Literature DB >> 21579190

N-(3,4-Difluoro-phen-yl)-3,4,5-trimethoxy-benzamide.

Hyeong Choi, Byung Hee Han, Taewoo Lee, Sung Kwon Kang, Chang Keun Sung.

Abstract

In the title amide, C(16)H(15)F(2)NO(4), the dihedral angle between the benzene rings is 2.33 (15)°. Mol-ecules are linked in the crystal structure by N-H⋯O hydrogen bonding involving N-H and C=O groups of the amide function, leading to a supra-molecular chain along [100].

Entities: Chemical Disease Gene

Year: 2010 PMID： 21579190 PMCID： PMC2979189 DOI： 10.1107/S1600536810013796

Source DB: PubMed Journal: Acta Crystallogr Sect E Struct Rep Online ISSN： 1600-5368

Related literature

For background to the development of potent inhibitory agents of tyrosinase and melanin formation as whitening agents, see: Cabanes et al. (1994 ▶); Dawley & Flurkey (1993 ▶); Ha et al. (2007 ▶); Hong et al. (2008 ▶); Kwak et al. (2010 ▶); Lee et al. (2007 ▶); Nerya et al. (2003 ▶); Park et al. (2010 ▶); Sung & Samyang Genex (2001 ▶); Yi et al. (2009 ▶, 2010 ▶).

Experimental

Crystal data

C16H15F2NO4 M = 323.29 Monoclinic, a = 5.0031 (3) Å b = 8.8986 (5) Å c = 32.726 (2) Å β = 93.896 (4)° V = 1453.59 (15) Å3 Z = 4 Mo Kα radiation μ = 0.12 mm−1 T = 174 K 0.12 × 0.05 × 0.04 mm

Data collection

Bruker SMART CCD area-detector diffractometer 10828 measured reflections 2634 independent reflections 1522 reflections with I > 2σ(I) R int = 0.080

Refinement

R[F 2 > 2σ(F 2)] = 0.065 wR(F 2) = 0.185 S = 1.05 2634 reflections 216 parameters H atoms treated by a mixture of independent and constrained refinement Δρmax = 0.32 e Å−3 Δρmin = −0.31 e Å−3 Data collection: SMART (Bruker, 2002 ▶); cell refinement: SAINT (Bruker, 2002 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶). Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810013796/tk2658sup1.cif Structure factors: contains datablocks I. DOI: 10.1107/S1600536810013796/tk2658Isup2.hkl Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C₁₆H₁₅F₂NO₄	F(000) = 672
M_r = 323.29	D_x = 1.477 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 761 reflections
a = 5.0031 (3) Å	θ = 2.6–19.9°
b = 8.8986 (5) Å	µ = 0.12 mm⁻¹
c = 32.726 (2) Å	T = 174 K
β = 93.896 (4)°	Needle, colourless
V = 1453.59 (15) Å³	0.12 × 0.05 × 0.04 mm
Z = 4

Bruker SMART CCD area-detector diffractometer	R_int = 0.080
φ and ω scans	θ_max = 25.5°, θ_min = 2.4°
10828 measured reflections	h = −4→6
2634 independent reflections	k = −10→6
1522 reflections with I > 2σ(I)	l = −39→34

Refinement on F²	H atoms treated by a mixture of independent and constrained refinement
Least-squares matrix: full	w = 1/[σ²(F_o²) + (0.0682P)² + 1.4724P] where P = (F_o² + 2F_c²)/3
R[F² > 2σ(F²)] = 0.065	(Δ/σ)_max < 0.001
wR(F²) = 0.185	Δρ_max = 0.32 e Å⁻³
S = 1.05	Δρ_min = −0.31 e Å⁻³
2634 reflections	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
216 parameters	Extinction coefficient: 0.014 (2)
0 restraints

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.

