Inversion dimers dominate the crystal packing in the structure of trimethyl citrate (trimethyl 2-hy-droxy-propane-1,2,3-tri-carboxyl-ate).

Trimethyl citrate, C9H14O7 (systematic name: trimethyl 2-hy-droxy-propane-1,2,3-tri-carboxyl-ate), 2, was prepared by the esterification of citric acid and methanol in the presence of thionyl chloride at 273 K. The bond lengths and angles in 2 compare closely with those observed in citric acid. The C-C bonds adjacent to the terminal carboxyl groups are significantly shorter than those around the central C atom. The central carboxyl-ate group and the hy-droxy group occur in the normal planar arrangement with an r.m.s. deviation of 0.0171 Å from the mean plane involving all six atoms in the central unit. The crystal structure is almost completely dominated by the formation of inversion dimers through an O-H⋯O hydrogen bond, together with an extensive array of weaker C-H⋯O contacts. These generate a three-dimensional network structure with mol-ecules stacked along the c-axis direction.

Chemical context

Esters of citric acid have received significant attention because of their many applications. Their use as plasticizers has grown because of their low toxicity, compatibility with the host materials and low volatility (Labrecque et al., 1997 ▸; Garg et al., 2014 ▸). They were investigated for use in degradable thermoset polymers (Halpern et al., 2014 ▸). In the biological field, trimethyl citrate is used to synthesize citrate-functionalized ciprofloxacin conjugates and their anti­microbial activities have been determined against a panel of clinically-relevant bacteria (Md-Saleh et al., 2009 ▸). Several different methods and catalysts have been employed for the synthesis of trimethyl citrate from citric acid and methanol using, for example, thionyl chloride (Ilewska & Chimiak, 1994 ▸) and zirconium(IV) dichloride oxide hydrate (Sun et al., 2006 ▸). We report here the esterification of citric acid to form trimethyl citrate, 2, together with its mol­ecular and crystal structure.

Structural commentary

The title compound, 2, crystallizes in the triclinic space group P , with one mol­ecule in the asymmetric unit. The mol­ecular structure of the compound, with the atom labelling, is shown in Fig. 1 ▸. The bond lengths and angles in 2 are comparable to those observed in citric acid, 1 (Glusker et al., 1969 ▸; Roelofsen & Kanters, 1972 ▸; King et al., 2011 ▸). The C2—C3 and C5—C6 bonds [1.506 (2) and 1.502 (2) Å, respectively] that bridge the outer terminal carboxyl groups are significantly shorter than those around the central C4 atom [C3—C4 = 1.5405 (19), C4—C5 = 1.5348 (19) and C4—C8 = 1.5398 (18) Å], an observation that mirrors what occurs in glycine itself. The carbonyl groups C2—O2, C8—O7 and C6—O5 are clearly double bonds with similar bond lengths [1.2046 (18), 1.2036 (18) and 1.2082 (18) Å, respectively]. Furthermore, the marked discrepancy between the C(=O)—O and O—Me distances, with the latter significantly longer in all instances, reflects considerable delocalization in the C(=O)—O units. This is again consistent with what is seen in other similar structures. The central carboxyl­ate group and the hydroxy group occur in the normal planar arrangement, with an O3—C4—C8—O6 torsion angle of −178.95 (11)° and an r.m.s. deviation of only 0.0171 Å from the best-fit mean plane through the O3, C4, C8, O7, O6 and C9 atoms.

Figure 1

The structure of 2, showing the atom numbering, with ellipsoids drawn at the 50% probability level.

Supra­molecular features

In the crystal, classical O3—H3⋯O5 hydrogen bonds form inversion dimers enclosing (12) rings. These contacts are supported by weaker inversion-related C7—H7C⋯O7v hydrogen bonds with (16) ring motifs (Table 1 ▸). These dimers are linked into chains parallel to (10) by inversion-related C9—H9B⋯O2iii contacts that also form (16) rings (Fig. 2 ▸). H atoms from both of the methyl­ene groups in the mol­ecule are also involved in inversion-dimer formation. Pairs of C3—H3A⋯O1iii hydrogen bonds enclose (8) rings that are linked by (12) ring C5—H5A⋯O2iv inter­actions into chains along the a-axis direction. Weaker C9—H9B⋯O3vi hydrogen bonds further stabilize these chains (Fig. 3 ▸). The (12) ring C5—H5A⋯O2iv inter­actions, mentioned previously, form more chains, this time linking another set of inversion dimers involving the (10) ring C9—H9C⋯O7vii contacts. These contacts form chains of dimers that run along the ac diagonal (Fig. 4 ▸).

