Polymorphic forms of bendamustine hydro­chloride: crystal structure, thermal properties and stability at ambient conditions

Crystallographic, thermal and stability analyses are presented of three different anhydrated forms of bendamustine hydro­chloride [(I), (III) and (IV)] and a fourth, monohydrated one (II). Since form (I) presents the higher melting point and the higher heat of fusion, according to the `heat of fusion' rule it should be the most stable in thermodynamic terms [Burger & Ramberger (1979). Mikrochim. Acta, 72, 259–271], though it is unstable in high-humidity conditions. The monohydrate structure (II), in turn, dehydrates by heating and topotactically transform into anhydrate (III). This latter form appears as less stable than anhydrate (I), to which it is linked via a monotropic relationship. For these three different forms, the crystal structure has been determined by single crystal X-ray diffraction. The crystal structures and molecular conformations of forms (II) and (III) are quite similar, as expected from the topotactic transformation linking them; furthermore, under high-humidity conditions, form (III) shows changes compatible with a transformation into form (II) within 24 h. The crystal structure of form (I) is different from the other two. The remaining polymorphic form (IV) could only be obtained as a powder, from which its crystalline structure could not be determined. The relative thermodynamic stability of the different crystalline forms was determined by differential scanning calorimetry and thermogravimetrical studies, and their stability under different humidity conditions analysed.

Computing details

For all structures, data collection: CrysAlis PRO (Oxford Diffraction, 2009); cell refinement: CrysAlis PRO (Oxford Diffraction, 2009); data reduction: CrysAlis PRO (Oxford Diffraction, 2009); program(s) used to solve structure: SHELXS Version 2013/1 (Sheldrick, 2013); program(s) used to refine structure: SHELXL2018/1 (Sheldrick, 2018); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXL2018/1 (Sheldrick, 2018).

y-[l-methyl-5-bis-([3-chloroethyl)-aminobenzimidazolo-(2)]-butyryl chloride (I)

Crystal data

C16H22Cl2N3O2·Cl	F(000) = 1648
Mr = 394.71	Dx = 1.445 Mg m^−3
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
a = 23.0502 (6) Å	Cell parameters from 684 reflections
b = 6.7836 (2) Å	θ = 3.9–20.2°
c = 25.4596 (7) Å	µ = 0.52 mm^−1
β = 114.262 (1)°	T = 150 K
V = 3629.33 (18) Å^3	Plate, colourless
Z = 8	0.42 × 0.38 × 0.12 mm

Data collection

CCD Oxford Diffraction Xcalibur, Eos, Gemini diffractometer	6634 reflections with I > 2σ(I)
Radiation source: Enhance (Mo) X-ray Source	Rint = 0.056
thick slices scans	θmax = 36.4°, θmin = 3.1°
Absorption correction: multi-scan CrysAlisPro (Oxford Diffraction, 2009)	h = −38→37
Tmin = 0.84, Tmax = 0.96	k = −11→11
64102 measured reflections	l = −42→42
8857 independent reflections

Refinement

Refinement on F^2	2 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F^2 > 2σ(F^2)] = 0.044	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.112	w = 1/[σ^2(Fo^2) + (0.0488P)^2 + 3.3772P] where P = (Fo^2 + 2Fc^2)/3
S = 1.03	(Δ/σ)max = 0.002
8857 reflections	Δρmax = 0.79 e Å^−3
224 parameters	Δρmin = −0.78 e Å^−3

