trans-4-[(2,6-Dimethyl­phen­oxy)methyl]cyclo­hexa­necarboxylic acid

Zhang, C.-H.; Li, Z.-C.; Song, H.; Huang, W.-C.

doi:10.1107/S1600536808035502

organic compounds

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ISSN: 2056-9890

Volume 64| Part 12| December 2008| Page o2263

doi:10.1107/S1600536808035502

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trans-4-[(2,6-Dimethylphenoxy)methyl]cyclohexanecarboxylic acid

Chun-Hong Zhang,^a Zi-Cheng Li,^a Hang Song ^a and Wen-Cai Huang ^a ^*

^aDepartment of Pharmaceutical and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu 610065, People's Republic of China
^*Correspondence e-mail: hwc@scu.edu.cn

(Received 28 October 2008; accepted 30 October 2008; online 8 November 2008)

The title compound, C₁₆H₂₂O₃, is a useful intermediate in the synthesis of poly(amidoamine) dendrimers. The cyclohexane ring adopts a chair conformation. In the crystal structure, molecules are linked into centrosymmetric dimers by pairs of O—H⋯O hydrogen bonds.

Related literature

For general background on poly(amidoamine) dendrimers, see: Ahmed et al. (2001 ); Grabchev et al. (2003 ); Wang et al. (2004 ). For related structures, see: Bucourt & Hainaut (1965 ); Dunitz & Strickler (1966 ); Luger et al. (1972 ).

Experimental

Crystal data

C₁₆H₂₂O₃
M_r = 262.34
Triclinic, $[P \overline 1]$
a = 7.162 (3) Å
b = 7.680 (4) Å
c = 14.451 (4) Å
α = 95.26 (4)°
β = 98.35 (4)°
γ = 106.44 (3)°
V = 746.9 (6) Å³
Z = 2
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 292 (2) K
0.60 × 0.52 × 0.42 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
Absorption correction: none
2886 measured reflections
2715 independent reflections
1461 reflections with I > 2σ(I)
R_int = 0.013
3 standard reflections every 250 reflections intensity decay: 2.3%

Refinement

R[F² > 2σ(F²)] = 0.066
wR(F²) = 0.196
S = 1.16
2715 reflections
175 parameters
H-atom parameters constrained
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯O3ⁱ	0.82	1.86	2.658 (3)	166
Symmetry code: (i) -x+3, -y-1, -z+2.

Data collection: DIFRAC (Gabe & White, 1993 ); cell refinement: DIFRAC; data reduction: NRCVAX (Gabe et al., 1989 ); 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: SHELXL97.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808035502/ci2698sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536808035502/ci2698Isup2.hkl

checkCIF report

Comment top

Poly(amidoamine) [PAMAM] dendrimers have attracted much interest for their symmetry, high degree of branching and high density of terminal functional groups, and with different structures they could be used in different fields. Various modifications of periphery of PAMAM dendrimers to change its physical or chemical properties have been reported recently (Wang et al., 2004; Grabchev et al., 2003; Ahmed et al., 2001). To change the lipophilicity of PAMAM dendrimers and provide a new type of linker with special stereostructure, a series of cyclohexanic acid derivatives were synthesized. In our synthetic work the title compound was obtained and here we report its crystal structure.

The cyclohexane ring of the title compound (Fig. 1) adopts a chair conformation. The average C—C bond length of the cyclohexane ring is 1.517 (4) Å, which is close to that of trans-1,4-cyclohexane dicarboxylic acid (1.523 (3) Å, Luger et al., 1972). The mean endocyclic angle of the cyclohexane is 111.1 (3)°, which is close to that observed for cyclohexane rings (111.1°, Bucourt & Hainaut, 1965; 111.4 (4)°, Dunitz & Strickler, 1966; Luger et al., 1972).

In the crystal structure, the molecules are linked into centrosymmetric dimers by O—H···O hydrogen bonds (Table 1).

Related literature top

For general background on poly(amidoamine) dendrimers, see: Ahmed et al. (2001); Grabchev et al. (2003); Wang et al. (2004). For related structures, see: Bucourt & Hainaut (1965); Dunitz & Strickler (1966); Luger et al. (1972)

Experimental top

Methyl trans-4-(tosylmethyl)cyclohexanecarboxylate (3.26 g, 10 mmol), 2,6-dimethylphenol (3.66 g, 30 mmol) and potassium phosphate (10.6 g, 50 mmol) were suspended in dry DMF (20 ml) and heated at 368 K for 8 h, and then water (30 ml) and toluene (30 ml) were added. After agitation, the water layer separated was washed twice with toluene and the organic layer combined was washed with water and then dried with sodium sulfate. After filtration and distillation under vaccum, the crude product obtained was further purified by column chromatography to give pure methyl ester. The ester was then hydrolyzed in a ethanol (15 ml)–1 N NaOH (15 ml) solution for 5 h at 313 K. After cooling and acidification with hydrochloride, the white solid precipitated was collected. Colourless crystals were obtained by slow evaporation in chloroform at room temperature.

