The 1:1 adduct of Kemp's triacid with 2-aminopyridine

The crystal structure determination of the molecular proton-transfer adduct of Kemp's triacid (cis-cis-1,3,5-tri­methyl­cyclo­hexane-1,3,5-tri­carboxylic acid, KTA) with 2-amino­pyridine (2-APY), namely 2-amino­pyridinium 3,5-di­carboxy-1,3,5-tri­methyl­cyclo­hexane­carboxyl­ate, 2-APY⁺·KTA⁻ or C₅H₇N₂⁺·C₁₂H₁₇O₆⁻, has revealed a centrosymmetric hydrogen-bonded cyclic KTA homodimer repeating unit [O...O 2.524 (4) Å] linked into a polymer structure through the pyridinium and amino groups of the 2-APY mol­ecule [O...N 2.736 (4), 2.989 (4) and 2.999 (4) Å].

S1. Comment

Kemp's triacid (cis-cis-1,3,5-trimethylcyclohexane-1,3,5-tricarboxylic acid, KTA; Kemp & Petrakis, 1981; Hazell & Toftlund, 1999 [120 K]) is a unique triprotic acid, having all of its carboxylic acid groups axially oriented. The crystal structure analysis (Rebek et al., 1985; Chan et al., 1991) also indicated that the molecules had no intramolecular hydrogen-bonding associations between the carboxylic acid groups, as might have been expected with this configuration. Instead, the molecules formed into an unusual convoluted hydrogen-bonded chain structure made up of intermolecular head-to-tail cyclic hydrogen bonds [graph set R₂²(8); Etter, 1990; Etter & MacDonald, 1990], with two at the head and one at the tail. This is also found in the acetonitrile solvate structure (Hirose et al., 1998). This same framework structure is found in the 2:1 adduct of KTA with 8-aminoquinoline (8-AQ), where the chains are linked peripherally by hydrogen bonds through the hetero-N atom and the amino group of the substituted quinoline molecules (Smith et al., 2000). No proton transfer is found in this compound [pK_a1 = 3.3 (KTA) and pK_a2 (hetero-N) = 4.0 (8-AQ)]. This is in contrast with the 1:1 adduct with the analogous compound quinolin-8-ol (8-HQ) (Smith et al., 2000), where proton transfer is found [pK_a2 = 5.0 (hetero-N)] in a structure which no longer retains the KTA chain backbone. Instead, the singly deprotonated KTA molecules form centrosymmetric dimer interactions, which differ from conventional hydrogen-bonded cyclic dimers in that they involve both cis-related carboxylic acid groups. One of these O atoms then links to the protonated hetero-N atom of the 8-HQ molecule, while the 8-hydroxy group of 8-HQ completes the polymer link to an adjacent dimer unit. In addition, a single intermolecular hydrogen bond is found between two of the carboxylic acid groups. This work indicated that Kemp's triacid has particular affinity for the 8-amino-substituted quinoline system, and reinforced the potential of KTA in molecular recognition processes (Bencini et al., 1992, 1994). In a continuation of this work on the self-assembly of KTA in the presence of Lewis bases, a 1:1 adduct, (I), of KTA with 2-aminopyridine was synthesized and the structure determined. \sch

The structure of (I) reveals a proton-transfer complex (Fig. 1), which is analogous to the complex with 8-HQ in having cyclic centrosymmetric hydrogen-bonded dimers [O4—H4···O2ⁱ 2.524 (4) Å and O—H—O 179 (3)°; symmetry code: (i) 1 − x, 1 − y, 1 − z] (Fig. 2). A similar short intramolecular hydrogen bond is also found [O5—H5···O1 2.552 (4) Å and O—H—O 162 (3)°]. The same carboxylate O atom is then linked to the protonated pyridinium N atom of 2-APY [O1···H12—N12 2.736 (4) Å and O—H—N 161 (3)°], while the 2-amino substituent gives a bidentate linkage to a second carboxylate O atom [N22—H2···O3 2.999 (4) Å and N—H—O 162 (3)°]. The second proton of the amino group provides the peripheral linkage between dimer units in the chain polymer structure [N22—H1···O6ⁱⁱ 2.989 (4) Å and N—H—O 158 (3)°; symmetry code: (ii) 1 − x, 1 − y, −z].

