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Acta Cryst. (2009). E65, o1536-o1537    [ doi:10.1107/S1600536809020856 ]

5-Ethyl-4a-methoxy-1,3-dimethyl-4a,5-dihydrobenzo[g]pteridine-2,4(1H,3H)dione

P. Ménová, V. Eigner, R. Cibulka, J. Cejka and H. Dvoráková

Abstract top

The title compound, C15H18N4O3, was formed by the reaction of methanol with 5-ethyl-1,3-dimethylalloxazinium perchlorate. Its structure mimics those of possible flavin intermediates in flavoenzymes. The heterocyclic rings are substituted with methyl, ethyl and methoxy groups. The central tricyclic skeleton is bent due to the presence of an sp3 C atom. There are weak intermolecular C-H...O interactions in the structure, forming a three-dimensional network.

Comment top

Flavinium salts (both, isoalloxazinium and alloxazinium) represent suitable models (Müller, 1991; Kemal & Bruice, 1976; Kemal et al., 1977) of natural flavin derivatives which are important cofactors in many types of oxido-reductases and monooxygenases (Massey, 2000; Palfey & Massey, 1998). Similarly to natural flavins, flavinium salts react easily with various nucleophiles (water, methanol, primary amines etc.) with the formation of the covalent C4a-adducts (C4a-adduct means a compound with the covalently bound nucleophile to the C4a-atom of the flavin fragment; see Kemal & Bruice, 1976; Kemal et al., 1977; Hoegy & Mariano, 1997). The C4a-adducts of flavins are important intermediates of the reactions catalyzed by flavoenzymes.

In this paper, the first crystal structure of the C4a-adduct of alloxazinium salt (Figs. 1 and 2) is reported. The adduct is formed by the reaction of methanol with 5-ethyl-1,3-dimethylalloxazinium perchlorate (Fig. 2). By this reaction, the hybridization of C20 atom (C4a atom in IUPAC numbering of alloxazine moiety) is changed from sp2 to sp3 (Fig. 2). This change of hybridization causes a folding of the tricyclic alloxazine skeleton. The value of the interplanar angle between the plane determined by the C2, N3, C5, and N7 atoms and the plane determined by the C9, N10, C11, C12, C13, C14, C15, C16, and N17 atoms is 15.69 (5)°. This angle is larger in comparison with that found in the case of the similar adducts of C-nucleophiles with isoalloxazine derivatives; e.g. the angle between the analogous planes in 4a,5-dihydro-4a-isopropyl-3,10-dimethylisoalloxazine (Bolognesi et al., 1978) is only 6.85 (9)°. The observed 'butterfly' arrangement of the tricyclic alloxazine subunit in the title compound corresponds to the structure of dihydroflavins already published by Werner & Rönnquist (1970) and Norrestam & Von Glehn (1972).

Due to the sp3 hybridization, C20 atom is shifted out of the alloxazine plane by 0.313 (1)Å. On the other hand, the values of the bond angles around C20 are different from those expected for an sp3 carbon atom, probably due to the rigidity of the dihydroalloxazine system. The conformation of the ring 1 (C2, N3, C5, N7, C9, C20) is between 5H6 and E6. The conformation of the ring 2 (C9, N10, C11, C16, N17, C20) is between 5S6 and E6, rather closer to E6. The distances, angles and puckering parameters (Cremer & Pople, 1975) were calculated using PARST97 (Nardelli, 1999).

Three weak intermolecular C—H···O interactions were found forming a three-dimensional network.

