1,4,8,11-Tetra­kis(carboxy­meth­yl)-5,5,7,12,12,14-hexa­methyl-4,11-diaza-1,8-diazo­niacyclo­tetra­decane dichloride dihydrate

Abstract

The title compound, C₂₄H₄₆N₄O₈ ²⁺·2Cl⁻·2H₂O, was synthes­ized by the hydrolysis of tetra­ethyl 2,2′,2′′,2′′′-(5,5,7,12,12,14-hexa­methyl-1,4,8,11-tetra­azacyclo­tetra­decane-1,4,8,11-tetra­yl) tetra­acetate in hydro­chloric acid solution. The crystal structure of the title compound consists of a 14-membered C₁₀N₄ centrosymmetric cationic macrocycle which inter­acts with the chloride ions and water mol­ecules of crystallization to give a three-dimensional hydrogen-bonded network.

Related literature

For related literature, see: Marinelli et al. (2002 ▶); Wang (2001 ▶); Xu et al. (1988 ▶).

Experimental

Crystal data

• C₂₄H₄₆N₄O₈ ²⁺·2Cl⁻·2H₂O

• M _r = 625.58

• Monoclinic,

• a = 9.977 (5) Å

• b = 13.475 (7) Å

• c = 11.572 (6) Å

• β = 104.220 (9)°

• V = 1508.1 (13) ų

• Z = 2

• Mo Kα radiation

• μ = 0.27 mm⁻¹

• T = 293 (2) K

• 0.10 × 0.10 × 0.08 mm

Data collection

• Bruker SMART CCD area-detector diffractometer

• Absorption correction: none

• 15242 measured reflections

• 2946 independent reflections

• 2036 reflections with I > 2σ(I)

• R _int = 0.143

Refinement

• R[F ² > 2σ(F ²)] = 0.056

• wR(F ²) = 0.141

• S = 0.98

• 2946 reflections

• 194 parameters

• H atoms treated by a mixture of independent and constrained refinement

• Δρ_max = 0.63 e Å⁻³

• Δρ_min = −0.37 e Å⁻³

Data collection: SMART (Bruker, 2001 ▶); cell refinement: SAINT (Bruker, 2001 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and local programs.

Supplementary Material

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O4—H4⋯Cl1i	0.82	2.24	3.012 (3)	158
O2—H2A⋯O1Wii	0.82	1.82	2.610 (3)	162
O1W—H2W⋯Cl1iii	0.76 (3)	2.40 (3)	3.152 (3)	169 (3)

Symmetry codes: (i) ; (ii) ; (iii) .

supplementary crystallographic information

Comment

N-functionalized macrocyclic acids are an important class of compounds for their utility as MRI contrast agents (Marinelli et al., 2002) and their strong chelating ability (Xu et al., 1988). For this reason, we have synthesized the title compound by the hydrolysis of tetraethyl 2,2',2'',2'''-(5,5,7,12,12,14-hexamethyl- 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetrayl) tetraacetate (Wang et al., 2001) in hydrochloric acid solution.

The bond lengths and angles in the title compound are within normal ranges. The structural data confirm that the 14-membered macrocycle lies on a center of inversion and each N atom is linked to a carboxymethyl group. The macrocycle carries two positive charges arising from the protonation of N atoms. The net charge is balanced by two chloride ions. The cations and anions interact with each other and with the water molecules of crystallization to furnish a hydrogen-bonded network structure (Table 1). The structure of the title compound, showing 50% probability displacement ellipsoids is shown in Fig. 1 and a view of the hydrogen bonding in Fig. 2.

Experimental

Tetraethyl 2,2',2'',2'''-(5,5,7,12,12,14-hexamethyl- 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetrayl)tetraacetate (0.625 g, 1 mmol) was dissolved in 200 ml of hydrochloric acid solution (v:v, 1:1) and allowed to stand in air at room temperature over a period of three weeks. Colourless block crystals suitable for X-ray diffraction analysis were formed at the bottom of the vessel (yield 87%).

Refinement

The water hydrogen atoms were refined freely, resulting in O—H bond lengths of 0.76 (3) and 0.88 (5) Å. Other H atoms were positioned geometrically, with N—H = 0.91 Å, O—H = 0.82 Å, C—H = 0.96 Å for methyl, 0.97 Å for methylene and 0.98 Å for methine. U_iso(H) = xU_eq(carrier atom), where x = 1.5 for O and methyl, x = 1.2 for all other carrier atoms. The value of R_int (0.14) is high because of the quality of the diffraction data.

Figures

Fig. 1.

The structure of the title compound, showing 50% probability displacement ellipsoids and the atom-numbering scheme. Hydrogen atoms are drawn as spheres of arbitrary radius. Symmetry code: (a) 1-x, 2-y, -z.

Fig. 2.

