Crystal structure of 4-meth­oxy­quinazoline

The title compound, C₉H₈N₂O, is almost planar, with the C atom of the meth­oxy group deviating from the mean plane of the quinazoline ring system (r.m.s. deviation = 0.011 Å) by 0.068 (4) Å. In the crystal, mol­ecules form [pi]-[pi] stacks parallel to the b-axis direction [centroid-centroid separation = 3.5140 (18) Å], leading to a herringbone packing arrangement.

Key indicators

• Single-crystal X-ray study
• T = 150 K
• Mean [sigma](C-C) = 0.005 Å
• R factor = 0.054
• wR factor = 0.159
• Data-to-parameter ratio = 13.0

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT340_ALERT_3_C Low Bond Precision on  C-C Bonds ...............     0.0046 Ang.
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.600          3 Report
PLAT915_ALERT_3_C Low Friedel Pair Coverage ......................         86 %

Alert level G
PLAT072_ALERT_2_G SHELXL First  Parameter in WGHT Unusually Large.       0.11 Report
PLAT912_ALERT_4_G Missing # of FCF Reflections Above STh/L=  0.600         21 Note

   0 ALERT level A = Most likely a serious problem - resolve or explain
   0 ALERT level B = A potentially serious problem, consider carefully
   3 ALERT level C = Check. Ensure it is not caused by an omission or oversight
   2 ALERT level G = General information/check it is not something unexpected

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 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
   1 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

---

S1. Structural commentary

Copper-catalyzed processes offer convenient approaches to various quinazoline derivatives starting from (2-bromo­phenyl)­methyl­amines, 2-amino­benzyl­amines or 2-bromo­benzo­nitriles (Wang et al., 2010; Yang et al., 2010; Han et al., 2012). For ring substitution and modification of 4-meth­oxy­quinazolines, see: Smith et al. (2005). 4-Meth­oxy­quinazoline was synthesized in 81% yield from reaction of quinazoline-4(3H)-thione with iodo­methane in aqueous methanol containing potassium hydroxide at room temperature for 24 h (Bogert & May, 1909). For the X-ray structures for related compounds, see Alshammari et al. (2014); Derabli et al. (2013); Gao et al. (2012); Huang & Tan (2012); Jia et al. (2011).

The asymmetric unit consists of one molecule of C₉H₈N₂O (Fig. 1). The molecule is almost planar apart from the methyl hydrogen atoms, with C9 deviating from the least squares plane of the quinazoline group by 0.068 (4)Å. The molecules form π-π stacks parallel to the b-axis leading to a herring-bone pattern in the crystal structure (Fig. 2).

S2. Synthesis and crystallization

To a solution of quinazoline-4(3H)-thione (4.9 g, 30.2 mmol) in a 1:1 mixture of methanol and water (50 ml) containing potassium hydroxide (3.0 g), was added iodo­methane (5.7 g, 40.1 mmol) at room temperature. The reaction mixture was stirred for 24 h, then methanol was removed under reduced pressure and the remaining aqueous layer was extracted with di­ethyl ether (2 × 20 ml). The organic layer was separated, washed with water (2 × 10 ml), dried (MgSO₄), and evaporated under reduced pressure. The residue obtained was purified by column chromatography (silica gel, di­ethyl ether–hexane, 1:1) to give 4-meth­oxy­quinazoline (3.9 g, 24.4 mmol, 81%) as a white solid. Crystallization from a mixture of ethyl acetate and di­ethyl ether (1:3 by volume) gave the title compound as colorless needles. mp 34–35°C [lit. 35.4°C; Bogert & May, (1909)]. ¹H NMR (400 MHz, CDCl₃, δ p.p.m.): 8.77 (s, 1 H, H-2), 8.08 (dd, J = 1, 8 Hz, 1 H, H-8), 7.88 (dd, J = 1,8 Hz, 1 H, H-5), 7.76 (app. dt, J = 1, 8 Hz, 1 H, H-7), 7.50 (app. t, J = 8 Hz, 1 H, H-6), 4.13 (s, 3 H, OCH₃). ¹³C NMR (100 MHz, CDCl₃, δ, p.p.m.): 167.4 (s, C-4), 154.6 (d, C-2), 151.1 (s, C-8a), 133.8 (d, C-7), 128.0 (d, C-8), 127.3 (d, C-5), 123.8 (d, C-6), 116.9 (s, C-4a), 54.6 (q, OCH₃). EI–MS (m/z, %): 160 (M⁺, 68), 131 (32), 130 (30), 103 (100), 90 (22), 76 (28), 63 (21). CI–MS (m/z, %): 161 (MH⁺, 100). HRMS (CI): calculated for C₉H₉N₂O [MH] 161.0709; found, 161.0708.

