C. Enrique-Mir6n, {~) M. Quir6s-Olozdbal, {1) M.A. Romero-Molina, a). J.M. Salas-Peregrin ... M.N. Moreno-Carretero, ~2) and J.D. Martln-Ramos {3). Received ...
Journal of Chemical Crystallography, Vol. 24, No. 7, 1994
Synthesis, characterization, and crystal structure of 1,3,7,9tetramethylpyrido-[2,3-d: 6,5-d ']-dipyrimidine-2,4,6,8-tetrone C. Enrique-Mir6n, {~) M. Quir6s-Olozdbal, {1) M.A. Romero-Molina, a) J.M. Salas-Peregrin, {1);* M . P . Sdnchez-Sdnchez, a) F. Hueso-Urefia, {2) M.N. Moreno-Carretero, ~2) and J.D. M a r t l n - R a m o s {3)
Received December 22, 1993; Accepted March 4, 1994
A new and easy method for the preparation of 1,3,7,9-tetramethylpyrido-[2,3-d:6,5-d']-dipyrimidine-2,4,6,8-tetrone is described. The structure of this compound has been solved by means of X-ray diffraction methods. The chemical characterization by spectral (mass, ultraviolet, infrared, and proton nuclear magnetic resonance) and thermal (thermogravimetry and differential scanning calorimetry) method is also reported. The compound is monoclinic, space group P21/c, a = 12.720(5), b = 13.688(7), c = 8.079(2),~,/~ = 107.06(4) ~ Z = 4. The structure consists of discrete tricyclic molecules, stacking playing an important role in crystal packing. KEY WORDS: Pyrimidine, uracil, crystal structure.
Introduction
late different pyrido-[2,3-d:6,5-d']dipyrimidine compounds. As a part of our studies on pyrimidine derivatives and their metal complexes 7-17 we now describe the synthesis of 1,3,7,9-tetramethylpyrido-[2,3-d : 6,5-d']dipyrimidine-2,4,6,8-tetrone, its chemical characterization and crystal structure.
Pyridopyrimidines are of interest as NAD(P) + model compounds I and are structurally cyclized compounds of the amino analogs of the Hantzch esters and also have a conjugated system similar to that of 5-deazaflavins. This type of compounds have been found to oxidize a variety of alcohols under neutral conditions to yield the corresponding carbonyl compounds, l 6-Aminouracil derivatives have been employed as a convenient starting material for the preparation of this type of compounds. 2 Recently, it has been found 3 that 5-dimethylamino-methylene-6-imino-1,3-dimethyluracil hydrochloride, easily obtained by the Vilsmeier reaction of 6amino-l,3-dimethyluracil, is an useful precursor for the preparation of pyrido[2,3-d : 6,5-d']-dipyrimidines. Several authors 4-6 have also described methods to iso-
Experimental Synthesis o f 1,3, 7,9-tetramethylpyrido-[2,3-d : 6,5-d']dipyrimidine-2 , 4 , 6, 8-tetrone The synthesis of the title compound was carried out by adding 15.9 g (0.1 mol) of 6-amino-l,3-dimethyluracil to 100 ml of a mixture of acetic anhydride and formic acid (50% v/v). The resulting solution is then heated with stirring at 90~ for 2 hr and cooled at room temperature. On standing overnight, a colorless crystalline solid can be isolated. This was filtered by suction and washed with a little amount of ethanol. Anal. calcd. for CI3HI3NsO4: 51.49% C, 4.29% H, 23.10% N; Found: 51.48% C, 4.29% H, 23.10% N.
"~Departamento de Qufmica Inorgdnica. Universidad de Granada. 18071 Granada, Spain. t2~Departamento de Qufmica Inorgdnica y Orgdnica, Universidad de Ja6n. 23071 JAI~N, Spain. ~ de Mineralogfa y Petrologfa. Universidad de Granada. 18071 Granada, Spain.