	x	y	z	U_iso*/U_eq
C1	0.6607 (7)	0.3453 (4)	0.11117 (12)	0.0287 (9)
C2	0.4753 (7)	0.2630 (5)	0.13169 (11)	0.0295 (9)
H2	0.3569	0.1988	0.1172	0.035*
C3	0.4671 (7)	0.2766 (4)	0.17375 (12)	0.0290 (9)
C4	0.6362 (7)	0.3786 (4)	0.19522 (11)	0.0269 (9)
C5	0.8177 (7)	0.4651 (4)	0.17433 (12)	0.0308 (10)
C6	0.8325 (7)	0.4471 (4)	0.13255 (12)	0.0297 (9)
H6	0.9558	0.5022	0.1187	0.036*
O7	0.3015 (5)	0.1970 (3)	0.19728 (8)	0.0361 (7)
C8	0.1331 (8)	0.0851 (5)	0.17712 (13)	0.0387 (11)
H8A	0.0082	0.1328	0.1577	0.058*
H8B	0.0368	0.0323	0.1971	0.058*
H8C	0.2416	0.0154	0.1632	0.058*
O9	0.6159 (5)	0.3968 (3)	0.23691 (8)	0.0372 (8)
C10	0.8440 (8)	0.3424 (5)	0.26132 (13)	0.0436 (12)
H10A	0.8604	0.2359	0.2575	0.065*
H10B	0.8218	0.3633	0.2897	0.065*
H10C	1.0027	0.3915	0.2531	0.065*
O11	0.9674 (5)	0.5622 (3)	0.19817 (8)	0.0402 (8)
C12	1.1391 (8)	0.6627 (5)	0.17819 (14)	0.0445 (12)
H12A	1.2818	0.6068	0.1672	0.067*
H12B	1.2129	0.7351	0.1976	0.067*
H12C	1.0381	0.7138	0.1564	0.067*
C13	0.6990 (7)	0.3258 (4)	0.06673 (12)	0.0317 (10)
O14	0.9186 (5)	0.3442 (3)	0.05305 (8)	0.0409 (8)
N15	0.4757 (6)	0.2891 (4)	0.04286 (10)	0.0299 (8)
H15	0.313 (8)	0.294 (4)	0.0547 (11)	0.029 (10)*
C16	0.4673 (7)	0.2563 (5)	0.00065 (12)	0.0305 (9)
C17	0.2768 (8)	0.1532 (5)	−0.01466 (13)	0.0389 (11)
H17	0.1633	0.1069	0.0028	0.047*
C18	0.2571 (9)	0.1203 (5)	−0.05565 (13)	0.0426 (11)
C19	0.4247 (9)	0.1857 (5)	−0.08182 (12)	0.0415 (11)
C20	0.6105 (9)	0.2881 (6)	−0.06747 (13)	0.0493 (13)
H20	0.7228	0.3337	−0.0853	0.059*
C21	0.6312 (8)	0.3240 (5)	−0.02595 (12)	0.0402 (11)
H21	0.7571	0.3944	−0.0161	0.048*
F22	0.0737 (6)	0.0196 (3)	−0.07070 (8)	0.0697 (9)
F23	0.3998 (5)	0.1491 (3)	−0.12188 (7)	0.0625 (9)

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0233 (19)	0.032 (2)	0.030 (2)	0.0051 (18)	−0.0008 (16)	−0.0001 (18)
C2	0.0215 (18)	0.035 (2)	0.032 (2)	−0.0027 (17)	0.0031 (16)	−0.0032 (18)
C3	0.0236 (19)	0.030 (2)	0.034 (2)	0.0022 (17)	0.0048 (17)	0.0008 (19)
C4	0.0277 (19)	0.032 (2)	0.021 (2)	0.0052 (18)	0.0021 (16)	−0.0014 (18)
C5	0.028 (2)	0.028 (2)	0.035 (3)	0.0000 (18)	−0.0016 (17)	−0.0020 (19)
C6	0.027 (2)	0.030 (2)	0.031 (2)	−0.0011 (18)	0.0014 (16)	0.0047 (18)
O7	0.0376 (15)	0.0399 (18)	0.0314 (16)	−0.0088 (14)	0.0071 (12)	0.0033 (13)
C8	0.039 (2)	0.033 (2)	0.045 (3)	−0.005 (2)	0.008 (2)	0.007 (2)
O9	0.0331 (15)	0.0477 (19)	0.0311 (17)	0.0038 (14)	0.0041 (12)	−0.0016 (14)
C10	0.037 (2)	0.060 (3)	0.034 (3)	0.008 (2)	0.0027 (19)	0.005 (2)
O11	0.0464 (17)	0.0383 (17)	0.0351 (18)	−0.0121 (14)	−0.0030 (13)	−0.0064 (14)
C12	0.042 (2)	0.040 (3)	0.051 (3)	−0.007 (2)	−0.004 (2)	0.001 (2)
C13	0.025 (2)	0.035 (2)	0.035 (2)	0.0000 (18)	0.0010 (17)	−0.0018 (19)
O14	0.0242 (14)	0.066 (2)	0.0332 (17)	−0.0050 (14)	0.0079 (12)	−0.0011 (15)
N15	0.0239 (17)	0.041 (2)	0.025 (2)	0.0001 (16)	0.0027 (14)	−0.0020 (16)
C16	0.0235 (19)	0.036 (2)	0.032 (2)	0.0010 (18)	0.0012 (16)	−0.0018 (19)
C17	0.038 (2)	0.044 (3)	0.034 (3)	−0.005 (2)	0.0042 (19)	−0.004 (2)
C18	0.046 (3)	0.039 (3)	0.041 (3)	0.000 (2)	−0.003 (2)	−0.008 (2)
C19	0.047 (3)	0.056 (3)	0.021 (2)	0.013 (2)	0.0002 (19)	−0.005 (2)
C20	0.044 (3)	0.074 (4)	0.031 (3)	−0.001 (3)	0.006 (2)	0.011 (3)
C21	0.038 (2)	0.051 (3)	0.032 (3)	−0.007 (2)	0.0018 (19)	0.001 (2)
F22	0.085 (2)	0.072 (2)	0.0507 (18)	−0.0236 (18)	−0.0041 (15)	−0.0209 (16)
F23	0.0721 (18)	0.087 (2)	0.0284 (16)	0.0145 (16)	0.0001 (13)	−0.0119 (14)