Although no further examples of Lewis base adducts with KTA have been isolated, the examples characterized so far indicate that there is a critical minimum pK_a difference (ΔpK_a) between the first dissociation constant for KTA and that for the hetero-N atom of the Lewis base, which determines which structure type exists (chain or dimer variant) [for 8-AQ, ΔpK_a = 0.7 (no proton transfer, chain structure); for 8-HQ, ΔpK_a = 1.7, and for 2-APY, ΔpK_a = 3.4 (both proton transfer, both dimer structures)]. This threshold value appears to be considerably smaller than the corresponding ΔpK_a minimum for the unsubstituted pyridine system (3.5; Johnson & Rumon, 1965). By analogy, the relatively strong nitro-substituted aromatic carboxylic acids [2,4-dinitrobenzoic acid (pK_a = 3.7), 5-nitrosalicylic acid (pK_a = 2.2) and 3,5-dinitrosalicylic acid (pK_a = 2.1)] readily protonate the hetero-N atom in both 8-AQ and 8-HQ, giving 1:1 adducts based on cyclic hydrogen-bonded A—B heterodimers [Smith, Wermuth & White (2000). Unpublished data].

S2. Experimental

The synthesis of (I) was carried out by refluxing equimolar amounts (1 mmol) of 2-aminopyridine and cis-cis-1,3,5-trimethylcyclohexane-1,3,5-tricarboxylic acid for 15 min at ca 350 K in 50% aqueous ethanol (20 ml). Crystals of (I) were obtained by the evaporation of the solvent at room temperature.

S3. Refinement

Only the positional parameters for those H atoms involved in hydrogen bonding (H1, H2, H4, H5 and H12) were refined. All other H atoms were constrained, with C—H 0.95 Å and U_iso = 1.2U_eq of the bonded C atom.

Computing details

Data collection: MSC/AFC Diffractometer Control Software (Molecular Structure Corporation, 1994); cell refinement: MSC/AFC Diffractometer Control Software; data reduction: TEXSAN for Windows (Molecular Structure Corporation, 1997-1999); program(s) used to solve structure: SIR92 (Altomare et al. 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); software used to prepare material for publication: TEXSAN for Windows.

Figures

	Fig. 1. The molecular configuration and atom-labelling scheme for the individual Kemp's triacid anion and the pyridinium cation in (I). Displacement ellipsoids are shown at the 30% probability level and H atoms are drawn as small spheres of arbitrary radii.
	Fig. 2. The dimeric KTA anion units and the cross-linking 2-aminopyridinium cations in (I), with the hydrogen-bonding scheme shown as broken lines.

(I)

Crystal data

C5H7N2^+·C12H17O6^−	Z = 2
Mr = 352.39	F(000) = 376.00
Triclinic, P1	Dx = 1.321 Mg m^−3
a = 8.767 (2) Å	Mo Kα radiation, λ = 0.71070 Å
b = 12.228 (2) Å	Cell parameters from 25 reflections
c = 8.600 (3) Å	θ = 19.4–19.9°
α = 94.12 (2)°	µ = 0.10 mm^−1
β = 90.07 (3)°	T = 293 K
γ = 105.44 (1)°	Plate, colourless
V = 886.2 (4) Å^3	0.3 × 0.2 × 0.1 mm

Data collection

Rigaku AFC-7R diffractometer	Rint = 0.029
Radiation source: Rigaku rotating anode	θmax = 25.0°, θmin = 2.4°
Graphite monochromator	h = 0→10
ω/2θ scans	k = −14→14
3350 measured reflections	l = −10→10
3128 independent reflections	3 standard reflections every 150 reflections
1699 reflections with I > 2σ(I)	intensity decay: −1.8%

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.049	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.168	w = 1/[σ^2(Fo^2) + (0.08P)^2 + 0.369P] where P = (Fo^2 + 2Fc^2)/3
S = 1.02	(Δ/σ)max < 0.001
3128 reflections	Δρmax = 0.36 e Å^−3
242 parameters	Δρmin = −0.36 e Å^−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.022 (5)

Special details

Experimental. The scan width was (1.57 + 0.35tanθ)° with an ω scan speed of 0° per minute (up to 5 scans to achieve I/σ(I) > 15). Stationary background counts were recorded at each end of the scan, and the scan time:background time ratio was 2:1.