Related literature top

in the context of this article, a C4a-adduct is a compound with a nucleophile covalently bound to the C4a-atom of the flavin fragment; isoalloxazines are natural flavin derivatives, alloxazines are their isomers. For the biological relevance of C4a-adducts in flavoenzymes, see: Palfey & Massey (1998); Massey (2000); Müller (1991). For the preparation of C4a-isoalloxazine adducts, see: Kemal & Bruice (1976); Kemal et al. (1977); Hoegy & Mariano (1997). For the crystal structures of isoalloxazine adducts, see: Bolognesi et al. (1978). For the crystal structures of reduced isoalloxazines, see: Werner & Rönnquist (1970); Norrestam & Von Glehn (1972). For puckering parameters, see: Cremer & Pople (1975). For the extinction correction, see: Larson (1970).

Experimental top

The crystals of the title compound were obtained from a solution of 1,3-dimethyl-5-ethylalloxazinium perchlorate (20 mg, 0.054 mmol) and dry triethylamine (7.5 µl, 0.054 mmol) in dry methanol (1.8 ml). Single crystals suitable for analysis were grown overnight directly from the reaction mixture. M. p. 384 - 386 K.

Refinement top

The H atoms were found in the Δρ map and initially refined with the restraints on the bond lengths and angles to regularize their geometry (Cmethyl—H = 0.96 (2), Cmethylene—H = 0.97 (2), Caryl = 0.93 (2) Å. Uiso(H) = 1.5 UeqCmethyl or 1.2 UeqCmethylene/aryl. After the convergement the geometrical restraints were substituted by the geometrical constraints.

1H NMR (pyridine-d5; 600 MHz): 1.57 (t, 3H; CH2CH3), 2.82 (s, 3H; OCH3), 3.31 (s, 3H; 3 N–CH3), 3.56 (s, 3H; 1 N–CH3), 3.58–3.62 (m, 1H; 5 N–CH2CH3), 4.17–4.21 (m, 1H; 5 N–CH2CH3), 7.03–7.07 (m, 2H; 6,8–CH), 7.33 (t, 2J = 7.20 Hz, 1H; 7–CH), 7.63 (d, 2J = 7.14 Hz, 1H; 9–CH). 13C NMR (pyridine-d5; 150 MHz): 50.9 (OCH3), 82.2 (4a–C).

Computing details top

Data collection: CrysAlis CCD (Oxford Diffraction, 2005); cell refinement: CrysAlis RED (Oxford Diffraction, 2005); data reduction: CrysAlis RED (Oxford Diffraction, 2005); program(s) used to solve structure: Superflip (Palatinus & Chapuis, 2006); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: CRYSTALS (Betteridge et al., 2003) and PARST97 (Nardelli, 1997).

