1-[3-(4-Methoxy­phen­yl)-6-methyl-1,6-dihydro-1,2,4,5-tetra­zin-1-yl]propanone

Yang, Z.; Xu, F.; Chen, H.

doi:10.1107/S1600536810011165

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 66| Part 4| April 2010| Page o969

doi:10.1107/S1600536810011165

Open

access

1-[3-(4-Methoxyphenyl)-6-methyl-1,6-dihydro-1,2,4,5-tetrazin-1-yl]propanone

Zhen-zhen Yang,^a Feng Xu ^a ^* and Hong-yun Chen ^a

^aDepartment of Biological and Chemical Engineering, Taizhou Vocational and Technical college, Taizhou 318000, People's Republic of China
^*Correspondence e-mail: xufeng901@126.com

(Received 22 March 2010; accepted 24 March 2010; online 27 March 2010)

In the title compound, C₁₃H₁₆N₄O₂, the central tetrazine ring adopts an unsymmetrical boat conformation with the two C atoms as flagpoles. This compound can be considered as having homoaromaticity.

Related literature

For the biological activity of 1,2,4,5-tetrazine derivatives, see: Sauer (1996 ). For related structures, see: Jennison et al. (1986 ); Stam et al. (1982 ); Xu et al. (2010 ). For the structure–activity relationships of 1,6-dihydro-1,2,4,5-tetrazine derivatives, see: Hu et al. (2004 , 2005 ).

Experimental

Crystal data

C₁₃H₁₆N₄O₂
M_r = 260.30
Triclinic, $[P \overline 1]$
a = 8.345 (2) Å
b = 8.4898 (19) Å
c = 10.245 (3) Å
α = 113.232 (6)°
β = 99.820 (15)°
γ = 93.268 (11)°
V = 651.0 (3) Å³
Z = 2
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 93 K
0.50 × 0.37 × 0.23 mm

Data collection

Rigaku AFC10/Saturn724+ diffractometer
6410 measured reflections
2920 independent reflections
2207 reflections with I > 2σ(I)
R_int = 0.022

Refinement

R[F² > 2σ(F²)] = 0.036
wR(F²) = 0.081
S = 1.00
2920 reflections
175 parameters
H-atom parameters constrained
Δρ_max = 0.32 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Data collection: CrystalClear (Rigaku/MSC, 2008 ); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810011165/ci5067sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536810011165/ci5067Isup2.hkl

checkCIF report

Comment top

1,2,4,5-Tetrazine derivatives have high potential for biological activity, possessing a wide spectrum of antiviral and antitumor properties. They have been widely used in pesticides and herbicides (Sauer, 1996). Dihydro-1,2,4,5- tetrazine has four isomers, namely 1,2-, 1,4-, 1,6- and 3,6-dihydro-1,2,4,5- tetrazines. The 1,6-dihydro structures (Stam et al., 1982; Jennison et al., 1986) were found, by X-ray diffraction, to be homoaromatic. In continuation of our work on the structure-activity relationship of 1,6-dihydro-1,2,4,5-tetrazine derivatives (Hu et al., 2004,2005), we report here the crystal structure of the title compound (I) (Fig. 1).

In the tetrazine ring, atoms N1, N2, N3 and N4 are coplanar, while atoms C7 and C8 deviate from the plane by 0.239 (2) and 0.595 (2) Å, respectively. The N2/C7/N3 and N1/C8/N4 planes make dihedral angles of 21.0 (2)° and 42.2 (1)°, respectively, with the N1/N2/ N3/N4 plane, i.e. the tetrazine ring adopts an unsymmetrical boat conformation. The benzene ring make dihedral angle of 16.7 (1)° with the N1/N2/N3/N4 plane. Atom N1 is almost sp² hybridized due to the angles around it add up to 360.0 (2)°. In keeping with similar situations in 3-phenyl-6-ethyl-1,6-dihydro- 1,2,4,5-tetrazine (Stam et al., 1982), N-(2-methylphenyl)-3-phenyl-6-methyl-1,6-dihydro-1,2,4,5-tetrazine (Xu et al., 2010) and 1-acetyl-3,6-dimethyl-1,2,4,5-tetrazine (Jennison et al., 1986), it can be considered that the molecule is homoaromatic.

