Crystal structure of 3-amino-2-ethyl­quinazolin-4(3H)-one

The mol­ecule of the title compound, C₁₀H₁₁N₃O, is planar, including the ethyl group, as indicated by the N-C-C-C torsion angle of 1.5 (2)°. In the crystal, inversion-related mol­ecules are stacked along the a axis. Mol­ecules are oriented head-to-tail and display [pi]-[pi] inter­actions with a centroid-to-centroid distance of 3.6664 (8) Å. N-H...O hydrogen bonds between mol­ecules generate a `step' structure through formation of an R₂²(10) ring.

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.061
• wR factor = 0.196
• Data-to-parameter ratio = 13.7

checkCIF/PLATON results

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Alert level C
PLAT420_ALERT_2_C D-H Without Acceptor        N3     -   H3B    ..     Please Check
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.600          7 Report
PLAT913_ALERT_3_C Missing # of Very Strong Reflections in FCF ....          2 Note

Alert level G
PLAT072_ALERT_2_G SHELXL First  Parameter in WGHT Unusually Large.       0.15 Report
PLAT199_ALERT_1_G Reported _cell_measurement_temperature ..... (K)        293 Check
PLAT200_ALERT_1_G Reported   _diffrn_ambient_temperature ..... (K)        293 Check
PLAT910_ALERT_3_G Missing # of FCF Reflection(s) Below Th(Min) ...          2 Report
PLAT912_ALERT_4_G Missing # of FCF Reflections Above STh/L=  0.600         56 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
   5 ALERT level G = General information/check it is not something unexpected

   2 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   2 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

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S1. Introduction

Quinazolines have various inter­esting biological applications (Sasmal et al., 2012; Rohini et al., 2010). Quinazolin-4(3H)-ones synthesis involves use of various synthetic procedures. The most common starting materials are 2-amino­benzo­nitrile (Ma et al., 2013), 2-bromo­benzamides (Xu et al., 2012), isatoic anhydride (Adib et al., 2012), anthranilic acid (Kumar et al., 2011), methyl 2-amino­benzoate (Davies et al., 2010). Li­thia­tion of 2-n-alkyl- and 2-unsubstituted 3-acyl­amino­quinazolin-4(3H)-ones with a lithium reagent in tetra­hydro­furan at a low temperature followed by reactions of various electrophiles with the lithium reagents produced in-situ gave the corresponding 2-substituted derivatives in good to excellent yields (Smith et al., 2004, 1996, 1995). For the X-ray structures for related compounds, see: El-Hiti et al. (2014); Yang et al. (2009); Coogan et al. (1999).

S2. Experimental

S2.1. Synthesis and crystallization

A mixture of methyl 2-amino­benzoate and propionic anhydride (1.4 mole equivalents) was heated for 30 minutes at 105 °C. The mixture was cooled to 75 °C and diluted with ethanol (50 mL). Hydrazine monohydrate (10 mole equivalents) was added in a dropwise manner over 10 minutes and the mixture was refluxed for 1 h. The mixture was cooled to room temperature and the solvent was removed under reduced pressure. The residue obtained was purified by column chromatography (silica gel hexane/di­ethyl ether in 4:1 by volume) to give 3-amino-2-ethyl­quinazolin-4(3H)-one in 82% yield (Davies et al., 2010). Crystallization from a mixture of ethyl acetate and di­ethyl ether (1:2 by volume) gave colourless crystals of the title compound. The spectroscopic data for the title compound were identical with those reported (Davies et al., 2010).

S2.2. Refinement

H atoms were positioned geometrically and refined using a riding model with U_iso(H) constrained to be 1.2 times U_eq for the atom it is bonded to except for methyl groups where it was 1.5 times with free rotation about the C—C bond. The amide hydrogen atoms were located in the difference Fourier map and refined freely.

S3. Results and discussion

The asymmetric unit comprises a molecule of C₁₀H₁₁N₃O (Fig. 1). The molecule is planar, including the ethyl group as indicated by the N2—C1—C9—C10 torsion angle of 1.5 (2)°. Inversion related molecules are stacked along the a axis (Fig. 2). Molecules (x,y,z) and (1-x, -y,1-z) are oriented head-to-tail and display π - π inter­action with a centroid to centroid distance of 3.66 (2)Å. N—H···O hydrogen bonds between molecules (x,y,z) and (-x,-y+1, -z+1) generate a 'step' structure through formation of a R₂²(10) ring.