C1—C2	1.390 (5)	O11—C12	1.429 (5)
C1—C6	1.402 (5)	C12—H12A	0.96
C1—C13	1.490 (5)	C12—H12B	0.96
C2—C3	1.385 (5)	C12—H12C	0.96
C2—H2	0.93	C13—O14	1.226 (4)
C3—O7	1.367 (4)	C13—N15	1.358 (5)
C3—C4	1.397 (5)	N15—C16	1.410 (5)
C4—O9	1.384 (4)	N15—H15	0.93 (4)
C4—C5	1.403 (5)	C16—C21	1.375 (5)
C5—O11	1.355 (4)	C16—C17	1.392 (5)
C5—C6	1.383 (5)	C17—C18	1.370 (6)
C6—H6	0.93	C17—H17	0.93
O7—C8	1.436 (5)	C18—F22	1.352 (5)
C8—H8A	0.96	C18—C19	1.368 (6)
C8—H8B	0.96	C19—F23	1.348 (5)
C8—H8C	0.96	C19—C20	1.362 (6)
O9—C10	1.432 (4)	C20—C21	1.393 (6)
C10—H10A	0.96	C20—H20	0.93
C10—H10B	0.96	C21—H21	0.93
C10—H10C	0.96

C2—C1—C6	120.4 (4)	C5—O11—C12	117.5 (3)
C2—C1—C13	123.0 (4)	O11—C12—H12A	109.5
C6—C1—C13	116.6 (3)	O11—C12—H12B	109.5
C3—C2—C1	120.0 (4)	H12A—C12—H12B	109.5
C3—C2—H2	120	O11—C12—H12C	109.5
C1—C2—H2	120	H12A—C12—H12C	109.5
O7—C3—C2	125.1 (3)	H12B—C12—H12C	109.5
O7—C3—C4	115.0 (3)	O14—C13—N15	123.0 (4)
C2—C3—C4	119.9 (3)	O14—C13—C1	121.3 (3)
O9—C4—C3	119.3 (3)	N15—C13—C1	115.7 (3)
O9—C4—C5	120.6 (3)	C13—N15—C16	125.6 (3)
C3—C4—C5	120.1 (3)	C13—N15—H15	118 (2)
O11—C5—C6	125.3 (4)	C16—N15—H15	117 (2)
O11—C5—C4	114.8 (3)	C21—C16—C17	119.0 (4)
C6—C5—C4	119.8 (4)	C21—C16—N15	123.4 (4)
C5—C6—C1	119.7 (4)	C17—C16—N15	117.6 (3)
C5—C6—H6	120.1	C18—C17—C16	119.7 (4)
C1—C6—H6	120.1	C18—C17—H17	120.2
C3—O7—C8	117.4 (3)	C16—C17—H17	120.2
O7—C8—H8A	109.5	F22—C18—C19	118.9 (4)
O7—C8—H8B	109.5	F22—C18—C17	120.0 (4)
H8A—C8—H8B	109.5	C19—C18—C17	121.1 (4)
O7—C8—H8C	109.5	F23—C19—C20	120.8 (4)
H8A—C8—H8C	109.5	F23—C19—C18	119.1 (4)
H8B—C8—H8C	109.5	C20—C19—C18	120.1 (4)
C4—O9—C10	113.7 (3)	C19—C20—C21	119.6 (4)
O9—C10—H10A	109.5	C19—C20—H20	120.2
O9—C10—H10B	109.5	C21—C20—H20	120.2
H10A—C10—H10B	109.5	C16—C21—C20	120.6 (4)
O9—C10—H10C	109.5	C16—C21—H21	119.7
H10A—C10—H10C	109.5	C20—C21—H21	119.7
H10B—C10—H10C	109.5

