5-Bromo-N-(3,4-dimeth­oxy­benz­yl)pyridin-2-amine

Li, J.; Lu, L.-Y.; Shen, W.-X.; Shi, J.-Y.

doi:10.1107/S1600536812015796

organic compounds

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Volume 68| Part 5| May 2012| Page o1405

doi:10.1107/S1600536812015796

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5-Bromo-N-(3,4-dimethoxybenzyl)pyridin-2-amine

Jie Li,^a Lin-Yan Lu,^a Wang-Xing Shen ^a and Jian-You Shi ^b ^*

^aSchool of Medicine and Life Sciences, Zhejiang University City College, Hangzhou 310015, Zhejiang, People's Republic of China, and ^bSichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, People's Republic of China
^*Correspondence e-mail: shijianyoude@126.com

(Received 21 March 2012; accepted 11 April 2012; online 18 April 2012)

The title compound, C₁₄H₁₅BrN₂O₂, an intermediate in drug discovery, was synthesized by the reaction of 5-bromopyridin-2-amine and 3,4-dimethoxybenzaldehyde. In the crystal, molecules are linked via pairs ofN—H⋯N hydrogen bonds, leading to the formation of inversion dimers. A short contact occurs between the aryl H atom (ortho position from N) and the centroid of the benzene ring.

Related literature

For the anti-tumor activity of related compounds, see: Kovala-Demertzi et al. (2007 ). For the anti-ulcer activity of related compounds, see: Cho et al. (2001 ). For the anti-viral activity of related compounds, see: Mavel et al. (2002 ). For the anti-microbial activity of related compounds, see: Yeong et al. (2004 ).

Experimental

Crystal data

C₁₄H₁₅BrN₂O₂
M_r = 323.18
Monoclinic, P 2₁ /c
a = 6.3202 (2) Å
b = 13.7940 (4) Å
c = 15.8582 (6) Å
β = 100.961 (4)°
V = 1357.31 (8) Å³
Z = 4
Mo Kα radiation
μ = 3.03 mm⁻¹
T = 130 K
0.42 × 0.30 × 0.15 mm

Data collection

Agilent Xcalibur Eos diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011 ) T_min = 0.509, T_max = 1.000
8188 measured reflections
2384 independent reflections
2055 reflections with I > 2σ(I)
R_int = 0.030

Refinement

R[F² > 2σ(F²)] = 0.027
wR(F²) = 0.060
S = 1.03
2384 reflections
174 parameters
H-atom parameters constrained
Δρ_max = 0.47 e Å⁻³
Δρ_min = −0.49 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

Cg is the centroid of the C7–C12 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2⋯N1ⁱ	0.88	2.31	3.090 (3)	149
C2—H2A⋯Cgⁱ	0.95	2.50	3.397 (3)	158
Symmetry code: (i) -x+1, -y+2, -z.

Data collection: CrysAlis PRO (Agilent, 2011); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009 ); software used to prepare material for publication: OLEX2.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536812015796/rk2346sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536812015796/rk2346Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536812015796/rk2346Isup3.cml

checkCIF report

Comment top

The pyridine skeleton is a great importance to chemistry as well as biology which are well known for their versatile pharmacological activities such as anti-tumor (Kovala-Demertzi et al., 2007), anti-ulcer (Cho et al., 2001), anti-viral (Mavel et al., 2002) and antimicrobial (Yeong et al., 2004). The title compound is one of these compounds. The crystal packing is stabilized by a pair of strong intermolecular N2–H2···N1ⁱ classical hydrogen bonds conecting two moleculars to form a centrosymmtric dimer. The H2A atom from pyridine moiety has short contact (2.50Å) with Cgⁱ of phenyl ring (C7-C12). Symmetry code: (i) 1-x, 2-y, -z.

Related literature top

For the anti-tumor activity of related compounds, see: Kovala-Demertzi et al. (2007). For the anti-ulcer activity of related compounds, see: Cho et al. (2001). For the anti-viral activity of related compounds, see: Mavel et al. (2002). For the anti-microbial activity of related compounds, see: Yeong et al. (2004).

Experimental top

A methanol solution of 5-bromopyridin-2-amine (1.73 g, 0.01 mol), 3,4-dimethoxybenzaldehyde (1.66 g, 0.01 mol) with sodium cyanoborohydride (0.69 g, 0.011 mol) was heated to reflux for 3 h. The mixture was poured into cold water and then filtered to get this compound. Single crystals were obtained from the powder in ethanol after 5 days.

