11-Nitroso-6,7,10,11,12,13,15,16-octa­hydro-9H-5,8,14,17-tetra­oxa-11-aza­benzocyclo­penta­decene

The title compound, C₁₄H₂₀N₂O₅, was prepared by the nitro­sation of 6,7,10,11,12,13,15,16-octa­hydro-9H-5,8,14,17-tetra­oxa-11-aza­benzocyclo­penta­decene. The ligand has an intra­molecular C—H...O hydrogen bond, resulting in the formation of a six-membered ring. Apart from the near planar OC₆H₄O segment, the macrocycle contains gauche C—N and a mixture of gauche and anti C—O and C—C linkages. The nitroso group is not involved in any significant inter­molecular inter­actions.

Key indicators

• Single-crystal X-ray study
• T = 130 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.029
• wR factor = 0.071
• Data-to-parameter ratio = 7.4

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT089_ALERT_3_C Poor Data / Parameter Ratio (Zmax .LT. 18) .....       7.38

Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           25.06
           From the CIF: _reflns_number_total               1402
           Count of symmetry unique reflns         1404
           Completeness (_total/calc)             99.86%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured         0
           Fraction of Friedel pairs measured     0.000
           Are heavy atom types Z>Si present         no

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   1 ALERT level C = Check and explain
   1 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   1 ALERT type 3 Indicator that the structure quality may be low
   1 ALERT type 4 Improvement, methodology, query or suggestion

---

S1. Comment

Aza crown ethers find wide applications in catalysis, chromatographic separation of metal cations and molecular recognition, due to their pronounced complexing abilities (Gokel, 1991; Gokel et al., 2004). Different functionalities, introduced to the N atoms as pendant arms, can tailor the properties of these macrocyclic compounds. Despite potential application as selective complexing agents, these mixed donor–acceptor crown ethers have not been fully examined. A survey of the Cambridge Structural Database (CSD, Version 5.26, plus one 2005 update, 338445 entries; Allen, 2002) revealed a substantial list of complexes that incorporate monoaza-15-crown-5 as a ligand, covering a range of over 14 metal cations, while only a very few representatives of benzoaza-15-crown ethers (Clegg et al., 1996), their pendant derivatives (Liu et al., 1998; Chen et al., 1989; Landis et al., 2000; Bian et al., 2001) and complexes have been reported so far.

N-Nitroso derivatives are known to possess carcinogenic properties (Lijinsky, 1992), and the route of inhibition of the nitrosation process is currently under discussion (Simonov et al., 2005).

The nitrosation of amines is possible in two ways, namely by endogenous nitrogen oxide (NO) in the conditions of the oxidation reaction and by exogenous nitrites in the acidic medium. The typical reagents for this reaction are sodium nitrite and aqueous solutions of hydrochloric (HCl) or sulfuric (H₂SO₄) acids (this mixture yields nitrous acid, HNO₂). The actual nitrosation reagent is the nitrosyl cation, NO⁺, which is formed in situ. The nature of the product depends on the nature of the initial amine. Primary alkyl or aryl amines yield diazonium salts. Secondary alkyl or aryl amines yield N-nitrosoamines. Tertiary alkyl amines do not react in a useful fashion. Tertiary aryl amines undergo nitrosation of the ring. The scheme shows the route by which secondary amines are transformed to the dangerous N-nitroso compounds. Such nitrosamines, like many chemical carcinogens, are thought to promote mutagenesis and carcinogenesis via their ability to alkylate specific sites in DNA. For example, these types of nitrosamines undergo enzymatic α-hydroxylation. α-Hydroxy nitrosamine decomposes to form the alkyl diazonium ion and free alkyl carbocation. The alkyl diazonium salt or carbocations then can react with nucleophilic sites in DNA.

The task is to develop suitable ways for the effective inhibition of N-nitrosation. Among the suitable agents, it was found that the addition of a number of simple alcohols and carbohydrates to reactions of nitrous acid with amines in dilute acidic solution resulted in a reduction in the overall rate constant for N-nitrosation, although complete suppression of nitrosation was not achieved (Williams & Aldred, 1982). The results are all consistent with the rapid equilibrium formation of the corresponding alkyl nitrite, which is itself virtually inactive as a direct nitrosating agent. Addition of the two thiols, L-cysteine and N-acetylpenicillamine, had a much more marked effect and it was possible to prevent nitrosation of the amine completely in both cases. The O₂⁻ dianion was also mentioned among the other agents that partially inhibit the N-nitrosation of primary and secondary amines (Jourd'heuil et al., 1997).

