b Isolated yield.

After optimization of the reaction conditions, the scope and limitations of this protocol were examined using various thioazlactones and diamines in the reaction with nitroketene dithioacetal 3 (Table [2]). We confirmed that thio­azlactones with electron-withdrawing groups on the aryl group are suitable substrates for this protocol (4am), but those containing an electron-donating group gave an inseparable mixture containing only trace amounts of the desired product. Varying the substitution pattern from benzylthio to butylthio on the thioazlactones gave similar yields (Table [2], entries 12 and 13). In addition, similar reactivities and yields were obtained using 1,2-diaminoethane, 1,3-diaminopropane, and 2,2-dimethyl-1,3-diaminopropane.

Table 2 Regioselective Synthesis of Bicyclic Pyridonesa

Entry

Ar

R1

R2

Product

Yield (%)b

1

4-NCC6H4

Bn

–(CH2)3

4a

88

2

4-ClC6H4

Bn

–(CH2)3

4b

86

3

2,4-Cl2C6H4

Bn

–(CH2)3

4c

83

4

3,4-Cl2C6H4

Bn

–(CH2)3

4d

85

5

2-O2NC6H4

Bn

–(CH2)3

4e

80

6

4-BrC6H4

Bn

–(CH2)3

4f

87

7

3-FC6H4

Bn

–(CH2)2

4g

79

8

3,4-Cl2C6H4

Bn

–(CH2)2

4h

84

9

2,4-Cl2C6H4

Bn

–(CH2)2

4i

82

10

2-O2NC6H4

Bn

–CH2–C(CH3)2–CH2

4j

78

11

3-O2NC6H4

Bn

–CH2–C(CH3)2–CH2

4k

80

12

2,4-Cl2C6H4

n-Bu

–(CH2)3

4l

87

13

3,4-Cl2C6H4

n-Bu

–(CH2)3

4m

89

a Reaction conditions: 1 (1 mmol), 2 (1 mmol), 3 (1 mmol), in refluxing EtOH (5 mL) for 3 h.

b Isolated yield.

The structures of all desired products 4am were confirmed by FT-IR, 1H NMR, and 13C NMR spectroscopy and CHN analyses (see the Supporting Information). The 1H NMR spectra showed four characteristic signals; two signals between δ = 5.00–6.50 ppm for the aliphatic CH resonances of the 3,4-dihydropyridone ring and two signals above δ = 9.0 ppm for the NH groups of the dithiocarbamate and enamine moieties. The 13C NMR spectra also confirmed the product structure; the chemical shifts for the carbonyl groups of the pyridone ring being between δ = 165–168 ppm, and the dithiocarbamate group between δ = 198–201 ppm. Unequivocal evidence for the structure of bicyclic pyridone 3f was obtained from single-crystal X-ray analysis (Figure [1]).[24] The same structure patterns were assumed for the other derivatives on the basis of their NMR spectroscopic similarities.

Zoom Image
Figure 1 X-ray crystal structure of 4c (thermal ellipsoids set at the 40% probability level)[24]

A proposed mechanism for the formation of these bicyclic pyridones is presented in Scheme [2]. The first event is condensation of diamine 2 and nitroketene dithioacetal 3 to give the isolable ketene aminal 5. According to the regio- and stereochemistry of the products, it is conceivable that the next event is the ring opening of thioazlactone 1 with the nitrogen of ketene aminal 5 to afford intermediate 6 after tautomerism. Finally, an intramolecular Michael addition[25] provides the intermediate 7, followed by subsequent imine–enamine tautomerism to result in the desired product 4.

Zoom Image
Scheme 2 A plausible mechanism for the regioselective formation of bicyclic pyridone derivatives 4

In summary, we have reported an efficient protocol for the synthesis of novel bicyclic pyridone derivatives via the reaction of 2-(alkylthio)thioazlactones, diamines, and nitroketene dithioacetal in EtOH under catalyst-free conditions. The reported method gives a straightforward route to novel category of highly substituted bicyclic scaffolds containing pyridone and dithiocarbamate groups, both of which are interesting building blocks for biological studies.

Available reagents and solvents were purchased from commercial sources and were used without further purification. All 1H NMR and 13C NMR spectra were recorded on a Bruker 500 MHz/125 MHz spectrometer in DMSO-d 6 and chemical shifts are reported in ppm. IR spectra were recorded on a Perkin-Elmer spectrum RX1 FT-IR spectrometer. Elemental analyses were conducted with a Perkin-Elmer 2400 Series II CHN analyzer. The X-ray diffraction measurement was carried out on a STOE IPDS-2T diffractometer with graphite-monochromated Mo Kα radiation. Column chromatography was performed with 230–400 mesh silica gel.


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General Procedure for the Preparation of Compounds 4a–m

A mixture of diamine (1 mmol) and nitroketene dithioacetal (1 mmol) in EtOH was heated at reflux for 1 h. Then, the thioazlactone (1 mmol) was added to the reaction mixture. Upon completion of the reaction after 2 h, as indicated by TLC, the mixture was cooled to room temperature. The reaction mixture was filtered, and the residue was washed with hot water (5 mL) and then ethanol (2 mL) to give final pure product 4am.


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Benzyl {8-(4-Cyanophenyl)-9-nitro-6-oxo-1,3,4,6,7,8-hexahydro-2H-pyrido[1,2-a]pyrimidin-7-yl}carbamodithioate (4a)

Colorless powder, mp 220–222 °C; yield 0.43 g (88%).

IR (KBr): νmax = 3187, 2976, 2233, 1720, 1623, 1325, 1150 cm–1.

