3,14-Diethyl-2,13-di­aza-6,17-diazonia­tri­cyclo­[16.4.0.0^7,12]docosane dichloride tetra­hydrate from synchrotron radiation

The asymmetric unit of title hydrated salt, C₂₂H₄₆N₄²⁺·2Cl⁻·4H₂O, comprises half a centrosymmetric dication, one Cl⁻ anion and two water mol­ecules of crystallization. The structure determination reveals that protonation has occurred at diagonally opposite amine N atoms, and that the dication features intra­molecular N—H...N hydrogen bonds. In the crystal, a three-dimensional artchitecture is formed by O—H...Cl/N and N—H...Cl/O hydrogen bonds.

Key indicators

• Single-crystal synchrotron study
• T = 95 K
• Mean [sigma](C-C) = 0.001 Å
• R factor = 0.029
• wR factor = 0.079
• Data-to-parameter ratio = 20.6

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT250_ALERT_2_C Large U3/U1 Ratio for Average U(i,j) Tensor ....        2.4 Note
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.600         30
PLAT913_ALERT_3_C Missing # of Very Strong Reflections in FCF ....         10

Alert level G
ABSMU01_ALERT_1_G  Calculation of _exptl_absorpt_correction_mu
                not performed for this radiation type.
PLAT005_ALERT_5_G No _iucr_refine_instructions_details  in the CIF     Please Do !
PLAT128_ALERT_4_G Alternate Setting for Input Space-Group  C2/c       I2/a    Note
PLAT152_ALERT_1_G The Supplied and Calc. Volume s.u. Differ by ...          2 Units
PLAT720_ALERT_4_G Number of Unusual/Non-Standard Labels ..........          8
PLAT793_ALERT_4_G The Model has Chirality at C2           (Verify)          S
PLAT793_ALERT_4_G The Model has Chirality at C7           (Verify)          S
PLAT793_ALERT_4_G The Model has Chirality at C8           (Verify)          S

   0 ALERT level A = Most likely a serious problem - resolve or explain
   0 ALERT level B = A potentially serious problem, consider carefully
   3 ALERT level C = Check. Ensure it is not caused by an omission or oversight
   8 ALERT level G = General information/check it is not something unexpected

   2 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 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
   5 ALERT type 4 Improvement, methodology, query or suggestion
   1 ALERT type 5 Informative message, check

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S1. Comment

The coordination chemistry of tetraazamacrocycles with steric hindrance on the macrocyclic ring, and their complexes are of interest because of their various applications (Choi et al., 2010). Recently, the constrained cyclam derivatives have been reported to exhibit anti-HIV effects and to stimulate the activity of stem cells from the bone marrow (De Clercq, 2010).

The title compound, Fig. 1, containing a positively charged macrocycle, Cl^- and water molecules was characterized during the studies of di-N-substituted macrocyclic ligands as well as their corresponding copper(II) complexes. The macrocylic ligand lies on a center-of-inversion. Thus, the asymmetric unit contains half of a macrocylic dication, one chloride anion and two water molecules. The four N atoms are coplanar, and the ethyl substituents are anti with respect to the macrocyclic plane as a result of the symmetry of the molecule. The C—C and C—N lengths and associated angles are in the normal range (Choi et al., 2006, 2011). As expected, the N–C distances involving the protonated nitrogen atom, N1 are slightly longer than the other N–C distances. The cyclohexane ring that is fused to the 14-membered ring exists in a stable chair conformation, and the N1—C2—C3—N2 torsion angle displays a gauche conformation. The crystal structure is stabilized by different types of hydrogen bonds, Table 1.

Related literature

For background to the coordination chemistry of tetraazamacrocycles, see: Choi et al. (2010); De Clercq (2010). For the synthesis of the precursor macrocycle, see: Lim et al. (2006). For related structures, see: Choi et al. (2006, 2011).