Related literature top

For the biological activity of 1,2,4,5-tetrazine derivatives, see: Sauer (1996). For related structures, see: Jennison et al. (1986); Stam et al. (1982); Xu et al. (2010). For the structure–activity relationship of 1,6-dihydro-1,2,4,5-tetrazine derivatives, see: Hu et al. (2004, 2005).

Experimental top

3-(4-Methoxyphenyl)-6-methyl-1,6-dihydro-1,2,4,5-tetrazine (3.0 mmol), chloroform (10 ml) and pyridine (0.25 ml,3.1 mmol) were mixed. Propionyl chloride(3.0 mmol) in chloroform (10 ml) was added dropwise with stirring at room temperature. After the starting, 1,6-dihydro-1,2,4,5-tetrazine was completely consumed (the reaction courses was monitored by TLC, dichloromethane system), evaporation of the chloroform, crude 1-propionyl-3-(4-methoxyphenyl)-6-methyl- 1,6-dihydro-1,2,4,5-tetrazine was obtained and purified by preparative thin-layer chromatography over silica gel GF254(2 mm) (dichloromethane-petroleum ether, 1:1). The solution of the compound in anhydrous ethanol was concentrated gradually at room temperature to afford single crystals, which was suitable for X-ray diffraction (m.p. 340–342 K).¹H NMR (CDCl₃) δ p.p.m.: 8.10 (d,2H, J = 8.8 Hz), 7.03 (d,2H, J = 8.8 Hz), 6.84 (q,1H, J = 6.4 Hz), 3.89 (s,3H), 2.95–3.05(m,1H,CH₂), 2.72–2.85(m,1H,CH₂),1.20(t,3H, J = 7.6 Hz), 1.04 (d,3H, J = 6.4 Hz).

Computing details top

Data collection: CrystalClear (Rigaku/MSC, 2008); cell refinement: CrystalClear (Rigaku/MSC, 2008); data reduction: CrystalClear (Rigaku/MSC, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top

Fig. 1. The molecular structure of the title compound, showing 50% probability displacement ellipsoids and the atomic numbering.

1-[3-(4-Methoxyphenyl)-6-methyl-1,6-dihydro-1,2,4,5-tetrazin-1-yl]propanone top

Crystal data top

C₁₃H₁₆N₄O₂	Z = 2
M_r = 260.30	F(000) = 276
Triclinic, P1	D_x = 1.328 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 8.345 (2) Å	Cell parameters from 1846 reflections
b = 8.4898 (19) Å	θ = 3.4–27.5°
c = 10.245 (3) Å	µ = 0.09 mm⁻¹
α = 113.232 (6)°	T = 93 K
β = 99.820 (15)°	Prism, red
γ = 93.268 (11)°	0.50 × 0.37 × 0.23 mm
V = 651.0 (3) Å³

Data collection top

Rigaku AFC10/Saturn724+ diffractometer	2207 reflections with I > 2σ(I)
Radiation source: Rotating Anode	R_int = 0.022
Graphite monochromator	θ_max = 27.5°, θ_min = 3.4°
Detector resolution: 28.5714 pixels mm^-1	h = −10→10
ϕ and ω scans	k = −11→11
6410 measured reflections	l = −13→12
2920 independent reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.036	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.081	H-atom parameters constrained
S = 1.00	w = 1/[σ²(F_o²) + (0.0282P)² + 0.16P] where P = (F_o² + 2F_c²)/3
2920 reflections	(Δ/σ)_max = 0.001
175 parameters	Δρ_max = 0.32 e Å⁻³
0 restraints	Δρ_min = −0.21 e Å⁻³

Crystal data top

C₁₃H₁₆N₄O₂	γ = 93.268 (11)°
M_r = 260.30	V = 651.0 (3) Å³
Triclinic, P1	Z = 2
a = 8.345 (2) Å	Mo Kα radiation
b = 8.4898 (19) Å	µ = 0.09 mm⁻¹
c = 10.245 (3) Å	T = 93 K
α = 113.232 (6)°	0.50 × 0.37 × 0.23 mm
β = 99.820 (15)°

Data collection top

Rigaku AFC10/Saturn724+ diffractometer	2207 reflections with I > 2σ(I)
6410 measured reflections	R_int = 0.022
2920 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.036	0 restraints
wR(F²) = 0.081	H-atom parameters constrained
S = 1.00	Δρ_max = 0.32 e Å⁻³
2920 reflections	Δρ_min = −0.21 e Å⁻³
175 parameters