465 1074-1542/9410700-0465507.00/09 1994Plenum PublishingCorporation
466
Enrique-Mir6n et al. Table 2. Atomic coordinates ( x 104) and equivalent isotropic
Apparatus
displacement coefficients (~2 . 104) M e l t i n g point was d e t e r m i n e d on a M e t t l e r D S C 20 differential scanning calorimeter. E l e m e n t a l analysis was c a r d e d out at the M i c r o a n a l y t i c a l L a b o r a t o r y o f the T e c h n i c a l S e r v i c e s o f G r a n a d a U n i v e r s i t y . M a s s spectrum was taken on a H e w l e t t - P a c k a r d H P - 5 9 8 0 - A machine, operating at 70 eV. Infrared and ultraviolet spectra w e r e registered using P e r k i n - E l m e r 9 8 3 - G (4000-250 c m - I , K B r pellet) and Hitachi U - 2 0 0 0 (190-400 nm, 9 9 10 -5 M ethanolic solution) s p e c t r o p h o t o m e t e r s , respectively. Proton n u c l e a r m a g n e t i c r e s o n a n c e s p e c t r u m w e r e recorded on a B r u k e r A - 3 0 0 apparatus (300 M H z ) using t e t r a m e t h y l s i l a n e as internal standard and dim e t h y l s u l p h o x i d e - d 6 as solvent. T h e r m o g r a v i m e t r i c
Table 1. Crystal data Empirical formula: C~3H~3NsO4 Aspect: Colourless needles. Crystal dimensions: 0.27 x 0.34 x 0.23 mm. Formula weight: 303.3 Crystal system: Monoclinic Space group: P2 ~/c Temperature: 20"C. Cell constants (25 reflections used, 25 < 20 < 45~ a = 12.720(5) b = 13.688(7) A. c = 8.079(2) ~, /3 = 107.06(4) ~ Volume: 1344.7(9) /k~ Formula units/unit cell: 4. Density (talc): 1.498 g 9 cm -3 Absorption coefficient: 0.924 mmF(000): 632 Diffractometer: Siemens R3m/V Kristalloflex Radiation: Cu Kct (h = 1.54184 ,~,), graphite monochromated. Standarl:l reflections: 3 measured every 90 min, with no apparent decay. 20 range: 5-125" Rangeofh, k,l: - 1 4 _< h 3o(1)). 9Corrections applied: Lp. Computer programs: SHELTXL PLUS on a MicroVax II computer, scattering factors included in. Structure solution: Direct methods. Hydrogen atoms: Refined with fixed C--H (I).95 .~,) and geminal H--H (1.54 ~ ) distances. A common isotropic thermal parameter was refined. Number of parameters: 239 Weights: w-~ = tr2(F) + 0.05F 2. Final R = 0.059 Final Rw = 0.066 Goodness-of-Fit = 0.45 Largest peak final AF map: 0.47 e/~ -3
Atom NI C1 C2 02 N3 C3 C4 04 C4a C5 C5a C6 06 N7 C7 C8 O8 C9a N9 C9 N t0 Cl0a
x/a
y/b
z/c
2135(2) 2018(2) 1172(2) 279(2) 1284(1) 286(2) 2271 (2) 2298(1) 3243(2) 4285(2) 5193(2) 6303(2) 6498(1) 7137(1) 8273(2) 6981 (2) 7754(1) 5016(2) 5908(2) 5763(2) 4022(2) 3158(2)
936(1) 669(2) 1087(2) 981(2) 1357(1) 1434(2) 1572(2) 1849(1) 1440(1) 1613(1) 1453(1) 1617(1) 1890(1) 1431(1) 1670(2) 1098(2) 928(1) 1132(1) 954(1) 678(2) 964( 1) 1118(1)
4812(3) 6520(3) 3476(3) 3692(3) 1873(2) 413(4) 1566(3) 132(2) 3025(3) 2875(3) 4282(3) 4160(3) 2842(2) 5664(2) 5700(4) 7214(3) 8463(2) 5824(2) 7237(2) 8911 (3) 6017 (2) 4630(3)
Ucq~ 496(7) 668(10) 559(9) 869(9) 517(7) 786(11) 471 (7) 612(6) 403(7) 412(7) 388(7) 417(7) 555(6) 457(7) 659(10) 460(8) 642(7) 369(7) 433(6) 573(9) 426(7) 400(7)
a Equivalent isotropic U defined as one third of the trace of the orthogonalized Uij tensor.
