Spectroscopic characterization and mol­ecular structure of 3,14-dimethyl-2,6,13,17-tetra­aza­penta­cyclo­[16.4.0.1^2,17.1^6,13.0^7,12]tetra­cosa­ne

Constrained cyclam derivatives have been found to exhibit anti-HIV effects. The strength of binding to the CXCR4 receptor correlates with anti-HIV activity. The conformation of the macrocyclic compound is very important for co-receptor recognition. Therefore, knowledge of the conformation and crystal packing of macrocycles has become important in developing new highly effective anti-HIV drugs. Structural modifications of N-functionalized polyaza macrocyclic compounds have been achieved using various methods. A new synthesis affording single crystals of the title tetra­aza­penta­cyclo­[16.4.0.1^2,17.1^6,13.0^7,12]tetra­cosa­ne macrocycle, C₂₂H₄₀N₄, is reported. Formaldehyde reacts readily at room tem­perature with the tetraazatricyclo[16.4.0.0^2,17]docosane precursor to yield a macropolycycle containing two five-membered rings. Characterization by elemental, spectroscopic and single-crystal X-ray diffraction analyses shows that the asymmetric unit contains half of a centrosymmetric mol­ecule. The mol­ecular structure shows a trans conformation for the two methyl­ene bridges owing to mol­ecular symmetry. The crystal structure is stabilized by intra­molecular C—H...N hydrogen bonds. NMR and IR spectroscopic properties support the methyl­ene-bridged macrocyclic structure.

Computing details

Data collection: PAL BL2D-SMDC Program (Shin et al., 2016); cell refinement: HKL3000sm (Otwinowski & Minor, 1997); data reduction: HKL3000sm (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXT2014 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: DIAMOND (Putz & Brandenburg, 2014); software used to prepare material for publication: publCIF (Westrip, 2010).

3,14-Dimethyl-2,6,13,17-tetraazapentacyclo[16.4.0.1^2,17.1^6,13.0^7,12]tetracosane

Crystal data

C22H40N4	Z = 1
Mr = 360.58	F(000) = 200
Triclinic, P1	Dx = 1.192 Mg m^−3
a = 5.2990 (11) Å	Synchrotron radiation, λ = 0.63001 Å
b = 9.0720 (18) Å	Cell parameters from 13155 reflections
c = 10.604 (2) Å	θ = 0.4–33.6°
α = 92.30 (3)°	µ = 0.06 mm^−1
β = 90.10 (3)°	T = 101 K
γ = 99.61 (3)°	Plate, colourless
V = 502.18 (18) Å^3	0.10 × 0.05 × 0.01 mm

Data collection

ADSC Q210 CCD area detector diffractometer	1732 reflections with I > 2σ(I)
Radiation source: PLSII 2D bending magnet	Rint = 0.039
ω scan	θmax = 26.0°, θmin = 2.0°
Absorption correction: empirical (using intensity measurements) HKL3000sm SCALEPACK; Otwinowski & Minor, 1997)	h = −7→7
Tmin = 0.994, Tmax = 0.999	k = −12→12
5243 measured reflections	l = −14→14
2661 independent reflections

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.062	w = 1/[σ^2(Fo^2) + (0.1256P)^2] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.189	(Δ/σ)max < 0.001
S = 0.97	Δρmax = 0.41 e Å^−3
2661 reflections	Δρmin = −0.35 e Å^−3
120 parameters	Extinction correction: SHELXL2014 (Sheldrick, 2015b), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
0 restraints	Extinction coefficient: 0.17 (4)