Computing details top

Data collection: CrysAlis PRO (Agilent, 2011); cell refinement: CrysAlis PRO (Agilent, 2011); data reduction: CrysAlis PRO (Agilent, 2011); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

Figures top

Fig. 1. The molecular structure of title compound with the atom numbering scheme. Displacement ellipsoids are drawn at 50% probability level. H atoms are presented as a small spheres of arbitrary radius.

5-Bromo-N-(3,4-dimethoxybenzyl)pyridin-2-amine top

Crystal data top

C₁₄H₁₅BrN₂O₂	F(000) = 656
M_r = 323.18	D_x = 1.582 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.7107 Å
Hall symbol: -P 2ybc	Cell parameters from 3191 reflections
a = 6.3202 (2) Å	θ = 3.0–29.3°
b = 13.7940 (4) Å	µ = 3.03 mm⁻¹
c = 15.8582 (6) Å	T = 130 K
β = 100.961 (4)°	Block, colourless
V = 1357.31 (8) Å³	0.42 × 0.30 × 0.15 mm
Z = 4

Data collection top

Agilent Xcalibur Eos diffractometer	2384 independent reflections
Radiation source: Enhance (Mo) X-ray Source	2055 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.030
Detector resolution: 16.0874 pixels mm^-1	θ_max = 25.0°, θ_min = 3.0°
ω–scans	h = −7→7
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011)	k = −15→16
T_min = 0.509, T_max = 1.000	l = −18→15
8188 measured 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)] = 0.027	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.060	H-atom parameters constrained
S = 1.03	w = 1/[σ²(F_o²) + (0.0214P)² + 1.0069P] where P = (F_o² + 2F_c²)/3
2384 reflections	(Δ/σ)_max = 0.001
174 parameters	Δρ_max = 0.47 e Å⁻³
0 restraints	Δρ_min = −0.49 e Å⁻³

Crystal data top

C₁₄H₁₅BrN₂O₂	V = 1357.31 (8) Å³
M_r = 323.18	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 6.3202 (2) Å	µ = 3.03 mm⁻¹
b = 13.7940 (4) Å	T = 130 K
c = 15.8582 (6) Å	0.42 × 0.30 × 0.15 mm
β = 100.961 (4)°

Data collection top

Agilent Xcalibur Eos diffractometer	2384 independent reflections
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011)	2055 reflections with I > 2σ(I)
T_min = 0.509, T_max = 1.000	R_int = 0.030
8188 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.027	0 restraints
wR(F²) = 0.060	H-atom parameters constrained
S = 1.03	Δρ_max = 0.47 e Å⁻³
2384 reflections	Δρ_min = −0.49 e Å⁻³
174 parameters

Special details top

Experimental. Absorption correction: CrysAlis Pro (Agilent Technologies, 2011) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm.