S2. Experimental

The starting material, the macrocycle 3,14-diethyl-2,6,13,17-tetraazatricyclo(16.4.0.0^7,12)docosane (L) was prepared according to published procedure (Lim et al., 2006). L (0.67 g, 0.2 mmol) was taken in a round bottomed flask in EtOH (10 ml). 2-Chloro-N,N-diethylacetamide (0.0936 g, 0.5 mmol) in EtOH (5 ml) was added. Then triethylamine (1.33 g, 0.2 mmol) in EtOH (2 ml) was added. The mixture was heated to reflux for 24 h. Colourless crystals suitable for X-ray analysis were obtained from the solution at 298 K over a period of a few days.

S3. Refinement

The C-bound H-atoms were placed in calculated positions (C—H = 0.98–1.00 Å) and were included in the refinement in the riding model approximation with U_iso(H) set to 1.2–1.5U_eq(C). The O- and N-bound H-atoms were located in a difference Fourier map and refined freely. One of the H atoms of the O2w water molecule was disordered over two sites of equal weight.

Computing details

Data collection: PAL ADSC Quantum-210 ADX (Arvai & Nielsen, 1983); cell refinement: HKL3000sm (Otwinowski & Minor, 1997); data reduction: HKL3000sm (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXL2013 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg, 2007); software used to prepare material for publication: WinGX (Farrugia, 2012).

Figures

Fig. 1. The molecular structure of title compound with displacements ellipsoids drawn at the 50% probability level for non-H atoms. Primed atoms are related by the symmetry operation 1/2-x, 1/2-y, 1-z.

3,14-Diethyl-2,13-diaza-6,17-diazoniatricyclo[16.4.0.0^7,12]docosane dichloride tetrahydrate

Crystal data

C22H46N4^2+·2Cl^−·4H2O	F(000) = 1120
Mr = 509.59	Dx = 1.176 Mg m^−3
Monoclinic, C2/c	Synchrotron radiation, λ = 0.72000 Å
a = 22.122 (4) Å	Cell parameters from 31113 reflections
b = 13.616 (3) Å	θ = 1.3–66.4°
c = 10.565 (2) Å	µ = 0.27 mm^−1
β = 115.23 (3)°	T = 95 K
V = 2878.5 (10) Å^3	Block, colourless
Z = 4	0.31 × 0.28 × 0.25 mm

Data collection

ADSC Q210 CCD area-detector diffractometer	3663 independent reflections
Radiation source: PLSII 2D bending magnet	3446 reflections with I > 2σ(I)
Si(111) double crystal monochromator	Rint = 0.028
ω scan	θmax = 29.0°, θmin = 1.8°
Absorption correction: empirical (using intensity measurements) (HKL-3000 SCALEPACK; Otwinowski & Minor, 1997)	h = −29→29
Tmin = 0.922, Tmax = 0.937	k = −18→18
13046 measured reflections	l = −14→14