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
O1	1.03435 (11)	0.17376 (12)	0.48191 (9)	0.0240 (2)
O2	0.16763 (10)	0.73207 (11)	0.11227 (10)	0.0240 (2)
N1	0.33360 (12)	0.55086 (13)	0.15664 (11)	0.0189 (2)
N2	0.47200 (12)	0.53199 (13)	0.23910 (11)	0.0186 (2)
N3	0.47565 (13)	0.27926 (13)	0.02813 (11)	0.0209 (2)
N4	0.34190 (13)	0.29167 (14)	−0.04264 (11)	0.0224 (2)
C1	0.69924 (15)	0.41266 (16)	0.41273 (13)	0.0193 (3)
H1	0.6425	0.5041	0.4631	0.023*
C2	0.82340 (15)	0.36341 (16)	0.49081 (13)	0.0198 (3)
H2	0.8512	0.4207	0.5938	0.024*
C3	0.90723 (14)	0.22979 (16)	0.41785 (13)	0.0179 (3)
C4	0.86288 (15)	0.14452 (16)	0.26693 (13)	0.0213 (3)
H4	0.9183	0.0516	0.2169	0.026*
C5	0.73919 (15)	0.19411 (16)	0.18974 (13)	0.0198 (3)
H5	0.7102	0.1351	0.0869	0.024*
C6	0.65589 (14)	0.33049 (15)	0.26145 (13)	0.0166 (3)
C7	0.52322 (15)	0.38258 (16)	0.18025 (13)	0.0174 (3)
C8	0.23071 (15)	0.39564 (16)	0.04682 (13)	0.0197 (3)
H8	0.1475	0.4295	−0.0163	0.024*
C9	0.14232 (16)	0.29206 (17)	0.11103 (14)	0.0229 (3)
H9A	0.2213	0.2738	0.1846	0.027*
H9B	0.0908	0.1798	0.0339	0.027*
H9C	0.0577	0.3556	0.1561	0.027*
C10	0.29499 (15)	0.71638 (16)	0.18095 (13)	0.0188 (3)
C11	0.41530 (15)	0.86447 (16)	0.29536 (13)	0.0211 (3)
H11A	0.5256	0.8546	0.2720	0.025*
H11B	0.4215	0.8583	0.3906	0.025*
C12	0.36603 (17)	1.03756 (17)	0.30564 (15)	0.0267 (3)
H12A	0.3573	1.0429	0.2109	0.032*
H12B	0.4492	1.1311	0.3782	0.032*
H12C	0.2598	1.0506	0.3345	0.032*
C13	1.07827 (16)	0.24669 (18)	0.63702 (14)	0.0246 (3)
H13A	1.1083	0.3722	0.6737	0.030*
H13B	1.1719	0.1957	0.6680	0.030*
H13C	0.9848	0.2222	0.6757	0.030*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0227 (5)	0.0325 (5)	0.0196 (5)	0.0115 (4)	0.0026 (4)	0.0134 (4)
O2	0.0192 (5)	0.0280 (5)	0.0261 (5)	0.0064 (4)	0.0008 (4)	0.0134 (4)
N1	0.0169 (5)	0.0206 (5)	0.0185 (5)	0.0019 (4)	−0.0015 (4)	0.0094 (4)
N2	0.0166 (5)	0.0217 (5)	0.0192 (5)	0.0028 (4)	0.0004 (4)	0.0114 (4)
N3	0.0206 (6)	0.0244 (6)	0.0174 (5)	0.0031 (4)	0.0013 (4)	0.0094 (5)
N4	0.0210 (6)	0.0256 (6)	0.0195 (5)	0.0030 (5)	0.0004 (5)	0.0096 (5)
C1	0.0184 (6)	0.0202 (6)	0.0187 (6)	0.0047 (5)	0.0037 (5)	0.0073 (5)
C2	0.0205 (6)	0.0224 (6)	0.0151 (6)	0.0019 (5)	0.0014 (5)	0.0073 (5)
C3	0.0147 (6)	0.0219 (6)	0.0200 (6)	0.0027 (5)	0.0020 (5)	0.0123 (5)
C4	0.0239 (7)	0.0220 (6)	0.0199 (6)	0.0088 (5)	0.0065 (5)	0.0091 (5)
C5	0.0227 (7)	0.0210 (6)	0.0144 (6)	0.0033 (5)	0.0022 (5)	0.0066 (5)
C6	0.0147 (6)	0.0182 (6)	0.0181 (6)	0.0001 (5)	0.0017 (5)	0.0096 (5)
C7	0.0157 (6)	0.0207 (6)	0.0169 (6)	0.0007 (5)	0.0026 (5)	0.0094 (5)
C8	0.0173 (6)	0.0218 (6)	0.0180 (6)	0.0017 (5)	−0.0015 (5)	0.0083 (5)
C9	0.0200 (6)	0.0238 (7)	0.0237 (7)	0.0003 (5)	0.0008 (5)	0.0103 (5)
C10	0.0188 (6)	0.0232 (6)	0.0184 (6)	0.0053 (5)	0.0057 (5)	0.0118 (5)
C11	0.0212 (7)	0.0218 (7)	0.0209 (7)	0.0048 (5)	0.0024 (5)	0.0101 (5)
C12	0.0261 (7)	0.0213 (7)	0.0332 (8)	0.0049 (5)	0.0047 (6)	0.0120 (6)
C13	0.0222 (7)	0.0329 (7)	0.0200 (7)	0.0043 (6)	−0.0006 (5)	0.0141 (6)