Figures top
[Figure 1] Fig. 1. The title molecule with the displacement ellipsoids drawn at the 50% probability level. The H atoms are shown as spheres of arbitrary radius.
[Figure 2] Fig. 2. Formation of the adduct by the reaction of 5-ethyl-1,3-dimethylalloxazinium perchlorate with methanol.
5-Ethyl-4a-methoxy-1,3-dimethyl-4a,5-dihydrobenzo[g]pteridine- 2,4(1H,3H)dione top
Crystal data top
C15H18N4O3F(000) = 640
Mr = 302.33Dx = 1.412 Mg m−3
Monoclinic, P21/nMelting point = 384–386 K
Hall symbol: -P 2ynCu Kα radiation, λ = 1.54184 Å
a = 10.3958 (2) ÅCell parameters from 11727 reflections
b = 12.7174 (2) Åθ = 4–77°
c = 10.9421 (2) ŵ = 0.83 mm−1
β = 100.4727 (16)°T = 150 K
V = 1422.53 (4) Å3Prism, colourless
Z = 40.50 × 0.28 × 0.15 mm
Data collection top
Oxford Diffraction Xcalibur
diffractometer		2996 independent reflections
graphite2692 reflections with I > 2σ(I)
Detector resolution: 8.1917 pixels mm-1Rint = 0.025
φ and ω scansθmax = 77.5°, θmin = 5.4°
Absorption correction: analytical
(de Meulenaer & Tompa, 1965)		h = −13→13
Tmin = 0.76, Tmax = 0.88k = −15→15
18511 measured reflectionsl = −12→13
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.041H-atom parameters constrained
wR(F2) = 0.121 Modified Sheldrick (2008) w = 1/[σ2(F2) + (0.08P)2 + 0.33P],
where P = [max(Fo2,0) + 2Fc2]/3
S = 0.99(Δ/σ)max = 0.0003
2996 reflectionsΔρmax = 0.23 e Å−3
200 parametersΔρmin = −0.21 e Å−3
0 restraintsExtinction correction: Larson (1970), Equation 22
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 29 (5)
Crystal data top
C15H18N4O3V = 1422.53 (4) Å3
Mr = 302.33Z = 4
Monoclinic, P21/nCu Kα radiation
a = 10.3958 (2) ŵ = 0.83 mm−1
b = 12.7174 (2) ÅT = 150 K
c = 10.9421 (2) Å0.50 × 0.28 × 0.15 mm
β = 100.4727 (16)°
Data collection top
Oxford Diffraction Xcalibur
diffractometer		2996 independent reflections
Absorption correction: analytical
(de Meulenaer & Tompa, 1965)		2692 reflections with I > 2σ(I)
Tmin = 0.76, Tmax = 0.88Rint = 0.025
18511 measured reflectionsθmax = 77.5°
Refinement top
R[F2 > 2σ(F2)] = 0.041H-atom parameters constrained
wR(F2) = 0.121Δρmax = 0.23 e Å−3
S = 0.99Δρmin = −0.21 e Å−3
2996 reflectionsAbsolute structure: ?
200 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.43813 (9)0.38054 (7)0.10771 (8)0.0341
C20.53277 (11)0.36250 (9)0.18746 (11)0.0269
N30.65728 (10)0.37227 (8)0.16350 (9)0.0295
C40.67024 (14)0.39751 (11)0.03524 (12)0.0394
C50.77221 (12)0.37049 (9)0.25223 (12)0.0308
O60.87775 (9)0.38486 (8)0.22244 (10)0.0413
N70.75942 (9)0.35479 (8)0.37412 (10)0.0293
C80.87888 (12)0.36402 (11)0.46793 (13)0.0388
C90.63877 (10)0.35461 (8)0.41330 (11)0.0249
N100.63770 (9)0.37433 (8)0.52755 (9)0.0272
C110.51698 (11)0.37383 (9)0.56668 (11)0.0260
C120.51588 (13)0.38898 (10)0.69269 (11)0.0317