1H NMR (500 MHz, DMSO-d 6): δ = 2.05–2.07 (2 H, m), 3.49 (1 H, m), 3.61 (1 H, m), 3.70 (1 H, m), 3.97 (1 H, m), 4.52 (1 H, d, 3 J = 14 Hz, CH2), 4.56 (1 H, d, 3 J = 14 Hz, CH2), 5.23 (1 H, d, 3 J = 8.0 Hz, CH), 5.93 (1 H, dd, J = 8.0, 7.5 Hz, CH), 7.11 (2 H, d, 3 J = 8.0 Hz, Ar), 7.28 (1 H, t, 3 J = 7.0 Hz, Ar), 7.35 (2 H, t, 3 J = 7.5 Hz, Ar), 7.39 (2 H, d, 3 J = 7.45 Hz, Ar), 7.70 (2 H, d, 3 J = 8.0 Hz, Ar), 10.11 (1 H, d, 3 J = 7.0 Hz, NH), 11.45 (1 H, br s, NH).

13C NMR (125.7 MHz, DMSO-d 6): δ = 19.7, 39.4, 40.4, 40.8, 40.9, 60.0, 107.9, 111.1, 119.6, 128.1, 129.3, 129.7, 130.0, 133.3, 137.9, 143.8, 152.5, 167.1, 198.9.

Anal. Calcd for C23H21N5O3S2 (479.57): C, 57.60; H, 4.41; N, 14.60. Found: C, 57.80; H, 4.45; N, 14.75.


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Benzyl{8-(4-chlorophenyl)-9-nitro-6-oxo-1,3,4,6,7,8-hexahydro-2H-pyrido[1,2-a]pyrimidin-7-yl}carbamodithioate (4b)

Colorless powder, mp 220–222 °C; yield 0.420 g (86%).

IR (KBr): νmax = 3184, 2980, 1716, 1619, 1103 cm–1.

1H NMR (500 MHz, DMSO-d 6): δ = 2.04–2.06 (2 H, m), 3.48 (1 H, m), 3.63 (1 H, m), 3.69 (1 H, m), 3.96 (1 H, m), 4.51 (1 H,d, 3 J = 13.0 Hz), 4.56 (1 H, d, 3 J = 13.5 Hz), 5.16 (1 H, d, 3 J = 7.5 Hz), 5.87 (1 H, dd, J = 7.5, 7.0 Hz), 6.93 (2 H, d, 3 J = 8.2 Hz, Ar), 7.28 (3 H, d, 3 J = 8.1 Hz, Ar), 7.34 (2 H, t, 3 J = 7.6 Hz, Ar), 7.39 (2 H, d, 3 J = 7.6 Hz, Ar), 10.12 (1 H, d, 3 J = 7.0 Hz, NH), 11.45 (1 H, br s, NH).

13C NMR (125.7 MHz, DMSO-d 6): δ = 19.8, 39.4, 39.5, 40.6, 40.8, 60.3, 108.4, 128.0, 129.3, 129.3, 129.7, 130.7, 132.9, 136.8, 138.0, 152.5, 167.3, 198.8.

Anal. Calcd for C22H21ClN4O3S2 (489.01): C, 54.03; H, 4.33; N, 11.46. Found: C, 54.14; H, 4.37; N, 11.22.


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Benzyl{8-(2,4-dichlorophenyl)-9-nitro-6-oxo-1,3,4,6,7,8-hexa­hydro-2H-pyrido[1,2-a]pyrimidin-7-yl}carbamodithioate (4c)

Colorless powder, mp 225–227 °C; yield 0.434 g (83%).

IR (KBr): νmax = 3357, 3205, 1712, 1623, 1379 cm–1.

1H NMR (500 MHz, DMSO-d 6): δ = 2.06–2.08 (2 H, m), 3.49 (1 H, m), 3.60 (1 H, m), 3.71 (1 H, m), 3.97 (1 H, m), 4.47 (1 H, d, 3 J = 13.7 Hz), 4.61 (1 H, d, 3 J = 13.7 Hz), 5.38 (1 H, d, 3 J = 7.5 Hz), 6.23 (1 H, dd, 3 J = 8.5, 7.5 Hz), 7.12 (1 H, d, 3 J = 8.3 Hz, Ar), 7.24–7.28 (2 H, m, Ar), 7.31 (2 H, t, 3 J = 7.6 Hz, Ar), 7.37 (2 H, d, 3 J = 7.27 Hz, Ar), 7.51 (1 H, s, Ar), 10.24 (1 H, d, 3 J = 8.0 Hz, NH), 11.42 (1 H, br s, NH).

13C NMR (125.7 MHz, DMSO-d 6): δ = 19.3, 31.1 , 37.1, 39.0, 40.3, 59.4, 108.4, 127.6, 128.0, 128.8, 128.8, 129.3, 130.4, 133.1, 134.7, 136.6, 137.7, 152.3, 166.8, 200.0.

Anal. Calcd for C22H20Cl2N4O3S2 (523.45): C, 50.48; H, 3.85; N, 10.70. Found: C, 50.75; H, 3.92; N, 10.82.


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Benzyl{8-(3,4-dichlorophenyl)-9-nitro-6-oxo-1,3,4,6,7,8-hexa­hydro-2H-pyrido[1,2-a]pyrimidin-7-yl}carbamodithioate (4d)

Colorless powder, mp 189–191 °C; yield 0.445 g (85%).

IR (KBr): νmax = 3178, 3003, 1718, 1617, 1325, 1149 cm–1.

