Aug 6, 2016 - Cyanothioacetamide in Heterocyclic Synthesis: A New Approach for the Synthesis of 2-Pyridothione and. 2-Pyridazinothione Derivatives.
Cyanothioacetamide in Heterocyclic Synthesis: A New Approach for the Synthesis of 2-Pyridothione and 2-Pyridazinothione Derivatives R. M. M ohareb and S. M. Fahmy* Chemistry D epartm en t, Faculty o f Science, Cairo University, Giza, Egypt Z. N aturforsch. 41b, 105—109 (1986); received July 8, 1985 Heterocyclic Synthesis, C yanothioacetam ide, Pyridazine Derivatives Cyanothioacetam ide (1) undergoes self condensation to give 4,6-diamino-3-cyano-2-pyridothione (2). The latter was utilised in synthesis of pyrido[2,3-c]pyrazole, pyrido[2,3-d]pyrim idine, bis-(pyridothione derivatives) through reaction with hydrazine hydrate, ethoxycarbonyl isothiocyanate and cinnam onitrile derivatives. Also 1 undergoes self dimerisation to give 13, the latter form the pyridazine derivative on coupling with benzenediazonium chloride.
As a part of our program dealing with the scope and limitations of the use of activated nitriles in heterocyclic synthesis [1—3]. The title reagent seems very suitable for our purpose as it is known to be of high potential activity [4]. Recently we have reported for the self condensation of two moles of cyanothio acetam ide (1) in presence of sodium ethoxide to give 4,6-diamino-3-cyano-2-pyridothione (2). Now we found that 2 reacts with hydrazine hydrate to give the hydrazone derivative 3. On the o ther hand, conduct ing the reaction in dimethylform am ide instead of ethanol a pyrido[2,3-c]pyrazole derivative 4 is ob tained. Com pound 4 can also be obtained via refluxing of 3 in dim ethylform amide. Structures of com pounds 3 and 4 were established based on analytical and spectral data. 2 reacts with ethoxycarbonyl isothiocyanate to give a pyrido[2,3-d]pyrimidine derivative 6 through cyclisation of the non-isolable adduct 5. Structure of com pound 6 was established based on analytical and spectral data. 2 reacts with benzylidene m alononitrile (7) to give a product of molecular formula C9H 8SN6. Two pos sible isomeric structures 8 an 9 were proposed for the reaction product. Structure 9 was assigned for the reaction product based on spectral data in IR spectrum revealed only one CN stretching band at 2220 cm -1. !H N M R spectrum revealed the p re sence of six D 20 exchangeable protons four of which appear at d 5 .5 4 -5 .8 3 ppm , the other two at 6 6.18 ppm assigned for the three am ino functions, * R eprint requests to Prof. D r. S. M. Fahmy. V erlag der Zeitschrift für N aturforschung, D-7400 Tübingen 0 3 4 0 - 5087/86/0100-0105/$ 01.00/0
and a multiplet at 300
Q H 8N6
>300
c 6h 8n 6
44.00 (43.89 44.10 (43.89 38.4 (38.24 59.79 (60.00 54.67 (54.28 48.56 (48.33 36.34 (36.00 49.99 (50.18 48.56 (48.48 59.56 (59.24 70.31 (70.56 43.34 (43.12 33.41 (33.57
Colour
3
Ethanol
yellow
70
4
Dioxan
orange
6
Dioxan
yellow
65 (a) 71 (b) 75
9
Dioxan
yellow
68
12 a
DM F
orange
12 b
Dioxan
orange
13
Dioxan
yellow
57 64 52 57 80
16
DM F
brown
84
17
Ethanol
yellow
80
18 a
E thanol
yellow
76
260--262
CgH10N4
18 b
D ioxan
orange
65
289--300
C 14H 14N4
19
DMF
yellow
72
>300
c 6h 5n 3o s
21
E thanol
white
69
172
c 4h 5n 3o s
OH
Yield [%]
m.p. [°C]
Cryst. solvent
(a) (b) (a) (b)
210--212
c 8h 5n 5o s 2
220--222
c
285--288
Ci9H]6NgS2
185--188
c
>300 150--152 >300
16h 12n 6s
15h 16n 8s 2
c 6h 8n 4s 2 c
12h 9n 5s 2
c 8h 8n 2s
