Month 2013
Selective Iodination at C-5 Position of Activated Pyrimidinediones
5-Iodo-1,3-dimethyl-6-(hydrazino)pyrimidine-2,4(1H,3H)-dione
(2i). Sticky solid; MS: m/z [M]+ Calcd for C9H9IN4O2: 295.98;
found 296.02. IR: 3452, 3302, 2928, 2385, 2278, 1706, 1626,
Calcd for C14H15ClIN3O2: 418.99; found 419.01. IR: 3460, 3309,
2931, 2372, 2279, 1706, 1635, 1532, 1454cmꢀ1 1H NMR
.
(400 MHz, deuteriochloroform): d = 3.16 (s, 3H, CH3), 3.25 (s,
3H, CH3), 3.36 (s, 3H, CH3), 6.96–7.45 (m, 4H, Ph); 13C NMR
(100 MHz, deuteriochloroform): d 31.45, 32.34, 34.74, 61.42,
119.14, 120.17, 125.03, 129.57, 129.11, 140.05, 151.10, 152.09,
164.05. Anal. Calcd for C14H15ClIN3O2: C, 40.07; H, 3.60; N,
10.01. Found: C, 40.08; H, 3.56; N, 10.04.
.
1548, 1447 cmꢀ1 1H NMR (400 MHz, deuteriochloroform):
d = 3.07 (s, 3H, CH3), 3.15 (s, 3H, CH3), 3.43 (b, s, 2H, NH2), 4.33
(b, s, 1H, NH); 13C NMR (100 MHz, deuteriodimethylsulphoxide):
d 27.32, 29.80, 52.21, 152.10, 156.90, 162.2. Anal. Calcd for
C9H9IN4O2: C, 24.34; H, 3.06; N, 18.92. Found: C, 24.38; H,
3.07; N, 19.98.
6-(N-(4-Methylbenzyl)-N-methylamino)-5-iodo-1,3-dimethylpy-
6-(2-Phenylhydrazinyl)-5-iodo-1,3-dimethylpyrimidine-2,4
rimidine-2,4(1H,3H)-dione (2p).
Calcd for C15H18IN3O2: 399.04; found 399.09. IR: 3457, 3304,
2930, 2382, 2279, 1718, 1642, 1546, 1468 cmꢀ1 1H NMR
Sticky solid; MS: m/z [M]+
(1H,3H)-dione (2j).
Sticky solid; MS: m/z [M]+ Calcd for
C12H13IN4O2: 372.16; found 372.10. IR: 3419, 3371, 3037,
2957, 1672, 1618, 1532, 1431 cmꢀ. 1 1H NMR (400 MHz,
deuteriochloroform): d = 1.24 (b, s, 1H, NH), 3.48 (s, 3H,
CH3), 3.64 (s, 3H, CH3), 6.9–7.5 (m, 5H, Ph), 8.24 (b, s,
.
(400 MHz, deuteriochloroform): d =1.96 (s, 3H, CH3), 3.10 (s, 3H,
CH3), 3.35 (s, 3H, CH3), 3.49 (s, 3H, CH3), 6.99–7.50 (m, 4H,
Ph); 13C NMR (100 MHz, deuteriochloroform): d 24.35, 31.47,
32.89, 34.93, 60.89, 119.25, 120.10, 125.04, 129.29, 130.00,
140.02, 151.12, 152.19, 159.78. Anal. Calcd for C15H18IN3O2: C,
45.13; H, 4.54; N, 10.53. Found: C, 45.09; H, 4.50; N, 10.55.
Computational details. All the density functional calculations
were carried out using the DMol3 program (California, USA) [24].
The selected molecules were subjected to full geometry
optimization using double numerical with polarization basis set
[25] in combination with three generalized gradient approximation
exchange-correlation functionals BLYP. The double numerical
with polarization basis is comparable with Gaussian 6–31G**
basis set. We calculated local reactivity descriptors such as Fukui
functions and relative nucleophilicity values of each atom using
Mulliken population scheme, details of which are discussed
elsewhere [26,27].
1H, NH). 13C NMR (100 MHz, deuteriochloroform):
d
27.68, 30.75, 55.24, 111.24, 119.57, 121.97, 122.44,
123.91, 134.75, 145.07, 151.58, 159.07. Anal. Calcd for
C12H13IN4O2: C, 38.73; H, 3.52; N, 15.05. Found: C,
38.75; H, 3.50; N, 15.03.
6-(Benzylamino)-5-iodo-1,3-dimethylpyrimidine-2,4(1H,3H)-
dione (2k).
Sticky solid; MS: m/z [M]+ Calcd for
C13H14IN3O2: 371.17; found 371.15. IR: 3421, 3389, 3112,
2987, 1682, 1650, 1557, 1442 cmꢀ. 1 1H NMR (400 MHz,
deuteriochloroform): d = 3.23 (s, 3H, CH3), 3.45 (s, 3H, CH3),
4.13 (s, 2H, CH2), 4.73 (b, s, 1H, NH), 6.91–7.38 (m, 5H, Ph).
13C NMR (100 MHz, deuteriochloroform): d 27.87, 28.79,
47.40, 127.63, 128.36, 129.15, 136.02, 151.94, 152.88, 163.07.