1H NMR (500 MHz, DMSO-d 6): δ = 2.04–2.06 (2 H, m), 3.47 (1 H, m), 3.60–3.70 (2 H, m), 3.99 (1 H, m), 4.51 (1 H, d, 3 J = 13.8 Hz), 4.61 (1 H, d, 3 J = 13.8 Hz), 5.14 (1 H, d, 3 J = 7.0 Hz), 5.90 (1 H, dd, J = 7.5, 7.5 Hz), 6.91 (1 H, dd, J = 1.9, 8.3 Hz, 7.08 (1 H, s), 7.27 (1 H, t, 3 J = 7.2 Hz, Ar), 7.34 (2 H, t, 3 J = 7.6 Hz, Ar), 7.39 (2 H, d, 3 J = 7.3 Hz, Ar), 7.48 (1 H, d, 3 J = 8.2 Hz, Ar), 10.19 (1 H, d, 3 J = 7.5 Hz, NH), 11.45 (1 H, br s, NH).

13C NMR (125.7 MHz, DMSO-d 6): δ = 19.4, 38.9, 39.0, 40.2, 40.4, 59.6, 107.4, 127.6, 128.5, 128.9, 129.3, 130.6, 130.6, 131.1, 131.6, 137.6, 138.7, 152.1, 166.7, 198.6.

Anal. Calcd for C22H20Cl2N4O3S2 (523.45): C, 50.48; H, 3.85; N, 10.70. Found: C, 50.67; H, 3.95; N, 10.91.


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Benzyl{9-nitro-8-(2-nitrophenyl)-6-oxo-1,3,4,6,7,8-hexahydro-2H-pyrido[1,2-a]pyrimidin-7-yl}carbamodithioate (4e)

Colorless powder, mp 210–213 °C; yield 0.399 g (80%).

IR (KBr): νmax = 3171, 2999, 1717, 1615, 1343 cm–1.

1H NMR (500 MHz, DMSO-d 6): δ = 2.07 (2 H, m), 3.49 (1 H, m), 3.61 (1 H, m), 3.76 (1 H, m), 3.98 (1 H, m), 4.50 (1 H, d, 3 J = 13.5 Hz), 4.56 (1 H, d, 3 J = 13.5 Hz), 5.61 (1 H, d, 3 J = 8.0 Hz), 6.34 (1 H, dd, J = 8.5, 7.0 Hz), 7.24–7.32 (4 H, m), 7.38 (2 H, d, 3 J = 7.3 Hz, Ar), 7.51 (1 H, t, 3 J = 7.6 Hz, Ar), 7.60 (1 H, t, 3 J = 7.4 Hz, Ar), 7.85 (1 H, d, 3 J = 7.9 Hz, Ar), 10.27 (1 H, d, 3 J = 8.0 Hz, NH), 11.42 (1 H, br s, NH).

13C NMR (125.7 MHz, DMSO-d 6): δ = 19.3, 35.5, 40.0, 40.2, 40.4, 59.1, 108.5, 125.0, 127.6, 128.8, 129.1, 129.4, 129.6, 132.2, 133.9, 137.4, 151.0, 152.2, 167.0, 200.0.

Anal. Calcd for C22H21N5O5S2 (499.56): C, 52.89; H, 4.24; N, 14.02. Found: C, 53.01; H, 4.28; N, 14.15.


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Benzyl{8-(4-bromophenyl)-9-nitro-6-oxo-1,3,4,6,7,8-hexahydro-2H-pyrido[1,2-a]pyrimidin-7-yl}carbamodithioate (4f)

Colorless powder, mp 195–197 °C; yield 0.464 g (87%).

IR (KBr): νmax = 3184, 2980, 1716, 1619, 1103 cm–1.

1H NMR (500 MHz, DMSO-d 6): δ = 2.04–2.06 (2 H, m), 3.48 (1 H, m), 3.63 (1 H, m), 3.68 (1 H, m), 3.96 (1 H, m), 4.52 (1 H, d, 3 J = 13.7 Hz), 4.56 (1 H, d, 3 J = 13.7 Hz), 5.15 (1 H, d, 3 J = 7.5 Hz), 5.87 (1 H, dd, J = 7.2, 7.2 Hz), 6.87 (2 H, d, 3 J = 8.1 Hz), 7.28 (1 H, d, 3 J = 7.0 Hz, Ar), 7.34 (2 H, t, 3 J = 7.5 Hz, Ar), 7.41 (4 H, t, J = 8.5 Hz, Ar), 10.14 (1 H, d, 3 J = 7.0 Hz, NH), 11.46 (1 H, br s, NH).

13C NMR (125.7 MHz, DMSO-d 6): δ = 19.4, 31.1, 40.2, 40.4, 40.6, 59.9, 108.0, 121.1, 127.6, 128.9, 129.4, 130.7, 131.8, 136.9, 137.6, 152.1, 166.9, 198.4.

Anal. Calcd for C22H21BrN4O3S2 (533.46): C, 49.53; H, 3.97; N, 10.50. Found: C, 49.84; H, 4.03; N, 10.62.


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Benzyl{7-(3-fluorophenyl)-8-nitro-5-oxo-1,2,3,5,6,7-hexahydroimidazo[1,2-a]pyridin-6-yl}carbamodithioate (4g)

Colorless powder, mp 209–211 °C; yield 0.362 g (79%).

IR (KBr): νmax = 3184, 2980, 1716, 1619, 1103 cm–1.

1H NMR (500 MHz, DMSO-d 6): δ = 3.77 (1 H, m), 3.89 (1 H, m), 3.94–4.05 (2 H, m), 4.50 (1 H, d, 3 J = 14 Hz), 4.58 (1 H, d, 3 J = 14 Hz), 5.12 (1 H, d, 3 J = 7.7 Hz), 5.86 (1 H, d, 3 J = 7.0 Hz), 6.74 (1 H, d, 3 J = 10 Hz), 6.79 (1 H, d, 3 J = 7.5 Hz, Ar), 7.07 (1 H, t, 3 J = 8.5 Hz, Ar), 7.25–7.29 (2 H, m, Ar), 7.33 (2 H, t, 3 J = 7.6 Hz, Ar), 7.38 (2 H, d, 3 J = 7.3 Hz, Ar), 9.81 (1 H, br s, NH), 10.22 (1 H, br s, NH).