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
Cl1	0.24309 (2)	1.51415 (4)	0.40707 (2)	0.02180 (6)
Cl2	0.59057 (3)	−0.38243 (9)	0.78128 (2)	0.06521 (18)
Cl3	0.71751 (2)	0.22949 (5)	0.77895 (2)	0.03581 (9)
O1	0.37026 (5)	1.41128 (15)	0.41972 (5)	0.0320 (2)
H1O	0.3334 (8)	1.426 (3)	0.4177 (9)	0.038*
O2	0.45162 (4)	1.20862 (15)	0.45452 (5)	0.0307 (2)
N1	0.37307 (4)	0.48988 (13)	0.57752 (4)	0.01502 (15)
N2	0.45725 (4)	0.59515 (13)	0.56726 (4)	0.01614 (15)
H2N	0.4816 (7)	0.664 (2)	0.5573 (7)	0.019*
N3	0.59399 (4)	0.04575 (14)	0.67377 (4)	0.01808 (16)
C1	0.39716 (5)	1.24790 (17)	0.44682 (5)	0.01975 (19)
C2	0.35860 (5)	1.11280 (15)	0.46699 (5)	0.01588 (17)
H2A	0.321742	1.062101	0.433176	0.019*
H2B	0.342062	1.188095	0.491219	0.019*
C3	0.39820 (5)	0.93992 (16)	0.50149 (5)	0.01611 (17)
H3A	0.435294	0.990511	0.535120	0.019*
H3B	0.414371	0.863675	0.477154	0.019*
C4	0.35907 (5)	0.80478 (15)	0.52230 (5)	0.01605 (17)
H4A	0.343310	0.881429	0.546865	0.019*
H4B	0.321624	0.756560	0.488575	0.019*
C5	0.39599 (4)	0.63353 (15)	0.55540 (4)	0.01443 (16)
C6	0.30768 (5)	0.47940 (17)	0.57290 (5)	0.02031 (19)
H6A	0.278089	0.472597	0.532191	0.030*
H6B	0.298430	0.597049	0.590450	0.030*
H6C	0.302758	0.361542	0.592952	0.030*
C7	0.42142 (4)	0.35331 (15)	0.60517 (4)	0.01484 (16)
C8	0.42436 (5)	0.17921 (16)	0.63504 (5)	0.01779 (18)
H8	0.388318	0.130036	0.639957	0.021*
C9	0.48208 (5)	0.08060 (16)	0.65731 (5)	0.01825 (18)
H9	0.485144	−0.038270	0.678019	0.022*
C10	0.53716 (5)	0.14934 (15)	0.65059 (4)	0.01574 (17)
C11	0.59641 (6)	−0.15099 (16)	0.69710 (5)	0.02032 (19)
H11A	0.631819	−0.225382	0.693988	0.024*
H11B	0.556281	−0.221148	0.674074	0.024*
C12	0.60586 (6)	−0.1451 (2)	0.75981 (5)	0.0277 (2)
H12A	0.576606	−0.047147	0.764654	0.033*
H12B	0.650053	−0.104807	0.784394	0.033*
C13	0.64952 (5)	0.11955 (18)	0.66676 (5)	0.0216 (2)
H13A	0.636531	0.156748	0.625883	0.026*
H13B	0.680836	0.011108	0.675359	0.026*
C14	0.68217 (6)	0.2951 (2)	0.70404 (6)	0.0290 (3)