A view of the hydrogen bonding. Dashed lines indicate hydrogen bonds.

Crystal data

C24H46N4O82+·2Cl–·2H2O	F000 = 672
Mr = 625.58	Dx = 1.378 Mg m−3
Monoclinic, P21/n	Mo Kα radiation λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 17651 reflections
a = 9.977 (5) Å	θ = 2.4–24.9º
b = 13.475 (7) Å	µ = 0.27 mm−1
c = 11.572 (6) Å	T = 293 (2) K
β = 104.220 (9)º	BLOCK, colorless
V = 1508.1 (13) Å3	0.10 × 0.10 × 0.08 mm
Z = 2

Data collection

Bruker SMART CCD area-detector diffractometer	2036 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.143
Monochromator: graphite	θmax = 26.0º
T = 293(2) K	θmin = 2.4º
φ and ω scans	h = −12→12
Absorption correction: none	k = −16→16
15242 measured reflections	l = −14→14
2946 independent reflections

Refinement

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.056	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.141	w = 1/[σ2(Fo2) + (0.0715P)2] where P = (Fo2 + 2Fc2)/3
S = 0.99	(Δ/σ)max = 0.032
2946 reflections	Δρmax = 0.63 e Å−3
194 parameters	Δρmin = −0.37 e Å−3
Primary atom site location: structure-invariant direct methods	Extinction correction: none

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
C1	0.5351 (3)	0.98193 (17)	−0.1532 (2)	0.0292 (6)
H1A	0.4667	0.9400	−0.1306	0.035*
H1B	0.5360	0.9664	−0.2348	0.035*
C2	0.7189 (3)	0.85672 (17)	−0.0818 (2)	0.0335 (6)
H2	0.8150	0.8530	−0.0349	0.040*
C3	0.6370 (3)	0.78525 (17)	−0.0239 (2)	0.0323 (6)
H3A	0.6485	0.7189	−0.0525	0.039*
H3B	0.5398	0.8021	−0.0511	0.039*
C4	0.6741 (3)	0.78252 (17)	0.1120 (2)	0.0319 (6)
C5	0.5034 (2)	0.90943 (16)	0.1443 (2)	0.0285 (6)
H5A	0.4752	0.8726	0.2064	0.034*
H5B	0.4516	0.8836	0.0682	0.034*
C6	0.7192 (4)	0.8235 (2)	−0.2076 (3)	0.0495 (8)
H6A	0.6257	0.8156	−0.2537	0.074*
H6B	0.7673	0.7614	−0.2041	0.074*
H6C	0.7649	0.8726	−0.2444	0.074*
C7	0.8226 (3)	0.7482 (2)	0.1616 (3)	0.0422 (7)
H7A	0.8371	0.6866	0.1248	0.063*
H7B	0.8394	0.7391	0.2462	0.063*
H7C	0.8850	0.7974	0.1450	0.063*
C8	0.5799 (3)	0.70891 (19)	0.1556 (3)	0.0442 (7)
H8A	0.6022	0.6425	0.1369	0.066*
H8B	0.4851	0.7228	0.1169	0.066*
H8C	0.5933	0.7154	0.2403	0.066*
C9	0.7378 (2)	0.91341 (19)	0.2780 (2)	0.0328 (6)
H9A	0.7422	0.8550	0.3278	0.039*
H9B	0.6935	0.9660	0.3121	0.039*
C10	0.8828 (3)	0.94509 (17)	0.2765 (2)	0.0303 (6)
C11	0.7806 (3)	1.03008 (17)	−0.0922 (2)	0.0338 (6)