13C NMR (125.7 MHz, DMSO-d 6): δ = 19.0, 37.6, 43.9, 44.7, 60.9, 106.0, 115.1, 127.6, 127.9, 128.0, 128.8, 129.2, 129.7, 131.0, 132.4, 138.0, 152.8, 166.1, 199.1.

Anal. Calcd for C21H19FN4O3S2 (458.53): C, 55.01; H, 4.18; N, 12.22. Found: C, 55.12; H, 4.21; N, 12.28.


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Benzyl{7-(3,4-dichlorophenyl)-8-nitro-5-oxo-1,2,3,5,6,7-hexa­hydroimidazo[1,2-a]pyridin-6-yl}carbamodithioate (4h):

Colorless powder, mp 210–212 °C; yield 0.428 g (84%).

IR (KBr): νmax = 3324, 1706, 1637, 1330 cm–1.

1H NMR (500 MHz, DMSO-d 6): δ = 3.86–4.04 (3 H, m), 4.11 (1 H, m), 4.41 (1 H, d, 3 J = 14.0 Hz), 4.48 (1 H, d, 3 J = 14.0 Hz), 5.30 (1 H, d, 3 J = 8 Hz), 5.71 (1 H, d, 3 J = 7.5 Hz), 6.77 (1 H, d, 3 J = 7.0 Hz), 6.98 (1 H, s), 7.16–7.24 (4 H, m, Ar), 7.28 (2 H, t, 3 J = 7.5 Hz, Ar), 8.37 (1 H, br s, NH), 9.17 (1 H, br s, NH).

13C NMR (125.7 MHz, DMSO-d 6): δ = 19.0, 37.6, 43.7, 43.9, 60.1, 105.9, 127.7, 127.9, 128.8, 129.3, 129.9, 130.9, 132.0, 132.8, 136.6, 137.5, 151.7, 165.5, 199.4.

Anal. Calcd for C21H18Cl2N4O3S2 (509.42): C, 49.51; H, 3.56; N, 11.00. Found: C, 49.58; H, 3.60; N, 11.08.


#

Benzyl{7-(2,4-dichlorophenyl)-8-nitro-5-oxo-1,2,3,5,6,7-hexa­hydroimidazo[1,2-a]pyridin-6-yl}carbamodithioate (4i)

Colorless powder, mp 192–194 °C; yield 0.428 g (84%).

IR (KBr): νmax = 3358, 3205, 1712, 1623, 1379 cm–1.

1H NMR (500 MHz, DMSO-d 6): δ = 3.41–3.47 (2 H, m), 3.96–4.03 (2 H, m), 4.48 (1 H, d, 3 J = 13.5 Hz), 4.50 (1 H, d, 3 J = 13.5 Hz), 5.33 (1 H, d, 3 J = 7.5 Hz), 6.23 (1 H, dd, J = 8.0, 7.5 Hz), 7.19 (1 H, d, 3 J = 8.4 Hz, Ar), 7.24–7.28 (2 H, m, Ar), 7.31 (2 H, t, 3 J = 7.5 Hz, Ar), 7.36 (2 H, d, 3 J = 7.5 Hz, Ar), 7.51 (1 H, s, Ar), 9.83 (1 H, br s, NH), 10.24 (1 H, d, 3 J = 8.0 Hz, NH).

13C NMR (125.7 MHz, DMSO-d 6): δ = 19.0, 37.6, 44.4, 56.5, 60.0, 106.0, 127.6, 128.1, 128.8, 129.3, 129.4, 132.8, 133.1, 135.1, 136.4, 137.7, 152.6, 165.5, 200.0.

Anal. Calcd for C21H18Cl2N4O3S2 (509.42): C, 49.51; H, 3.56; N, 11.00. Found: C, 49.58; H, 3.60; N, 11.08.


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Benzyl{3,3-dimethyl-9-nitro-8-(2-nitrophenyl)-6-oxo-1,3,4,6,7,8-hexahydro-2H-pyrido[1,2-a]pyrimidin-7-yl}carbamodithioate (4j)

Colorless powder, mp 199–202 °C; yield 0.411 g (78%).

IR (KBr): νmax = 3187, 1719, 1623, 1528 cm–1.

1H NMR (500 MHz, DMSO-d 6): δ = 1.07 (3 H, m), 1.09 (3 H, m), 3.28 (1 H, m), 3.35 (1 H, m), 3.59 (1 H, d, 3 J = 12.6 Hz), 3.70 (1 H, d, 3 J = 12.6 Hz), 4.51 (1 H, d, 3 J = 13.6 Hz), 4.57 (1 H, d, 3 J = 13.6 Hz), 5.64 (1 H, d, 3 J = 7.8 Hz), 6.41 (1 H, dd, J = 7.9, 7.9 Hz), 7.22–7.27 (2 H, m, Ar), 7.31 (2 H, t, 3 J = 7.4 Hz, Ar), 7.38 (2 H, d, 3 J = 7.3 Hz, Ar), 7.51 (1 H, t, 3 J = 7.5 Hz, Ar), 7.61 (1 H, t, 3 J = 7.5 Hz, Ar), 7.87 (1 H, d, 3 J = 8.0 Hz, Ar), 10.27 (1 H, d, 3 J = 8.0 Hz, NH), 11.38 (1 H, br s, NH).

13C NMR (125.7 MHz, DMSO-d 6): δ = 23.8, 24.2, 27.4, 35.6, 39.3, 50.6, 50.8, 59.0, 108.5, 125.1, 127.6, 128.8, 129.1, 129.3, 129.4, 132.2, 133.8, 137.4, 151.1, 151.1, 167.3, 200.2.