H14A	0.650709	0.401667	0.697902	0.035*
H14B	0.715544	0.345466	0.692515	0.035*
C15	0.53301 (5)	0.32413 (16)	0.62009 (5)	0.01645 (17)
H15	0.568544	0.374435	0.614530	0.020*
C16	0.47484 (5)	0.42099 (15)	0.59830 (4)	0.01486 (16)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl1	0.01733 (10)	0.02133 (12)	0.02558 (13)	0.00173 (9)	0.00765 (9)	−0.00146 (9)
Cl2	0.0773 (4)	0.0628 (3)	0.0422 (2)	−0.0276 (3)	0.0110 (2)	0.0264 (2)
Cl3	0.03073 (15)	0.03170 (16)	0.02932 (16)	−0.00741 (12)	−0.00351 (12)	0.00414 (12)
O1	0.0213 (4)	0.0284 (5)	0.0517 (6)	0.0081 (3)	0.0204 (4)	0.0229 (4)
O2	0.0168 (4)	0.0320 (5)	0.0485 (6)	0.0063 (3)	0.0188 (4)	0.0175 (4)
N1	0.0116 (3)	0.0146 (3)	0.0184 (4)	0.0007 (3)	0.0057 (3)	0.0026 (3)
N2	0.0119 (3)	0.0154 (4)	0.0210 (4)	0.0013 (3)	0.0066 (3)	0.0052 (3)
N3	0.0153 (3)	0.0153 (4)	0.0212 (4)	0.0032 (3)	0.0051 (3)	0.0048 (3)
C1	0.0153 (4)	0.0208 (5)	0.0248 (5)	0.0025 (3)	0.0100 (4)	0.0068 (4)
C2	0.0127 (4)	0.0160 (4)	0.0203 (4)	0.0020 (3)	0.0082 (3)	0.0046 (3)
C3	0.0126 (4)	0.0171 (4)	0.0189 (4)	0.0031 (3)	0.0067 (3)	0.0044 (3)
C4	0.0123 (4)	0.0147 (4)	0.0204 (4)	0.0022 (3)	0.0060 (3)	0.0042 (3)
C5	0.0117 (3)	0.0148 (4)	0.0164 (4)	0.0005 (3)	0.0053 (3)	0.0016 (3)
C6	0.0122 (4)	0.0203 (5)	0.0296 (5)	0.0006 (3)	0.0096 (4)	0.0041 (4)
C7	0.0115 (3)	0.0152 (4)	0.0167 (4)	0.0009 (3)	0.0046 (3)	0.0023 (3)
C8	0.0145 (4)	0.0176 (4)	0.0206 (4)	−0.0008 (3)	0.0065 (3)	0.0047 (3)
C9	0.0158 (4)	0.0168 (4)	0.0199 (4)	−0.0001 (3)	0.0051 (3)	0.0051 (3)
C10	0.0133 (4)	0.0157 (4)	0.0157 (4)	0.0012 (3)	0.0034 (3)	0.0017 (3)
C11	0.0230 (5)	0.0157 (4)	0.0210 (5)	0.0049 (4)	0.0078 (4)	0.0039 (4)
C12	0.0254 (5)	0.0339 (6)	0.0207 (5)	−0.0013 (5)	0.0064 (4)	0.0074 (5)
C13	0.0167 (4)	0.0233 (5)	0.0243 (5)	0.0057 (4)	0.0079 (4)	0.0051 (4)
C14	0.0214 (5)	0.0266 (6)	0.0304 (6)	−0.0039 (4)	0.0021 (4)	0.0088 (5)
C15	0.0124 (4)	0.0168 (4)	0.0193 (4)	0.0019 (3)	0.0056 (3)	0.0046 (3)
C16	0.0125 (4)	0.0147 (4)	0.0168 (4)	0.0006 (3)	0.0053 (3)	0.0030 (3)