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)] = 0.029	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.079	H atoms treated by a mixture of independent and constrained refinement
S = 1.05	w = 1/[σ^2(Fo^2) + (0.0412P)^2 + 2.157P] where P = (Fo^2 + 2Fc^2)/3
3663 reflections	(Δ/σ)max < 0.001
178 parameters	Δρmax = 0.46 e Å^−3
0 restraints	Δρmin = −0.35 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	Occ. (<1)
N1	0.24338 (3)	0.30241 (5)	0.30460 (7)	0.00545 (13)
H1N1	0.2484 (6)	0.3678 (10)	0.3234 (13)	0.013 (3)*
H2N1	0.2370 (6)	0.2756 (9)	0.3766 (13)	0.014 (3)*
N2	0.34493 (3)	0.23871 (5)	0.55886 (7)	0.00584 (14)
H1N2	0.3460 (6)	0.1738 (10)	0.5533 (13)	0.012 (3)*
C1	0.18207 (4)	0.28405 (6)	0.17163 (8)	0.00738 (15)
H1A	0.1831	0.2160	0.1398	0.009*
H1B	0.1819	0.3293	0.0981	0.009*
C2	0.30641 (4)	0.26138 (6)	0.30527 (8)	0.00612 (15)
H2	0.3004	0.1891	0.2872	0.007*
C3	0.32229 (4)	0.30822 (7)	0.19167 (8)	0.01049 (16)
H3A	0.3289	0.3798	0.2083	0.013*
H3B	0.2844	0.2980	0.0990	0.013*
C4	0.38574 (4)	0.26195 (8)	0.19333 (9)	0.01451 (18)
H4A	0.3775	0.1916	0.1680	0.017*
H4B	0.3971	0.2947	0.1226	0.017*
C5	0.44453 (4)	0.27145 (8)	0.33736 (9)	0.01465 (18)
H5A	0.4836	0.2358	0.3377	0.018*
H5B	0.4569	0.3415	0.3572	0.018*
C6	0.42661 (4)	0.22968 (7)	0.45105 (9)	0.01216 (17)
H6A	0.4645	0.2403	0.5436	0.015*
H6B	0.4194	0.1580	0.4370	0.015*
C7	0.36367 (4)	0.27744 (6)	0.44987 (8)	0.00632 (15)
H7	0.3718	0.3497	0.4651	0.008*
C8	0.39051 (4)	0.27036 (6)	0.70259 (8)	0.00656 (15)
H8	0.4375	0.2635	0.7134	0.008*
C9	0.38146 (4)	0.20090 (6)	0.80803 (8)	0.00776 (15)
H9A	0.3820	0.1324	0.7770	0.009*
H9B	0.4203	0.2089	0.8998	0.009*
C10	0.37854 (4)	0.37876 (6)	0.72406 (9)	0.01032 (16)
H10A	0.3825	0.4182	0.6492	0.012*
H10B	0.3324	0.3865	0.7153	0.012*
C11	0.42749 (5)	0.41859 (7)	0.86611 (10)	0.01776 (19)
H11A	0.4227	0.3815	0.9408	0.027*
H11B	0.4179	0.4881	0.8734	0.027*
H11C	0.4733	0.4117	0.8753	0.027*
Cl1	0.256487 (11)	0.526092 (15)	0.35905 (2)	0.01378 (8)
O1W	0.16965 (4)	0.51673 (5)	0.02378 (8)	0.01737 (15)
H1O1	0.1926 (9)	0.5195 (12)	0.110 (2)	0.038 (4)*
H2O1	0.1952 (8)	0.5022 (12)	−0.0111 (17)	0.033 (4)*
O2W	0.52804 (5)	0.02912 (8)	0.40229 (12)	0.0354 (2)
H1O2	0.5693 (11)	0.0172 (13)	0.4382 (19)	0.044 (5)*
H2O2	0.512 (2)	0.016 (3)	0.328 (5)	0.062 (14)*	0.50
H3O2	0.5140 (19)	0.015 (3)	0.457 (4)	0.041 (10)*	0.50