study was carried out on a M e t t l e r T G - 5 0 t h e r m o b a l ance, using a s a m p l e mass o f 4 . 8 7 4 m g , a heating rate o f 2 0 ~ 9 m i n - I and a d y n a m i c a t m o s p h e r e o f pure air (100 ml m i n - l ) . G e n e r a l details o f the c r y s t a l l o g r a p h i c d e t e r m i n a tion are listed in T a b l e 1 and final a t o m i c c o o r d i n a t e s are i n c l u d e d in T a b l e 2.
Results and discussion Thermal and spectral study D u r i n g o u r i n v e s t i g a t i o n s on the synthesis o f m e t a l c o m p l e x e s o f Schiff bases d e r i v e d o f p y r i m i d i n e s , t8 w e h a v e found an easy and c o n v e n i e n t m e t h o d for the preparation o f 1 , 3 , 7 , 9 - t e t r a m e t h y l p y r i d o [ 2 , 3 - d : 6 , 5 - d ' ] dip y r i m i d i n e 2 , 4 , 6 , 8 - t e t r o n e , w h i c h has b e e n d e s c r i b e d in the e x p e r i m e n t a l section. D S C c u r v e o f this c o m p o u n d s h o w s a c l e a r e n d o t h e r m i c effect at 3 1 7 ~ that c o r r e s p o n d s to the m e l t i n g o f the sample. T h i s v a l u e is in a c c o r d a n c e with that obtained by B r e d e r e c k ( 3 1 9 - 3 2 1 ~ 5 The corresponding enthalpy value, c a l c u l a t e d f r o m the area o f the effect, is 26 kJ mol - j . T h e t h e r m o g r a v i m e t r i c c u r v e s h o w s that
Structure of 1,3,7,9-tetramethyl-pyrido-[2,3-d : 6,5-d']-dipyrimidin thermal degradation occurs through one single step between 320 and 450~ (weight loss = 100%). This weight loss effect is reflected in DSC curve by the appearance of one exothermic effect (DSC peak temperature 340~ indicative that total combustion of sample takes place in this temperature range. The mass spectrum shows clearly, although with low intensity (l 1% relative abundance), the molecular peak at 303.05 a.m.u. Signals at 274.20, 246.20, 218.15,191.15,161.15,133.15 and 106.15 a.m.u. (between 5 and 20% abundance) are also present and may be tentatively assigned to the successive loss of either N - - C H 3 or CO fragments from original structure. The elimination of all CO and N--CH3 groups yields a pyridine moiety. The corresponding peak appears, with a relative abundance of ca. 80%, at 78.00 a.m.u. The strongest peak (100%, q/m -- 62.95) corresponds to the radical resultant from the loss of N atom of pyridine. The ultraviolet spectrum of a 9 9 10 -5 M ethanolic solution of the title compound shows four bands centered at 337 nm (e = 8700), 330 nm (shoulder, e = 7700), 288 nm (e = 2800) and 230 nm (~ = 18600). The position and intensity of these bands remain practically unaltered, within the experimental error, in the 1-13 pH range, this being indicative that any process of either protonation or deprotonation does not occur. The no evidence of deprotonation processes is in accordance with the chemical structure of the studied compound, since there is not any acidic proton. Also, these results permit to suggest that the basicity of nitrogen atom of the pyridine moiety is very much lower than that corresponding to free pyridine. In the infrared spectrum, the following bands have been assigned: 3094 cm-1 (~,(c_H)=C_H) ' 2958 c m - i (p(c_H)--CH3), 1715 cm-1 (V(c=o)C2=O and C 8 = O ) , 1666 c m - ' (V(c=o)C4=O and C 6 = O , 1613 and 1592
C3
(;40
C5o
-
Fig. 1. Molecular structure and numbering scheme for 1,3,7,9-tetramethylpyrido[2,3-d:6,5-d'ldipyrimidine-2,4,6,8-tetmne. A t o m s are represented as 50% probability ellipsoids.