Geometric parameters (Å, º)

Cl2—C12	1.7814 (15)	C4—H4B	0.9900
Cl3—C14	1.7951 (14)	C6—H6A	0.9800
O1—C1	1.3181 (14)	C6—H6B	0.9800
O1—H1O	0.837 (15)	C6—H6C	0.9800
O2—C1	1.2177 (13)	C7—C16	1.3910 (14)
N1—C5	1.3380 (13)	C7—C8	1.3912 (14)
N1—C7	1.3969 (13)	C8—C9	1.3853 (15)
N1—C6	1.4645 (13)	C8—H8	0.9500
N2—C5	1.3426 (13)	C9—C10	1.4273 (15)
N2—C16	1.3861 (13)	C9—H9	0.9500
N2—H2N	0.847 (13)	C10—C15	1.3989 (15)
N3—C10	1.3868 (13)	C11—C12	1.5206 (17)
N3—C13	1.4522 (15)	C11—H11A	0.9900
N3—C11	1.4525 (14)	C11—H11B	0.9900
C1—C2	1.5061 (15)	C12—H12A	0.9900
C2—C3	1.5236 (14)	C12—H12B	0.9900
C2—H2A	0.9900	C13—C14	1.5159 (19)
C2—H2B	0.9900	C13—H13A	0.9900
C3—C4	1.5256 (14)	C13—H13B	0.9900
C3—H3A	0.9900	C14—H14A	0.9900
C3—H3B	0.9900	C14—H14B	0.9900
C4—C5	1.4815 (14)	C15—C16	1.3879 (14)
C4—H4A	0.9900	C15—H15	0.9500
C1—O1—H1O	112.4 (15)	C16—C7—N1	106.37 (9)
C5—N1—C7	108.89 (8)	C8—C7—N1	133.48 (9)
C5—N1—C6	124.95 (9)	C9—C8—C7	117.16 (9)
C7—N1—C6	126.15 (9)	C9—C8—H8	121.4
C5—N2—C16	109.13 (8)	C7—C8—H8	121.4
C5—N2—H2N	126.2 (11)	C8—C9—C10	123.03 (10)
C16—N2—H2N	124.7 (11)	C8—C9—H9	118.5
C10—N3—C13	119.95 (9)	C10—C9—H9	118.5
C10—N3—C11	120.70 (9)	N3—C10—C15	120.19 (9)
C13—N3—C11	118.64 (9)	N3—C10—C9	120.97 (9)
O2—C1—O1	120.02 (10)	C15—C10—C9	118.84 (9)
O2—C1—C2	121.71 (10)	N3—C11—C12	111.72 (10)
O1—C1—C2	118.26 (9)	N3—C11—H11A	109.3
C1—C2—C3	111.55 (8)	C12—C11—H11A	109.3
C1—C2—H2A	109.3	N3—C11—H11B	109.3
C3—C2—H2A	109.3	C12—C11—H11B	109.3
C1—C2—H2B	109.3	H11A—C11—H11B	107.9
C3—C2—H2B	109.3	C11—C12—Cl2	109.72 (10)
H2A—C2—H2B	108.0	C11—C12—H12A	109.7
C2—C3—C4	111.29 (8)	Cl2—C12—H12A	109.7
C2—C3—H3A	109.4	C11—C12—H12B	109.7
C4—C3—H3A	109.4	Cl2—C12—H12B	109.7
C2—C3—H3B	109.4	H12A—C12—H12B	108.2
C4—C3—H3B	109.4	N3—C13—C14	115.44 (11)
H3A—C3—H3B	108.0	N3—C13—H13A	108.4
C5—C4—C3	112.66 (8)	C14—C13—H13A	108.4
C5—C4—H4A	109.1	N3—C13—H13B	108.4
C3—C4—H4A	109.1	C14—C13—H13B	108.4
C5—C4—H4B	109.1	H13A—C13—H13B	107.5
C3—C4—H4B	109.1	C13—C14—Cl3	111.25 (9)
H4A—C4—H4B	107.8	C13—C14—H14A	109.4
N1—C5—N2	108.96 (9)	Cl3—C14—H14A	109.4
N1—C5—C4	125.21 (9)	C13—C14—H14B	109.4
N2—C5—C4	125.82 (9)	Cl3—C14—H14B	109.4
N1—C6—H6A	109.5	H14A—C14—H14B	108.0
N1—C6—H6B	109.5	C16—C15—C10	117.23 (9)
H6A—C6—H6B	109.5	C16—C15—H15	121.4
N1—C6—H6C	109.5	C10—C15—H15	121.4
H6A—C6—H6C	109.5	N2—C16—C15	129.77 (9)
H6B—C6—H6C	109.5	N2—C16—C7	106.64 (8)
C16—C7—C8	120.15 (9)	C15—C16—C7	123.59 (9)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2N···O2^i	0.85 (1)	1.89 (1)	2.7293 (13)	169 (2)
C15—H15···O1^i	0.95	2.42	3.3283 (14)	159
O1—H1O···Cl1	0.84 (2)	2.07 (2)	2.8994 (10)	170 (2)
C4—H4B···Cl1^ii	0.99	2.68	3.6325 (11)	161
C4—H4A···Cl1^iii	0.99	2.79	3.7105 (11)	156
C6—H6A···Cl1^ii	0.98	2.96	3.8640 (13)	154
C6—H6B···Cl1^iii	0.98	2.82	3.7314 (12)	156
C6—H6C···Cl1^iv	0.98	2.76	3.6510 (12)	152
C8—H8···Cl1^iv	0.95	2.93	3.7904 (11)	151
C13—H13B···Cl3^v	0.99	2.87	3.8502 (12)	169
C14—H14B···Cl3^vi	0.99	2.96	3.6600 (13)	128
C12—H12B···Cl3	0.99	2.79	3.5053 (14)	130

Symmetry codes: (i) −x+1, −y+2, −z+1; (ii) x, y−1, z; (iii) −x+1/2, −y+5/2, −z+1; (iv) −x+1/2, −y+3/2, −z+1; (v) −x+3/2, y−1/2, −z+3/2; (vi) −x+3/2, y+1/2, −z+3/2.

y-[l-methyl-5-bis-([3-chloroethyl)-aminobenzimidazolo-(2)]-butyryl chloride, hydrate (II)