Related literature

For related compounds, see: Ma et al. (2013); Adib et al. (2012); Xu et al. (2012); Sasmal et al. (2012); Kumar et al. (2011); Rohini et al. (2010); Davies et al. (2010). For quinazolin-4(3H)-one ring-system modification through lithiation, see: Smith et al. (2004, 1996, 1995). For the crystal structures of related compounds, see: El-Hiti et al. (2014); Yang et al. (2009); Coogan et al. (1999).

Structure description

Quinazolines have various inter­esting biological applications (Sasmal et al., 2012; Rohini et al., 2010). Quinazolin-4(3H)-ones synthesis involves use of various synthetic procedures. The most common starting materials are 2-amino­benzo­nitrile (Ma et al., 2013), 2-bromo­benzamides (Xu et al., 2012), isatoic anhydride (Adib et al., 2012), anthranilic acid (Kumar et al., 2011), methyl 2-amino­benzoate (Davies et al., 2010). Li­thia­tion of 2-n-alkyl- and 2-unsubstituted 3-acyl­amino­quinazolin-4(3H)-ones with a lithium reagent in tetra­hydro­furan at a low temperature followed by reactions of various electrophiles with the lithium reagents produced in-situ gave the corresponding 2-substituted derivatives in good to excellent yields (Smith et al., 2004, 1996, 1995). For the X-ray structures for related compounds, see: El-Hiti et al. (2014); Yang et al. (2009); Coogan et al. (1999).

The asymmetric unit comprises a molecule of C₁₀H₁₁N₃O (Fig. 1). The molecule is planar, including the ethyl group as indicated by the N2—C1—C9—C10 torsion angle of 1.5 (2)°. Inversion related molecules are stacked along the a axis (Fig. 2). Molecules (x,y,z) and (1-x, -y,1-z) are oriented head-to-tail and display π - π inter­action with a centroid to centroid distance of 3.66 (2)Å. N—H···O hydrogen bonds between molecules (x,y,z) and (-x,-y+1, -z+1) generate a 'step' structure through formation of a R₂²(10) ring.

For related compounds, see: Ma et al. (2013); Adib et al. (2012); Xu et al. (2012); Sasmal et al. (2012); Kumar et al. (2011); Rohini et al. (2010); Davies et al. (2010). For quinazolin-4(3H)-one ring-system modification through lithiation, see: Smith et al. (2004, 1996, 1995). For the crystal structures of related compounds, see: El-Hiti et al. (2014); Yang et al. (2009); Coogan et al. (1999).

Synthesis and crystallization

A mixture of methyl 2-amino­benzoate and propionic anhydride (1.4 mole equivalents) was heated for 30 minutes at 105 °C. The mixture was cooled to 75 °C and diluted with ethanol (50 mL). Hydrazine monohydrate (10 mole equivalents) was added in a dropwise manner over 10 minutes and the mixture was refluxed for 1 h. The mixture was cooled to room temperature and the solvent was removed under reduced pressure. The residue obtained was purified by column chromatography (silica gel hexane/di­ethyl ether in 4:1 by volume) to give 3-amino-2-ethyl­quinazolin-4(3H)-one in 82% yield (Davies et al., 2010). Crystallization from a mixture of ethyl acetate and di­ethyl ether (1:2 by volume) gave colourless crystals of the title compound. The spectroscopic data for the title compound were identical with those reported (Davies et al., 2010).

Refinement details

H atoms were positioned geometrically and refined using a riding model with U_iso(H) constrained to be 1.2 times U_eq for the atom it is bonded to except for methyl groups where it was 1.5 times with free rotation about the C—C bond. The amide hydrogen atoms were located in the difference Fourier map and refined freely.

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, 2015); 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 asymmetric unit of C10H11N3O, with atom labels and 50% probability displacement ellipsoids for non-hydrogen atoms.
	Fig. 2. Crystal packing with hydrogen-bonding contacts shown as dotted lines.

3-Amino-2-ethylquinazolin-4(3H)-one

Crystal data

C10H11N3O	F(000) = 200
Mr = 189.22	Dx = 1.328 Mg m^−3
Triclinic, P1	Melting point: 398 K
a = 7.0230 (5) Å	Cu Kα radiation, λ = 1.54184 Å
b = 7.6198 (7) Å	Cell parameters from 1907 reflections
c = 9.7868 (6) Å	θ = 6.5–73.7°
α = 69.709 (7)°	µ = 0.73 mm^−1
β = 89.242 (5)°	T = 293 K
γ = 75.191 (7)°	Block, colourless
V = 473.27 (7) Å^3	0.38 × 0.20 × 0.08 mm
Z = 2