The title compound, (I), was prepared as a part of study of the products of nitrosation of secondary amines by sodium nitrite in an acidic medium.

Figs. 1 and 2 depict the structure of (I), while selected intramolecular geometric data are listed in Table 1. The shape of the molecule is best described as a dentist-chair, with the five macrocyclic heteroatoms lying approximately in the saddle part (to within 0.16 Å), and with the atoms of the benzene ring located above this plane and the atoms of the nitroso group located below it. The N—N═O moiety is nearly coplanar with the benzene ring, making a dihedral angle of 3.2 (2)°. The macrocyclic cavity is distorted and far from the crown-like shape of benzo-15-crown-5 (Hanson, 1978).

Atom C14 is involved in an intramolecular C—H···O hydrogen bond with an O atom flanking the aromatic ring, C14···O10 3.090 (2) Å. This bond closes the six-membered intramolecular cycle (Fig. 1). The shape of the macrocyclic ring is similar to that found in 2,3-benzo-10-N-(4'-methoxyphenyl)-1,4,7,13-tetraoxa-10-azacyclopentadecane (CSD refcode GIVFIA; Liu et al., 1998), and N-(5-bromo-2-hydroxy-3-(hydroxymethyl)benzyl)-benzo-9-aza-15-crown-5 (VEHREF; Chen et al., 1989). The rapprochement of C14 and O10 is probably dictated by the electrostatic repulsion induced by the N-substituent, in the present case by the polarized NO group.

The macrocyclic strand of the molecule displays a series of anti, gauche and one cis torsion angles for the C—C, C—O and C—N bonds (Table 1). The individual X—C—C—X segments are gga, aga, acisa, agg- and aag, with a very uncommon distribution of anti and gauche torsion angles around the heterocyclic framework.

The presence of the NO group in the predominant polarized form is evident from the N1—N2 bond length of 1.314 (2) Å, which is significantly shorter than the expected distance between pyramidal and planar N atoms [1.420 (2) Å; Allen et al., 1987]. The N2—O20 distance is 1.244 (3) Å and the N1—N2—O20 angle is 114.62 (17)°. The geometry of the N—NO group is similar to those observed in related compounds, as is evident from a survey of the CSD. Our search found 121 hits for organic compounds containing an N-nitroso group. We selected 55 hits with R < 0.05 and analysed the geometry of the N-nitroso group, and the results are depicted in Fig. 4. The geometric parameters in (I) fall in the most populated ranges, both for the N—N and N═O bond distances and for the N—N═O angle.

The crystal packing of (I) reveals an intermolecular hydrogen bond of the type C—H···O [C16—H16···O10, with C···O 3.458 (2) Å], which combines the molecules into polar chains running along the c direction (Fig. 3). Two neighbouring chains in the unit cell meet each other in a face-to-face fashion via their nitroso groups, although specific contacts between them are absent, except for van der Waals contacts.

S2. Experimental

8,9-Benzo-1-aza-4,7,10,13-tetraoxacyclopentadeca-8-ene (2.67 g, 0.01 mol) was dissolved in a minimal amount of acetic acid and then added to an aqueous saturated solution (Volume?) of sodium nitrite (3.45 g, 0.05 mol). The crude precipitate of (I) was filtered off (yield 2.5 g, 86%; m.p. 353 K). Diffraction-quality crystals were obtained by recrystallization of the crude product from a mixture of ethanol and ethyl acetate (1:2) (m.p. 358–360 K). ¹H NMR (DMSO-d₆, 300 MHz, δ, p.p.m.): 2.72 (m, 4H, CH₂N), 3.48, 3.80, 4.12 (m, 12H, CH₂), 6.67 and 6.74 (m, 4H, CH).

S3. Refinement

Determination of the absolute structure has not been carried out, due to the absence of significant anomalous dispersion. H atoms were generated in their ideal positions and their parameters were constrained during the refinement [C—H = 0.97 Å, C—H = 0.93 Å and U_iso(H) = 1.2 U_eq(C)].

Computing details

Data collection: CrysAlis CCD (Oxford Diffraction, 2000); cell refinement: CrysAlis CCD; data reduction: CrysAlis CCD CrysAlis RED?; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: SHELXL97.