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0030 (3)	0.0080 (3)	0.0048 (3)	−0.0006 (2)	0.0011 (2)	−0.0001 (2)
N2	0.0045 (3)	0.0083 (3)	0.0045 (3)	−0.0011 (2)	0.0017 (2)	−0.0001 (2)
C1	0.0037 (3)	0.0124 (4)	0.0044 (3)	−0.0012 (3)	0.0001 (3)	0.0005 (3)
C2	0.0030 (3)	0.0095 (3)	0.0061 (3)	0.0000 (3)	0.0021 (3)	−0.0009 (3)
C3	0.0072 (4)	0.0190 (4)	0.0057 (3)	−0.0013 (3)	0.0032 (3)	0.0007 (3)
C4	0.0084 (4)	0.0291 (5)	0.0080 (4)	−0.0005 (3)	0.0054 (3)	−0.0023 (3)
C5	0.0058 (4)	0.0308 (5)	0.0093 (4)	−0.0008 (3)	0.0050 (3)	−0.0001 (3)
C6	0.0050 (3)	0.0232 (4)	0.0093 (4)	0.0032 (3)	0.0040 (3)	0.0019 (3)
C7	0.0032 (3)	0.0109 (4)	0.0049 (3)	−0.0011 (3)	0.0018 (3)	0.0000 (3)
C8	0.0036 (3)	0.0099 (4)	0.0053 (3)	−0.0008 (3)	0.0010 (3)	−0.0002 (3)
C9	0.0041 (3)	0.0111 (4)	0.0069 (3)	0.0010 (3)	0.0012 (3)	0.0023 (3)
C10	0.0131 (4)	0.0091 (4)	0.0081 (3)	−0.0011 (3)	0.0039 (3)	−0.0007 (3)
C11	0.0209 (5)	0.0151 (4)	0.0129 (4)	−0.0049 (4)	0.0030 (3)	−0.0055 (3)
Cl1	0.01970 (12)	0.00834 (11)	0.01508 (12)	−0.00076 (7)	0.00912 (9)	0.00064 (7)
O1W	0.0187 (3)	0.0182 (3)	0.0168 (3)	0.0023 (3)	0.0092 (3)	0.0010 (3)
O2W	0.0226 (5)	0.0488 (6)	0.0330 (5)	0.0101 (4)	0.0101 (4)	0.0081 (4)

Geometric parameters (Å, º)