D—H···A	D—H	H···A	D···A	D—H···A
N15—H15···O14ⁱ	0.93 (4)	2.02 (4)	2.872 (4)	152 (3)

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N15—H15⋯O14ⁱ	0.93 (4)	2.02 (4)	2.872 (4)	152 (3)

Symmetry code: (i) .

10 in total

1. Synthetic tyrosyl gallate derivatives as potent melanin formation inhibitors.

Authors: Chan Woo Lee; Eun-Mi Son; Han Sung Kim; Pan Xu; Tuyagerel Batmunkh; Burm-Jong Lee; Kyung Ah Koo
Journal: Bioorg Med Chem Lett Date: 2007-07-25 Impact factor: 2.823

2. A short history of SHELX.

Authors: George M Sheldrick
Journal: Acta Crystallogr A Date: 2007-12-21 Impact factor: 2.290

3. Synthesis and biological evaluation of novel 4-hydroxybenzaldehyde derivatives as tyrosinase inhibitors.

Authors: Wei Yi; Rihui Cao; Wenlie Peng; Huan Wen; Qin Yan; Binhua Zhou; Lin Ma; Huacan Song
Journal: Eur J Med Chem Date: 2009-11-10 Impact factor: 6.514

4. Natural ortho-dihydroxyisoflavone derivatives from aged Korean fermented soybean paste as potent tyrosinase and melanin formation inhibitors.

Authors: Jun-Seong Park; Dong Hyun Kim; Jae Kyoung Lee; Jin Young Lee; Duck Hee Kim; Han Kon Kim; Hak-Ju Lee; Ho Cheol Kim
Journal: Bioorg Med Chem Lett Date: 2009-12-06 Impact factor: 2.823

5. Design, synthesis and biological evaluation of hydroxy- or methoxy-substituted phenylmethylenethiosemicarbazones as tyrosinase inhibitors.

Authors: Wei Yi; Ri-Hui Cao; Zhi-Yong Chen; Liang Yu; Lin Ma; Hua-Can Song
Journal: Chem Pharm Bull (Tokyo) Date: 2009-11 Impact factor: 1.645

6. Glabrene and isoliquiritigenin as tyrosinase inhibitors from licorice roots.

Authors: Ohad Nerya; Jacob Vaya; Ramadan Musa; Sarit Izrael; Ruth Ben-Arie; Snait Tamir
Journal: J Agric Food Chem Date: 2003-02-26 Impact factor: 5.279

7. Enhanced cell permeability of kojic acid-phenylalanine amide with metal complex.

Authors: Seon-Yeong Kwak; Jin-Mi Noh; So-Hee Park; Jang-Woong Byun; Hye-Ryung Choi; Kyoung-Chan Park; Yoon-Sik Lee
Journal: Bioorg Med Chem Lett Date: 2009-12-03 Impact factor: 2.823

8. 4-(6-Hydroxy-2-naphthyl)-1,3-bezendiol: a potent, new tyrosinase inhibitor.

Authors: Young Mi Ha; Sang Woon Chung; Suhee Song; Hyojin Lee; Hongsuk Suh; Hae Young Chung
Journal: Biol Pharm Bull Date: 2007-09 Impact factor: 2.233

9. 3,4-Dihydroxy-phenyl 3,4,5-trimethoxy-benzoate.

Authors: Won Ki Hong; Ji Youn Heo; Byung Hee Han; Chang Keun Sung; Sung Kwon Kang
Journal: Acta Crystallogr Sect E Struct Rep Online Date: 2007-12-06

10. Kojic acid, a cosmetic skin whitening agent, is a slow-binding inhibitor of catecholase activity of tyrosinase.

Authors: J Cabanes; S Chazarra; F Garcia-Carmona
Journal: J Pharm Pharmacol Date: 1994-12 Impact factor: 3.765