Special details

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
N1	0.4470 (3)	0.80439 (15)	0.96704 (14)	0.0220 (3)
N2	0.7265 (3)	0.90734 (15)	0.80978 (13)	0.0225 (3)
C1	0.7074 (3)	0.88539 (19)	0.94602 (16)	0.0225 (4)
H1A	0.7352	0.9830	0.9936	0.027*
H1B	0.8368	0.8262	0.9738	0.027*
C2	0.4173 (3)	0.70172 (18)	0.85647 (17)	0.0225 (4)
H2	0.5419	0.6308	0.8635	0.027*
C3	0.5047 (3)	0.80842 (18)	0.75189 (16)	0.0230 (4)
H3	0.3674	0.8692	0.7365	0.028*
C4	0.5419 (3)	0.7176 (2)	0.63095 (17)	0.0273 (4)
H4A	0.6727	0.6535	0.6446	0.033*
H4B	0.6003	0.7855	0.5622	0.033*
C5	0.2841 (3)	0.6204 (2)	0.59532 (18)	0.0285 (4)
H5A	0.1611	0.6861	0.5725	0.034*
H5B	0.3072	0.5559	0.5201	0.034*
C6	0.1720 (3)	0.52165 (19)	0.70209 (19)	0.0289 (4)
H6A	0.2806	0.4447	0.7154	0.035*
H6B	−0.0011	0.4695	0.6770	0.035*
C7	0.1543 (3)	0.61207 (19)	0.82656 (18)	0.0262 (4)
H7A	0.0280	0.6802	0.8180	0.031*
H7B	0.0986	0.5438	0.8954	0.031*
C8	0.4259 (3)	0.73355 (19)	1.08768 (17)	0.0256 (4)
H8A	0.5584	0.6689	1.0930	0.031*
H8B	0.2566	0.6686	1.0920	0.031*
C9	0.4564 (3)	0.84492 (19)	1.20105 (17)	0.0250 (4)
H9A	0.6153	0.9178	1.1900	0.030*
H9B	0.4792	0.7896	1.2777	0.030*
C10	0.7685 (3)	1.06609 (19)	0.77571 (17)	0.0240 (4)
H10	0.9151	1.1180	0.8291	0.029*
C11	0.8570 (4)	1.0779 (2)	0.63924 (17)	0.0302 (4)
H11A	0.9926	1.0178	0.6250	0.045*
H11B	0.9231	1.1827	0.6226	0.045*
H11C	0.7123	1.0407	0.5824	0.045*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0211 (7)	0.0207 (7)	0.0244 (7)	0.0046 (5)	−0.0011 (5)	−0.0001 (5)
N2	0.0218 (7)	0.0235 (7)	0.0223 (7)	0.0050 (6)	−0.0027 (5)	−0.0013 (6)
C1	0.0215 (8)	0.0241 (8)	0.0230 (8)	0.0072 (6)	−0.0024 (6)	0.0000 (6)
C2	0.0205 (7)	0.0202 (8)	0.0277 (9)	0.0066 (6)	−0.0030 (6)	−0.0022 (6)
C3	0.0204 (7)	0.0235 (8)	0.0262 (9)	0.0073 (6)	−0.0026 (6)	−0.0024 (6)
C4	0.0279 (8)	0.0286 (9)	0.0260 (9)	0.0079 (7)	−0.0022 (7)	−0.0036 (7)
C5	0.0291 (9)	0.0284 (9)	0.0293 (9)	0.0098 (7)	−0.0049 (7)	−0.0048 (7)
C6	0.0276 (8)	0.0238 (9)	0.0357 (10)	0.0065 (7)	−0.0061 (7)	−0.0030 (7)
C7	0.0237 (8)	0.0224 (9)	0.0319 (10)	0.0030 (7)	−0.0023 (7)	−0.0017 (7)
C8	0.0287 (8)	0.0222 (8)	0.0269 (9)	0.0071 (7)	0.0002 (7)	0.0013 (6)
C9	0.0266 (8)	0.0235 (8)	0.0259 (9)	0.0073 (7)	−0.0011 (6)	0.0010 (6)
C10	0.0221 (8)	0.0249 (9)	0.0253 (9)	0.0049 (6)	−0.0001 (6)	0.0004 (6)
C11	0.0322 (9)	0.0322 (10)	0.0264 (10)	0.0057 (8)	0.0026 (7)	0.0023 (7)

Geometric parameters (Å, º)

