4-Imino-1,3-diaza­bicyclo­[3.1.0]hexan-2-one

The title compound, also known as imexon, C₄H₅N₃O, is an imino­pyrrolidone that, due to its selective growth inhibitory effect against multiple myeloma, has been under investigation as an anti­cancer agent since the 1970s. Crystals of the title compound were grown from absolute ethanol saturated with imexon at 296 K, by slow evaporation. Under these conditions, imexon crystallizes as plates with well developed (100) faces. The crystals readily twin by a twofold rotation about the a axis. When crystallized via rapid evaporation of solvent, the resulting powder has a slightly larger unit cell. Simulation of the powder pattern using the atomic parameters and the larger powder cell agree well with measured powder patterns but indicate some preferred orientation towards the (100) plane. The anti­cancer mol­ecule crystallizes as a zwitterion, with the imino N atom doubly protonated. Each mol­ecule makes four hydrogen bonds which form continuous tapes of mol­ecules along [010].

Key indicators

• Single-crystal X-ray study
• T = 173 K
• Mean [sigma]() = 0.000 Å
• Disorder in main residue
• R factor = 0.059
• wR factor = 0.141
• Data-to-parameter ratio = 166.7

checkCIF/PLATON results

No syntax errors found



Alert level A
REFLT03_ALERT_3_A  Reflection count > 15% excess reflns - sys abs data present?
           From the CIF: _diffrn_reflns_theta_max           25.99
           From the CIF: _diffrn_reflns_theta_full          25.99
           From the CIF: _reflns_number_total              13504
           TEST2: Reflns within _diffrn_reflns_theta_max
           Count of symmetry unique reflns          936
           Completeness (_total/calc)           1442.73%

Author Response: Merging of unique reflections was not preformed due to overlap of twin components.

PLAT021_ALERT_1_A Ratio Unique / Expected Reflections too High ...      14.43

Author Response: Merging of unique reflections was not preformed due to overlap of twin components.

Alert level B
PLAT026_ALERT_3_B Ratio Observed / Unique Reflections too Low ....         33 Perc.
PLAT301_ALERT_3_B Main Residue  Disorder .........................      50.00 Perc.

Alert level C
GOODF01_ALERT_2_C  The least squares goodness of fit parameter lies
            outside the range 0.80 <> 2.00
            Goodness of fit given =      0.703
PLAT030_ALERT_1_C _diffrn_reflns_number .LE.  _reflns_number_total          ?

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

   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
   3 ALERT type 3 Indicator that the structure quality may be low
   0 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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Computing details

Data collection: APEX2 (Bruker, 2005); cell refinement: APEX2; data reduction: SAINT (Bruker, 2005); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 1997) and Mercury (Macrae et al., 2006); software used to prepare material for publication: SHELXTL.

4-Imino-1,3-diazabicyclo[3.1.0]hexan-2-one

Crystal data

C4H5N3O	F(000) = 232
Mr = 111.11	Dx = 1.540 Mg m^−3
Monoclinic, P21/c	Melting point: 438 (dec) K
Hall symbol: -P 2ybc	Mo Kα radiation, λ = 0.71073 Å
a = 10.3612 (12) Å	Cell parameters from 1346 reflections
b = 6.5999 (6) Å	θ = 3.7–20.1°
c = 7.2077 (11) Å	µ = 0.12 mm^−1
β = 103.685 (9)°	T = 173 K
V = 478.89 (10) Å^3	Plate, colourless
Z = 4	0.28 × 0.16 × 0.03 mm

Data collection

Bruker APEXII CCD area-detector diffractometer	13504 independent reflections
Radiation source: fine-focus sealed tube	4436 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.000
φ and ω scans	θmax = 26.0°, θmin = 2.0°
Absorption correction: multi-scan (TWINABS; Sheldrick, 2005)	h = −12→12
Tmin = 0.938, Tmax = 0.997	k = −8→8
13504 measured reflections	l = −8→8