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C1—H1B⋯O4i	0.98	2.65	3.393 (2)	133
C1—H1C⋯O5ii	0.98	2.56	3.520 (2)	167
C3—H3A⋯O1iii	0.99	2.66	3.6388 (18)	170
C5—H5A⋯O2iv	0.99	2.51	3.4610 (18)	160
C7—H7C⋯O7v	0.98	2.53	3.3008 (19)	135
C9—H9B⋯O2iii	0.98	2.61	3.423 (2)	140
C9—H9B⋯O3vi	0.98	2.64	3.2576 (17)	121
C9—H9C⋯O7vii	0.98	2.61	3.4147 (19)	140
O3—H3⋯O5v	0.80 (2)	2.14 (2)	2.8428 (15)	147 (2)

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) ; (v) ; (vi) ; (vii) .

Figure 2

A view along c of chains of mol­ecules of 2 formed along (10) from pairs of inversion dimers.

Figure 3

Chains of mol­ecules of 2 along the a-axis direction formed from pairs of inversion dimers.

Figure 4

Pairs of inversion dimers that link mol­ecules of 2 into chains along the ac diagonal.

The only significant inter­molecular contacts in the crystal structure not to result in inversion-dimer formation involve weak C—H⋯O hydrogen bonds formed by the peripheral C1 and central C9 methyl groups. C1 acts as a bifurcated donor forming C1—H1B⋯O4i and C1—H1C⋯O5ii contacts that combine with C9—H9B⋯O3vi hydrogen bonds to generate a sheet of mol­ecules in the ab plane (Fig. 5 ▸). Overall, this extensive array of both classical and nonclassical inter­molecular contacts generates a three-dimensional network structure with mol­ecules stacked along the c-axis direction (Fig. 6 ▸).

Figure 5

A view along c of the sheet of mol­ecules of 2 formed in the ab plane by weak C—H⋯O hydrogen bonds.

Figure 6

The overall packing of 2 viewed along the c-axis direction.

Database survey

A search of the Cambridge Structural Database (Version 5.39, updated February 2018; Groom et al., 2016 ▸) for the title compound gave no hits. In contrast, a search for the O2CCH2C(O)(CO2)CH2CO2 fragment incorporating both organic and metal organic structures gave an impressive 404 hits. Limiting the search to organic structures, which eliminates the numerous metals salts of the citrate anions and the use of citrate as a ligand, reduced the hits to 124. In what follows, with few exceptions, only one or two recent examples of the plethora of different related systems are cited. The structure of citric acid itself has been reported several times, both in isolation (Glusker et al., 1969 ▸) and as the monohydrate (Roelofsen & Kanters, 1972 ▸; King et al., 2011 ▸). Eighteen examples of citric acid cocrystallized with various organic bases are also found (see, for example, Kerr et al., 2016 ▸; Wang et al., 2016 ▸). This search also revealed a lone neutral 1,5-di­methyl citrate (Li et al., 2007a ▸) and a single monoanionic dimethyl citrate derivative, (−)-brucinium (R)-1,2-di­methyl­citrate hydrate (Bergeron et al., 1997 ▸), with no related dianions. No examples of 1-methyl citrate or any of its anions were found, but 6-methyl citrate with the carboxyl­ate group on the central C atom has been reported (Li et al., 2007b ▸; Aliyu et al., 2009 ▸). In contrast, structures of more than 80 citrate anions have been reported; these included 48 monoanions with the proton lost from both the central (Inukai et al., 2017 ▸; Wang et al., 2017 ▸) and peripheral carboxyl­ate OH groups (Abraham et al., 2016 ▸; Rammohan & Kaduk, 2016a ▸). Sixteen examples of citrate dianions (Rammohan & Kaduk, 2016b ▸, 2017a ▸) and 17 citrate trianions (Rammohan & Kaduk, 2017b ▸,c ▸) were also found.

Synthesis and crystallization

Citric acid (0.01 mol, 2.00 g) was dissolved in absolute methanol (50 mL) and the solution was cooled in an ice-bath under a nitro­gen atmosphere. To this solution, thionyl chloride (0.08 mol, 6.0 mL) was added dropwise with efficient stirring at 273 K for 1 h and the solution was left stirring overnight at 298 K (Fig. 7 ▸). The solvent was removed in vacuo and the solid residue was dissolved in ethyl acetate (15 mL), dried over MgSO4 and filtered. The solvent was removed under reduced pressure and the solid residue was purified by recrystallization from hexa­ne/ethyl acetate (1:3 v/v) to yield 1.6 g (80%) of the title compound as white crystals.