Anal. Calcd for C24H25N5O5S2 (527.61): C, 54.63; H, 4.78; N, 13.27. Found: C, 54.95; H, 4.93; N, 13.56.


#

Benzyl{3,3-dimethyl-9-nitro-8-(3-nitrophenyl)-6-oxo-1,3,4,6,7,8-hexahydro-2H-pyrido[1,2-a]pyrimidin-7-yl}carbamodithioate (4k)

Colorless powder, mp 216–218 °C; yield 0.422 g (80%).

IR (KBr): νmax = 3187, 1719, 1623, 1528 cm–1.

1H NMR (500 MHz, DMSO-d 6): δ = 1.10 (3 H, s), 1.12 (3 H, s), 3.24 (1 H, m), 3.42 (1 H, m), 3.60 (2 H, m), 4.52 (1 H, d, 3 J = 13.5 Hz), 4.58 (1 H, d, 3 J = 14 Hz), 5.33 (1 H, d, J = 7.5 Hz), ), 6.06 (1 H, dd, J = 7.5, 7.5 Hz), 7.27 (1 H, t, 3 J = 7.5 Hz, Ar), 7.34 (2 H, t, 3 J = 7.5 Hz, Ar), 7.36–7.39 (3 H, m, Ar), 7.57 (1 H, t, 3 J = 8.0 Hz, Ar), 7.72 (1 H, s, Ar), 8.15 (1 H, dd, J = 8.0, 1.5 Hz, Ar), 10.15 (1 H, d, 3 J = 7.5 Hz, NH), 11.4 (1 H, br s, NH).

13C NMR (125.7 MHz, DMSO-d 6): δ = 24.3, 24.3, 27.9, 39.4, 40.4, 50.9, 51.5, 59.8, 107.8, 123.1, 123.5, 128.0, 129.3, 129.7, 131.0, 135.6, 137.8, 140.1, 148.8, 151.4, 167.5, 199.1.

Anal. Calcd for C24H25N5O5S2 (527.61): C, 54.63; H, 4.78; N, 13.27. Found: C, 54.97; H, 5.02; N, 13.33.


#

Butyl{8-(2,4-dichlorophenyl)-9-nitro-6-oxo-1,3,4,6,7,8-hexa­hydro-2H-pyrido[1,2-a]pyrimidin-7-yl}carbamodithioate (4l)

Colorless powder, mp 230–232 °C; yield 0.382 g (78%).

IR (KBr): νmax = 3175, 1718, 1617, 1325, 1149 cm–1.

1H NMR (500 MHz, DMSO-d 6): δ = 0.90 (3 H, t, 3 J = 7.3 Hz), 1.34–1.41 (2 H, m), 1.56–1.62 (2 H, m), 2.07 (2 H, t, 3 J = 5.6 Hz), 3.15 (1 H, m), 3.25 (1 H, m), 3.49 (1 H, m), 3.61 (1 H, m), 3.72 (1 H, m), 3.98 (1 H, m), 5.38 (1 H, d, 3 J = 7.9 Hz), 6.23 (1 H, dd, J = 7.8, 7.8 Hz), 7.12 (1 H, d, J = 8.4 Hz, Ar), 7.27 (1 H, dd, J = 8.4, 1.9 Hz, Ar), 7.53 (1 H, d, 3 J = 1.9 Hz, Ar), 10.0 (1 H, d, 3 J = 8.0 Hz, NH), 11.42 (1 H, br s, NH).

13C NMR (125.7 MHz, DMSO-d 6): δ = 14.0, 19.3, 21.8, 31.3, 31.4, 34.5, 34.6, 37.1, 59.1, 108.4, 128.0, 129.4, 130.4, 133.0, 134.8, 136.6, 152.3, 166.9, 200.6.

Anal. Calcd for C19H22Cl2N4O3S2 (489.43): C, 46.63; H, 4.53; N, 11.45. Found: C, 46.85; H, 4.67; N, 11.63.


#

Butyl{8-(3,4-dichlorophenyl)-9-nitro-6-oxo-1,3,4,6,7,8-hexa­hydro-2H-pyrido[1,2-a]pyrimidin-7-yl}carbamodithioate (4m)

Colorless powder, mp 193–195 °C; yield 0.386 g (79%).

IR (KBr): νmax = 3175, 3003, 1718, 1617, 1325, 1149 cm–1.

1H NMR (500 MHz, DMSO-d 6): δ = 0.91 (3 H, t, 3 J = 7.3 Hz), 1.36–1.43 (2 H, m), 1.59–1.65 (2 H, m), 2.05 (2 H, t, 3 J = 5.5 Hz), 3.20 (1 H, m), 3.28 (1 H, m), 3.49 (1 H, m), 3.61–3.69 (2 H, m), 3.99 (1 H, m), 5.14 (1 H, d, 3 J = 7.7 Hz), 5.90 (1 H, dd, J = 7.4, 7.4 Hz), 6.94 (1 H, d, 3 J = 8.2 Hz, Ar), 7.07 (1 H, s, Ar), 7.51 (1 H, d, 3 J = 8.2 Hz, Ar), 10.0 (1 H, d, 3 J = 7.2 Hz, NH), 11.45 (1 H, br s, NH).

13C NMR (125.7 MHz, DMSO-d 6): δ = 14.0, 19.3, 21.8, 21.8, 25.7, 31.4, 34.4, 39.1, 59.4, 107.4, 128.5, 130.6, 130.7, 131.1, 131.6, 138.8, 152.1, 166.7, 199.2.

Anal. Calcd for C19H22Cl2N4O3S2 (489.43): C, 46.63; H, 4.53; N, 11.45. Found: C, 46.71; H, 4.60; N, 11.72.