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)] = 0.059	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.141	H-atom parameters constrained
S = 0.70	w = 1/[σ^2(Fo^2) + (0.0342P)^2] where P = (Fo^2 + 2Fc^2)/3
13504 reflections	(Δ/σ)max = 0.001
81 parameters	Δρmax = 0.30 e Å^−3
318 restraints	Δρmin = −0.27 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. Non-merohedral twinning of the single crystals examined was obvious from initial diffraction patterns and concurrent difficulty in indexing. The correct unit cell and twin law relating two components was determined using the program CELL_NOW (Sheldrick, 2005). Twinning occurred via a 180° rotation about the real a axis. Reflections from both components, including overlaps, were integrated simultaneously using SAINT (Bruker, 2005) and two orientation matrices. Data was corrected for absorption and decay effects with TWINABS (Sheldrick, 2005). The structure was solved using direct methods on nonoverlapped reflections from domain one and was refined using all reflections from both components including overlaps. Merging of equivalent reflections was not performed due to the overlap of twin components. A whole molecule disorder, by rotation about the carbonyl, of 3.2 (1)% was modeled with a second part constrained to have approximately the same shape as the dominant molecule. Atom components which could not be separated were fixed to have identical positions and thermal parameters·Thermal ellipsoid simularity and rigid bond constraints were applied to both parts. All H atoms were positioned geometrically and allowed to ride on the atom to which they were bonded with fixed X—H distances and U_iso= 1.2 or 1.5 times that of the bonded atom.

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
N1	0.85631 (13)	0.37481 (17)	0.35979 (19)	0.0370 (4)	0.9683 (11)
C2	0.74670 (19)	0.2581 (2)	0.2473 (3)	0.0377 (4)	0.9683 (11)
N3	0.64292 (12)	0.37348 (18)	0.14670 (19)	0.0373 (4)	0.9683 (11)
C4	0.68131 (18)	0.5688 (2)	0.1829 (2)	0.0340 (5)	0.9683 (11)
C5	0.81695 (18)	0.5843 (2)	0.3052 (2)	0.0356 (5)	0.9683 (11)
H5	0.8400	0.6959	0.4011	0.043*	0.9683 (11)
C6	0.92297 (15)	0.48639 (19)	0.2271 (2)	0.0413 (5)	0.9683 (11)
H6B	1.0158	0.5316	0.2775	0.050*	0.9683 (11)
H6A	0.9006	0.4466	0.0908	0.050*	0.9683 (11)
O7	0.75089 (11)	0.07101 (11)	0.25220 (15)	0.0442 (3)	0.9683 (11)
N8	0.60593 (12)	0.72271 (16)	0.11440 (19)	0.0463 (4)	0.9683 (11)
H8B	0.5262	0.7021	0.0410	0.070*	0.9683 (11)
H8A	0.6349	0.8471	0.1416	0.070*	0.9683 (11)
N1B	0.64292 (12)	0.37348 (18)	0.14670 (19)	0.0373 (4)	0.0317 (11)
C2B	0.74670 (19)	0.2581 (2)	0.2473 (3)	0.0377 (4)	0.0317 (11)
N3B	0.85631 (13)	0.37481 (17)	0.35979 (19)	0.0370 (4)	0.0317 (11)
C4B	0.81695 (18)	0.5843 (2)	0.3052 (2)	0.0356 (5)	0.0317 (11)
C5B	0.68131 (18)	0.5688 (2)	0.1829 (2)	0.0340 (5)	0.0317 (11)
H5B	0.6532	0.6703	0.0781	0.041*	0.0317 (11)
C6B	0.573 (3)	0.474 (4)	0.271 (5)	0.0413 (5)	0.0317 (11)
H6C	0.5967	0.4394	0.4089	0.050*	0.0317 (11)
H6D	0.4795	0.5143	0.2188	0.050*	0.0317 (11)
O7B	0.75089 (11)	0.07101 (11)	0.25220 (15)	0.0442 (3)	0.0317 (11)
N8B	0.905 (3)	0.694 (4)	0.408 (5)	0.0463 (4)	0.0317 (11)
H8C	0.9716	0.6388	0.4907	0.070*	0.0317 (11)
H8D	0.8994	0.8272	0.3969	0.070*	0.0317 (11)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0402 (10)	0.0252 (7)	0.0445 (10)	0.0029 (7)	0.0079 (9)	0.0030 (8)
C2	0.0442 (10)	0.0368 (8)	0.0346 (10)	−0.0108 (13)	0.0145 (8)	−0.0032 (12)
N3	0.0402 (10)	0.0245 (7)	0.0443 (11)	0.0030 (7)	0.0039 (9)	0.0010 (8)
C4	0.0345 (12)	0.0357 (11)	0.0339 (13)	0.0041 (10)	0.0127 (10)	0.0022 (9)
C5	0.0446 (12)	0.0166 (10)	0.0442 (14)	−0.0030 (9)	0.0074 (10)	−0.0036 (8)
C6	0.0461 (11)	0.0312 (9)	0.0448 (13)	−0.0033 (8)	0.0074 (11)	−0.0028 (8)
O7	0.0582 (7)	0.0201 (5)	0.0514 (8)	−0.0036 (6)	0.0073 (6)	0.0011 (6)
N8	0.0497 (9)	0.0231 (7)	0.0615 (11)	0.0033 (7)	0.0036 (8)	0.0013 (8)
N1B	0.0402 (10)	0.0245 (7)	0.0443 (11)	0.0030 (7)	0.0039 (9)	0.0010 (8)
C2B	0.0442 (10)	0.0368 (8)	0.0346 (10)	−0.0108 (13)	0.0145 (8)	−0.0032 (12)
N3B	0.0402 (10)	0.0252 (7)	0.0445 (10)	0.0029 (7)	0.0079 (9)	0.0030 (8)
C4B	0.0446 (12)	0.0166 (10)	0.0442 (14)	−0.0030 (9)	0.0074 (10)	−0.0036 (8)
C5B	0.0345 (12)	0.0357 (11)	0.0339 (13)	0.0041 (10)	0.0127 (10)	0.0022 (9)
C6B	0.0461 (11)	0.0312 (9)	0.0448 (13)	−0.0033 (8)	0.0074 (11)	−0.0028 (8)
O7B	0.0582 (7)	0.0201 (5)	0.0514 (8)	−0.0036 (6)	0.0073 (6)	0.0011 (6)
N8B	0.0497 (9)	0.0231 (7)	0.0615 (11)	0.0033 (7)	0.0036 (8)	0.0013 (8)