Computing details top

Data collection: DIFRAC (Gabe & White, 1993); cell refinement: DIFRAC (Gabe & White, 1993); data reduction: NRCVAX (Gabe et al., 1989); 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: SHELXL97 (Sheldrick, 2008).

Figures top

Fig. 1. The molecular structure of the title compound. Displacement ellipsoids are drawn at the 50% probability level.

trans-4-[(2,6-Dimethylphenoxy)methyl]cyclohexanecarboxylic acid top

Crystal data top

C₁₆H₂₂O₃	Z = 2
M_r = 262.34	F(000) = 284
Triclinic, P1	D_x = 1.167 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 7.162 (3) Å	Cell parameters from 26 reflections
b = 7.680 (4) Å	θ = 4.3–7.4°
c = 14.451 (4) Å	µ = 0.08 mm⁻¹
α = 95.26 (4)°	T = 292 K
β = 98.35 (4)°	Block, colourless
γ = 106.44 (3)°	0.60 × 0.52 × 0.42 mm
V = 746.9 (6) Å³

Data collection top

Enraf–Nonius CAD-4 diffractometer	R_int = 0.013
Radiation source: fine-focus sealed tube	θ_max = 25.5°, θ_min = 1.4°
Graphite monochromator	h = −8→8
ω/2θ scans	k = −5→9
2886 measured reflections	l = −17→17
2715 independent reflections	3 standard reflections every 250 reflections
1461 reflections with I > 2σ(I)	intensity decay: 2.3%

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)] = 0.066	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.196	H-atom parameters constrained
S = 1.16	w = 1/[σ²(F_o²) + (0.0902P)² + 0.0605P] where P = (F_o² + 2F_c²)/3
2715 reflections	(Δ/σ)_max = 0.001
175 parameters	Δρ_max = 0.18 e Å⁻³
0 restraints	Δρ_min = −0.20 e Å⁻³

Crystal data top

C₁₆H₂₂O₃	γ = 106.44 (3)°
M_r = 262.34	V = 746.9 (6) Å³
Triclinic, P1	Z = 2
a = 7.162 (3) Å	Mo Kα radiation
b = 7.680 (4) Å	µ = 0.08 mm⁻¹
c = 14.451 (4) Å	T = 292 K
α = 95.26 (4)°	0.60 × 0.52 × 0.42 mm
β = 98.35 (4)°

Data collection top

Enraf–Nonius CAD-4 diffractometer	R_int = 0.013
2886 measured reflections	3 standard reflections every 250 reflections
2715 independent reflections	intensity decay: 2.3%
1461 reflections with I > 2σ(I)

Refinement top

R[F² > 2σ(F²)] = 0.066	0 restraints
wR(F²) = 0.196	H-atom parameters constrained
S = 1.16	Δρ_max = 0.18 e Å⁻³
2715 reflections	Δρ_min = −0.20 e Å⁻³
175 parameters

Special details top

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.