5.15 4.91 5.63 4.91 1.9 1.99 3.78 3.75 3.89 3.80 4.32 4.30 3.89 4.03 3.45 3.16 5.79 6.06 6.45 6.21 5.61 5.92 2.79 3.02 3.31 3.52
51.34 51.20) 51.41 51.20) 27.8 27.88 26.59 26.85 26.43 26.63 30.31 30.07 27.81 27.99 24.67 24.38 21.57 21.21 34.24 34.55) 23.51 23.51) 25.45 25.15 29.68 29.37
NH2 CN
h n^^y^T 1 •N H
OEt
NH,
HN
C-0 r T CNl
s
N
N
S
Ph-CH=C(CN)2
c IhA CN
12a: x=Ph b : x=OEt
10
Chart 1
- 10.1515/znb-1986-0122 Downloaded from PubFactory at 08/06/2016 11:59:16AM via free access
S [% ]
25.00 25.49) 10.41 10.00) 14.98 15.23) 17.31 17.18) 31.59 31.97) 22.51 22.28) 24.01 24.24)
19.19 19.16) 22.21 22.39)
R. M. M ohareb—S. M. Fahmy • C yanothioacetam ide in Heterocyclic Synthesis
107
Table II. IR and ‘H NMR spectra of the compounds 3—21. Compound
IR [cm "1]
‘H NMR [ppm]
3
3450-3300 (three N H ,); 2980 (C H 2); 2220 (CN) and 1625 (N H 2 deform ation)
5.61 (s, 2 H , N H ,); 5 .9 5 -6 .1 0 (2 s, 4 H , 2 N H 2) and 6.98 (s, 2H , C H ,)
4
3450-3320 (three N H 2); 2980 (C H 2) and 1630 (N H 2 deform ation)
6
3500 (O H ); 3450-3300 (N H 2, N H ), 2220 (CN); 1635 (N H 2 deform ation) and 1210—1190 (two C =S )
5.55 (s, 2H , N H ,); 9.0 (s, 1H , O H ) and 9.59-10.11 ppm (br, 2 s, 2 H , 2 NH)
9
3460-3300 (three N H ,); 3040-3000 (aromatic CH and exocyclic C H ); 222~0 (CN ); 1630 (N H, deform a tion and 1200-1195 (C = S ))
5 .5 4 -5 .8 3 (m, 4 H , 2 N H ,); 6.18 (s, 2 H , N H ,) and 7.35—7.58 (m, 6 H , exocyclic C H , C6H 5)
12 a
3450—3300 (four N H 2); 3050 (arom atic C H ); 2220 (two sym CN); 1635 (N H , deform ation) and 1220-1200 (C = S )
12b
3450-3300 (four N H 2); 2980, 2895 (C H 2, C H 3); 2220 (two sym CN); 1650 (N H , deform ation) and 1222-1200 (C = S )
13
3450-3300 (three N H ,); 2980 (C H ,); 2220 (CN); 1635 (N H , deform ation) and 1210—1200 (two C =S)
4.10 (s, 2 H , C H ,); 4.89 (s, 2 H , N H ,); 6 .2 4 -6 .4 2 (2 s, 4 H , 2 N H ,)
16
3450-3300 (two N H ,); 3050 (arom atic C H ); 2220 (CN); 1635 (N H , deform ation) and 1210—1200 (two C =S)
4.89 (s, 2 H , N H 2); 6.14 (s, 2 H , N H 2) and 7.38 (m, 5H , C6H 5)
17
3010 (ring C H ): 2980 (two C H ,); 2220 (CN); 1205 (C =S)
18 a
3450-3300 (N H „ N H ); 3040 (ring C H ); 2980 (two CH 3); 2220 (C N ); 1630 (N H , deform ation)
1.16, 1.24 (2 s, 6 H , 2C H ); 6.01 (s, 2 H , N H ,); 7.11 (m, 2 H , ring C H ); 9.36 (s, br, 1H , NH)
18 b
3330—3300 (N H ); 3050 (arom atic and ring CH); 2980 (two C H ,) and 222 (CN)
1.18, 1.24 (2 s, 6 H , 2 C H 3); 7 .2 4 -7 .3 9 (m, 7H , pyridine C-3, C-5 and C6H S); 9.48—9.61 (2 s, br, 2 H , 2 NH)
19
3580 (O H ); 3450-3300 (N H ,); 3040 (ring C H ,); 2220 (CN); 1205-1190 (C = S )
21
3450-3300 (2 N H ,); 2890 (C H ); 2220 (CN); 1680 ( C = 0 ) and 1190 (C = S )
pound reacts with hydrazine hydrate and phenylhydrazine to give the hydrazone derivatives 18 a and 18b, respectively. 1 was found to react with ethyl cyanoacetate in presence of a catalytic am ount of piperidine to give the 2-pyridothione derivative 19. M oreover, reaction of 1 with cyanoacetamide in sodium ethoxide solu tion gave the same product 19 which seems to proceed via loss of am m onia from the nonisolable acyclic adduct 20. 1 react with trichloroacetam ide to give a product of the m olecular formula C4H 5N 0 5. Two possible isomeric structures are possible, 21 and 22. Structure 21 is established for the reaction product based on *H NM R which revealed the presence of 4 D 20 ex
4.68 and 5.19 (2 s, 4 H , 2 N H ,); 6.25 (s, 1H , CH)
changeable protons assigned for two N H 2 groups at