Geometric parameters (Å, º)

N1—C2	1.4507 (16)	C5—H5	1.000
N1—C5	1.4685 (15)	C6—H6B	0.990
N1—C6	1.4990 (18)	C6—H6A	0.990
C2—O7	1.2358 (12)	N8—H8B	0.880
C2—N3	1.3759 (16)	N8—H8A	0.880
N3—C4	1.3562 (15)	C6B—H6C	0.990
C4—N8	1.3050 (15)	C6B—H6D	0.990
C4—C5	1.4751 (15)	N8B—H8C	0.880
C5—C6	1.4944 (18)	N8B—H8D	0.880
C2—N1—C5	102.65 (12)	C4—C5—H5	120.1
C2—N1—C6	108.80 (13)	C6—C5—H5	120.1
C5—N1—C6	60.47 (8)	C5—C6—N1	58.76 (9)
O7—C2—N3	125.86 (17)	C5—C6—H6B	117.9
O7—C2—N1	119.81 (17)	N1—C6—H6B	117.9
N3—C2—N1	114.30 (11)	C5—C6—H6A	117.9
C4—N3—C2	105.52 (13)	N1—C6—H6A	117.9
N8—C4—N3	123.02 (17)	H6B—C6—H6A	115.1
N8—C4—C5	124.93 (16)	C4—N8—H8B	120.0
N3—C4—C5	112.04 (15)	C4—N8—H8A	120.0
N1—C5—C4	105.07 (14)	H8B—N8—H8A	120.0
N1—C5—C6	60.78 (9)	H6C—C6B—H6D	115.6
C4—C5—C6	115.24 (14)	H8C—N8B—H8D	120.0
N1—C5—H5	120.1
C5—N1—C2—O7	176.51 (16)	C6—N1—C5—C4	110.82 (13)
C6—N1—C2—O7	113.73 (16)	C2—N1—C5—C6	−104.62 (14)
C5—N1—C2—N3	−5.42 (19)	N8—C4—C5—N1	175.03 (16)
C6—N1—C2—N3	−68.21 (17)	N3—C4—C5—N1	−5.68 (14)
O7—C2—N3—C4	179.98 (17)	N8—C4—C5—C6	−120.57 (17)
N1—C2—N3—C4	2.05 (19)	N3—C4—C5—C6	58.72 (16)
C2—N3—C4—N8	−178.33 (15)	C4—C5—C6—N1	−93.76 (15)
C2—N3—C4—C5	2.37 (16)	C2—N1—C6—C5	94.19 (13)
C2—N1—C5—C4	6.20 (14)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N8—H8B···N3^i	0.88	2.01	2.8805 (19)	172
N8—H8A···O7^ii	0.88	1.95	2.7966 (14)	160
N8B—H8D···O7^ii	0.88	2.30	3.02 (3)	139
N8B—H8C···N1^iii	0.88	1.85	2.68 (2)	155

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