H11A	0.7562	1.0512	−0.1749	0.041*
H11B	0.8669	0.9937	−0.0793	0.041*
C12	0.8052 (3)	1.12186 (18)	−0.0142 (2)	0.0319 (6)
Cl1	0.27157 (7)	0.97170 (5)	0.43440 (7)	0.0480 (3)
N1	0.6734 (2)	0.96203 (13)	−0.07355 (18)	0.0270 (5)
H1N	0.6660	0.9714	0.0025	0.032*
N2	0.6540 (2)	0.89074 (14)	0.15548 (17)	0.0275 (5)
O1	0.74179 (19)	1.14840 (14)	0.05549 (17)	0.0405 (5)
O2	0.9133 (2)	1.17039 (15)	−0.0337 (2)	0.0572 (6)
H2A	0.9260	1.2212	0.0065	0.086*
O3	0.9143 (2)	0.97572 (14)	0.19069 (18)	0.0449 (5)
O4	0.96439 (19)	0.93712 (15)	0.38441 (16)	0.0434 (5)
H4	1.0409	0.9596	0.3849	0.065*
O1W	0.5390 (3)	0.84981 (16)	0.4486 (2)	0.0519 (6)
H2W	0.594 (4)	0.887 (2)	0.479 (3)	0.042 (10)*
H1W	0.457 (5)	0.877 (3)	0.443 (4)	0.092 (14)*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
C1	0.0262 (13)	0.0260 (12)	0.0318 (13)	0.0029 (10)	0.0005 (11)	0.0006 (10)
C2	0.0304 (14)	0.0251 (12)	0.0417 (15)	0.0084 (11)	0.0026 (12)	−0.0014 (11)
C3	0.0336 (14)	0.0220 (12)	0.0357 (14)	0.0030 (11)	−0.0019 (11)	−0.0050 (10)
C4	0.0332 (14)	0.0217 (12)	0.0356 (14)	0.0055 (10)	−0.0012 (11)	−0.0029 (10)
C5	0.0218 (12)	0.0263 (12)	0.0340 (14)	−0.0011 (10)	0.0002 (11)	0.0031 (10)
C6	0.070 (2)	0.0378 (15)	0.0471 (18)	0.0086 (15)	0.0258 (16)	−0.0046 (13)
C7	0.0435 (17)	0.0368 (14)	0.0398 (15)	0.0101 (13)	−0.0021 (13)	−0.0001 (12)
C8	0.0569 (19)	0.0261 (13)	0.0446 (16)	−0.0013 (13)	0.0031 (14)	0.0076 (12)
C9	0.0271 (13)	0.0387 (14)	0.0279 (13)	0.0018 (11)	−0.0022 (11)	−0.0041 (11)
C10	0.0298 (14)	0.0239 (12)	0.0324 (14)	0.0020 (10)	−0.0017 (11)	−0.0037 (10)
C11	0.0292 (13)	0.0320 (13)	0.0405 (15)	−0.0007 (11)	0.0094 (12)	−0.0045 (11)
C12	0.0279 (14)	0.0287 (13)	0.0365 (14)	−0.0008 (11)	0.0029 (12)	0.0030 (11)
Cl1	0.0331 (4)	0.0426 (4)	0.0634 (5)	−0.0038 (3)	0.0023 (3)	0.0034 (3)
N1	0.0249 (11)	0.0246 (10)	0.0298 (11)	0.0013 (8)	0.0036 (9)	−0.0025 (8)
N2	0.0248 (11)	0.0229 (10)	0.0298 (11)	0.0027 (8)	−0.0025 (9)	−0.0029 (8)
O1	0.0330 (10)	0.0486 (11)	0.0384 (11)	−0.0090 (9)	0.0060 (9)	−0.0126 (9)
O2	0.0537 (14)	0.0430 (12)	0.0839 (17)	−0.0206 (10)	0.0339 (13)	−0.0177 (11)
O3	0.0393 (12)	0.0501 (12)	0.0415 (12)	−0.0057 (9)	0.0023 (9)	0.0060 (9)
O4	0.0286 (10)	0.0547 (12)	0.0392 (11)	−0.0042 (9)	−0.0065 (9)	−0.0003 (9)
O1W	0.0484 (15)	0.0327 (11)	0.0759 (17)	0.0025 (11)	0.0176 (13)	0.0018 (11)