Figures

	Fig. 1. The structure of (I), viewed on the plane of the heteroatoms of the macrocyclic backbone. Displacement ellipsoids are drawn at the 50% probability level. The intramolecular hydrogen bond is shown as a dashed line.
	Fig. 2. A side view of (I). Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 3. The packing of the molecules in (I) sustained by C—H···O hydrogen bonds. The O atom marked with an asterisk (*) is at the symmetry position (1/2 − x, y, 1/2 + z).
	Fig. 4. The distribution of the bond distances, (a) N═O and (b) N—N, and (c) the bond angles N—N═O in metal-free N-nitroso compounds with R < 0.05.

11-Nitroso-6,7,10,11,12,13,15,16-octahydro-9H-5,8,14,17- tetraoxa-11-azabenzocyclopentadecene

Crystal data

C14H20N2O5	Dx = 1.339 Mg m^−3
Mr = 296.32	Melting point: 359(1) K
Orthorhombic, Pca21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2c -2ac	Cell parameters from 3505 reflections
a = 8.3002 (6) Å	θ = 4–25°
b = 20.6868 (14) Å	µ = 0.10 mm^−1
c = 8.5584 (6) Å	T = 130 K
V = 1469.52 (18) Å^3	Prism, colourless
Z = 4	0.25 × 0.20 × 0.20 mm
F(000) = 632

Data collection

Kuma KM-4 CCD area-detector diffractometer	1349 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.031
Graphite monochromator	θmax = 25.1°, θmin = 3.0°
ω scans	h = −9→9
10917 measured reflections	k = −24→24
1402 independent reflections	l = −10→7