S3. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1.

Related literature

For the synthesis of quinazoline derivatives, see: Bogert & May (1909); Smith et al. (2005); Wang et al. (2010); Yang et al. (2010); Han et al. (2012). For the crystal structures of related compounds, see Alshammari et al. (2014); Derabli et al. (2013); Gao et al. (2012); Huang & Tan (2012); Jia et al. (2011).

Computing details

Data collection: CrysAlis PRO (Agilent, 2014); cell refinement: CrysAlis PRO (Agilent, 2014); data reduction: CrysAlis PRO (Agilent, 2014); program(s) used to solve structure: SHELXS2013 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: WinGX (Farrugia, 2012) and CHEMDRAW Ultra (Cambridge Soft, 2001).

Figures

Fig. 1. The title molecule showing 50% probability displacement ellipsoids.

Fig. 2. Crystal packing viewed down the a axis.

4-Methoxyquinazoline

Crystal data

C9H8N2O	F(000) = 168
Mr = 160.17	Dx = 1.389 Mg m^−3
Monoclinic, P21	Cu Kα radiation, λ = 1.54184 Å
a = 6.9590 (6) Å	Cell parameters from 1311 reflections
b = 4.0517 (3) Å	θ = 3.3–67.7°
c = 13.5858 (12) Å	µ = 0.77 mm^−1
β = 91.754 (8)°	T = 150 K
V = 382.88 (6) Å^3	Needle, colourless
Z = 2	0.57 × 0.12 × 0.08 mm

Data collection

Agilent SuperNova (Dual, Cu at zero, Atlas) diffractometer	1311 reflections with I > 2σ(I)
ω scans	Rint = 0.040
Absorption correction: gaussian (CrysAlis PRO; Agilent, 2014)	θmax = 74.6°, θmin = 3.3°
Tmin = 0.641, Tmax = 0.895	h = −8→8
2166 measured reflections	k = −4→5
1435 independent reflections	l = −11→16

Refinement

Refinement on F^2	1 restraint
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.054	H-atom parameters constrained
wR(F^2) = 0.159	w = 1/[σ^2(Fo^2) + (0.110P)^2 + 0.0483P] where P = (Fo^2 + 2Fc^2)/3
S = 1.08	(Δ/σ)max < 0.001
1435 reflections	Δρmax = 0.24 e Å^−3
110 parameters	Δρmin = −0.23 e Å^−3

Special details

Experimental. Absorption correction: CrysAlisPro, Agilent Technologies, Version 1.171.37.33 (release 27-03-2014 CrysAlis171 .NET) (compiled Mar 27 2014,17:12:48) Numerical absorption correction based on gaussian integration over a multifaceted crystal model Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm.