Geometric parameters (Å, º) top

O1—C3	1.3596 (14)	C5—C6	1.3995 (17)
O1—C13	1.4291 (15)	C5—H5	0.95
O2—C10	1.2155 (14)	C6—C7	1.4647 (16)
N1—N2	1.3669 (14)	C8—C9	1.5160 (17)
N1—C10	1.3941 (16)	C8—H8	1.00
N1—C8	1.4531 (15)	C9—H9A	0.98
N2—C7	1.3044 (16)	C9—H9B	0.98
N3—N4	1.2571 (14)	C9—H9C	0.98
N3—C7	1.4236 (16)	C10—C11	1.5015 (17)
N4—C8	1.4917 (16)	C11—C12	1.5169 (17)
C1—C2	1.3852 (17)	C11—H11A	0.99
C1—C6	1.3952 (17)	C11—H11B	0.99
C1—H1	0.95	C12—H12A	0.98
C2—C3	1.3911 (17)	C12—H12B	0.98
C2—H2	0.95	C12—H12C	0.98
C3—C4	1.3939 (17)	C13—H13A	0.98
C4—C5	1.3791 (17)	C13—H13B	0.98
C4—H4	0.95	C13—H13C	0.98

C3—O1—C13	118.23 (10)	N1—C8—H8	108.9
N2—N1—C10	119.47 (10)	N4—C8—H8	108.9
N2—N1—C8	118.20 (10)	C9—C8—H8	108.9
C10—N1—C8	122.32 (10)	C8—C9—H9A	109.5
C7—N2—N1	113.70 (10)	C8—C9—H9B	109.5
N4—N3—C7	120.02 (11)	H9A—C9—H9B	109.5
N3—N4—C8	115.25 (10)	C8—C9—H9C	109.5
C2—C1—C6	121.25 (12)	H9A—C9—H9C	109.5
C2—C1—H1	119.4	H9B—C9—H9C	109.5
C6—C1—H1	119.4	O2—C10—N1	119.15 (11)
C1—C2—C3	119.76 (11)	O2—C10—C11	124.57 (12)
C1—C2—H2	120.1	N1—C10—C11	116.27 (10)
C3—C2—H2	120.1	C10—C11—C12	111.53 (11)
O1—C3—C2	125.16 (11)	C10—C11—H11A	109.3
O1—C3—C4	115.33 (11)	C12—C11—H11A	109.3
C2—C3—C4	119.50 (11)	C10—C11—H11B	109.3
C5—C4—C3	120.48 (12)	C12—C11—H11B	109.3
C5—C4—H4	119.8	H11A—C11—H11B	108.0
C3—C4—H4	119.8	C11—C12—H12A	109.5
C4—C5—C6	120.64 (11)	C11—C12—H12B	109.5
C4—C5—H5	119.7	H12A—C12—H12B	109.5
C6—C5—H5	119.7	C11—C12—H12C	109.5
C1—C6—C5	118.35 (11)	H12A—C12—H12C	109.5
C1—C6—C7	120.72 (11)	H12B—C12—H12C	109.5
C5—C6—C7	120.91 (11)	O1—C13—H13A	109.5
N2—C7—N3	121.12 (11)	O1—C13—H13B	109.5
N2—C7—C6	121.13 (11)	H13A—C13—H13B	109.5
N3—C7—C6	116.68 (11)	O1—C13—H13C	109.5
N1—C8—N4	106.07 (9)	H13A—C13—H13C	109.5
N1—C8—C9	112.98 (10)	H13B—C13—H13C	109.5
N4—C8—C9	110.99 (10)