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) = 0.071	H-atom parameters constrained
S = 1.07	w = 1/[σ^2(Fo^2) + (0.0543P)^2] where P = (Fo^2 + 2Fc^2)/3
1402 reflections	(Δ/σ)max < 0.001
190 parameters	Δρmax = 0.16 e Å^−3
1 restraint	Δρmin = −0.17 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
N2	0.6196 (2)	0.46146 (8)	0.3637 (2)	0.0332 (4)
O20	0.7441 (2)	0.44505 (7)	0.2931 (2)	0.0411 (4)
N1	0.57137 (19)	0.42042 (8)	0.4711 (2)	0.0253 (4)
C2	0.4345 (2)	0.44257 (9)	0.5636 (3)	0.0286 (5)
H2A	0.4194	0.4885	0.5461	0.034*
H2B	0.4586	0.4364	0.6735	0.034*
C3	0.2797 (2)	0.40771 (9)	0.5252 (3)	0.0308 (5)
H3A	0.1900	0.4287	0.5773	0.037*
H3B	0.2605	0.4092	0.4134	0.037*
O4	0.29148 (15)	0.34255 (6)	0.57528 (17)	0.0262 (3)
C5	0.1554 (2)	0.30607 (9)	0.5274 (3)	0.0267 (4)
H5A	0.1514	0.3039	0.4143	0.032*
H5B	0.0574	0.3266	0.5641	0.032*
C6	0.1685 (2)	0.23950 (9)	0.5941 (2)	0.0255 (4)
H6A	0.1830	0.2416	0.7064	0.031*
H6B	0.0715	0.2150	0.5721	0.031*
O7	0.30550 (15)	0.20927 (6)	0.52210 (16)	0.0248 (3)
C8	0.3488 (2)	0.14988 (9)	0.5773 (2)	0.0224 (4)
C9	0.4914 (2)	0.12412 (9)	0.5137 (2)	0.0232 (4)
O10	0.56600 (16)	0.16250 (7)	0.40496 (15)	0.0271 (3)
C11	0.7350 (3)	0.15413 (9)	0.3825 (3)	0.0282 (5)
H11A	0.7553	0.1179	0.3134	0.034*
H11B	0.7877	0.1458	0.4816	0.034*
C12	0.7982 (2)	0.21583 (9)	0.3112 (3)	0.0292 (5)
H12A	0.9098	0.2097	0.2810	0.035*
H12B	0.7370	0.2257	0.2176	0.035*
O13	0.78748 (16)	0.26892 (6)	0.41658 (17)	0.0286 (3)
C14	0.6472 (2)	0.30824 (9)	0.3980 (2)	0.0241 (4)
H14A	0.5507	0.2837	0.4219	0.029*
H14B	0.6395	0.3242	0.2917	0.029*
C15	0.6675 (2)	0.36381 (9)	0.5121 (3)	0.0274 (5)
H15A	0.6370	0.3493	0.6157	0.033*
H15B	0.7803	0.3761	0.5155	0.033*
C16	0.2657 (3)	0.11534 (9)	0.6889 (2)	0.0269 (4)
H16	0.1716	0.1322	0.7315	0.032*
C17	0.3221 (3)	0.05547 (10)	0.7377 (3)	0.0329 (5)
H17	0.2666	0.0327	0.8145	0.039*
C18	0.4595 (3)	0.02967 (10)	0.6734 (3)	0.0333 (5)
H18	0.4956	−0.0108	0.7053	0.040*
C19	0.5448 (2)	0.06407 (9)	0.5604 (2)	0.0289 (5)
H19	0.6376	0.0465	0.5166	0.035*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N2	0.0382 (11)	0.0293 (9)	0.0321 (10)	−0.0034 (8)	0.0037 (9)	−0.0001 (8)
O20	0.0428 (9)	0.0385 (8)	0.0420 (10)	−0.0045 (8)	0.0165 (8)	−0.0021 (8)
N1	0.0263 (9)	0.0243 (8)	0.0252 (8)	−0.0003 (7)	0.0018 (7)	0.0001 (7)
C2	0.0281 (11)	0.0267 (9)	0.0310 (11)	0.0037 (8)	0.0039 (9)	−0.0012 (9)
C3	0.0270 (11)	0.0279 (10)	0.0375 (12)	0.0059 (8)	0.0019 (10)	0.0061 (10)
O4	0.0216 (7)	0.0248 (6)	0.0321 (8)	0.0017 (5)	−0.0021 (6)	0.0042 (6)
C5	0.0184 (9)	0.0317 (10)	0.0301 (10)	0.0022 (7)	−0.0004 (8)	0.0010 (9)
C6	0.0195 (9)	0.0298 (10)	0.0273 (11)	−0.0001 (7)	0.0044 (8)	0.0003 (9)
O7	0.0254 (7)	0.0255 (7)	0.0235 (7)	0.0042 (5)	0.0059 (6)	0.0025 (6)
C8	0.0242 (10)	0.0229 (9)	0.0200 (9)	−0.0008 (7)	−0.0039 (9)	−0.0032 (8)
C9	0.0249 (10)	0.0274 (10)	0.0174 (9)	−0.0035 (8)	−0.0009 (8)	−0.0027 (7)
O10	0.0236 (7)	0.0331 (7)	0.0246 (7)	0.0027 (5)	0.0036 (6)	0.0022 (6)
C11	0.0234 (10)	0.0367 (10)	0.0245 (11)	0.0057 (9)	0.0020 (9)	−0.0061 (9)
C12	0.0250 (11)	0.0381 (12)	0.0247 (11)	0.0028 (8)	0.0052 (8)	−0.0066 (9)
O13	0.0241 (8)	0.0348 (7)	0.0269 (8)	0.0053 (6)	−0.0011 (6)	−0.0072 (7)
C14	0.0202 (9)	0.0283 (10)	0.0239 (10)	0.0018 (8)	−0.0012 (8)	0.0001 (9)
C15	0.0273 (11)	0.0299 (10)	0.0249 (10)	0.0025 (8)	−0.0028 (9)	−0.0030 (9)
C16	0.0252 (10)	0.0311 (10)	0.0243 (10)	−0.0014 (9)	0.0001 (8)	0.0012 (8)
C17	0.0335 (12)	0.0330 (11)	0.0321 (12)	−0.0047 (9)	−0.0013 (10)	0.0106 (10)
C18	0.0347 (12)	0.0264 (10)	0.0388 (13)	0.0006 (9)	−0.0076 (10)	0.0056 (9)
C19	0.0293 (11)	0.0278 (10)	0.0295 (11)	0.0041 (8)	−0.0039 (9)	−0.0056 (9)

Geometric parameters (Å, º)