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'s 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
Br1	0.29705 (4)	0.620125 (18)	0.137802 (17)	0.02180 (10)
O1	0.8391 (3)	1.38453 (12)	0.14221 (11)	0.0181 (4)
O2	1.1319 (3)	1.40582 (12)	0.05188 (11)	0.0185 (4)
N1	0.4443 (3)	0.89466 (14)	0.06525 (13)	0.0164 (5)
N2	0.7225 (3)	1.00200 (15)	0.10747 (13)	0.0178 (5)
H2	0.6482	1.0443	0.0722	0.021*
C1	0.4393 (4)	0.74052 (17)	0.13319 (15)	0.0148 (5)
C2	0.3514 (4)	0.80926 (17)	0.07365 (16)	0.0165 (5)
H2A	0.2181	0.7951	0.0368	0.020*
C3	0.6333 (4)	0.91502 (18)	0.11831 (15)	0.0147 (5)
C4	0.7300 (4)	0.84807 (18)	0.18126 (16)	0.0177 (5)
H4	0.8617	0.8637	0.2186	0.021*
C5	0.6323 (4)	0.76009 (18)	0.18814 (16)	0.0182 (6)
H5	0.6958	0.7138	0.2297	0.022*
C6	0.9380 (4)	1.02800 (18)	0.15245 (16)	0.0176 (6)
H6A	1.0436	0.9803	0.1387	0.021*
H6B	0.9432	1.0263	0.2152	0.021*
C7	0.9971 (4)	1.12777 (17)	0.12650 (15)	0.0154 (5)
C8	0.8867 (4)	1.20894 (18)	0.14866 (15)	0.0153 (5)
H8	0.7767	1.2007	0.1814	0.018*
C9	0.9355 (4)	1.30058 (17)	0.12366 (15)	0.0144 (5)
C10	1.0981 (4)	1.31318 (18)	0.07442 (15)	0.0148 (5)
C11	1.2084 (4)	1.23269 (18)	0.05377 (16)	0.0175 (6)
H11	1.3198	1.2404	0.0217	0.021*
C12	1.1576 (4)	1.14027 (18)	0.07967 (16)	0.0175 (6)
H12	1.2342	1.0856	0.0649	0.021*
C13	0.6735 (4)	1.37654 (19)	0.19176 (17)	0.0209 (6)
H13A	0.5605	1.3329	0.1627	0.031*
H13B	0.6116	1.4407	0.1979	0.031*
H13C	0.7347	1.3506	0.2487	0.031*
C14	1.2631 (4)	1.41893 (19)	−0.01160 (17)	0.0214 (6)
H14A	1.2102	1.3772	−0.0611	0.032*
H14B	1.4126	1.4018	0.0130	0.032*
H14C	1.2564	1.4868	−0.0301	0.032*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Br1	0.02543 (15)	0.01635 (15)	0.02437 (16)	−0.00657 (11)	0.00660 (11)	0.00055 (11)
O1	0.0203 (9)	0.0166 (9)	0.0204 (10)	0.0020 (7)	0.0109 (8)	0.0025 (8)
O2	0.0218 (9)	0.0140 (9)	0.0227 (10)	−0.0044 (7)	0.0116 (8)	−0.0004 (7)
N1	0.0156 (10)	0.0169 (11)	0.0153 (11)	−0.0021 (9)	−0.0002 (9)	0.0000 (9)
N2	0.0173 (10)	0.0137 (11)	0.0193 (12)	−0.0020 (9)	−0.0044 (9)	0.0042 (9)
C1	0.0196 (12)	0.0115 (13)	0.0146 (13)	−0.0018 (10)	0.0067 (11)	−0.0018 (10)
C2	0.0154 (12)	0.0180 (13)	0.0155 (14)	−0.0032 (10)	0.0017 (11)	−0.0036 (11)
C3	0.0146 (12)	0.0162 (13)	0.0131 (13)	−0.0010 (10)	0.0024 (10)	−0.0010 (10)
C4	0.0163 (12)	0.0185 (13)	0.0161 (14)	−0.0007 (10)	−0.0021 (11)	0.0030 (11)
C5	0.0194 (13)	0.0185 (14)	0.0167 (14)	0.0007 (11)	0.0037 (11)	0.0045 (11)
C6	0.0136 (12)	0.0178 (14)	0.0194 (14)	−0.0014 (10)	−0.0014 (11)	0.0006 (11)
C7	0.0145 (12)	0.0159 (13)	0.0135 (13)	−0.0030 (10)	−0.0034 (10)	−0.0010 (10)
C8	0.0136 (12)	0.0197 (14)	0.0124 (13)	−0.0030 (10)	0.0019 (10)	0.0018 (10)
C9	0.0121 (12)	0.0176 (13)	0.0129 (13)	0.0002 (10)	0.0008 (10)	−0.0018 (11)
C10	0.0138 (12)	0.0168 (13)	0.0129 (13)	−0.0033 (10)	0.0000 (10)	−0.0018 (10)
C11	0.0145 (12)	0.0213 (14)	0.0180 (14)	−0.0034 (11)	0.0061 (11)	−0.0018 (11)
C12	0.0157 (12)	0.0150 (14)	0.0212 (14)	0.0003 (10)	0.0018 (11)	−0.0039 (11)
C13	0.0179 (12)	0.0259 (15)	0.0206 (14)	0.0019 (11)	0.0076 (11)	−0.0013 (12)
C14	0.0215 (13)	0.0210 (14)	0.0236 (15)	−0.0048 (11)	0.0095 (12)	0.0014 (12)

Geometric parameters (Å, º) top

Br1—C1	1.897 (2)	C6—H6B	0.9900
O1—C9	1.366 (3)	C6—C7	1.504 (3)
O1—C13	1.427 (3)	C7—C8	1.399 (3)
O2—C10	1.355 (3)	C7—C12	1.377 (3)
O2—C14	1.432 (3)	C8—H8	0.9500
N1—C2	1.334 (3)	C8—C9	1.377 (3)
N1—C3	1.353 (3)	C9—C10	1.414 (3)
N2—H2	0.8800	C10—C11	1.383 (3)
N2—C3	1.350 (3)	C11—H11	0.9500
N2—C6	1.457 (3)	C11—C12	1.395 (3)
C1—C2	1.378 (3)	C12—H12	0.9500
C1—C5	1.384 (3)	C13—H13A	0.9800
C2—H2A	0.9500	C13—H13B	0.9800
C3—C4	1.411 (3)	C13—H13C	0.9800
C4—H4	0.9500	C14—H14A	0.9800
C4—C5	1.375 (3)	C14—H14B	0.9800
C5—H5	0.9500	C14—H14C	0.9800
C6—H6A	0.9900