#
#

Conflict of Interest

The authors declare no conflict of interest.

Supporting Information

  • References

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    • 16f Yu CY, Yang PH, Zhao MX, Huang ZT. Synlett 2006; 1835
    • 16g Sukach VA, Bolbut AV, Petin AY, Vovk MV. Synthesis 2007; 835
    • 17a Kanchi S, Singh P, Bisetty K. Arab. J. Chem. 2014; 7: 11
    • 17b Hussein MA, El-Shorbagi A.-N, Khallil A.-R. Arch. Pharm. Med. Chem. 2001; 334: 305
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    • 18a Kiran Kumar ST. V. S, Kumar L, Sharma VL, Jain A, Jain RK, Maikhuri JP, Kumar M, Shukla PK, Gupta G. J. Med. Chem. 2008; 43: 2247
    • 18b Kumar L, Lal N, Kumar V, Sarswat A, Jangir S, Bala V, Kumar L, Kushwaha B, Pandey AK, Siddiqi MI, Shukla PK, Maikhuri JP, Gupta G, Sharma VL. Eur. J. Med. Chem. 2013; 70: 68
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    • 18d Ates O, Kocabalkanli A, Cesur N, Otuk G. Farmaco 1998; 53: 541
    • 18e Nofal ZM, Fahmy HH, Mohamed HS. Arch. Pharm. Res. 2002; 25: 28
    • 18f Singh N, Gupta S, Nath G. Appl. Organomet. Chem. 2000; 14: 484
    • 19a Cheng Y, Yang H.-B, Huang Z.-T, Wang M.-X. Tetrahedron Lett. 2001; 42: 1757
    • 19b Nazarenko KG, Shvidenko KV, Pinchuk AM, Tolmachev AA. Monatsh. Chem. 2005; 136: 211
    • 19c Zhou A, Pittman CU. Tetrahedron Lett. 2006; 46: 2045
    • 19d Huang Z.-T, Wang M.-X. Heterocycles 1994; 37: 1233
    • 19e Yan S.-J, Chen Y.-L, Liu L, He N.-Q, Lin J. Green Chem. 2010; 12: 2043
    • 19f Yu F.-C, Huang R, Ni H.-C, Fan J, Yan S.-J, Lin J. Green Chem. 2013; 15: 453
    • 19g Wen L.-R, Li Z.-R, Li M, Cao H. Green Chem. 2012; 14: 707
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    • 19j Wen L.-R, Liu C, Li M, Wang L.-J. J. Org. Chem. 2010; 75: 7605
    • 20a Cui B.-D, Zuo J, Zhao J.-Q, Zhou M.-Q, Wu Z.-J, Zhang X.-M, Yuan W.-C. J. Org. Chem. 2014; 79: 5305
    • 20b Matiadis D, Igglessi-Markopoulou O, McKee V, Markopoulos J. Tetrahedron 2014; 70: 2439
    • 20c Conway PA, Devine K, Paradisi F. Tetrahedron 2009; 65: 2935
    • 20d Sun W, Zhu G, Wu C, Li G, Hong L, Wang R. Angew. Chem. Int. Ed. 2013; 52: 8633
    • 20e Cui B.-D, Zuo J, Zhao J.-Q, Zhou M.-Q, Wu Z.-J, Zhang X.-M, Yuan W.-C. J. Org. Chem. 2014; 79: 5305
    • 20f Melhado AD, Amarante GW, Wang ZJ, Luparia M, Toste FD. J. Am. Chem. Soc. 2011; 133: 3517
    • 20g Rodríguez-Docampo Z, Quigley C, Tallon S, Connon SJ. J. Org. Chem. 2012; 77: 2407
    • 20h Trost BM, Czabaniuk LC. J. Am. Chem. Soc. 2012; 134: 5778
    • 21a Bernabe M, Cuevas O, Fernandez-Alvarez E. Synthesis 1977; 191
    • 21b Arenal I, Bernabe M, Cuevas O, Fernandez-Alvarez E. Tetrahedron 1983; 39: 1387
    • 21c Bernabe M, Cuevas O, Fernandez-Alvarez E. Eur. J. Med. Chem. 1979; 14: 33
    • 21d Bernabe M, Cuevas O, Fernandez-Alvarez E. Tetrahedron Lett. 1977; 18: 895
  • 22 Ziyaei Halimehjani A, Khoshdoun M. J. Org. Chem. 2016; 81: 5699
    • 23a Ziyaei Halimehjani A, Hosseinkhany S. Synthesis 2015; 47: 3147
    • 23b Ziyaei Halimehjani A, Alaei MA, Soleymani Movahed F, Jomeh N, Saidi MR. J. Sulf. Chem. 2016; 37: 529
    • 23c Schlüter T, Ziyaei Halimehjani A, Wachtendorf D, Schmidtmann M, Martens J. ACS Comb. Sci. 2016; 18: 456
    • 23d Ziyaei Halimehjani A, Hasani L, Alaei MA, Saidi MR. Tetrahedron Lett. 2016; 57: 883
    • 23e Ziyaei Halimehjani A, Hajiloo Shayegan M, Hashemi MM, Notash B. Org. Lett. 2012; 14: 3838
    • 23f Ziyaei Halimehjani A, Martens J, Schluter T. Tetrahedron 2016; 72: 3958
  • 24 CCDC 1570967 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures.
  • 25 Zhao MX, Wang MX, Huang ZT. Tetrahedron 2002; 58: 1309

Corresponding Authors

Salman Taheri
Chemistry & Chemical Engineering Research Center of Iran
P.O. Box 14335-186, Tehran
Iran   
Azim Ziyaei Halimehjani
Faculty of Chemistry, Kharazmi University
P. O. Box 15719-14911, 49 Mofateh Street, Tehran
Iran   