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

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
C1	−0.1179 (5)	0.8736 (9)	0.7198 (2)	0.0403 (8)
H1	−0.2391	0.7831	0.7078	0.048*
C2	0.1829 (4)	0.9515 (7)	0.6650 (2)	0.0330 (7)
C3	0.2338 (4)	1.1283 (7)	0.7527 (2)	0.0330 (7)
C4	0.0855 (4)	1.1608 (7)	0.8208 (2)	0.0349 (7)
C5	0.1265 (5)	1.3290 (8)	0.9096 (3)	0.0426 (8)
H5	0.0308	1.3526	0.9554	0.051*
C6	0.3034 (5)	1.4570 (8)	0.9292 (2)	0.0431 (8)
H6	0.3276	1.5675	0.9883	0.052*
C7	0.4520 (5)	1.4246 (10)	0.8608 (3)	0.0411 (7)
H7	0.5731	1.5127	0.8751	0.049*
C8	0.4169 (5)	1.2640 (7)	0.7739 (2)	0.0364 (7)
H8	0.5138	1.2440	0.7287	0.044*
C9	0.2674 (5)	0.7530 (9)	0.5079 (3)	0.0433 (8)
H9A	0.1669	0.8757	0.4745	0.065*
H9B	0.2226	0.5340	0.5215	0.065*
H9C	0.3771	0.7410	0.4669	0.065*
N1	−0.0945 (4)	1.0312 (7)	0.8028 (2)	0.0412 (7)
N2	0.0121 (4)	0.8237 (6)	0.6479 (2)	0.0378 (7)
O1	0.3208 (3)	0.9159 (6)	0.59930 (16)	0.0381 (6)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0293 (13)	0.0351 (16)	0.0562 (19)	−0.0019 (13)	−0.0033 (12)	0.0037 (15)
C2	0.0334 (14)	0.0278 (15)	0.0374 (15)	0.0007 (13)	−0.0059 (11)	0.0054 (12)
C3	0.0310 (14)	0.0268 (14)	0.0408 (15)	0.0051 (11)	−0.0036 (12)	0.0073 (12)
C4	0.0356 (16)	0.0283 (15)	0.0405 (16)	0.0033 (13)	−0.0020 (12)	0.0071 (13)
C5	0.0473 (18)	0.0386 (17)	0.0423 (18)	0.0053 (15)	0.0052 (14)	0.0023 (15)
C6	0.0528 (19)	0.0364 (18)	0.0396 (17)	0.0030 (15)	−0.0075 (14)	−0.0008 (14)
C7	0.0367 (14)	0.0373 (16)	0.0486 (17)	0.0006 (14)	−0.0104 (12)	0.0020 (14)
C8	0.0327 (14)	0.0346 (16)	0.0416 (18)	0.0033 (13)	−0.0051 (12)	0.0057 (14)
C9	0.0445 (17)	0.0437 (18)	0.0414 (17)	0.0051 (16)	−0.0052 (13)	−0.0020 (14)
N1	0.0336 (13)	0.0372 (14)	0.0528 (17)	−0.0001 (11)	0.0023 (11)	0.0013 (13)
N2	0.0346 (13)	0.0336 (14)	0.0446 (14)	−0.0001 (10)	−0.0084 (11)	0.0044 (11)
O1	0.0346 (10)	0.0430 (13)	0.0367 (11)	−0.0004 (11)	−0.0016 (8)	−0.0004 (10)

Geometric parameters (Å, º)

C1—N1	1.302 (4)	C5—H5	0.9300
C1—N2	1.366 (4)	C6—C7	1.417 (5)
C1—H1	0.9300	C6—H6	0.9300
C2—N2	1.311 (4)	C7—C8	1.363 (5)
C2—O1	1.338 (4)	C7—H7	0.9300
C2—C3	1.425 (4)	C8—H8	0.9300
C3—C8	1.409 (4)	C9—O1	1.445 (4)
C3—C4	1.413 (4)	C9—H9A	0.9600
C4—N1	1.373 (4)	C9—H9B	0.9600
C4—C5	1.407 (5)	C9—H9C	0.9600
C5—C6	1.355 (5)
N1—C1—N2	128.6 (3)	C7—C6—H6	119.6
N1—C1—H1	115.7	C8—C7—C6	119.8 (3)
N2—C1—H1	115.7	C8—C7—H7	120.1
N2—C2—O1	120.3 (3)	C6—C7—H7	120.1
N2—C2—C3	123.2 (3)	C7—C8—C3	120.0 (3)
O1—C2—C3	116.5 (2)	C7—C8—H8	120.0
C8—C3—C4	120.2 (3)	C3—C8—H8	120.0
C8—C3—C2	124.6 (3)	O1—C9—H9A	109.5
C4—C3—C2	115.2 (3)	O1—C9—H9B	109.5
N1—C4—C5	119.8 (3)	H9A—C9—H9B	109.5
N1—C4—C3	121.9 (3)	O1—C9—H9C	109.5
C5—C4—C3	118.2 (3)	H9A—C9—H9C	109.5
C6—C5—C4	120.9 (3)	H9B—C9—H9C	109.5
C6—C5—H5	119.6	C1—N1—C4	115.5 (3)
C4—C5—H5	119.6	C2—N2—C1	115.6 (3)
C5—C6—C7	120.8 (3)	C2—O1—C9	116.9 (2)
C5—C6—H6	119.6