C9—O1—C13	117.18 (18)	C12—C7—C8	119.3 (2)
C10—O2—C14	116.51 (18)	C7—C8—H8	119.6
C2—N1—C3	118.3 (2)	C9—C8—C7	120.8 (2)
C3—N2—H2	119.0	C9—C8—H8	119.6
C3—N2—C6	122.0 (2)	O1—C9—C8	125.6 (2)
C6—N2—H2	119.0	O1—C9—C10	114.5 (2)
C2—C1—Br1	119.77 (18)	C8—C9—C10	119.8 (2)
C2—C1—C5	119.3 (2)	O2—C10—C9	115.4 (2)
C5—C1—Br1	120.93 (18)	O2—C10—C11	125.6 (2)
N1—C2—C1	123.2 (2)	C11—C10—C9	118.9 (2)
N1—C2—H2A	118.4	C10—C11—H11	119.7
C1—C2—H2A	118.4	C10—C11—C12	120.6 (2)
N1—C3—C4	121.1 (2)	C12—C11—H11	119.7
N2—C3—N1	116.5 (2)	C7—C12—C11	120.5 (2)
N2—C3—C4	122.4 (2)	C7—C12—H12	119.8
C3—C4—H4	120.2	C11—C12—H12	119.8
C5—C4—C3	119.5 (2)	O1—C13—H13A	109.5
C5—C4—H4	120.2	O1—C13—H13B	109.5
C1—C5—H5	120.7	O1—C13—H13C	109.5
C4—C5—C1	118.5 (2)	H13A—C13—H13B	109.5
C4—C5—H5	120.7	H13A—C13—H13C	109.5
N2—C6—H6A	109.6	H13B—C13—H13C	109.5
N2—C6—H6B	109.6	O2—C14—H14A	109.5
N2—C6—C7	110.42 (19)	O2—C14—H14B	109.5
H6A—C6—H6B	108.1	O2—C14—H14C	109.5
C7—C6—H6A	109.6	H14A—C14—H14B	109.5
C7—C6—H6B	109.6	H14A—C14—H14C	109.5
C8—C7—C6	120.1 (2)	H14B—C14—H14C	109.5
C12—C7—C6	120.6 (2)

Hydrogen-bond geometry (Å, º) top

Cg is the centroid of the C7–C12 ring.

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···N1ⁱ	0.88	2.31	3.090 (3)	149
C2—H2A···Cgⁱ	0.95	2.50	3.397 (3)	158

Symmetry code: (i) −x+1, −y+2, −z.

Experimental details

Crystal data
Chemical formula	C₁₄H₁₅BrN₂O₂
M_r	323.18
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	130
a, b, c (Å)	6.3202 (2), 13.7940 (4), 15.8582 (6)
β (°)	100.961 (4)
V (Å³)	1357.31 (8)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	3.03
Crystal size (mm)	0.42 × 0.30 × 0.15

Data collection
Diffractometer	Agilent Xcalibur Eos diffractometer
Absorption correction	Multi-scan (CrysAlis PRO; Agilent, 2011)
T_min, T_max	0.509, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	8188, 2384, 2055
R_int	0.030
(sin θ/λ)_max (Å⁻¹)	0.595

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.027, 0.060, 1.03
No. of reflections	2384
No. of parameters	174
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.47, −0.49

Computer programs: CrysAlis PRO (Agilent, 2011), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), OLEX2 (Dolomanov et al., 2009).

Hydrogen-bond geometry (Å, º) top

Cg is the centroid of the C7–C12 ring.

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···N1ⁱ	0.88	2.31	3.090 (3)	148.5
C2—H2A···Cgⁱ	0.95	2.50	3.397 (3)	158

Symmetry code: (i) −x+1, −y+2, −z.

Acknowledgements

The authors thank Mr Zhi-Hua Mao of Sichuan University for the X-ray data collection.

References

Agilent (2011). CrysAlis PRO. Agilent Technologies, Yarnton, England. Google Scholar
Cho, S. Y., Kang, S. K., Kim, S. S., Cheon, H. G., Choi, J. K. & Yun, E. K. (2001). Bull. Korean Chem. Soc. 22, 1217–1223. CAS Google Scholar
Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341. Web of Science CrossRef CAS IUCr Journals Google Scholar
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Mavel, S., Renou, J., Galtier, C., Allouchi, H., Snoeck, R., Andrei, G., De Clercq, E., Balzarini, J. & Gueiffier, A. (2002). Bioorg. Med. Chem. 10, 941–946. Web of Science CSD CrossRef PubMed CAS Google Scholar
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doi:10.1107/S1600536812015796

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