Figure 7

The synthesis of the title compound (2).

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. Atom H3 of the OH group was located in a difference Fourier map and its coordinates refined with U iso(H) = 1.5U eq(O). The resulting O3—H3 distance of 0.80 (2) Å was acceptable. All H atoms bound to carbon were refined using a riding model, with C—H = 0.99 Å and U iso(H) = 1.2U eq(C) for CH2 H atoms, and C—H = 0.98 Å and U iso(H) = 1.5U eq(C) for CH3 H atoms.

Table 2

Experimental details

Crystal data
Chemical formula	C9H14O7
M r	234.20
Crystal system, space group	Triclinic, P
Temperature (K)	150
a, b, c (Å)	7.8428 (3), 8.0256 (3), 9.3965 (3)
α, β, γ (°)	109.915 (1), 92.832 (1), 104.493 (1)
V (Å3)	532.46 (3)
Z	2
Radiation type	Cu Kα
μ (mm−1)	1.11
Crystal size (mm)	0.24 × 0.16 × 0.10
Data collection
Diffractometer	Bruker APEXII CCD
Absorption correction	Multi-scan (SADABS; Bruker, 2001 ▸)
T min, T max	0.769, 0.897
No. of measured, independent and observed [I > 2σ(I)] reflections	4914, 1989, 1873
R int	0.030
(sin θ/λ)max (Å−1)	0.618
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.038, 0.110, 1.08
No. of reflections	1989
No. of parameters	151
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)	0.30, −0.28

Computer programs: APEX2 (Bruker, 2003 ▸), SAINT (Bruker, 2003 ▸), SHELXS97 (Sheldrick, 2008 ▸), Mercury (Macrae et al., 2008 ▸), SHELXL2018 (Sheldrick, 2015 ▸), PLATON (Spek, 2009 ▸), publCIF (Westrip 2010 ▸) and WinGX (Farrugia 2012 ▸).

Crystal structure: contains datablock(s) I. DOI: 10.1107/S2056989018011222/sj5563sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989018011222/sj5563Isup2.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989018011222/sj5563Isup3.cml

CCDC reference: 1500726

Additional supporting information: crystallographic information; 3D view; checkCIF report

C9H14O7	Z = 2
Mr = 234.20	F(000) = 248
Triclinic, P1	Dx = 1.461 Mg m−3
a = 7.8428 (3) Å	Cu Kα radiation, λ = 1.54178 Å
b = 8.0256 (3) Å	Cell parameters from 3559 reflections
c = 9.3965 (3) Å	θ = 5.1–72.3°
α = 109.915 (1)°	µ = 1.11 mm−1
β = 92.832 (1)°	T = 150 K
γ = 104.493 (1)°	Block, colourless
V = 532.46 (3) Å3	0.24 × 0.16 × 0.10 mm

Bruker APEXII CCD diffractometer	1873 reflections with I > 2σ(I)
Radiation source: X-ray, X-ray	Rint = 0.030
φ and ω scans	θmax = 72.3°, θmin = 5.1°
Absorption correction: multi-scan (SADABS; Bruker, 2001)	h = −9→9
Tmin = 0.769, Tmax = 0.897	k = −9→9
4914 measured reflections	l = −11→11
1989 independent reflections

Refinement on F2	0 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.038	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.110	w = 1/[σ2(Fo2) + (0.0525P)2 + 0.2284P] where P = (Fo2 + 2Fc2)/3
S = 1.08	(Δ/σ)max < 0.001
1989 reflections	Δρmax = 0.30 e Å−3
151 parameters	Δρmin = −0.28 e Å−3