N1—C8	1.451 (2)	C5—H5B	0.9900
N1—C2	1.459 (2)	C6—C7	1.537 (3)
N1—C1	1.473 (2)	C6—H6A	0.9900
N2—C1	1.468 (2)	C6—H6B	0.9900
N2—C3	1.471 (2)	C7—H7A	0.9900
N2—C10	1.480 (2)	C7—H7B	0.9900
C1—H1A	0.9900	C8—C9	1.530 (2)
C1—H1B	0.9900	C8—H8A	0.9900
C2—C7	1.518 (2)	C8—H8B	0.9900
C2—C3	1.523 (3)	C9—C10^i	1.562 (2)
C2—H2	1.0000	C9—H9A	0.9900
C3—C4	1.527 (2)	C9—H9B	0.9900
C3—H3	1.0000	C10—C11	1.524 (3)
C4—C5	1.535 (3)	C10—C9^i	1.562 (2)
C4—H4A	0.9900	C10—H10	1.0000
C4—H4B	0.9900	C11—H11A	0.9800
C5—C6	1.531 (3)	C11—H11B	0.9800
C5—H5A	0.9900	C11—H11C	0.9800
C8—N1—C2	115.17 (13)	C5—C6—C7	112.34 (14)
C8—N1—C1	111.88 (13)	C5—C6—H6A	109.1
C2—N1—C1	100.10 (13)	C7—C6—H6A	109.1
C1—N2—C3	105.97 (13)	C5—C6—H6B	109.1
C1—N2—C10	114.09 (13)	C7—C6—H6B	109.1
C3—N2—C10	117.19 (13)	H6A—C6—H6B	107.9
N2—C1—N1	106.03 (13)	C2—C7—C6	107.97 (15)
N2—C1—H1A	110.5	C2—C7—H7A	110.1
N1—C1—H1A	110.5	C6—C7—H7A	110.1
N2—C1—H1B	110.5	C2—C7—H7B	110.1
N1—C1—H1B	110.5	C6—C7—H7B	110.1
H1A—C1—H1B	108.7	H7A—C7—H7B	108.4
N1—C2—C7	118.50 (14)	N1—C8—C9	113.53 (14)
N1—C2—C3	101.10 (13)	N1—C8—H8A	108.9
C7—C2—C3	110.74 (14)	C9—C8—H8A	108.9
N1—C2—H2	108.7	N1—C8—H8B	108.9
C7—C2—H2	108.7	C9—C8—H8B	108.9
C3—C2—H2	108.7	H8A—C8—H8B	107.7
N2—C3—C2	102.64 (13)	C8—C9—C10^i	116.12 (14)
N2—C3—C4	119.13 (14)	C8—C9—H9A	108.3
C2—C3—C4	109.13 (14)	C10^i—C9—H9A	108.3
N2—C3—H3	108.5	C8—C9—H9B	108.3
C2—C3—H3	108.5	C10^i—C9—H9B	108.3
C4—C3—H3	108.5	H9A—C9—H9B	107.4
C3—C4—C5	107.94 (15)	N2—C10—C11	109.44 (14)
C3—C4—H4A	110.1	N2—C10—C9^i	117.33 (14)
C5—C4—H4A	110.1	C11—C10—C9^i	110.36 (14)
C3—C4—H4B	110.1	N2—C10—H10	106.3
C5—C4—H4B	110.1	C11—C10—H10	106.3
H4A—C4—H4B	108.4	C9^i—C10—H10	106.3
C6—C5—C4	112.80 (15)	C10—C11—H11A	109.5
C6—C5—H5A	109.0	C10—C11—H11B	109.5
C4—C5—H5A	109.0	H11A—C11—H11B	109.5
C6—C5—H5B	109.0	C10—C11—H11C	109.5
C4—C5—H5B	109.0	H11A—C11—H11C	109.5
H5A—C5—H5B	107.8	H11B—C11—H11C	109.5
C3—N2—C1—N1	−13.50 (15)	C7—C2—C3—C4	−65.46 (17)
C10—N2—C1—N1	116.93 (14)	N2—C3—C4—C5	177.59 (13)
C8—N1—C1—N2	161.60 (13)	C2—C3—C4—C5	60.31 (17)
C2—N1—C1—N2	39.11 (14)	C3—C4—C5—C6	−55.12 (18)
C8—N1—C2—C7	70.26 (18)	C4—C5—C6—C7	53.19 (19)
C1—N1—C2—C7	−169.60 (14)	N1—C2—C7—C6	176.36 (14)
C8—N1—C2—C3	−168.59 (13)	C3—C2—C7—C6	60.26 (17)
C1—N1—C2—C3	−48.46 (13)	C5—C6—C7—C2	−53.77 (18)
C1—N2—C3—C2	−16.48 (15)	C2—N1—C8—C9	−179.64 (13)
C10—N2—C3—C2	−145.11 (14)	C1—N1—C8—C9	66.93 (17)
C1—N2—C3—C4	−137.10 (15)	N1—C8—C9—C10^i	70.79 (19)
C10—N2—C3—C4	94.27 (18)	C1—N2—C10—C11	164.66 (13)
N1—C2—C3—N2	40.79 (14)	C3—N2—C10—C11	−70.70 (18)
C7—C2—C3—N2	167.25 (12)	C1—N2—C10—C9^i	−68.64 (18)
N1—C2—C3—C4	168.07 (12)	C3—N2—C10—C9^i	56.0 (2)

Symmetry code: (i) −x+1, −y+2, −z+2.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C1—H1A···N1^i	0.99	2.32	3.163 (2)	142

Symmetry code: (i) −x+1, −y+2, −z+2.