N1—C2	1.4995 (10)	C6—C7	1.5320 (11)
N1—C1	1.5003 (12)	C6—H6A	0.9900
N1—H1N1	0.909 (13)	C6—H6B	0.9900
N1—H2N1	0.907 (13)	C7—H7	1.0000
N2—C7	1.4774 (10)	C8—C10	1.5333 (12)
N2—C8	1.4842 (11)	C8—C9	1.5381 (11)
N2—H1N2	0.887 (13)	C8—H8	1.0000
C1—C9^i	1.5234 (11)	C9—C1^i	1.5233 (11)
C1—H1A	0.9900	C9—H9A	0.9900
C1—H1B	0.9900	C9—H9B	0.9900
C2—C3	1.5264 (11)	C10—C11	1.5276 (13)
C2—C7	1.5285 (12)	C10—H10A	0.9900
C2—H2	1.0000	C10—H10B	0.9900
C3—C4	1.5318 (12)	C11—H11A	0.9800
C3—H3A	0.9900	C11—H11B	0.9800
C3—H3B	0.9900	C11—H11C	0.9800
C4—C5	1.5286 (13)	O1W—H1O1	0.833 (19)
C4—H4A	0.9900	O1W—H2O1	0.820 (18)
C4—H4B	0.9900	O2W—H1O2	0.84 (2)
C5—C6	1.5262 (12)	O2W—H2O2	0.73 (4)
C5—H5A	0.9900	O2W—H3O2	0.78 (4)
C5—H5B	0.9900
C2—N1—C1	114.20 (6)	C5—C6—H6A	109.2
C2—N1—H1N1	109.7 (8)	C7—C6—H6A	109.2
C1—N1—H1N1	110.2 (8)	C5—C6—H6B	109.2
C2—N1—H2N1	108.8 (8)	C7—C6—H6B	109.2
C1—N1—H2N1	108.5 (8)	H6A—C6—H6B	107.9
H1N1—N1—H2N1	105.0 (11)	N2—C7—C2	109.85 (6)
C7—N2—C8	113.56 (6)	N2—C7—C6	113.46 (7)
C7—N2—H1N2	106.2 (8)	C2—C7—C6	108.08 (7)
C8—N2—H1N2	109.4 (8)	N2—C7—H7	108.4
N1—C1—C9^i	111.44 (7)	C2—C7—H7	108.4
N1—C1—H1A	109.3	C6—C7—H7	108.4
C9^i—C1—H1A	109.3	N2—C8—C10	110.24 (6)
N1—C1—H1B	109.3	N2—C8—C9	108.72 (6)
C9^i—C1—H1B	109.3	C10—C8—C9	113.61 (7)
H1A—C1—H1B	108.0	N2—C8—H8	108.0
N1—C2—C3	111.46 (7)	C10—C8—H8	108.0
N1—C2—C7	108.91 (7)	C9—C8—H8	108.0
C3—C2—C7	110.83 (7)	C1^i—C9—C8	115.61 (7)
N1—C2—H2	108.5	C1^i—C9—H9A	108.4
C3—C2—H2	108.5	C8—C9—H9A	108.4
C7—C2—H2	108.5	C1^i—C9—H9B	108.4
C2—C3—C4	109.63 (7)	C8—C9—H9B	108.4
C2—C3—H3A	109.7	H9A—C9—H9B	107.4
C4—C3—H3A	109.7	C11—C10—C8	113.10 (7)
C2—C3—H3B	109.7	C11—C10—H10A	109.0
C4—C3—H3B	109.7	C8—C10—H10A	109.0
H3A—C3—H3B	108.2	C11—C10—H10B	109.0
C5—C4—C3	111.30 (7)	C8—C10—H10B	109.0
C5—C4—H4A	109.4	H10A—C10—H10B	107.8
C3—C4—H4A	109.4	C10—C11—H11A	109.5
C5—C4—H4B	109.4	C10—C11—H11B	109.5
C3—C4—H4B	109.4	H11A—C11—H11B	109.5
H4A—C4—H4B	108.0	C10—C11—H11C	109.5
C6—C5—C4	110.83 (7)	H11A—C11—H11C	109.5
C6—C5—H5A	109.5	H11B—C11—H11C	109.5
C4—C5—H5A	109.5	H1O1—O1W—H2O1	106.6 (16)
C6—C5—H5B	109.5	H1O2—O2W—H2O2	111 (4)
C4—C5—H5B	109.5	H1O2—O2W—H3O2	108 (3)
H5A—C5—H5B	108.1	H2O2—O2W—H3O2	124 (5)
C5—C6—C7	112.06 (7)
C2—N1—C1—C9^i	162.93 (7)	C3—C2—C7—N2	175.38 (6)
C1—N1—C2—C3	62.08 (9)	N1—C2—C7—C6	176.69 (7)
C1—N1—C2—C7	−175.33 (6)	C3—C2—C7—C6	−60.34 (9)
N1—C2—C3—C4	−178.28 (7)	C5—C6—C7—N2	−179.94 (7)
C7—C2—C3—C4	60.24 (9)	C5—C6—C7—C2	57.97 (9)
C2—C3—C4—C5	−56.36 (10)	C7—N2—C8—C10	73.59 (8)
C3—C4—C5—C6	54.06 (11)	C7—N2—C8—C9	−161.26 (6)
C4—C5—C6—C7	−55.52 (11)	N2—C8—C9—C1^i	−75.02 (9)
C8—N2—C7—C2	−167.13 (6)	C10—C8—C9—C1^i	48.13 (9)
C8—N2—C7—C6	71.78 (9)	N2—C8—C10—C11	−175.53 (7)
N1—C2—C7—N2	52.42 (8)	C9—C8—C10—C11	62.15 (9)

Symmetry code: (i) −x+1/2, −y+1/2, −z+1.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N1···Cl1	0.909 (13)	2.182 (14)	3.0900 (9)	177.3 (12)
N1—H2N1···N2^i	0.907 (13)	2.200 (13)	2.9348 (11)	137.6 (10)
N2—H1N2···O1W^ii	0.887 (13)	2.262 (13)	3.1242 (12)	164.1 (11)
O1W—H1O1···Cl1	0.833 (19)	2.400 (19)	3.2329 (14)	178.6 (17)
O1W—H2O1···Cl1^iii	0.820 (18)	2.335 (18)	3.1479 (10)	171.1 (15)
O2W—H1O2···O1W^iv	0.84 (2)	2.06 (2)	2.9021 (15)	178.1 (18)

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