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	Uiso*/Ueq
C1	0.0409 (2)	−0.2623 (3)	0.7299 (2)	0.0381 (4)
H1A	−0.005169	−0.376371	0.639926	0.057*
H1B	−0.050722	−0.248183	0.796766	0.057*
H1C	0.146568	−0.268417	0.785887	0.057*
C2	0.22424 (19)	−0.0992 (2)	0.60115 (16)	0.0219 (3)
C3	0.26796 (18)	0.0716 (2)	0.56095 (16)	0.0207 (3)
H3A	0.160716	0.074354	0.502631	0.025*
H3B	0.361749	0.065717	0.494144	0.025*
C4	0.33242 (18)	0.25094 (19)	0.70328 (15)	0.0186 (3)
C5	0.40405 (19)	0.4110 (2)	0.64816 (16)	0.0212 (3)
H5A	0.503632	0.387793	0.590925	0.025*
H5B	0.308690	0.413571	0.576515	0.025*
C6	0.46821 (18)	0.5968 (2)	0.77536 (16)	0.0207 (3)
C7	0.6601 (2)	0.8984 (2)	0.8491 (2)	0.0328 (4)
H7A	0.565562	0.957176	0.844474	0.049*
H7B	0.768047	0.965634	0.821830	0.049*
H7C	0.685307	0.900853	0.953140	0.049*
C8	0.18196 (18)	0.28329 (18)	0.79919 (16)	0.0196 (3)
C9	−0.0983 (2)	0.3424 (2)	0.80083 (18)	0.0269 (3)
H9A	−0.130073	0.261138	0.858908	0.040*
H9B	−0.201720	0.322531	0.727756	0.040*
H9C	−0.061107	0.471599	0.871360	0.040*
O1	0.08823 (14)	−0.10558 (15)	0.68144 (14)	0.0288 (3)
O2	0.30055 (15)	−0.21698 (16)	0.56613 (13)	0.0314 (3)
O3	0.47114 (14)	0.22946 (16)	0.79070 (12)	0.0238 (3)
H3	0.472 (3)	0.284 (3)	0.880 (3)	0.036*
O4	0.60317 (14)	0.70848 (14)	0.74259 (12)	0.0262 (3)
O5	0.40234 (14)	0.64142 (15)	0.89107 (12)	0.0286 (3)
O6	0.04717 (13)	0.30097 (14)	0.71842 (11)	0.0220 (3)
O7	0.18789 (15)	0.29190 (16)	0.92982 (12)	0.0277 (3)

	U11	U22	U33	U12	U13	U23
C1	0.0306 (9)	0.0363 (9)	0.0600 (12)	0.0126 (7)	0.0154 (8)	0.0297 (9)
C2	0.0185 (7)	0.0249 (7)	0.0202 (7)	0.0083 (6)	−0.0007 (6)	0.0046 (6)
C3	0.0189 (7)	0.0253 (7)	0.0174 (7)	0.0085 (6)	0.0025 (5)	0.0056 (6)
C4	0.0160 (6)	0.0241 (7)	0.0160 (6)	0.0075 (5)	0.0018 (5)	0.0064 (5)
C5	0.0198 (7)	0.0260 (7)	0.0179 (7)	0.0071 (6)	0.0045 (5)	0.0076 (6)
C6	0.0164 (6)	0.0254 (7)	0.0209 (7)	0.0074 (5)	−0.0007 (5)	0.0088 (6)
C7	0.0347 (9)	0.0226 (8)	0.0398 (9)	0.0053 (6)	0.0003 (7)	0.0123 (7)
C8	0.0194 (7)	0.0188 (6)	0.0200 (7)	0.0062 (5)	0.0039 (6)	0.0055 (5)
C9	0.0188 (7)	0.0300 (8)	0.0304 (8)	0.0102 (6)	0.0073 (6)	0.0065 (6)
O1	0.0232 (5)	0.0287 (6)	0.0427 (7)	0.0120 (4)	0.0118 (5)	0.0189 (5)
O2	0.0350 (6)	0.0325 (6)	0.0339 (6)	0.0205 (5)	0.0107 (5)	0.0124 (5)
O3	0.0214 (5)	0.0358 (6)	0.0168 (5)	0.0152 (4)	0.0022 (4)	0.0078 (4)
O4	0.0247 (5)	0.0243 (5)	0.0306 (6)	0.0053 (4)	0.0054 (4)	0.0121 (4)
O5	0.0255 (6)	0.0327 (6)	0.0213 (5)	0.0058 (5)	0.0045 (4)	0.0037 (4)
O6	0.0166 (5)	0.0272 (5)	0.0212 (5)	0.0093 (4)	0.0026 (4)	0.0054 (4)
O7	0.0326 (6)	0.0366 (6)	0.0221 (5)	0.0174 (5)	0.0112 (4)	0.0145 (5)