C130.39963 (14)0.39033 (10)0.73696 (11)0.0340
C140.28241 (13)0.37940 (9)0.65335 (12)0.0333
C150.28184 (12)0.36561 (9)0.52737 (12)0.0301
C160.39920 (11)0.36095 (8)0.48170 (10)0.0248
N170.40282 (9)0.34548 (8)0.35602 (9)0.0257
C180.27877 (11)0.31653 (11)0.27437 (11)0.0328
C190.19478 (12)0.41186 (13)0.22860 (13)0.0412
C200.52333 (10)0.31848 (9)0.31740 (10)0.0249
O210.53556 (8)0.20753 (6)0.29281 (7)0.0295
C220.54526 (16)0.14088 (10)0.39936 (13)0.0417
H410.75670.38050.02560.0569*
H420.65300.47080.01770.0574*
H430.60970.3549−0.01970.0574*
H810.86960.31960.53690.0560*
H820.89320.43480.49480.0553*
H830.95250.34000.43450.0558*
H1210.59910.39890.74790.0377*
H1310.39990.39910.82140.0392*
H1410.20220.38140.68050.0402*
H1510.20030.35810.47380.0353*
H1810.22890.27030.32070.0369*
H1820.29820.27740.20360.0371*
H1910.10710.38890.19440.0565*
H1920.19170.45970.29700.0566*
H1930.23160.44950.16410.0564*
H2210.54530.06970.37210.0593*
H2220.62860.15450.45910.0602*
H2230.47250.15090.44320.0599*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0330 (5)0.0392 (5)0.0302 (4)0.0028 (4)0.0063 (3)0.0028 (3)
C20.0302 (6)0.0222 (5)0.0303 (5)0.0018 (4)0.0110 (4)−0.0008 (4)
N30.0308 (5)0.0291 (5)0.0322 (5)0.0028 (4)0.0156 (4)0.0040 (4)
C40.0483 (7)0.0396 (7)0.0363 (7)0.0079 (6)0.0236 (6)0.0081 (5)
C50.0302 (6)0.0237 (6)0.0425 (7)0.0025 (4)0.0174 (5)0.0041 (4)
O60.0300 (5)0.0432 (5)0.0566 (6)0.0001 (4)0.0231 (4)0.0068 (4)
N70.0218 (5)0.0302 (5)0.0379 (5)0.0017 (4)0.0107 (4)0.0035 (4)
C80.0229 (6)0.0440 (7)0.0491 (7)0.0016 (5)0.0056 (5)0.0067 (6)
C90.0226 (5)0.0207 (5)0.0328 (6)0.0009 (4)0.0085 (4)0.0025 (4)
N100.0256 (5)0.0260 (5)0.0306 (5)0.0007 (3)0.0068 (4)0.0020 (4)
C110.0271 (6)0.0218 (5)0.0305 (6)−0.0003 (4)0.0093 (4)0.0007 (4)
C120.0393 (6)0.0270 (6)0.0295 (6)0.0004 (5)0.0082 (5)−0.0004 (4)
C130.0481 (7)0.0271 (6)0.0307 (6)0.0007 (5)0.0179 (5)0.0006 (4)
C140.0388 (6)0.0261 (6)0.0407 (6)−0.0025 (5)0.0227 (5)−0.0008 (5)
C150.0285 (6)0.0265 (6)0.0381 (6)−0.0040 (4)0.0137 (5)−0.0029 (4)
C160.0272 (5)0.0202 (5)0.0292 (5)−0.0020 (4)0.0111 (4)−0.0005 (4)
N170.0220 (4)0.0279 (5)0.0286 (5)−0.0020 (4)0.0082 (3)−0.0034 (4)
C180.0247 (5)0.0412 (7)0.0334 (6)−0.0084 (5)0.0074 (4)−0.0088 (5)
C190.0238 (5)0.0612 (9)0.0373 (6)0.0020 (5)0.0020 (5)−0.0044 (6)
C200.0244 (5)0.0228 (5)0.0293 (5)−0.0003 (4)0.0097 (4)−0.0006 (4)
O210.0350 (4)0.0223 (4)0.0342 (4)0.0002 (3)0.0141 (3)−0.0013 (3)
C220.0614 (9)0.0254 (6)0.0435 (7)0.0023 (6)0.0231 (6)0.0045 (5)
Geometric parameters (Å, °) top
O1—C21.2124 (15)C12—H1210.969
C2—N31.3723 (15)C13—C141.3914 (19)
C2—C201.5476 (15)C13—H1310.930
N3—C41.4696 (15)C14—C151.3886 (18)
N3—C51.3961 (17)C14—H1410.935
C4—H410.949C15—C161.4012 (16)
C4—H420.962C15—H1510.944
C4—H430.955C16—N171.3965 (14)