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
O1	0.8686 (2)	0.1188 (2)	0.70598 (13)	0.0678 (5)
O2	1.2419 (3)	−0.5645 (3)	0.96803 (18)	0.0922 (7)
H2	1.3381	−0.5780	1.0015	0.138*
O3	1.4736 (3)	−0.3312 (3)	0.93470 (18)	0.0964 (8)
C1	0.7116 (4)	0.1817 (3)	0.6701 (2)	0.0628 (7)
C2	0.5908 (4)	0.2148 (4)	0.7308 (2)	0.0769 (8)
C3	0.4398 (5)	0.2823 (5)	0.6941 (4)	0.1122 (14)
H3	0.3518	0.3017	0.7324	0.135*
C4	0.4162 (6)	0.3209 (5)	0.6047 (5)	0.1232 (17)
H4	0.3148	0.3684	0.5828	0.148*
C5	0.5403 (6)	0.2907 (4)	0.5465 (3)	0.1052 (13)
H5	0.5235	0.3191	0.4853	0.126*
C6	0.6931 (4)	0.2174 (4)	0.5772 (2)	0.0728 (8)
C7	0.8312 (6)	0.1882 (5)	0.5141 (2)	0.1050 (11)
H7A	0.9250	0.1368	0.5466	0.157*
H7B	0.9000	0.3034	0.4965	0.157*
H7C	0.7576	0.1056	0.4584	0.157*
C8	0.6272 (6)	0.1818 (5)	0.8314 (3)	0.1143 (13)
H8A	0.6137	0.0542	0.8333	0.171*
H8B	0.5326	0.2158	0.8642	0.171*
H8C	0.7585	0.2541	0.8612	0.171*
C9	0.8238 (4)	−0.0765 (3)	0.6916 (2)	0.0710 (8)
H9A	0.8080	−0.1196	0.6249	0.085*
H9B	0.7005	−0.1320	0.7125	0.085*
C10	0.9881 (4)	−0.1320 (3)	0.74612 (18)	0.0610 (7)
H10	1.1123	−0.0654	0.7276	0.073*
C11	0.9560 (4)	−0.3349 (4)	0.7197 (2)	0.0764 (8)
H11A	0.9530	−0.3606	0.6524	0.092*
H11B	0.8287	−0.4032	0.7329	0.092*
C12	1.1171 (4)	−0.3994 (4)	0.7733 (2)	0.0746 (8)
H12A	1.2426	−0.3407	0.7551	0.089*
H12B	1.0871	−0.5308	0.7564	0.089*
C13	1.1352 (4)	−0.3548 (4)	0.8800 (2)	0.0712 (8)
H13	1.0096	−0.4209	0.8974	0.085*
C14	1.1699 (5)	−0.1513 (4)	0.9070 (2)	0.0838 (9)
H14A	1.2980	−0.0839	0.8942	0.101*
H14B	1.1718	−0.1259	0.9742	0.101*
C15	1.0103 (5)	−0.0858 (4)	0.8526 (2)	0.0789 (8)
H15A	1.0425	0.0460	0.8689	0.095*
H15B	0.8849	−0.1419	0.8716	0.095*
C16	1.2952 (4)	−0.4194 (4)	0.9309 (2)	0.0679 (7)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0677 (12)	0.0521 (10)	0.0835 (12)	0.0263 (9)	−0.0042 (9)	0.0107 (8)
O2	0.0857 (14)	0.0824 (15)	0.1224 (19)	0.0393 (12)	0.0165 (13)	0.0434 (13)
O3	0.0695 (14)	0.0986 (16)	0.136 (2)	0.0373 (12)	0.0181 (12)	0.0551 (14)
C1	0.0573 (15)	0.0486 (14)	0.0804 (18)	0.0191 (12)	−0.0007 (13)	0.0088 (12)
C2	0.0742 (19)	0.0565 (17)	0.104 (2)	0.0234 (15)	0.0221 (17)	0.0078 (15)
C3	0.083 (3)	0.071 (2)	0.193 (5)	0.0338 (19)	0.041 (3)	0.013 (3)
C4	0.074 (3)	0.079 (3)	0.216 (6)	0.037 (2)	−0.010 (3)	0.029 (3)
C5	0.103 (3)	0.074 (2)	0.122 (3)	0.024 (2)	−0.038 (2)	0.027 (2)
C6	0.0754 (19)	0.0592 (17)	0.0762 (19)	0.0179 (14)	−0.0078 (15)	0.0131 (14)
C7	0.130 (3)	0.105 (3)	0.085 (2)	0.038 (2)	0.024 (2)	0.0224 (19)
C8	0.154 (3)	0.100 (3)	0.102 (3)	0.040 (2)	0.062 (3)	0.012 (2)
C9	0.0734 (18)	0.0548 (16)	0.0841 (19)	0.0268 (13)	−0.0026 (14)	0.0088 (13)
C10	0.0652 (16)	0.0495 (14)	0.0686 (16)	0.0217 (12)	0.0039 (12)	0.0087 (12)
C11	0.0809 (19)	0.0603 (17)	0.090 (2)	0.0345 (14)	−0.0016 (15)	0.0030 (14)
C12	0.0780 (19)	0.0602 (17)	0.090 (2)	0.0348 (14)	0.0035 (15)	0.0051 (14)
C13	0.0676 (17)	0.0716 (18)	0.090 (2)	0.0353 (14)	0.0230 (14)	0.0304 (15)
C14	0.112 (2)	0.081 (2)	0.0727 (19)	0.0588 (19)	0.0024 (16)	0.0080 (15)
C15	0.098 (2)	0.0747 (19)	0.079 (2)	0.0534 (17)	0.0075 (15)	0.0093 (15)
C16	0.0757 (19)	0.0644 (17)	0.0816 (19)	0.0397 (15)	0.0238 (15)	0.0268 (15)