Anal. Calcd for C13H14IN3O2: C, 42.07; H, 3.80; N, 11.32.
Found: C, 42.05; H, 3.82; N, 11.35.
The condensed Fukui functions (FF) are calculated as follows:
6-(4-Chlorobenzylamino)-5-iodo-1,3-dimethylpyrimidine-2,4
Sticky solid; MS: m/z [M]+ Calcd for
1
(1H,3H)-dione (2l).
fkþ
fkꢀ
¼
¼
½qkðN0 þ ΔNÞ ꢀ qkðN0Þꢁðfor nucleophilic attackÞ
½qkðN0Þ ꢀ qkðN0 ꢀ ΔNÞꢁðfor electrophilic attackÞ
C13H13ClN3O2: 404.97; found 404.99. IR: 3460, 3307, 2930,
ΔN
1
1
2372, 2279, 1710, 1635, 1541, 1452 cmꢀ1. H NMR (400 MHz,
deuteriochloroform): d = 3.33 (s, 3H, CH3), 3.41 (s, 3H, CH3),
4.16 (s, 2H, CH2), 4.70 (b, s, 1H, NH), 6.88–7.41 (m, 4H, Ph).
13C NMR (100 MHz, deuteriochloroform): d 27.72, 28.81,
47.37, 127.56, 128.30, 129.22, 136.10, 151.88, 152.93, 167.12.
Anal. Calcd for C13H13ClN3O2: C, 38.49; H, 3.23; N, 10.36.
Found: C, 38.45; H, 3.21; N, 10.32.
ΔN
where qk is the electronic population of atom k in a molecule. In
conventional FF computations, a value of 1.0 is used for ΔN. In
this case, calculations on the cationic and anionic species are re-
quired. In the present study, we have used a value of 0.1 forΔN.
The stationary points are characterized by calculating vibra-
tional frequencies for all the molecules. No imaginary vibrational
frequency was found for any of the compound. Absence of imag-
inary frequency indicates that the optimized compounds are at
their local or global minimum energy states.
6-(4-Methylbenzylamino)-5-iodo-1,3-dimethylpyrimidine-2,4
(1H,3H)-dione (2m).
Sticky solid; MS: m/z [M]+ Calcd for
C14H16IN3O2: 385.03; found 385.03. IR: 3421, 3389, 3112,
2987, 1682, 1650, 1557, 1442 cmꢀ. 1 1H NMR (400 MHz,
deuteriochloroform): d = 1.35 (s, 3H, CH3), 3.28 (s, 3H, CH3),
3.39 (s, 3H, CH3), 4.68 (b, s, 1H, NH), 6.86–7.42 (m, 4H, Ph).
13C NMR (100 MHz, deuteriochloroform): d 27.69, 28.84,
47.64, 127.71, 128.31, 129.23, 136.10, 152.01, 153.10, 158.11.
Anal. Calcd for C14H16IN3O2: C, 43.65; H, 4.19; N, 10.91.
Found: C, 43.62; H, 4.17; N, 10.95.
Acknowledgments. This work was financially supported by
Council of Scientific and Industrial Research (CSIR) (grant no.
01(2147)/07/EMR-II), New Delhi, India. DT is thankful to
Tezpur University for an institutional fellowship. Authors are
also highly thankful to Prof. Mihir K. Chaudhuri, FNA, and
Vice Chancellor, Tezpur University for helpful discussions and
suggestions.
6-(N-Benzyl-N-methylamino)-5-iodo-1,3-dimethylpyrimidine-2,4
(1H,3H)-dione (2n).
C13H14IN3O2: 385.03; found 385.06. IR: 3425, 3388, 3118, 2989,
1685, 1653, 1559, 1444 cmꢀ1 1H NMR (400 MHz,
Sticky solid; MS: m/z [M]+ Calcd for
.
.
deuteriochloroform): d =2.86 (s, 3H, CH3), 3.25 (s, 3H, CH3), 3.48
(s, 3H, CH3), 4.11 (s, 2H, CH2), 6.871–7.40 (m, 5H, Ph). 13C NMR
(100 MHz, deuteriochloroform): d 27.06, 27.76, 28.58, 46.98,
128.63, 128.976, 129.07, 136.29, 152.04, 152.56, 163.11. Anal.
Calcd for C14H16IN3O2: C, 43.65; H, 4.19; N, 10.91. Found: C,
43.61; H, 4.22; N, 10.95.
REFERENCES AND NOTES
[1] (a) Miyaura, N.; Suzuki, A. Chem Rev 1995, 95, 2457; (b)
Suzuki, A. Metal Catalysed Cross–Coupling Reactions, Diederich, F.;
Stang, P. J.,eds.; Wiley-VCH: Weinheim, Germany, 1988.
[2] (a) Roy-Burman, P. Analogues of Nucleic Acid Components,
Springer-Verlag: New York, 1970; (b) Lin, T. S.; Chen, M. S.; Mclaren,
C.; Gao, Y. S.; Ghazzouli, I.; Prusoff, W. H. J Med Chem 1987, 30, 440.
6-(N-(4-Chlorobenzyl)-N-methylamino)-5-iodo-1,3-dimethyl-
pyrimidine-2,4(1H,3H)-dione (2o). Sticky solid; MS: m/z [M]+
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet