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

In the title mol­ecule, C₁₁H₁₃N₃O, the propyl group is almost perpendicular to the quinazolin-4(3H)-one mean plane, making a dihedral angle of 88.98 (9)°. In the crystal, mol­ecules related by an inversion centre are paired via [pi]-[pi] overlap, indicated by the short distances of 3.616 (5) and 3.619 (5) Å between the centroids of the aromatic rings of neighbouring mol­ecules. Inter­molecular N-H...N and N-H...O hydrogen bonds form R₆⁶(30) rings and C(5) chains, respectively, generating a three-dimensional network. Weak C-H...O inter­actions are also observed.

Key indicators

• Single-crystal X-ray study
• T = 296 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.040
• wR factor = 0.120
• Data-to-parameter ratio = 14.6

checkCIF/PLATON results

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Alert level C
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.600          5 Report

Alert level G
PLAT912_ALERT_4_G Missing # of FCF Reflections Above STh/L=  0.600         59 Note
PLAT951_ALERT_5_G Calculated (ThMax) and CIF-Reported Kmax Differ           4 Units

   0 ALERT level A = Most likely a serious problem - resolve or explain
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   1 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

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S1. Introduction

Quinazolines have a range of biological activities such as anti-cancer (Chandregowda et al., 2009), anti-bacterial (Rohini et al., 2010), anti-inflammatory (Alagarsamy et al., 2007), anti-obesity (Sasmal et al., 2012) and anti-spasm (Gupta et al., 2008). Synthesis of quinazolin-4(3H)-ones involves use of various synthetic procedures. Recent examples involve reactions of 2-amino­benzo­nitrile with carbon dioxide in water (Ma et al., 2013), 2-bromo­benzamides with formamide catalysed by CuI and 4-hy­droxy-l-proline (Xu et al., 2012) and isatoic anhydride, benzyl halides and primary amines under mild Kornblum conditions (Adib et al., 2012). 2-Alkyl-3-amino­quinazolin-4(3H)-ones can be obtained from reactions of 2-alkyl-4H-3,1-benzoxazin-4-ones with hydrazine hydrate (Kumar et al., 2011). Li­thia­tion of 2-unsubstituted and 2-n-alkyl-3-acyl­amino­quinazolin-4(3H)-ones followed by reactions of the lithium reagents produced in-situ with electrophiles gave the corresponding substituted derivatives in high 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

3-Amino-2-propyl­quinazolin-4(3H)-one was obtained in 82% yield by reaction of 2-propyl-4H-3,1-benzoxazin-4-one with excess hydrazine hydrate (three mole equivalents) in methanol under reflux conditions for 3 h (Kumar et al., 2011). Crystallization from ethanol gave colourless crystals of the title compound. The NMR and mass spectral data for the title compound were identical with those reported (Kumar et al., 2011).

S2.2. Refinement

The amino hydrogen atoms were located in the difference Fourier map and refined freely. The rest of the 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.

S3. Results and discussion

In the title compound (I) (Fig. 1), the propyl group is perpendicular to the quinazolin-4(3H)-one group with a dihedral angle of 88.98 (9)° between the least-squares planes of the two groups. In the crystal (Fig. 2), π–π overlap is observed for paired molecules with a centroid-centroid distance of ca 3.62 (1) Å between the benzene and pyrimidine rings of parallel 3-amino­quinazolin-4(3H)-one groups. N—H···N hydrogen bonds form R₆⁶(30) rings and N—H···O form C(5) chains to generate three dimensional packing. Weak C—H···O contacts (C(5)) are also observed.

Related literature

For biological applications of related compounds, see: Sasmal et al. (2012); Rohini et al. (2010); Chandregowda et al. (2009); Gupta et al. (2008); Alagarsamy et al. (2007). For thesynthesis of substituted quinazolin-4(3H)-ones, see: Ma et al. (2013); Adib et al. (2012); Xu et al. (2012); Kumar et al. (2011). For modification of the quinazolin-4(3H)-one ring system via lithiation, see: 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).

Structure description

Quinazolines have a range of biological activities such as anti-cancer (Chandregowda et al., 2009), anti-bacterial (Rohini et al., 2010), anti-inflammatory (Alagarsamy et al., 2007), anti-obesity (Sasmal et al., 2012) and anti-spasm (Gupta et al., 2008). Synthesis of quinazolin-4(3H)-ones involves use of various synthetic procedures. Recent examples involve reactions of 2-amino­benzo­nitrile with carbon dioxide in water (Ma et al., 2013), 2-bromo­benzamides with formamide catalysed by CuI and 4-hy­droxy-l-proline (Xu et al., 2012) and isatoic anhydride, benzyl halides and primary amines under mild Kornblum conditions (Adib et al., 2012). 2-Alkyl-3-amino­quinazolin-4(3H)-ones can be obtained from reactions of 2-alkyl-4H-3,1-benzoxazin-4-ones with hydrazine hydrate (Kumar et al., 2011). Li­thia­tion of 2-unsubstituted and 2-n-alkyl-3-acyl­amino­quinazolin-4(3H)-ones followed by reactions of the lithium reagents produced in-situ with electrophiles gave the corresponding substituted derivatives in high 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).

In the title compound (I) (Fig. 1), the propyl group is perpendicular to the quinazolin-4(3H)-one group with a dihedral angle of 88.98 (9)° between the least-squares planes of the two groups. In the crystal (Fig. 2), π–π overlap is observed for paired molecules with a centroid-centroid distance of ca 3.62 (1) Å between the benzene and pyrimidine rings of parallel 3-amino­quinazolin-4(3H)-one groups. N—H···N hydrogen bonds form R₆⁶(30) rings and N—H···O form C(5) chains to generate three dimensional packing. Weak C—H···O contacts (C(5)) are also observed.

For biological applications of related compounds, see: Sasmal et al. (2012); Rohini et al. (2010); Chandregowda et al. (2009); Gupta et al. (2008); Alagarsamy et al. (2007). For thesynthesis of substituted quinazolin-4(3H)-ones, see: Ma et al. (2013); Adib et al. (2012); Xu et al. (2012); Kumar et al. (2011). For modification of the quinazolin-4(3H)-one ring system via lithiation, see: 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).

Synthesis and crystallization

3-Amino-2-propyl­quinazolin-4(3H)-one was obtained in 82% yield by reaction of 2-propyl-4H-3,1-benzoxazin-4-one with excess hydrazine hydrate (three mole equivalents) in methanol under reflux conditions for 3 h (Kumar et al., 2011). Crystallization from ethanol gave colourless crystals of the title compound. The NMR and mass spectral data for the title compound were identical with those reported (Kumar et al., 2011).

Refinement details

The amino hydrogen atoms were located in the difference Fourier map and refined freely. The rest of the 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.

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. View of (I) showing the atom labels and 50% probability displacement ellipsoids.
	Fig. 2. Crystal packing viewed along the c axis.

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

Crystal data

C11H13N3O	Dx = 1.246 Mg m^−3
Mr = 203.24	Cu Kα radiation, λ = 1.54184 Å
Trigonal, R3:H	Cell parameters from 2040 reflections
a = 24.1525 (5) Å	θ = 5.0–74.1°
c = 9.6500 (2) Å	µ = 0.67 mm^−1
V = 4875.1 (2) Å^3	T = 296 K
Z = 18	Block, colourless
F(000) = 1944	0.34 × 0.25 × 0.19 mm

Data collection

Agilent SuperNova Dual Source diffractometer with an Atlas detector	1913 reflections with I > 2σ(I)
ω scans	Rint = 0.013
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2014)	θmax = 74.1°, θmin = 3.7°
Tmin = 0.975, Tmax = 0.984	h = −21→30
3734 measured reflections	k = −26→18
2136 independent reflections	l = −11→10

Refinement

Refinement on F^2	Hydrogen site location: mixed
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.040	w = 1/[σ^2(Fo^2) + (0.0637P)^2 + 1.4157P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.120	(Δ/σ)max < 0.001
S = 1.06	Δρmax = 0.17 e Å^−3
2136 reflections	Δρmin = −0.15 e Å^−3
146 parameters	Extinction correction: SHELXL2013 (Sheldrick, 2015), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
0 restraints	Extinction coefficient: 0.00114 (10)

Special details

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	0.23343 (6)	0.11120 (6)	0.00970 (12)	0.0453 (3)
C2	0.28221 (6)	0.06090 (5)	0.14259 (13)	0.0457 (3)
C3	0.27352 (5)	0.09197 (5)	0.26270 (12)	0.0440 (3)
C4	0.24674 (6)	0.13113 (6)	0.24439 (12)	0.0450 (3)
C5	0.29168 (6)	0.08293 (7)	0.39466 (14)	0.0535 (3)
H5	0.3089	0.0563	0.4064	0.064*
C6	0.28403 (7)	0.11345 (8)	0.50654 (14)	0.0618 (4)
H6	0.2958	0.1074	0.5946	0.074*
C7	0.25865 (8)	0.15367 (8)	0.48822 (14)	0.0630 (4)
H7	0.2544	0.1749	0.5643	0.076*
C8	0.23997 (7)	0.16241 (7)	0.36013 (14)	0.0567 (3)
H8	0.2228	0.1891	0.3498	0.068*
C9	0.20961 (7)	0.11882 (6)	−0.12831 (14)	0.0546 (3)
H9A	0.2357	0.1157	−0.2009	0.066*
H9B	0.2141	0.1610	−0.1337	0.066*
C10	0.13977 (8)	0.06846 (8)	−0.15299 (18)	0.0697 (4)
H10A	0.1359	0.0265	−0.1554	0.084*
H10B	0.1141	0.0691	−0.0763	0.084*
C11	0.11417 (10)	0.07946 (12)	−0.2869 (2)	0.0996 (7)
H11A	0.1222	0.1226	−0.2894	0.149*
H11B	0.0690	0.0503	−0.2924	0.149*
H11C	0.1351	0.0724	−0.3639	0.149*
N1	0.25905 (5)	0.07168 (5)	0.01918 (10)	0.0447 (3)
N2	0.22710 (5)	0.14035 (5)	0.11608 (11)	0.0486 (3)
N3	0.26483 (7)	0.04247 (6)	−0.10370 (12)	0.0550 (3)
O1	0.30729 (5)	0.02780 (5)	0.14300 (11)	0.0625 (3)
H3A	0.2287 (9)	0.0033 (10)	−0.1045 (18)	0.069 (5)*
H3B	0.2972 (10)	0.0370 (9)	−0.087 (2)	0.069 (5)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0447 (6)	0.0405 (6)	0.0464 (6)	0.0179 (5)	−0.0012 (5)	0.0016 (4)
C2	0.0425 (6)	0.0391 (5)	0.0518 (7)	0.0177 (5)	−0.0073 (5)	−0.0046 (5)
C3	0.0400 (6)	0.0401 (6)	0.0462 (6)	0.0158 (5)	−0.0028 (4)	−0.0002 (4)
C4	0.0441 (6)	0.0438 (6)	0.0439 (6)	0.0196 (5)	0.0021 (4)	0.0025 (4)
C5	0.0514 (7)	0.0554 (7)	0.0518 (7)	0.0253 (6)	−0.0067 (5)	0.0018 (5)
C6	0.0650 (8)	0.0724 (9)	0.0432 (7)	0.0307 (7)	−0.0043 (6)	0.0016 (6)
C7	0.0736 (9)	0.0695 (9)	0.0450 (7)	0.0350 (7)	0.0067 (6)	−0.0039 (6)
C8	0.0653 (8)	0.0603 (8)	0.0504 (7)	0.0358 (7)	0.0057 (6)	−0.0003 (6)
C9	0.0631 (8)	0.0512 (7)	0.0486 (7)	0.0279 (6)	−0.0060 (5)	0.0022 (5)
C10	0.0616 (9)	0.0732 (10)	0.0692 (9)	0.0300 (8)	−0.0086 (7)	0.0004 (7)
C11	0.0780 (12)	0.1036 (15)	0.0986 (15)	0.0315 (11)	−0.0333 (11)	0.0058 (12)
N1	0.0467 (5)	0.0401 (5)	0.0434 (5)	0.0189 (4)	−0.0036 (4)	−0.0052 (4)
N2	0.0546 (6)	0.0488 (6)	0.0462 (6)	0.0287 (5)	0.0001 (4)	0.0023 (4)
N3	0.0630 (7)	0.0499 (6)	0.0494 (6)	0.0263 (6)	−0.0042 (5)	−0.0120 (4)
O1	0.0729 (6)	0.0611 (6)	0.0683 (6)	0.0446 (5)	−0.0198 (5)	−0.0166 (4)

Geometric parameters (Å, º)

C1—N2	1.2963 (16)	C7—H7	0.9300
C1—N1	1.3760 (16)	C8—H8	0.9300
C1—C9	1.4981 (17)	C9—C10	1.526 (2)
C2—O1	1.2209 (15)	C9—H9A	0.9700
C2—N1	1.3945 (16)	C9—H9B	0.9700
C2—C3	1.4520 (17)	C10—C11	1.512 (2)
C3—C4	1.3984 (18)	C10—H10A	0.9700
C3—C5	1.3991 (18)	C10—H10B	0.9700
C4—N2	1.3832 (16)	C11—H11A	0.9600
C4—C8	1.4032 (18)	C11—H11B	0.9600
C5—C6	1.371 (2)	C11—H11C	0.9600
C5—H5	0.9300	N1—N3	1.4219 (14)
C6—C7	1.395 (2)	N3—H3A	0.91 (2)
C6—H6	0.9300	N3—H3B	0.87 (2)
C7—C8	1.368 (2)
N2—C1—N1	122.69 (11)	C1—C9—H9A	109.1
N2—C1—C9	118.73 (11)	C10—C9—H9A	109.1
N1—C1—C9	118.53 (11)	C1—C9—H9B	109.1
O1—C2—N1	120.11 (11)	C10—C9—H9B	109.1
O1—C2—C3	125.67 (12)	H9A—C9—H9B	107.9
N1—C2—C3	114.21 (10)	C11—C10—C9	112.30 (15)
C4—C3—C5	120.51 (12)	C11—C10—H10A	109.1
C4—C3—C2	118.94 (11)	C9—C10—H10A	109.1
C5—C3—C2	120.55 (11)	C11—C10—H10B	109.1
N2—C4—C3	122.27 (11)	C9—C10—H10B	109.1
N2—C4—C8	118.95 (12)	H10A—C10—H10B	107.9
C3—C4—C8	118.78 (12)	C10—C11—H11A	109.5
C6—C5—C3	119.73 (13)	C10—C11—H11B	109.5
C6—C5—H5	120.1	H11A—C11—H11B	109.5
C3—C5—H5	120.1	C10—C11—H11C	109.5
C5—C6—C7	119.93 (13)	H11A—C11—H11C	109.5
C5—C6—H6	120.0	H11B—C11—H11C	109.5
C7—C6—H6	120.0	C1—N1—C2	123.22 (10)
C8—C7—C6	121.04 (13)	C1—N1—N3	118.60 (10)
C8—C7—H7	119.5	C2—N1—N3	118.13 (10)
C6—C7—H7	119.5	C1—N2—C4	118.58 (11)
C7—C8—C4	119.99 (13)	N1—N3—H3A	104.0 (11)
C7—C8—H8	120.0	N1—N3—H3B	103.8 (13)
C4—C8—H8	120.0	H3A—N3—H3B	108.1 (17)
C1—C9—C10	112.34 (12)
O1—C2—C3—C4	176.78 (12)	N2—C1—C9—C10	−89.31 (15)
N1—C2—C3—C4	−3.10 (16)	N1—C1—C9—C10	88.39 (15)
O1—C2—C3—C5	−3.2 (2)	C1—C9—C10—C11	175.23 (16)
N1—C2—C3—C5	176.95 (11)	N2—C1—N1—C2	−1.99 (18)
C5—C3—C4—N2	−178.79 (11)	C9—C1—N1—C2	−179.59 (11)
C2—C3—C4—N2	1.26 (17)	N2—C1—N1—N3	−179.17 (11)
C5—C3—C4—C8	1.61 (18)	C9—C1—N1—N3	3.23 (16)
C2—C3—C4—C8	−178.34 (11)	O1—C2—N1—C1	−176.35 (11)
C4—C3—C5—C6	−0.98 (19)	C3—C2—N1—C1	3.54 (16)
C2—C3—C5—C6	178.97 (12)	O1—C2—N1—N3	0.84 (17)
C3—C5—C6—C7	−0.4 (2)	C3—C2—N1—N3	−179.27 (10)
C5—C6—C7—C8	1.2 (2)	N1—C1—N2—C4	−0.22 (18)
C6—C7—C8—C4	−0.6 (2)	C9—C1—N2—C4	177.38 (11)
N2—C4—C8—C7	179.55 (13)	C3—C4—N2—C1	0.51 (18)
C3—C4—C8—C7	−0.8 (2)	C8—C4—N2—C1	−179.89 (12)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3A···N2^i	0.91 (2)	2.16 (2)	3.0677 (17)	176.1 (16)
N3—H3B···O1^ii	0.87 (2)	2.51 (2)	3.0599 (16)	122.0 (15)
C5—H5···O1^iii	0.93	2.44	3.3163 (16)	157

Symmetry codes: (i) y, −x+y, −z; (ii) −y+1/3, x−y−1/3, z−1/3; (iii) −x+y+2/3, −x+1/3, z+1/3.