467
cm-t (~(c=c) + VCC=N)),"1380 and 1275 cm -I (UtC--N))" These assignations were realized by comparis6n of obtained results with infrared spectra of other pyrimidine derivatives. ' 9 'H-NMR spectrum shows three signals (6) at 3.28 ppm (6H, s), 3.59 ppm (6H, s) and 8.69 ppm (IH, s). These were assigned, in accordance with the bibliographic data 2 to the resonance of protons of methyl groups bonded to N1 and N9 (3.28 ppm) and N3 and N7 (3.59 ppm), whereas the signal at 8.69 ppm is due to the aromatic proton of the pyridine ring.
Crystallographic study The structure of this compound consists of discrete units of 1,3,7,9-tetramethyl-pyrido [2,3-d:6,5-d'] dipyrimidine 2,4,6,8-tetrone. A view of the molecule, including the numbering scheme, is presented in Fig. 1. Although the molecule is symmetric, there is not any crystallographic symmetry relationship between its two halves. Distances and angles (Table 3) are close to the ones observed in other pyrimidine derivativesl3.,5.17,2o, except the distances C4a--C10a Table 3. Bond lengths (A) and angles (~ N1--C2 N1--C10a C2--O2 C2--N3 N3--C3 N3--C4 C4--O4 C4--C4a C4a--C5 C4a--Cl0a C5--C5a
!.389(3) 1.375(3) 1.208(3) 1.394(4) 1.461(3) 1.380(3) 1.229(3) 1.448(3) 1.386(3) 1.403(3) 1.380(3)
C5a--C6 C5a--C9a C6--O6 C6--N7 N7--C8 C8--O8 C8--N9 Cga--N9 C9a--NI0 N9--C9 NI0--C10a
1.461(3) 1.401(3) 1.220(3) 1.383(3') 1.401(3) 1.207(3) 1.384(3) 1.375(2) 1,338(3) 1.467(3) 1.336(2)
C2--N1--C10a NI--C2--O2 NI --C2--N3 O2--C2--N3 C2--N3--C3 C2--N3--C4 C3--N3--C4 N3--C4--O4 N3--C4--C4a O4--C4--C4a C4--C4a--C5 C4--C4a--Cl0a C5--C4a--CI0a C4a--C5--C5a C5--C5a--C6 C5--C5a--C9a C6--C5a--C9a
122.4(2) 121.5(3) t 17.0(2) 121.5(2) 117.9(2) 124.7(2) 117.4(2) 120.9(2) 115.5(2) 123.5(2) 121.2(2) 120.8(2) 118.0(2) 119.5(2) 120.8(2) 117.9(2) 121.3(2)
C5a--C6--O6 C5a--C6--N7 O6--C6--N7 C6--N7--C8 N7--C8--O8 NT--C8--N9 O8--C8--N9 C5a--C9a--N9 C5a--C9a--NI0 N9--C9a--NI0 CS--N9--C9a C8--N9--C9 C9a--N9--C9 C9a--NI0--CI0a N1--CI0a--C4a NI--CI0a--NI0 C4a--C10a--NI0
123.6(2) 114.9(2) 121.5(2) 124.9(2) 121.0(2) 117.2(2) 121.7(2) 119.0(2) 124.2(2) "116.8(2) 122.7(2) 116.1(2) 120.9(2) 116.6(2) 119.2(2) 117.0(2) 123.8(2)
468 and C5a--C9a (corresponding to C 5 - - C 6 of uracil) that are lengthened in 0.07 A, as may be expected, since the localized double bond in uracil is delocalized now through the pyridine ring. The three fused rings are almost perfectly planar, the maximum deviations of the average plane being 0.121 A, (C3) for exocyclic atoms and 0.047 A, (C8) for endocyclic ones. Hydrogen bonding being absent, since no potentially donor atom is present; stacking becomes the most important intermolecular interaction. The molecules are stacked in couples around the symmetry center that relates two partners, so the plans are perfectly parallel, with a distance of 3.4 A between them. Stacking takes place in a way that the methyl groups of one of the molecules fall over the carbonyl groups of the other one. The two sets of parallel planes are placed roughly perpendicular to the ac plane. These two sets form a 35.3 ~ angle between them.