Publication History

Received: 19 March 2021

Accepted after revision: 26 April 2021

Publication Date:
27 April 2021 (online)

© 2021. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Georg Thieme Verlag KG
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  • References

    • 1a Taguchi H, Yazawa H, Arnett JF, Kishi Y. Tetrahedron Lett. 1977; 7: 627
    • 1b Shen W, Coburn CA, Bornmann WG, Danishefsky S. J. Org. Chem. 1993; 58: 611
    • 1c Paulvannan K, Stille JR. J. Org. Chem. 1994; 59: 1613
    • 1d Aaberg V, Almqvist F. Org. Biomol. Chem. 2007; 5: 1827
    • 1e Pinkner JS, Remaut H, Miller E, Aaberg V, Pemberton N, Hedenstroem M, Larsson A, Seed P, Waksman G, Hultgren SJ, Almqvist F. Proc. Natl. Acad. Sci. U.S.A. 2006; 103: 17897
    • 1f Marcaurelle LA, Johannes C, Yohannes D, Tillotson BP, Mann D. Bioorg. Med. Chem. Lett. 2009; 19: 2500
  • 2 Yin L, Hu Q.-Z, Hartmann LW. J. Med. Chem. 2013; 56: 460
  • 3 Collins I, Moyes C, Davey WB, Rowley M, Bromidge FA, Quirk K, Atack JR, McKernan RM, Thompson SA, Wafford K, Dawson GR, Pike A, Sohal B, Tsou NN, Ball RG, Castro JL. J. Med. Chem. 2002; 45: 1887
    • 4a Fan X, Feng D, Qu Y, Zhang X, Wang J, Loiseau PM, Andrei G, Snoeck R, De Clercq E. Bioorg. Med. Chem. Lett. 2010; 20: 809
    • 4b Hussain H, Al-Harrasi A, Al-Rawahi A, Green IR, Gissons S. Chem. Rev. 2014; 114: 10369
  • 5 Flamm RK, Vojtko C, Chu DT. W, Beyer QL. J, Hensey D, Ramer N, Clement JJ, Tanaka SK. Antimicrob. Agents Chemother. 1995; 4: 964
  • 6 Haga A, Tamoto H, Ishino M, Kimura E, Sugita T, Kinoshita K, Takahashi K, Shiro M, Koyama K. J. Nat. Prod. 2013; 76: 750
  • 7 Jones ED, Vandegraaff N, Le G, Choi N, Issa W, Macfarlane K, Thienthong N, Winfield LJ, Coates JA. V, Lu L, Li X.-M, Feng B, Yu C.-J, Rhodes DI, Deadman JJ. Bioorg. Med. Chem. Lett. 2010; 20: 5913
  • 8 Amr AG, Abdulla MM. Bioorg. Med. Chem. 2006; 14: 4341
    • 9a Zhao M.-X, Wang M.-X, Huang Z.-T. Tetrahedron 2002; 58: 1309
    • 9b Kubo K, Ito N, Souzu I, Isomura Y, Homma H, Murakami M. US4284778A, 1981
    • 9c Hehemann DG, Winnik W. J. Heterocycl. Chem. 1994; 31: 393
    • 9d Liao W.-L, Li S.-Q, Wang J, Zhang Z.-Y, Yang Z.-W, Xu D, Xu C, Lan H.-T, Chen Z.-Z, Xu Z.-G. ACS Comb. Sci. 2016; 18: 65
    • 9e Kavala V, Wang CC, Wang YH, Kuo CW, Janreddy D, Huang WC, Kuo TS, He CH, Chen ML, Yao CF. Adv. Synth. Catal. 2014; 356: 2609
    • 9f Lu J, Gong X, Yang H, Fu H. Chem. Commun. 2010; 46: 4172
    • 9g Sunke R, Adepu R, Kapavarapu R, Chintala S, Meda CL. T, Parsa KV. L, Pal M. Chem. Commun. 2013; 49: 3570
  • 10 Huang Z.-T, Liu Z.-R. Heterocycles 1986; 24: 2247
  • 11 Huang Z.-T, Tzai LH. Chem. Ber. 1986; 2208
  • 12 Yan S.-J, Niu Y.-F, Huang R, Lin J. Synlett 2009; 2821
  • 13 Yao C, Jiao W, Xiao Z, Xie Y, Li T, Wang X, Liu R, Yu C. RSC Adv. 2013; 3: 10801
  • 14 Chen X, Zhu D, Wang X, Yan S, Lin J. Tetrahedron 2013; 69: 9224
  • 15 Ren L, Lou Y, Chen N, Xia S, Shao X, Xu X, Li Z. Synth. Commun. 2014; 44: 858
    • 16a Zhao M.-X, Wang M.-X, Huang Z.-T. Tetrahedron 2002; 58: 1309
    • 16b Meyer H. Liebigs Ann. Chem. 1981; 9: 1523
    • 16c Takahashi M, Nozaki C, Shibazaki Y. Chem. Lett. 1987; 6: 1229
    • 16d Raymond CF. J, Pravin P. Tetrahedron 1998; 54: 6191
    • 16e Charkrabarti S, Panda K, Misra NC, Ila H, Junjappa H. Synlett 2005; 1437
    • 16f Yu CY, Yang PH, Zhao MX, Huang ZT. Synlett 2006; 1835
    • 16g Sukach VA, Bolbut AV, Petin AY, Vovk MV. Synthesis 2007; 835
    • 17a Kanchi S, Singh P, Bisetty K. Arab. J. Chem. 2014; 7: 11
    • 17b Hussein MA, El-Shorbagi A.-N, Khallil A.-R. Arch. Pharm. Med. Chem. 2001; 334: 305
    • 17c Eng G, Song X, Duong Q, Strickman D, Glass J, May L. Appl. Organomet. Chem. 2003; 17: 218