C1—O1	1.4497 (19)	C5—H5B	0.9900
C1—H1A	0.9800	C6—O5	1.2083 (18)
C1—H1B	0.9800	C6—O4	1.3279 (18)
C1—H1C	0.9800	C7—O4	1.4494 (19)
C2—O2	1.2047 (18)	C7—H7A	0.9800
C2—O1	1.3372 (18)	C7—H7B	0.9800
C2—C3	1.506 (2)	C7—H7C	0.9800
C3—C4	1.5405 (19)	C8—O7	1.2036 (18)
C3—H3A	0.9900	C8—O6	1.3352 (17)
C3—H3B	0.9900	C9—O6	1.4537 (17)
C4—O3	1.4107 (16)	C9—H9A	0.9800
C4—C5	1.5348 (19)	C9—H9B	0.9800
C4—C8	1.5398 (18)	C9—H9C	0.9800
C5—C6	1.502 (2)	O3—H3	0.80 (2)
C5—H5A	0.9900
O1—C1—H1A	109.5	C4—C5—H5B	108.8
O1—C1—H1B	109.5	H5A—C5—H5B	107.7
H1A—C1—H1B	109.5	O5—C6—O4	124.07 (14)
O1—C1—H1C	109.5	O5—C6—C5	124.44 (13)
H1A—C1—H1C	109.5	O4—C6—C5	111.46 (12)
H1B—C1—H1C	109.5	O4—C7—H7A	109.5
O2—C2—O1	123.32 (14)	O4—C7—H7B	109.5
O2—C2—C3	125.04 (13)	H7A—C7—H7B	109.5
O1—C2—C3	111.64 (12)	O4—C7—H7C	109.5
C2—C3—C4	112.59 (11)	H7A—C7—H7C	109.5
C2—C3—H3A	109.1	H7B—C7—H7C	109.5
C4—C3—H3A	109.1	O7—C8—O6	125.36 (13)
C2—C3—H3B	109.1	O7—C8—C4	123.63 (13)
C4—C3—H3B	109.1	O6—C8—C4	111.01 (11)
H3A—C3—H3B	107.8	O6—C9—H9A	109.5
O3—C4—C5	110.16 (11)	O6—C9—H9B	109.5
O3—C4—C8	109.64 (11)	H9A—C9—H9B	109.5
C5—C4—C8	111.26 (11)	O6—C9—H9C	109.5
O3—C4—C3	106.41 (11)	H9A—C9—H9C	109.5
C5—C4—C3	107.72 (11)	H9B—C9—H9C	109.5
C8—C4—C3	111.52 (11)	C2—O1—C1	115.46 (12)
C6—C5—C4	113.73 (11)	C4—O3—H3	109.9 (15)
C6—C5—H5A	108.8	C6—O4—C7	115.72 (12)
C4—C5—H5A	108.8	C8—O6—C9	115.65 (11)
C6—C5—H5B	108.8
O2—C2—C3—C4	−116.42 (15)	C5—C4—C8—O7	−120.73 (15)
O1—C2—C3—C4	63.70 (15)	C3—C4—C8—O7	118.97 (15)
C2—C3—C4—O3	51.89 (14)	O3—C4—C8—O6	−178.93 (11)
C2—C3—C4—C5	170.01 (11)	C5—C4—C8—O6	58.96 (15)
C2—C3—C4—C8	−67.63 (15)	C3—C4—C8—O6	−61.34 (15)
O3—C4—C5—C6	−65.67 (14)	O2—C2—O1—C1	2.2 (2)
C8—C4—C5—C6	56.14 (15)	C3—C2—O1—C1	−177.89 (13)
C3—C4—C5—C6	178.65 (11)	O5—C6—O4—C7	−5.5 (2)
C4—C5—C6—O5	−34.35 (19)	C5—C6—O4—C7	172.48 (12)
C4—C5—C6—O4	147.68 (12)	O7—C8—O6—C9	3.0 (2)
O3—C4—C8—O7	1.38 (19)	C4—C8—O6—C9	−176.68 (11)

D—H···A	D—H	H···A	D···A	D—H···A
C1—H1B···O4i	0.98	2.65	3.393 (2)	133
C1—H1C···O5ii	0.98	2.56	3.520 (2)	167
C3—H3A···O1iii	0.99	2.66	3.6388 (18)	170
C5—H5A···O2iv	0.99	2.51	3.4610 (18)	160
C7—H7C···O7v	0.98	2.53	3.3008 (19)	135
C9—H9B···O2iii	0.98	2.61	3.423 (2)	140
C9—H9B···O3vi	0.98	2.64	3.2576 (17)	121
C9—H9C···O7vii	0.98	2.61	3.4147 (19)	140
O3—H3···O5v	0.80 (2)	2.14 (2)	2.8428 (15)	147 (2)