C10—N1—N2—C7	−159.83 (10)	N4—N3—C7—C6	164.47 (10)
C8—N1—N2—C7	20.73 (14)	C1—C6—C7—N2	18.43 (17)
C7—N3—N4—C8	−9.80 (16)	C5—C6—C7—N2	−163.36 (11)
C6—C1—C2—C3	0.09 (18)	C1—C6—C7—N3	−173.30 (11)
C13—O1—C3—C2	5.43 (17)	C5—C6—C7—N3	4.91 (16)
C13—O1—C3—C4	−175.44 (11)	N2—N1—C8—N4	−52.33 (13)
C1—C2—C3—O1	177.78 (11)	C10—N1—C8—N4	128.25 (11)
C1—C2—C3—C4	−1.32 (18)	N2—N1—C8—C9	69.47 (13)
O1—C3—C4—C5	−177.85 (11)	C10—N1—C8—C9	−109.95 (13)
C2—C3—C4—C5	1.33 (18)	N3—N4—C8—N1	45.04 (13)
C3—C4—C5—C6	−0.12 (18)	N3—N4—C8—C9	−78.02 (13)
C2—C1—C6—C5	1.10 (17)	N2—N1—C10—O2	−176.38 (11)
C2—C1—C6—C7	179.36 (11)	C8—N1—C10—O2	3.04 (17)
C4—C5—C6—C1	−1.09 (17)	N2—N1—C10—C11	2.16 (16)
C4—C5—C6—C7	−179.34 (11)	C8—N1—C10—C11	−178.43 (10)
N1—N2—C7—N3	20.73 (16)	O2—C10—C11—C12	−5.10 (17)
N1—N2—C7—C6	−171.53 (10)	N1—C10—C11—C12	176.46 (11)
N4—N3—C7—N2	−27.26 (17)

Experimental details

Crystal data
Chemical formula	C₁₃H₁₆N₄O₂
M_r	260.30
Crystal system, space group	Triclinic, P1
Temperature (K)	93
a, b, c (Å)	8.345 (2), 8.4898 (19), 10.245 (3)
α, β, γ (°)	113.232 (6), 99.820 (15), 93.268 (11)
V (Å³)	651.0 (3)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.50 × 0.37 × 0.23

Data collection
Diffractometer	Rigaku AFC10/Saturn724+ diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	6410, 2920, 2207
R_int	0.022
(sin θ/λ)_max (Å⁻¹)	0.649

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.036, 0.081, 1.00
No. of reflections	2920
No. of parameters	175
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.32, −0.21

Computer programs: CrystalClear (Rigaku/MSC, 2008), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Acknowledgements

The authors are grateful to the Science Foundation for Excellent Youth Scholars of the Department of Education of Zhejiang province and the Foundation of Taizhou Vocational and Technical College (grant No. 2010ZD08) for financial support.

References

Hu, W. X., Rao, G. W. & Sun, Y. Q. (2004). Bioorg. Med. Chem. Lett. 14, 1177–1181. Web of Science CSD CrossRef PubMed CAS Google Scholar
Hu, W. X., Shi, H. B., Yuan, Q. & Sun, Y. Q. (2005). J. Chem. Res. pp. 291–293. Google Scholar
Jennison, C. P. R., Mackay, D., Watson, K. N. & Taylor, N. J. (1986). J. Org. Chem. 51, 3043–3051. CSD CrossRef CAS Web of Science Google Scholar
Rigaku/MSC (2008). CrystalClear. Rigaku/MSC Inc., The Woodlands, Texas, USA. Google Scholar
Sauer, J. (1996). Comprehensive Heterocyclic Chemistry, 2nd ed., edited by A. J. Boulton, Vol. 6, pp. 901–955. Oxford: Elsevier. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Stam, C. H., Counotte-Potman, A. D. & Van der Plas, H. C. (1982). J. Org. Chem. 47, 2856–2858. CSD CrossRef CAS Google Scholar
Xu, F., Yang, Z. Z., Hu, W. X. & Xi, L. M. (2010). Chin. J. Org. Chem. 30, 260–265. CAS Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.