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	0.1576 (3)	0.32310 (18)	0.3773 (3)	0.0490 (6)
O2	0.3246 (3)	0.38352 (17)	0.5806 (3)	0.0467 (6)
O3	0.5046 (3)	0.36551 (18)	0.2589 (3)	0.0511 (6)
O4	0.6839 (3)	0.41459 (18)	0.4510 (3)	0.0461 (6)
O5	0.2004 (3)	0.2534 (2)	0.0981 (3)	0.0588 (7)
O6	0.3963 (3)	0.2132 (2)	−0.0291 (3)	0.0626 (7)
N12	0.1598 (3)	0.5149 (2)	0.2311 (3)	0.0453 (7)
N22	0.4167 (4)	0.5671 (3)	0.1445 (4)	0.0539 (8)
C1	0.2729 (3)	0.1882 (2)	0.4907 (4)	0.0361 (7)
C2	0.4448 (4)	0.1909 (2)	0.5323 (4)	0.0380 (7)
C3	0.5623 (3)	0.2171 (2)	0.3987 (4)	0.0357 (7)
C4	0.4990 (4)	0.1328 (2)	0.2567 (4)	0.0405 (8)
C5	0.3263 (4)	0.1160 (3)	0.2029 (4)	0.0404 (8)
C6	0.2175 (4)	0.1070 (2)	0.3445 (4)	0.0410 (8)
C7	0.2527 (3)	0.3081 (2)	0.4802 (4)	0.0379 (7)
C8	0.5825 (3)	0.3405 (2)	0.3611 (4)	0.0338 (7)
C9	0.3143 (4)	0.2017 (3)	0.0847 (4)	0.0461 (8)
C10	0.1660 (4)	0.1406 (3)	0.6265 (4)	0.0509 (9)
C11	0.7229 (4)	0.2016 (3)	0.4501 (5)	0.0536 (10)
C12	0.2726 (5)	0.0006 (3)	0.1030 (5)	0.0604 (10)
C22	0.2736 (4)	0.5835 (3)	0.1522 (4)	0.0395 (7)
C32	0.2322 (4)	0.6703 (3)	0.0773 (4)	0.0477 (8)
C42	0.0822 (4)	0.6812 (3)	0.0858 (5)	0.0554 (10)
C52	−0.0314 (4)	0.6078 (3)	0.1688 (5)	0.0581 (10)
C62	0.0095 (4)	0.5259 (3)	0.2410 (4)	0.0545 (9)
H1	0.491 (4)	0.622 (3)	0.105 (4)	0.042*
H2	0.437 (4)	0.515 (3)	0.198 (4)	0.042*
H5	0.172 (4)	0.263 (3)	0.186 (4)	0.042*
H4	0.681 (4)	0.483 (3)	0.439 (4)	0.042*
H12	0.181 (4)	0.464 (3)	0.274 (4)	0.054*
H21	0.4449	0.1187	0.5660	0.046*
H22	0.4808	0.2476	0.6154	0.046*
H32	0.3095	0.7217	0.0211	0.057*
H41	0.5643	0.1584	0.1713	0.049*
H42	0.0548	0.7398	0.0343	0.067*
H40	0.5097	0.0606	0.2810	0.049*
H52	−0.1365	0.6155	0.1745	0.070*
H61	0.1206	0.1189	0.3099	0.050*
H62	−0.0667	0.4752	0.2992	0.066*
H60	0.1990	0.0318	0.3759	0.050*
H101	0.2214	0.1667	0.7228	0.062*
H102	0.1383	0.0598	0.6156	0.062*
H103	0.0727	0.1660	0.6244	0.062*
H111	0.7263	0.2000	0.5604	0.065*
H112	0.7360	0.1323	0.4027	0.065*
H113	0.8055	0.2633	0.4192	0.065*