Geometric parameters (Å, °)

C1—N1	1.483 (3)	C7—H7B	0.9600
C1—C5i	1.523 (3)	C7—H7C	0.9600
C1—H1A	0.9700	C8—H8A	0.9600
C1—H1B	0.9700	C8—H8B	0.9600
C2—N1	1.500 (3)	C8—H8C	0.9600
C2—C3	1.521 (4)	C9—N2	1.490 (3)
C2—C6	1.524 (4)	C9—C10	1.513 (4)
C2—H2	0.9800	C9—H9A	0.9700
C3—C4	1.525 (4)	C9—H9B	0.9700
C3—H3A	0.9700	C10—O3	1.186 (3)
C3—H3B	0.9700	C10—O4	1.317 (3)
C4—C7	1.523 (4)	C11—N1	1.465 (3)
C4—C8	1.535 (4)	C11—C12	1.515 (4)
C4—N2	1.571 (3)	C11—H11A	0.9700
C5—N2	1.497 (3)	C11—H11B	0.9700
C5—C1i	1.523 (3)	C12—O1	1.196 (3)
C5—H5A	0.9700	C12—O2	1.327 (3)
C5—H5B	0.9700	N1—H1N	0.9100
C6—H6A	0.9600	O2—H2A	0.8200
C6—H6B	0.9600	O4—H4	0.8200
C6—H6C	0.9600	O1W—H2W	0.76 (3)
C7—H7A	0.9600	O1W—H1W	0.88 (5)
N1—C1—C5i	110.10 (18)	C4—C7—H7C	109.5
N1—C1—H1A	109.6	H7A—C7—H7C	109.5
C5i—C1—H1A	109.6	H7B—C7—H7C	109.5
N1—C1—H1B	109.6	C4—C8—H8A	109.5
C5i—C1—H1B	109.6	C4—C8—H8B	109.5
H1A—C1—H1B	108.2	H8A—C8—H8B	109.5
N1—C2—C3	111.5 (2)	C4—C8—H8C	109.5
N1—C2—C6	114.2 (2)	H8A—C8—H8C	109.5
C3—C2—C6	111.3 (2)	H8B—C8—H8C	109.5
N1—C2—H2	106.4	N2—C9—C10	111.2 (2)
C3—C2—H2	106.4	N2—C9—H9A	109.4
C6—C2—H2	106.4	C10—C9—H9A	109.4
C2—C3—C4	116.7 (2)	N2—C9—H9B	109.4
C2—C3—H3A	108.1	C10—C9—H9B	109.4
C4—C3—H3A	108.1	H9A—C9—H9B	108.0
C2—C3—H3B	108.1	O3—C10—O4	126.4 (3)
C4—C3—H3B	108.1	O3—C10—C9	123.9 (2)
H3A—C3—H3B	107.3	O4—C10—C9	109.6 (2)
C7—C4—C3	111.3 (2)	N1—C11—C12	116.1 (2)
C7—C4—C8	107.3 (2)	N1—C11—H11A	108.3
C3—C4—C8	110.0 (2)	C12—C11—H11A	108.3
C7—C4—N2	110.47 (19)	N1—C11—H11B	108.3
C3—C4—N2	106.86 (18)	C12—C11—H11B	108.3
C8—C4—N2	111.0 (2)	H11A—C11—H11B	107.4
N2—C5—C1i	114.86 (19)	O1—C12—O2	123.7 (2)
N2—C5—H5A	108.6	O1—C12—C11	127.7 (2)
C1i—C5—H5A	108.6	O2—C12—C11	108.7 (2)
N2—C5—H5B	108.6	C11—N1—C1	113.39 (19)
C1i—C5—H5B	108.6	C11—N1—C2	109.8 (2)
H5A—C5—H5B	107.5	C1—N1—C2	112.43 (18)
C2—C6—H6A	109.5	C11—N1—H1N	106.9
C2—C6—H6B	109.5	C1—N1—H1N	106.9
H6A—C6—H6B	109.5	C2—N1—H1N	106.9
C2—C6—H6C	109.5	C9—N2—C5	111.37 (19)
H6A—C6—H6C	109.5	C9—N2—C4	114.14 (17)
H6B—C6—H6C	109.5	C5—N2—C4	109.45 (17)
C4—C7—H7A	109.5	C12—O2—H2A	109.5
C4—C7—H7B	109.5	C10—O4—H4	109.5
H7A—C7—H7B	109.5	H2W—O1W—H1W	107 (3)
N1—C2—C3—C4	−75.6 (3)	C6—C2—N1—C11	−71.7 (3)
C6—C2—C3—C4	155.6 (2)	C3—C2—N1—C1	−71.7 (3)
C2—C3—C4—C7	−62.6 (3)	C6—C2—N1—C1	55.5 (3)
C2—C3—C4—C8	178.6 (2)	C10—C9—N2—C5	−151.36 (19)
C2—C3—C4—N2	58.1 (3)	C10—C9—N2—C4	84.1 (2)
N2—C9—C10—O3	20.5 (3)	C1i—C5—N2—C9	67.6 (3)
N2—C9—C10—O4	−162.1 (2)	C1i—C5—N2—C4	−165.3 (2)
N1—C11—C12—O1	−5.1 (4)	C7—C4—N2—C9	−34.3 (3)
N1—C11—C12—O2	174.1 (2)	C3—C4—N2—C9	−155.5 (2)
C12—C11—N1—C1	92.6 (3)	C8—C4—N2—C9	84.6 (2)
C12—C11—N1—C2	−140.7 (2)	C7—C4—N2—C5	−159.9 (2)
C5i—C1—N1—C11	−52.7 (3)	C3—C4—N2—C5	78.9 (2)
C5i—C1—N1—C2	−178.0 (2)	C8—C4—N2—C5	−41.0 (2)
C3—C2—N1—C11	161.1 (2)

Symmetry codes: (i) −x+1, −y+2, −z.

Hydrogen-bond geometry (Å, °)

D—H···A	D—H	H···A	D···A	D—H···A
O4—H4···Cl1ii	0.82	2.24	3.012 (3)	158
O2—H2A···O1Wiii	0.82	1.82	2.610 (3)	162
O1W—H2W···Cl1iv	0.76 (3)	2.40 (3)	3.152 (3)	169 (3)

Symmetry codes: (ii) x+1, y, z; (iii) −x+3/2, y+1/2, −z+1/2; (iv) −x+1, −y+2, −z+1.