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

Petra Ménová; Václav Eigner; Radek Cibulka; Jan Čejka; Hana Dvořáková

doi:10.1107/S1600536809020856

. 2009 Jun 10;65(Pt 7):o1536–o1537. doi: 10.1107/S1600536809020856

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

Petra Ménová ^a, Václav Eigner ^b, Radek Cibulka ^a,^*, Jan Čejka ^b, Hana Dvořáková ^c

PMCID: PMC2969355 PMID: 21582825

Abstract

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 sp ³ C atom. There are weak intermolecular C—H⋯O interactions in the structure, forming a three-dimensional network.

Related literature

in the context of this article, a C4a-adduct is a compound with a nucleophile covalently bound to atom C4a 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

Crystal data

C₁₅H₁₈N₄O₃
M _r = 302.33
Monoclinic,
a = 10.3958 (2) Å
b = 12.7174 (2) Å
c = 10.9421 (2) Å
β = 100.4727 (16)°
V = 1422.53 (4) Å³
Z = 4
Cu Kα radiation
μ = 0.83 mm⁻¹
T = 150 K
0.50 × 0.28 × 0.15 mm

Data collection

Oxford Diffraction Xcalibur diffractometer
Absorption correction: analytical (de Meulenaer & Tompa, 1965 ▶) T _min = 0.76, T _max = 0.88
18511 measured reflections
2996 independent reflections
2692 reflections with I > 2σ(I)
R _int = 0.025

Refinement

R[F ² > 2σ(F ²)] = 0.041
wR(F ²) = 0.121
S = 0.99
2996 reflections
200 parameters
H-atom parameters constrained
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Data collection: CrysAlis CCD (Oxford Diffraction, 2005 ▶); cell refinement: CrysAlis RED (Oxford Diffraction, 2005 ▶); data reduction: CrysAlis RED; 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 and PARST97 (Nardelli, 1997).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809020856/fb2153sup1.cif

e-65-o1536-sup1.cif^{(17.2KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809020856/fb2153Isup2.hkl

e-65-o1536-Isup2.hkl^{(149.9KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C4—H42⋯O1ⁱ	0.96	2.43	3.3230 (18)	155
C14—H141⋯O21ⁱⁱ	0.94	2.56	3.3999 (18)	149
C19—H191⋯O6ⁱⁱⁱ	0.97	2.46	3.3021 (18)	146

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

Acknowledgments

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.

supplementary crystallographic information

Comment

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.

Experimental

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.