H121	0.2429	−0.0596	0.1700	0.073*
H122	0.1850	0.0008	0.0382	0.073*
H123	0.3576	−0.0095	0.0401	0.073*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0429 (13)	0.0421 (13)	0.0659 (16)	0.0160 (10)	−0.0037 (12)	0.0130 (11)
O2	0.0493 (13)	0.0283 (11)	0.0603 (15)	0.0080 (10)	0.0014 (11)	−0.0022 (11)
O3	0.0584 (15)	0.0323 (12)	0.0620 (16)	0.0099 (11)	−0.0163 (12)	0.0085 (11)
O4	0.0437 (13)	0.0266 (11)	0.0643 (15)	0.0035 (10)	−0.0103 (11)	0.0011 (11)
O5	0.0587 (16)	0.0663 (17)	0.0560 (16)	0.0225 (14)	−0.0104 (14)	0.0128 (14)
O6	0.0634 (16)	0.0709 (18)	0.0478 (15)	0.0062 (13)	−0.0005 (13)	0.0120 (13)
N12	0.0524 (18)	0.0379 (15)	0.0484 (17)	0.0143 (13)	0.0019 (14)	0.0122 (13)
N22	0.0474 (18)	0.056 (2)	0.066 (2)	0.0225 (15)	0.0047 (15)	0.0214 (16)
C1	0.0371 (16)	0.0258 (14)	0.0444 (18)	0.0052 (12)	0.0025 (14)	0.0077 (13)
C2	0.0448 (18)	0.0273 (15)	0.0425 (18)	0.0097 (13)	−0.0003 (14)	0.0067 (13)
C3	0.0360 (16)	0.0271 (15)	0.0457 (18)	0.0102 (12)	−0.0025 (14)	0.0071 (13)
C4	0.0450 (18)	0.0275 (15)	0.051 (2)	0.0129 (13)	0.0019 (15)	0.0015 (14)
C5	0.0435 (18)	0.0317 (16)	0.0434 (19)	0.0056 (13)	−0.0026 (15)	0.0017 (14)
C6	0.0383 (17)	0.0266 (15)	0.057 (2)	0.0046 (13)	−0.0006 (15)	0.0086 (14)
C7	0.0320 (16)	0.0305 (16)	0.051 (2)	0.0067 (13)	0.0101 (15)	0.0081 (15)
C8	0.0273 (15)	0.0280 (15)	0.0464 (18)	0.0072 (12)	0.0046 (14)	0.0053 (14)
C9	0.0420 (19)	0.0450 (19)	0.045 (2)	0.0013 (15)	−0.0080 (17)	0.0040 (16)
C10	0.055 (2)	0.0381 (18)	0.056 (2)	0.0040 (15)	0.0097 (17)	0.0108 (16)
C11	0.047 (2)	0.0428 (19)	0.076 (3)	0.0209 (16)	−0.0098 (18)	0.0074 (18)
C12	0.066 (2)	0.041 (2)	0.065 (3)	0.0024 (17)	0.000 (2)	−0.0131 (18)
C22	0.0391 (18)	0.0354 (17)	0.0443 (19)	0.0107 (14)	−0.0047 (15)	0.0018 (14)
C32	0.0471 (19)	0.0389 (18)	0.058 (2)	0.0102 (15)	−0.0039 (16)	0.0150 (16)
C42	0.057 (2)	0.0440 (19)	0.070 (3)	0.0229 (17)	−0.0165 (19)	0.0031 (18)
C52	0.042 (2)	0.062 (2)	0.074 (3)	0.0222 (18)	−0.0018 (18)	−0.003 (2)
C62	0.046 (2)	0.052 (2)	0.062 (2)	0.0077 (17)	0.0117 (17)	0.0035 (18)