N2—O20	1.244 (3)	C9—C19	1.378 (3)
N2—N1	1.314 (2)	O10—C11	1.426 (2)
N1—C2	1.459 (3)	C11—C12	1.509 (3)
N1—C15	1.460 (3)	C11—H11A	0.9700
C2—C3	1.510 (3)	C11—H11B	0.9700
C2—H2A	0.9700	C12—O13	1.424 (2)
C2—H2B	0.9700	C12—H12A	0.9700
C3—O4	1.418 (2)	C12—H12B	0.9700
C3—H3A	0.9700	O13—C14	1.429 (2)
C3—H3B	0.9700	C14—C15	1.517 (3)
O4—C5	1.419 (2)	C14—H14A	0.9700
C5—C6	1.495 (3)	C14—H14B	0.9700
C5—H5A	0.9700	C15—H15A	0.9700
C5—H5B	0.9700	C15—H15B	0.9700
C6—O7	1.436 (2)	C16—C17	1.389 (3)
C6—H6A	0.9700	C16—H16	0.9300
C6—H6B	0.9700	C17—C18	1.374 (3)
O7—C8	1.365 (2)	C17—H17	0.9300
C8—C16	1.377 (3)	C18—C19	1.394 (3)
C8—C9	1.408 (3)	C18—H18	0.9300
C9—O10	1.371 (2)	C19—H19	0.9300
O20—N2—N1	114.62 (17)	O10—C11—C12	107.08 (16)
N2—N1—C2	114.46 (16)	O10—C11—H11A	110.3
N2—N1—C15	121.32 (17)	C12—C11—H11A	110.3
C2—N1—C15	123.19 (17)	O10—C11—H11B	110.3
N1—C2—C3	113.25 (17)	C12—C11—H11B	110.3
N1—C2—H2A	108.9	H11A—C11—H11B	108.6
C3—C2—H2A	108.9	O13—C12—C11	112.01 (17)
N1—C2—H2B	108.9	O13—C12—H12A	109.2
C3—C2—H2B	108.9	C11—C12—H12A	109.2
H2A—C2—H2B	107.7	O13—C12—H12B	109.2
O4—C3—C2	109.23 (16)	C11—C12—H12B	109.2
O4—C3—H3A	109.8	H12A—C12—H12B	107.9
C2—C3—H3A	109.8	C12—O13—C14	114.79 (14)
O4—C3—H3B	109.8	O13—C14—C15	105.62 (15)
C2—C3—H3B	109.8	O13—C14—H14A	110.6
H3A—C3—H3B	108.3	C15—C14—H14A	110.6
C3—O4—C5	111.31 (14)	O13—C14—H14B	110.6
O4—C5—C6	108.78 (16)	C15—C14—H14B	110.6
O4—C5—H5A	109.9	H14A—C14—H14B	108.7
C6—C5—H5A	109.9	N1—C15—C14	113.10 (16)
O4—C5—H5B	109.9	N1—C15—H15A	109.0
C6—C5—H5B	109.9	C14—C15—H15A	109.0
H5A—C5—H5B	108.3	N1—C15—H15B	109.0
O7—C6—C5	107.15 (15)	C14—C15—H15B	109.0
O7—C6—H6A	110.3	H15A—C15—H15B	107.8
C5—C6—H6A	110.3	C8—C16—C17	120.2 (2)
O7—C6—H6B	110.3	C8—C16—H16	119.9
C5—C6—H6B	110.3	C17—C16—H16	119.9
H6A—C6—H6B	108.5	C18—C17—C16	120.37 (19)
C8—O7—C6	116.85 (15)	C18—C17—H17	119.8
O7—C8—C16	125.13 (17)	C16—C17—H17	119.8
O7—C8—C9	115.35 (17)	C17—C18—C19	120.08 (19)
C16—C8—C9	119.51 (18)	C17—C18—H18	120.0
O10—C9—C19	124.96 (18)	C19—C18—H18	120.0
O10—C9—C8	115.04 (16)	C9—C19—C18	119.83 (19)
C19—C9—C8	120.00 (18)	C9—C19—H19	120.1
C9—O10—C11	117.74 (15)	C18—C19—H19	120.1
N1—C2—C3—O4	68.5 (2)	C9—O10—C11—C12	−158.03 (16)
C2—C3—O4—C5	−173.97 (17)	O10—C11—C12—O13	66.7 (2)
C3—O4—C5—C6	−175.59 (17)	C11—C12—O13—C14	−95.9 (2)
O4—C5—C6—O7	−65.9 (2)	C12—O13—C14—C15	−175.78 (16)
C5—C6—O7—C8	173.99 (15)	O13—C14—C15—N1	158.29 (16)
C6—O7—C8—C9	−174.75 (16)	C14—C15—N1—C2	111.8 (2)
O7—C8—C9—O10	−0.1 (2)	C15—N1—C2—C3	−83.9 (2)
C8—C9—O10—C11	155.22 (16)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C14—H14A···O10	0.97	2.52	3.090 (2)	118
C16—H16···O10^i	0.93	2.55	3.457 (3)	166

Symmetry code: (i) −x+1/2, y, z+1/2.