C5—O61.2138 (15)N17—C181.4758 (14)
C5—N71.3786 (16)N17—C201.4347 (14)
N7—C81.4650 (16)C18—C191.524 (2)
N7—C91.3973 (14)C18—H1810.983
C8—H810.961C18—H1820.972
C8—H820.950C19—H1910.966
C8—H830.956C19—H1920.969
C9—N101.2771 (16)C19—H1930.985
C9—C201.5149 (15)C20—O211.4464 (13)
N10—C111.3977 (15)O21—C221.4300 (15)
C11—C121.3944 (16)C22—H2210.953
C11—C161.4060 (16)C22—H2221.002
C12—C131.3813 (18)C22—H2230.975
O1—C2—N3121.04 (11)C13—C14—C15120.70 (11)
O1—C2—C20123.43 (10)C13—C14—H141120.9
N3—C2—C20115.33 (10)C15—C14—H141118.4
C2—N3—C4117.11 (11)C14—C15—C16120.83 (12)
C2—N3—C5125.69 (10)C14—C15—H151118.1
C4—N3—C5116.89 (10)C16—C15—H151121.1
N3—C4—H41108.0C11—C16—C15117.99 (10)
N3—C4—H42110.9C11—C16—N17119.44 (10)
H41—C4—H42110.2C15—C16—N17122.56 (10)
N3—C4—H43108.2C16—N17—C18117.02 (9)
H41—C4—H43109.2C16—N17—C20120.34 (9)
H42—C4—H43110.3C18—N17—C20118.40 (9)
N3—C5—O6120.78 (12)N17—C18—C19112.69 (10)
N3—C5—N7117.02 (10)N17—C18—H181108.8
O6—C5—N7122.17 (12)C19—C18—H181108.7
C5—N7—C8116.60 (10)N17—C18—H182109.0
C5—N7—C9123.15 (10)C19—C18—H182109.6
C8—N7—C9118.62 (10)H181—C18—H182108.1
N7—C8—H81108.0C18—C19—H191109.3
N7—C8—H82111.0C18—C19—H192110.0
H81—C8—H82110.2H191—C19—H192109.2
N7—C8—H83110.0C18—C19—H193110.3
H81—C8—H83108.3H191—C19—H193109.3
H82—C8—H83109.3H192—C19—H193108.6
N7—C9—N10117.91 (10)C2—C20—C9110.62 (9)
N7—C9—C20115.48 (10)C2—C20—N17112.87 (9)
N10—C9—C20126.22 (10)C9—C20—N17110.34 (9)
C9—N10—C11117.84 (10)C2—C20—O2199.18 (8)
N10—C11—C12118.13 (11)C9—C20—O21109.84 (9)
N10—C11—C16121.37 (10)N17—C20—O21113.53 (9)
C12—C11—C16120.49 (11)C20—O21—C22114.97 (9)
C11—C12—C13120.89 (12)O21—C22—H221108.1
C11—C12—H121117.9O21—C22—H222110.8
C13—C12—H121121.2H221—C22—H222108.6
C12—C13—C14119.06 (11)O21—C22—H223112.2
C12—C13—H131120.3H221—C22—H223108.8
C14—C13—H131120.6H222—C22—H223108.2
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
C4—H42···O1i0.962.433.3230 (18)155
C14—H141···O21ii0.942.563.3999 (18)149
C19—H191···O6iii0.972.463.3021 (18)146
Symmetry codes: (i) −x+1, −y+1, −z; (ii) x−1/2, −y+1/2, z+1/2; (iii) x−1, y, z.
Table 1
Selected geometric parameters (°) top
C2—C20—C9110.62 (9)C2—C20—O2199.18 (8)
C2—C20—N17112.87 (9)C9—C20—O21109.84 (9)
C9—C20—N17110.34 (9)N17—C20—O21113.53 (9)
Table 2
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
C4—H42···O1i0.962.433.3230 (18)155
C14—H141···O21ii0.942.563.3999 (18)149
C19—H191···O6iii0.972.463.3021 (18)146
Symmetry codes: (i) −x+1, −y+1, −z; (ii) x−1/2, −y+1/2, z+1/2; (iii) x−1, y, z.
Acknowledgements top

Financial support from the Czech Science Foundation (grant No. 203/07/1246) and the Ministry of Education, Youth and Sports of the Czech Republic (grant No. 6046137302) is gratefully acknowledged.

references
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