References 1. Yoneda, F.; Yamato, J.; Ono, M. J. Am. Chem. Soc. 1981, 103, 5943. 2. Hirota, K.; Kitade, Y.; Senda, S. J. Heterocyclic Chem. 1985, 22, 345. 3. Hirota, K.; Kitade, Y.; Sajiki, H.; Maki, M. Synthesis 1984, 589. 4. Nagamatsu, T.; Sakuma, Y.; Yoneda, F. Synthesis 1983, 923.
Enrique-Mir6n et al. 5. Bredereck, H.: Effenberger, F.: Sauter, R. Chem. Ber. 1962, 95, 2409. 6. Bredereck, H.; Effenberger, F.; Simchen, G. Chem. Ber. 1964, 97, 1403. 7. Valenzuela-Calahorro, C.; Salas Peregrfn, J.M.; L6pez-Gonz~ilez, J.D. An. Qufm. 1980, 76B, 197. 8. L6pez-Gonz,'ilez, J.D.; Salas-Peregrtn, J.M.; Garcfa-Mino, J.S.; Valenzuela-Calahorro, C. An. QuEm. 1980, 76B, 256. 9. Garcia-Mino, J.S.; L6pez-Gonz~ilez, J.D.; Moreno-Carretero, M.N., Salas-Peregrfn, J.M. An. Quhn. 1981, 77B, 335. 10. Salas-Peregrin, J.M.; Moreno-Carretero. M.N.: Romero-Molina, M.A.; Colacio-Rodrfguez, E. Rev. Chim. Min~r. 1984, 21, 233. 11. Moreno-Carretero, M.N.; Salas-Peregrfn, J.M.J. ThermalAnal. 1985, 30, 377. 12. Salas-Peregn'n, J.M.; Moreno-Carretero, M.N. ; Colacio-Rodriguez, E. Can. J. Chem. 1985, 63, 3573. 13. Moreno-Carretero, M.N.; Salas-Peregn'n, J.M.; Colacio-Rodrfguez, E.: Sfinchez-Sfinchez, M.P.; Nieto-Garcfa, F. Acta Cryst. 1986, C42,407. 14. Salas-Peregrfn, J.M.; Moreno-Carretero, M.N.; L6pez-Gonzfilez, J.D.; Romero-Molina, M.A. Spectrochim. Acta 1986, 42A, 607. 15. Romero-Molina, M.A.; Moreno-Carretero, M.N.; Ruiz-S~inchez, J.; S~inchez-S~inchez,M.P.; Nieto-Garcia, F. lnorg. Chem. 1986, 25, 1498. 16. Romero-Molina, M.A. : Salas-Peregrin, J.M.; L6pez-Gar-z6n, R. ; Guti6rrez-Valero, M.D. Polyhedron 1988, 7, 659. 17. Romero-Molina, M.A.; Salas-Peregrin, J.M.; L6pez-Garz6n, R.; Gutierrez-Valero, M.D.; Pannerselvam, K.; Chacko, K.K.; Aoki, K.; Yamazaki. H. Inorg. Chim. Acta 1990, 172,253. 18. Enrique-Mir6n, C. PhD. Thesis University of Granada, 1990. 19. Hueso-Urefia, F.; Moreno-Carretero, M.N.; Salas-Peregrin, J.M. Thermochim. Acta 1990, 170, 225, and references therein. 20. Low, J.N.; Howie, R.A.; Moreno-Carretero, M.N.; HuesoUrefia, F. Acta Cryst. 1992, C48, 145.