Data collection

Agilent SuperNova Dual Source diffractometer with an Atlas detector	1657 reflections with I > 2σ(I)
ω scans	Rint = 0.015
Absorption correction: gaussian (CrysAlis PRO; Agilent, 2014)	θmax = 73.9°, θmin = 6.5°
Tmin = 0.741, Tmax = 0.924	h = −8→8
3303 measured reflections	k = −9→8
1858 independent reflections	l = −10→12

Refinement

Refinement on F^2	0 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F^2 > 2σ(F^2)] = 0.061	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.196	w = 1/[σ^2(Fo^2) + (0.1458P)^2 + 0.021P] where P = (Fo^2 + 2Fc^2)/3
S = 1.07	(Δ/σ)max < 0.001
1858 reflections	Δρmax = 0.35 e Å^−3
136 parameters	Δρmin = −0.22 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	0.26318 (18)	−0.0469 (2)	0.59059 (14)	0.0441 (4)
C2	0.18669 (19)	0.2641 (2)	0.38779 (16)	0.0485 (4)
C3	0.21085 (18)	0.1504 (2)	0.29325 (14)	0.0455 (4)
C4	0.25874 (19)	−0.0513 (2)	0.35723 (14)	0.0453 (4)
C5	0.1873 (2)	0.2421 (3)	0.14073 (16)	0.0585 (4)
H5	0.1547	0.3768	0.0991	0.070*
C6	0.2123 (3)	0.1324 (3)	0.05335 (16)	0.0711 (5)
H6	0.1976	0.1923	−0.0478	0.085*
C7	0.2597 (3)	−0.0691 (3)	0.11692 (19)	0.0738 (5)
H7	0.2761	−0.1428	0.0571	0.089*
C8	0.2829 (3)	−0.1613 (2)	0.26567 (18)	0.0616 (5)
H8	0.3144	−0.2961	0.3059	0.074*
C9	0.2868 (2)	−0.1443 (2)	0.75358 (14)	0.0541 (4)
H9A	0.1644	−0.0989	0.7931	0.065*
H9B	0.3894	−0.1063	0.7928	0.065*
C10	0.3393 (3)	−0.3628 (3)	0.80379 (17)	0.0703 (5)
H10A	0.2385	−0.4018	0.7655	0.105*
H10B	0.3492	−0.4162	0.9087	0.105*
H10C	0.4636	−0.4096	0.7691	0.105*
N1	0.21763 (16)	0.15389 (17)	0.53566 (13)	0.0475 (4)
N2	0.28333 (17)	−0.14907 (17)	0.50721 (12)	0.0479 (4)
N3	0.2043 (3)	0.2510 (2)	0.63756 (16)	0.0683 (5)
O1	0.14455 (19)	0.44171 (16)	0.34527 (14)	0.0704 (4)
H3A	0.080 (3)	0.329 (3)	0.630 (2)	0.079 (6)*
H3B	0.292 (4)	0.328 (5)	0.609 (3)	0.111 (9)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0404 (6)	0.0519 (7)	0.0392 (7)	−0.0129 (5)	0.0037 (5)	−0.0148 (5)
C2	0.0494 (7)	0.0445 (7)	0.0510 (8)	−0.0144 (5)	0.0072 (5)	−0.0151 (6)
C3	0.0457 (7)	0.0494 (8)	0.0400 (7)	−0.0154 (5)	0.0048 (5)	−0.0122 (6)
C4	0.0494 (7)	0.0498 (7)	0.0403 (7)	−0.0174 (5)	0.0067 (5)	−0.0173 (6)
C5	0.0588 (8)	0.0659 (9)	0.0424 (8)	−0.0201 (7)	0.0043 (6)	−0.0066 (6)
C6	0.0789 (11)	0.0986 (14)	0.0375 (7)	−0.0316 (10)	0.0073 (7)	−0.0206 (8)
C7	0.0926 (12)	0.0963 (13)	0.0520 (9)	−0.0368 (10)	0.0153 (8)	−0.0421 (9)
C8	0.0781 (10)	0.0627 (9)	0.0559 (9)	−0.0253 (8)	0.0121 (7)	−0.0312 (7)
C9	0.0482 (7)	0.0729 (9)	0.0367 (7)	−0.0158 (6)	0.0031 (5)	−0.0142 (6)
C10	0.0729 (10)	0.0711 (10)	0.0464 (8)	−0.0147 (8)	−0.0002 (7)	0.0010 (7)
N1	0.0511 (6)	0.0505 (7)	0.0451 (7)	−0.0128 (5)	0.0045 (4)	−0.0227 (5)
N2	0.0556 (7)	0.0458 (6)	0.0408 (7)	−0.0147 (5)	0.0055 (5)	−0.0129 (5)
N3	0.0801 (10)	0.0733 (9)	0.0628 (9)	−0.0136 (8)	0.0049 (7)	−0.0428 (7)
O1	0.0890 (8)	0.0436 (6)	0.0744 (8)	−0.0149 (5)	0.0118 (6)	−0.0182 (5)