    • 18a Kiran Kumar ST. V. S, Kumar L, Sharma VL, Jain A, Jain RK, Maikhuri JP, Kumar M, Shukla PK, Gupta G. J. Med. Chem. 2008; 43: 2247
    • 18b Kumar L, Lal N, Kumar V, Sarswat A, Jangir S, Bala V, Kumar L, Kushwaha B, Pandey AK, Siddiqi MI, Shukla PK, Maikhuri JP, Gupta G, Sharma VL. Eur. J. Med. Chem. 2013; 70: 68
    • 18c Tripathi RP, Khan AR, Setty BS, Bhaduri AP. Acta Pharm. 1996; 46: 169
    • 18d Ates O, Kocabalkanli A, Cesur N, Otuk G. Farmaco 1998; 53: 541
    • 18e Nofal ZM, Fahmy HH, Mohamed HS. Arch. Pharm. Res. 2002; 25: 28
    • 18f Singh N, Gupta S, Nath G. Appl. Organomet. Chem. 2000; 14: 484
    • 19a Cheng Y, Yang H.-B, Huang Z.-T, Wang M.-X. Tetrahedron Lett. 2001; 42: 1757
    • 19b Nazarenko KG, Shvidenko KV, Pinchuk AM, Tolmachev AA. Monatsh. Chem. 2005; 136: 211
    • 19c Zhou A, Pittman CU. Tetrahedron Lett. 2006; 46: 2045
    • 19d Huang Z.-T, Wang M.-X. Heterocycles 1994; 37: 1233
    • 19e Yan S.-J, Chen Y.-L, Liu L, He N.-Q, Lin J. Green Chem. 2010; 12: 2043
    • 19f Yu F.-C, Huang R, Ni H.-C, Fan J, Yan S.-J, Lin J. Green Chem. 2013; 15: 453
    • 19g Wen L.-R, Li Z.-R, Li M, Cao H. Green Chem. 2012; 14: 707
    • 19h Li M, Shao P, Wang S.-W, Kong W, Wen L.-R. J. Org. Chem. 2012; 77: 8956
    • 19i Yu F.-C, Yan S.-J, Hu L, Wang Y.-C, Lin J. Org. Lett. 2011; 13: 4782
    • 19j Wen L.-R, Liu C, Li M, Wang L.-J. J. Org. Chem. 2010; 75: 7605
    • 20a Cui B.-D, Zuo J, Zhao J.-Q, Zhou M.-Q, Wu Z.-J, Zhang X.-M, Yuan W.-C. J. Org. Chem. 2014; 79: 5305
    • 20b Matiadis D, Igglessi-Markopoulou O, McKee V, Markopoulos J. Tetrahedron 2014; 70: 2439
    • 20c Conway PA, Devine K, Paradisi F. Tetrahedron 2009; 65: 2935
    • 20d Sun W, Zhu G, Wu C, Li G, Hong L, Wang R. Angew. Chem. Int. Ed. 2013; 52: 8633
    • 20e Cui B.-D, Zuo J, Zhao J.-Q, Zhou M.-Q, Wu Z.-J, Zhang X.-M, Yuan W.-C. J. Org. Chem. 2014; 79: 5305
    • 20f Melhado AD, Amarante GW, Wang ZJ, Luparia M, Toste FD. J. Am. Chem. Soc. 2011; 133: 3517
    • 20g Rodríguez-Docampo Z, Quigley C, Tallon S, Connon SJ. J. Org. Chem. 2012; 77: 2407
    • 20h Trost BM, Czabaniuk LC. J. Am. Chem. Soc. 2012; 134: 5778
    • 21a Bernabe M, Cuevas O, Fernandez-Alvarez E. Synthesis 1977; 191
    • 21b Arenal I, Bernabe M, Cuevas O, Fernandez-Alvarez E. Tetrahedron 1983; 39: 1387
    • 21c Bernabe M, Cuevas O, Fernandez-Alvarez E. Eur. J. Med. Chem. 1979; 14: 33
    • 21d Bernabe M, Cuevas O, Fernandez-Alvarez E. Tetrahedron Lett. 1977; 18: 895
  • 22 Ziyaei Halimehjani A, Khoshdoun M. J. Org. Chem. 2016; 81: 5699
    • 23a Ziyaei Halimehjani A, Hosseinkhany S. Synthesis 2015; 47: 3147
    • 23b Ziyaei Halimehjani A, Alaei MA, Soleymani Movahed F, Jomeh N, Saidi MR. J. Sulf. Chem. 2016; 37: 529
    • 23c Schlüter T, Ziyaei Halimehjani A, Wachtendorf D, Schmidtmann M, Martens J. ACS Comb. Sci. 2016; 18: 456
    • 23d Ziyaei Halimehjani A, Hasani L, Alaei MA, Saidi MR. Tetrahedron Lett. 2016; 57: 883
    • 23e Ziyaei Halimehjani A, Hajiloo Shayegan M, Hashemi MM, Notash B. Org. Lett. 2012; 14: 3838
    • 23f Ziyaei Halimehjani A, Martens J, Schluter T. Tetrahedron 2016; 72: 3958
  • 24 CCDC 1570967 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures.
  • 25 Zhao MX, Wang MX, Huang ZT. Tetrahedron 2002; 58: 1309

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Scheme 1 Synthesis of novel dithiocarbamates and bicyclic pyridones containing a dithiocarbamate group
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Figure 1 X-ray crystal structure of 4c (thermal ellipsoids set at the 40% probability level)[24]
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Scheme 2 A plausible mechanism for the regioselective formation of bicyclic pyridone derivatives 4