Synthesis and Antimicrobial Activity of N-(Substituted)-N ꢀ-[6-Methyl-2-oxido-1,3,2-dioxaphosphinino(5,4-b)pyridine-2-yl]ureas 511
TABLE 2 1H NMR Spectral Data of Compounds 5 (δ from TMS)a
Ar-H
(7-H, 8-H and R)
Cyclohexyl/
CH2-Ph
CH2
6-CH3
R-CH3/R-OCH3
NHCO
CONH
5ab 6.95–7.58 (m, 7H) 4.94–5.02 (m, 2H) 2.40 (s, 3H)
5bb 6.70–7.43 (m, 6H) 4.28–4.74 (m, 2H) 2.52 (s, 3H)
5cb 6.92–7.46 (m, 6H) 4.46–4.81 (m, 2H) 2.51 (s, 3H)
5dc 6.74–7.25 (m, 6H) 4.53–4.70 (m, 2H) 2.51 (s, 3H)
–
–
–
–
–
–
–
–
8.47 (s, 1H)
8.76 (s, 1H)
5.79 (s, 1H)
5.92 (s, 1H)
–
–
–
–
5.29
–
2.12 (s, 3H)
3.53 (s, 3H)
5eb 7.14 (d, 6.9, 1H)
7.04 (d, 8.0, 1H)
4.18–4.41 (m, 2H) 2.46 (s, 3H)
6.66–6.86 (m, 4H)
5fb 6.77–7.34 (m, 5H) 4.35–4.53 (m, 2H) 2.39 (s, 3H)
2.28 (s, 3H)
2.34 (s, 3H)
3.52 (s, 3H)
3.56 (s, 3H)
–
–
–
–
8.75 (s, 1H)
5.28 (s, 1H)
5gb 6.89–7.32 (m, 5H) 4.42–4.68 (m, 2H) 2.46 (s, 3H)
–
–
5hb 7.45–8.25 (m, 9H) 4.44–4.96 (m, 2H) 2.51 (s, 3H)
5ib 7.09–7.65 (m, 6H) 3.97–4.31 (m, 2H) 2.45 (s, 3H)
9.18 (s, 1H) 6.64 (d, 7.5, 1H)
–
4.51 (s, 2H) 8.13 (s, 1H)
1.18–1.74 8.35 (s, 1H)
(m, 11 H)
6.62 (s, 1H)
6.60 (s, 1H)
5jb
7.17 (d, 8.1, 1H)
7.07 (d, 7.9, 1H)
5.12–5.26 (m, 2H) 2.40 (s, 3H)
aData in parentheses are coupling constants J in Hz.
bRecorded in DMSO-d6.
1
standard according to the Benson technique [17].
Most of the compounds exhibited significant toxic-
ity against both the fungi. Their antibacterial activity
was evaluated following the method of Vincent and
Vincent [18] on Escherichia coli and Staphylococcus
aureus, using pencillin and tetracycline as standards.
KBr pellets on a Perkin-Elmer 1430 unit. H NMR
and 13C NMR spectra were recorded on AMX 400
MHz spectrometer operating at 400 MHz for 1H, 100
MHz for 13C, and 161.9 MHz for 31P. Compounds
were dissolved in DMSO-d6. The chemical shifts were
referenced to TMS (1H and 13C) and 85% H3PO4 (31P).
3-Hydroxy-6-methyl-2-pyridinemethanol (4, lu-
tidine diol) was procured from Aldrich Chemical and
was used without recrystallization.
EXPERIMENTAL
All melting points were determined on a Mel-Temp
apparatus and are uncorrected. Elemental analyses
were performed by the Central Drug Research Insti-
tute, Lucknow, India. IR spectra were recorded as
Preparation of 4-Chlorophenyl
Carbamidophosphoric Dichloride (3b)
A solution of 4-chloro aniline (2b, 0.51 g, 0.004 mol)
in dry toluene (25 ml) was added dropwise (20 min)
to a cold solution (−15◦C) of 1 (0.64 g, 0.004 mol) in
dry toluene (30 ml). After the addition the tempera-
ture of the reaction mixture was maintained in be-
tween −15 and −5◦C for 30–40 min. Later the temper-
ature of the mixture was raised to room temperature,
with stirring for 30–40 min. Compound 3b being in-
soluble in toluene separated out. It was collected by
filtration and dried under reduced pressure.
TABLE 3 13C NMR Spectral Data of Compounds 5 of Suffi-
cient Solubility on DMSO-d6 (δ from TMS)
5a
5b
5d
5e
5f
C-4
C-6
C-7
C-8
C-9
C-10
56.24
52.97
57.21
56.18
55.33
148.28 146.26 150.26 149.68 151.34
126.36 125.95 126.42 123.48 127.58
130.12 128.35 128.97 127.61 131.21
139.27 137.70 139.50 143.11 143.14
142.68 142.21 144.21 147.11 146.33
Synthesis of N-Chlorophenyl-Nꢀ-[6-methyl-2-
oxido-1,3,2-dioxaphosphinino(5,4-b)pyridine-2-
yl]urea (5b)
C-11
C-12
21.62
21.39
22.06
21.87
23.47
153.67 150.06 152.89 153.38 154.97
145.72 142.21 143.64 143.11 143.14
115.91 116.39 116.18 114.60 124.44
129.06 128.35 130.22 114.10 130.84
119.84 123.62 127.64 149.68 128.31
128.68 128.05 131.18 114.10 125.32
114.22 117.88 115.57 114.60 113.51
C-1 (R)
C-2 (R)
C-3 (R)
C-4 (R)
C-5 (R)
C-6 (R)
R4-CH3
R2-CH3
R4-OCH3
A solution of 3b (0.575 g, 0.002 mol) in toluene
(20 ml) was added to the solution of 4 (0.278 g,
0.002 mol) and triethylamine (0.404 g, 0.004 mol)
in dry tetrahydrofuran (20 ml) at 0◦C. It was kept
for 1 h and then after 1 h of stirring at room tem-
perature, the temperature of the reaction mixture
was allowed to rise slowly to 45–50◦C, and stirring
–
–
–
–
–
–
20.46
–
–
–
–
21.83
20.66
–
55.15