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

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.

Key indicators

• Single-crystal X-ray study
• T = 93 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.036
• wR factor = 0.081
• Data-to-parameter ratio = 16.7

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT910_ALERT_3_C Missing # of FCF Reflections Below Th(Min) .....          5
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.600         17
PLAT913_ALERT_3_C Missing # of Very Strong Reflections in FCF ....          1
PLAT912_ALERT_4_C Missing # of FCF Reflections Above STh/L=  0.600         34

Alert level G
PLAT793_ALERT_4_G The Model has Chirality at C8      (Verify) ....          R

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   4 ALERT level C = Check and explain
   1 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   3 ALERT type 3 Indicator that the structure quality may be low
   2 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

---

S1. Comment

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

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).

S2. Experimental

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).

S3. Refinement

H atoms were placed in calculated positions with N—H = 0.86 Å, C-H = 0.93 (aromatic) and 0.96 Å (methyl), and refined in riding model, with U_iso(H) = 1.2U_eq(C,N) and 1.5U_eq(C_methyl).

Computing details

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

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

Crystal data

C13H16N4O2	Z = 2
Mr = 260.30	F(000) = 276
Triclinic, P1	Dx = 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) Å^3

Data collection

Rigaku AFC10/Saturn724+ diffractometer	2207 reflections with I > 2σ(I)
Radiation source: Rotating Anode	Rint = 0.022
Graphite monochromator	θmax = 27.5°, θmin = 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

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

Special details

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 (Ų)

	x	y	z	Uiso*/Ueq
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 (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
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)

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)