Geometric parameters (Å, º) top

O1—C1	1.397 (3)	C8—H8C	0.96
O1—C9	1.431 (3)	C9—C10	1.505 (3)
O2—C16	1.266 (3)	C9—H9A	0.97
O2—H2	0.82	C9—H9B	0.97
O3—C16	1.256 (3)	C10—C11	1.513 (4)
C1—C2	1.373 (4)	C10—C15	1.522 (4)
C1—C6	1.390 (4)	C10—H10	0.98
C2—C3	1.386 (5)	C11—C12	1.521 (4)
C2—C8	1.496 (5)	C11—H11A	0.97
C3—C4	1.350 (6)	C11—H11B	0.97
C3—H3	0.93	C12—C13	1.526 (4)
C4—C5	1.359 (6)	C12—H12A	0.97
C4—H4	0.93	C12—H12B	0.97
C5—C6	1.402 (5)	C13—C16	1.498 (4)
C5—H5	0.93	C13—C14	1.516 (4)
C6—C7	1.487 (5)	C13—H13	0.98
C7—H7A	0.96	C14—C15	1.521 (4)
C7—H7B	0.96	C14—H14A	0.97
C7—H7C	0.96	C14—H14B	0.97
C8—H8A	0.96	C15—H15A	0.97
C8—H8B	0.96	C15—H15B	0.97

C1—O1—C9	113.91 (18)	C9—C10—C15	113.2 (2)
C16—O2—H2	109.5	C11—C10—C15	110.1 (2)
C2—C1—C6	123.7 (3)	C9—C10—H10	107.8
C2—C1—O1	117.7 (3)	C11—C10—H10	107.8
C6—C1—O1	118.5 (3)	C15—C10—H10	107.8
C1—C2—C3	116.5 (3)	C10—C11—C12	112.2 (2)
C1—C2—C8	120.4 (3)	C10—C11—H11A	109.2
C3—C2—C8	123.1 (3)	C12—C11—H11A	109.2
C4—C3—C2	122.2 (4)	C10—C11—H11B	109.2
C4—C3—H3	118.9	C12—C11—H11B	109.2
C2—C3—H3	118.9	H11A—C11—H11B	107.9
C3—C4—C5	120.2 (4)	C11—C12—C13	111.6 (2)
C3—C4—H4	119.9	C11—C12—H12A	109.3
C5—C4—H4	119.9	C13—C12—H12A	109.3
C4—C5—C6	121.2 (4)	C11—C12—H12B	109.3
C4—C5—H5	119.4	C13—C12—H12B	109.3
C6—C5—H5	119.4	H12A—C12—H12B	108.0
C1—C6—C5	116.2 (3)	C16—C13—C14	112.1 (2)
C1—C6—C7	122.8 (3)	C16—C13—C12	110.4 (2)
C5—C6—C7	121.0 (3)	C14—C13—C12	110.0 (2)
C6—C7—H7A	109.5	C16—C13—H13	108.1
C6—C7—H7B	109.5	C14—C13—H13	108.1
H7A—C7—H7B	109.5	C12—C13—H13	108.1
C6—C7—H7C	109.5	C13—C14—C15	111.7 (2)
H7A—C7—H7C	109.5	C13—C14—H14A	109.3
H7B—C7—H7C	109.5	C15—C14—H14A	109.3
C2—C8—H8A	109.5	C13—C14—H14B	109.3
C2—C8—H8B	109.5	C15—C14—H14B	109.3
H8A—C8—H8B	109.5	H14A—C14—H14B	107.9
C2—C8—H8C	109.5	C14—C15—C10	112.6 (2)
H8A—C8—H8C	109.5	C14—C15—H15A	109.1
H8B—C8—H8C	109.5	C10—C15—H15A	109.1
O1—C9—C10	109.9 (2)	C14—C15—H15B	109.1
O1—C9—H9A	109.7	C10—C15—H15B	109.1
C10—C9—H9A	109.7	H15A—C15—H15B	107.8
O1—C9—H9B	109.7	O3—C16—O2	122.8 (2)
C10—C9—H9B	109.7	O3—C16—C13	119.9 (2)
H9A—C9—H9B	108.2	O2—C16—C13	117.3 (3)
C9—C10—C11	109.9 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O3ⁱ	0.82	1.86	2.658 (3)	166

Symmetry code: (i) −x+3, −y−1, −z+2.

Experimental details

Crystal data
Chemical formula	C₁₆H₂₂O₃
M_r	262.34
Crystal system, space group	Triclinic, P1
Temperature (K)	292
a, b, c (Å)	7.162 (3), 7.680 (4), 14.451 (4)
α, β, γ (°)	95.26 (4), 98.35 (4), 106.44 (3)
V (Å³)	746.9 (6)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.08
Crystal size (mm)	0.60 × 0.52 × 0.42

Data collection
Diffractometer	Enraf–Nonius CAD-4 diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	2886, 2715, 1461
R_int	0.013
(sin θ/λ)_max (Å⁻¹)	0.606

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.066, 0.196, 1.16
No. of reflections	2715
No. of parameters	175
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.18, −0.20

Computer programs: DIFRAC (Gabe & White, 1993), NRCVAX (Gabe et al., 1989), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 1997).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O3ⁱ	0.82	1.86	2.658 (3)	166

Symmetry code: (i) −x+3, −y−1, −z+2.

References

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doi:10.1107/S1600536808035502

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