Geometric parameters (Å, º)

O1—C7	1.271 (4)	C4—H41	0.95
O2—C7	1.252 (4)	C4—H40	0.95
O3—C8	1.217 (3)	C5—C9	1.534 (5)
O4—C8	1.295 (4)	C5—C6	1.539 (5)
O4—H4	0.86 (3)	C5—C12	1.556 (5)
O5—C9	1.317 (4)	C6—H61	0.95
O5—H5	0.81 (3)	C6—H60	0.95
O6—C9	1.210 (4)	C10—H101	0.95
N12—C22	1.340 (4)	C10—H102	0.95
N12—C62	1.361 (5)	C10—H103	0.95
N12—H12	0.81 (4)	C11—H111	0.95
N22—C22	1.323 (4)	C11—H112	0.95
N22—H1	0.89 (3)	C11—H113	0.95
N22—H2	0.87 (3)	C12—H121	0.95
C1—C7	1.531 (4)	C12—H122	0.95
C1—C6	1.538 (5)	C12—H123	0.95
C1—C2	1.539 (4)	C22—C32	1.406 (4)
C1—C10	1.547 (4)	C32—C42	1.358 (5)
C2—C3	1.537 (4)	C32—H32	0.95
C2—H21	0.95	C42—C52	1.387 (5)
C2—H22	0.95	C42—H42	0.95
C3—C8	1.530 (4)	C52—C62	1.341 (5)
C3—C11	1.538 (4)	C52—H52	0.95
C3—C4	1.542 (4)	C62—H62	0.95
C4—C5	1.538 (4)
C8—O4—H4	113 (2)	H61—C6—H60	109.5
C9—O5—H5	115 (2)	O2—C7—O1	124.3 (3)
C22—N12—C62	123.3 (3)	O2—C7—C1	117.2 (3)
C22—N12—H12	118 (3)	O1—C7—C1	118.4 (3)
C62—N12—H12	119 (3)	O3—C8—O4	123.8 (3)
C22—N22—H1	116 (2)	O3—C8—C3	122.0 (3)
C22—N22—H2	118 (2)	O4—C8—C3	114.2 (3)
H1—N22—H2	123 (3)	O6—C9—O5	119.4 (3)
C7—C1—C6	114.8 (3)	O6—C9—C5	121.0 (3)
C7—C1—C2	111.8 (2)	O5—C9—C5	119.1 (3)
C6—C1—C2	109.2 (2)	C1—C10—H101	109.4
C7—C1—C10	104.2 (2)	C1—C10—H102	109.4
C6—C1—C10	107.8 (2)	H101—C10—H102	109.5
C2—C1—C10	108.7 (3)	C1—C10—H103	109.4
C3—C2—C1	115.3 (3)	H101—C10—H103	109.5
C3—C2—H21	108.0	H102—C10—H103	109.5
C1—C2—H21	108.1	C3—C11—H111	109.4
C3—C2—H22	107.9	C3—C11—H112	109.6
C1—C2—H22	108.0	H111—C11—H112	109.5
H21—C2—H22	109.4	C3—C11—H113	109.4
C8—C3—C2	108.4 (2)	H111—C11—H113	109.4
C8—C3—C11	109.6 (2)	H112—C11—H113	109.5
C2—C3—C11	109.5 (3)	C5—C12—H121	109.4
C8—C3—C4	111.9 (2)	C5—C12—H122	109.5
C2—C3—C4	109.1 (2)	H121—C12—H122	109.6
C11—C3—C4	108.4 (2)	C5—C12—H123	109.4
C5—C4—C3	118.1 (2)	H121—C12—H123	109.5
C5—C4—H41	107.3	H122—C12—H123	109.5
C3—C4—H41	107.2	N22—C22—N12	120.4 (3)
C5—C4—H40	107.3	N22—C22—C32	122.6 (3)
C3—C4—H40	107.3	N12—C22—C32	117.0 (3)
H41—C4—H40	109.4	C42—C32—C22	120.0 (3)
C9—C5—C4	111.1 (3)	C42—C32—H32	120.0
C9—C5—C6	117.5 (3)	C22—C32—H32	119.9
C4—C5—C6	110.4 (3)	C32—C42—C52	120.7 (3)
C9—C5—C12	102.2 (3)	C32—C42—H42	119.6
C4—C5—C12	108.1 (3)	C52—C42—H42	119.7
C6—C5—C12	106.9 (3)	C62—C52—C42	118.8 (3)
C1—C6—C5	119.0 (2)	C62—C52—H52	120.6
C1—C6—H61	107.0	C42—C52—H52	120.6
C5—C6—H61	107.1	C52—C62—N12	120.2 (3)
C1—C6—H60	107.0	C52—C62—H62	119.9
C5—C6—H60	107.1	N12—C62—H62	119.9
C7—C1—C2—C3	−75.4 (3)	C2—C1—C7—O1	143.7 (3)
C6—C1—C2—C3	52.8 (3)	C10—C1—C7—O1	−99.1 (3)
C10—C1—C2—C3	170.2 (2)	C2—C3—C8—O3	−94.3 (3)
C1—C2—C3—C8	67.9 (3)	C11—C3—C8—O3	146.3 (3)
C1—C2—C3—C11	−172.7 (2)	C4—C3—C8—O3	26.0 (4)
C1—C2—C3—C4	−54.1 (3)	C2—C3—C8—O4	83.2 (3)
C8—C3—C4—C5	−70.4 (3)	C11—C3—C8—O4	−36.3 (4)
C2—C3—C4—C5	49.5 (3)	C4—C3—C8—O4	−156.6 (3)
C11—C3—C4—C5	168.7 (3)	C4—C5—C9—O6	51.7 (4)
C3—C4—C5—C9	88.9 (3)	C6—C5—C9—O6	−180.0 (3)
C3—C4—C5—C6	−43.2 (3)	C12—C5—C9—O6	−63.4 (4)
C3—C4—C5—C12	−159.8 (3)	C4—C5—C9—O5	−136.4 (3)
C7—C1—C6—C5	79.5 (3)	C6—C5—C9—O5	−8.1 (4)
C2—C1—C6—C5	−47.1 (3)	C12—C5—C9—O5	108.5 (3)
C10—C1—C6—C5	−164.9 (3)	C62—N12—C22—N22	−178.7 (3)
C9—C5—C6—C1	−86.6 (3)	C62—N12—C22—C32	0.0 (5)
C4—C5—C6—C1	42.2 (4)	N22—C22—C32—C42	178.2 (4)
C12—C5—C6—C1	159.5 (3)	N12—C22—C32—C42	−0.5 (5)
C6—C1—C7—O2	−165.6 (3)	C22—C32—C42—C52	0.4 (6)
C2—C1—C7—O2	−40.4 (4)	C32—C42—C52—C62	0.2 (6)
C10—C1—C7—O2	76.7 (3)	C42—C52—C62—N12	−0.6 (6)
C6—C1—C7—O1	18.5 (4)	C22—N12—C62—C52	0.5 (6)