Geometric parameters (Å, º)

C1—N2	1.2937 (19)	C6—H6	0.9300
C1—N1	1.3840 (19)	C7—C8	1.370 (2)
C1—C9	1.4986 (18)	C7—H7	0.9300
C2—O1	1.2245 (18)	C8—H8	0.9300
C2—N1	1.3853 (19)	C9—C10	1.508 (2)
C2—C3	1.453 (2)	C9—H9A	0.9700
C3—C4	1.394 (2)	C9—H9B	0.9700
C3—C5	1.4027 (19)	C10—H10A	0.9600
C4—N2	1.3862 (18)	C10—H10B	0.9600
C4—C8	1.406 (2)	C10—H10C	0.9600
C5—C6	1.370 (3)	N1—N3	1.4227 (16)
C5—H5	0.9300	N3—H3A	0.91 (2)
C6—C7	1.392 (3)	N3—H3B	0.93 (3)
N2—C1—N1	122.58 (12)	C7—C8—H8	120.1
N2—C1—C9	120.35 (13)	C4—C8—H8	120.1
N1—C1—C9	117.07 (12)	C1—C9—C10	113.52 (13)
O1—C2—N1	120.90 (14)	C1—C9—H9A	108.9
O1—C2—C3	124.96 (14)	C10—C9—H9A	108.9
N1—C2—C3	114.14 (12)	C1—C9—H9B	108.9
C4—C3—C5	120.75 (14)	C10—C9—H9B	108.9
C4—C3—C2	118.64 (13)	H9A—C9—H9B	107.7
C5—C3—C2	120.61 (14)	C9—C10—H10A	109.5
N2—C4—C3	123.07 (12)	C9—C10—H10B	109.5
N2—C4—C8	118.33 (13)	H10A—C10—H10B	109.5
C3—C4—C8	118.60 (14)	C9—C10—H10C	109.5
C6—C5—C3	119.79 (16)	H10A—C10—H10C	109.5
C6—C5—H5	120.1	H10B—C10—H10C	109.5
C3—C5—H5	120.1	C1—N1—C2	123.65 (12)
C5—C6—C7	119.60 (14)	C1—N1—N3	117.72 (12)
C5—C6—H6	120.2	C2—N1—N3	118.63 (13)
C7—C6—H6	120.2	C1—N2—C4	117.90 (12)
C8—C7—C6	121.48 (16)	N1—N3—H3A	110.0 (14)
C8—C7—H7	119.3	N1—N3—H3B	104.8 (18)
C6—C7—H7	119.3	H3A—N3—H3B	109 (2)
C7—C8—C4	119.78 (16)
O1—C2—C3—C4	−179.89 (12)	N2—C1—C9—C10	1.5 (2)
N1—C2—C3—C4	0.7 (2)	N1—C1—C9—C10	−179.13 (11)
O1—C2—C3—C5	0.4 (2)	N2—C1—N1—C2	0.9 (2)
N1—C2—C3—C5	−178.98 (10)	C9—C1—N1—C2	−178.40 (10)
C5—C3—C4—N2	−179.87 (11)	N2—C1—N1—N3	−178.35 (11)
C2—C3—C4—N2	0.4 (2)	C9—C1—N1—N3	2.30 (19)
C5—C3—C4—C8	0.0 (2)	O1—C2—N1—C1	179.18 (12)
C2—C3—C4—C8	−179.75 (11)	C3—C2—N1—C1	−1.4 (2)
C4—C3—C5—C6	−0.3 (2)	O1—C2—N1—N3	−1.5 (2)
C2—C3—C5—C6	179.44 (12)	C3—C2—N1—N3	177.87 (11)
C3—C5—C6—C7	0.4 (3)	N1—C1—N2—C4	0.3 (2)
C5—C6—C7—C8	−0.2 (3)	C9—C1—N2—C4	179.64 (10)
C6—C7—C8—C4	−0.1 (3)	C3—C4—N2—C1	−1.0 (2)
N2—C4—C8—C7	−179.95 (14)	C8—C4—N2—C1	179.19 (11)
C3—C4—C8—C7	0.2 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3A···O1^i	0.91 (2)	2.12 (2)	2.974 (2)	157.1 (19)

Symmetry code: (i) −x, −y+1, −z+1.