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

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.

Key indicators

• Single-crystal X-ray study
• T = 292 K
• Mean [sigma](C-C) = 0.005 Å
• R factor = 0.066
• wR factor = 0.196
• Data-to-parameter ratio = 15.5

checkCIF/PLATON results

No syntax errors found



Alert level C
            Value of measurement temperature given =   292.000
            Value of melting point given =     0.000
PLAT029_ALERT_3_C _diffrn_measured_fraction_theta_full Low .......       0.97
PLAT242_ALERT_2_C Check Low       Ueq as Compared to Neighbors for         C2
PLAT242_ALERT_2_C Check Low       Ueq as Compared to Neighbors for         C6
PLAT242_ALERT_2_C Check Low       Ueq as Compared to Neighbors for        C16
PLAT340_ALERT_3_C Low Bond Precision on C-C Bonds (x 1000) Ang ...          5
PLAT234_ALERT_4_C Large Hirshfeld Difference O2     --  C16     ..       0.11  Ang.
PLAT234_ALERT_4_C Large Hirshfeld Difference C2     --  C3      ..       0.13  Ang.
PLAT234_ALERT_4_C Large Hirshfeld Difference C4     --  C5      ..       0.11  Ang.
PLAT380_ALERT_4_C Check Incorrectly? Oriented X(sp2)-Methyl Moiety         C7

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   9 ALERT level C = Check and explain
   0 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   3 ALERT type 2 Indicator that the structure model may be wrong or deficient
   2 ALERT type 3 Indicator that the structure quality may be low
   4 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. Comment

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

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)

S2. Experimental

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.

S3. Refinement

H atoms were positioned geometrically (O—H = 0.82 Å and C—H = 0.93–0.98 Å) and refined using a riding model, with U_iso(H) = 1.2–1.5U_eq(C). A rotating group model was used for methyl and hydroxyl groups.

Computing details

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

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

Crystal data

C16H22O3	Z = 2
Mr = 262.34	F(000) = 284
Triclinic, P1	Dx = 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) Å^3

Data collection

Enraf–Nonius CAD-4 diffractometer	Rint = 0.013
Radiation source: fine-focus sealed tube	θmax = 25.5°, θmin = 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

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.066	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.196	H-atom parameters constrained
S = 1.16	w = 1/[σ^2(Fo^2) + (0.0902P)^2 + 0.0605P] where P = (Fo^2 + 2Fc^2)/3
2715 reflections	(Δ/σ)max = 0.001
175 parameters	Δρmax = 0.18 e Å^−3
0 restraints	Δρmin = −0.20 e Å^−3

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.

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 (Ų)

	x	y	z	Uiso*/Ueq
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 (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
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)

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)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O3^i	0.82	1.86	2.658 (3)	166

Symmetry code: (i) −x+3, −y−1, −z+2.