Crystal data

C16H22Cl2N3O2·Cl·H2O	F(000) = 864
Mr = 412.73	Dx = 1.411 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 4.6490 (6) Å	Cell parameters from 453 reflections
b = 47.213 (5) Å	θ = 1.3–28.3°
c = 8.9051 (10) Å	µ = 0.49 mm^−1
β = 96.222 (7)°	T = 100 K
V = 1943.1 (4) Å^3	Needle, colourless
Z = 4	0.24 × 0.06 × 0.04 mm

Data collection

CCD Oxford Diffraction Xcalibur, Eos, Gemini diffractometer	2180 reflections with I > 2σ(I)
Radiation source: Enhance (Mo) X-ray Source	Rint = 0.188
thick slices scans	θmax = 25.3°, θmin = 2.3°
Absorption correction: multi-scan CrysAlisPro (Oxford Diffraction, 2009)	h = −5→5
Tmin = 0.92, Tmax = 0.96	k = −56→56
19169 measured reflections	l = −10→8
3545 independent reflections

Refinement

Refinement on F^2	5 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F^2 > 2σ(F^2)] = 0.081	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.157	w = 1/[σ^2(Fo^2) + (0.0253P)^2 + 8.2062P] where P = (Fo^2 + 2Fc^2)/3
S = 1.10	(Δ/σ)max < 0.001
3545 reflections	Δρmax = 0.40 e Å^−3
239 parameters	Δρmin = −0.51 e Å^−3

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
Cl1	0.5030 (3)	−0.10517 (3)	0.06192 (16)	0.0179 (4)
Cl2	1.9159 (3)	0.24305 (3)	0.55536 (19)	0.0262 (4)
Cl3	1.3510 (4)	0.19906 (3)	−0.18388 (17)	0.0277 (4)
O1	0.7927 (10)	−0.01123 (8)	0.1394 (5)	0.0242 (10)
H1O	0.854 (13)	−0.0271 (7)	0.113 (7)	0.029*
O2	0.5765 (10)	−0.03454 (9)	0.3136 (5)	0.0326 (12)
N1	0.9362 (10)	0.09702 (9)	0.4886 (5)	0.0115 (11)
N2	0.8392 (10)	0.10743 (10)	0.2498 (5)	0.0129 (10)
H2N	0.743 (11)	0.1059 (12)	0.164 (3)	0.015*
N3	1.5490 (10)	0.18500 (9)	0.2608 (5)	0.0129 (11)
C1	0.6199 (13)	−0.01289 (12)	0.2501 (7)	0.0177 (14)
C2	0.4849 (12)	0.01485 (11)	0.2816 (7)	0.0160 (14)
H2A	0.377554	0.012808	0.371175	0.019*
H2B	0.343776	0.020002	0.194616	0.019*
C3	0.7064 (12)	0.03883 (11)	0.3104 (7)	0.0150 (13)
H3A	0.815627	0.040882	0.221581	0.018*
H3B	0.845772	0.033990	0.398729	0.018*
C4	0.5581 (12)	0.06693 (11)	0.3399 (6)	0.0118 (13)
H4A	0.412079	0.071288	0.253677	0.014*
H4B	0.456437	0.065119	0.431531	0.014*
C5	0.7700 (12)	0.09051 (11)	0.3608 (6)	0.0113 (12)
C6	0.9282 (13)	0.08437 (12)	0.6379 (6)	0.0170 (13)
H6A	0.788322	0.068773	0.631175	0.026*
H6B	0.870468	0.098742	0.708158	0.026*
H6C	1.120617	0.077108	0.674503	0.026*
C7	1.1186 (12)	0.11960 (11)	0.4585 (6)	0.0125 (13)
C8	1.3258 (12)	0.13446 (11)	0.5476 (6)	0.0139 (13)
H8	1.369720	0.130245	0.651873	0.017*
C9	1.4674 (12)	0.15575 (11)	0.4793 (6)	0.0139 (13)
H9	1.613259	0.166163	0.538632	0.017*
C10	1.4046 (12)	0.16279 (11)	0.3243 (6)	0.0117 (13)
C11	1.7706 (12)	0.20164 (12)	0.3520 (6)	0.0125 (13)
H11A	1.898290	0.210870	0.284549	0.015*
H11B	1.891034	0.188821	0.420736	0.015*
C12	1.6363 (13)	0.22410 (12)	0.4444 (7)	0.0163 (13)
H12A	1.506270	0.215060	0.511243	0.020*
H12B	1.520146	0.237356	0.376265	0.020*
C13	1.4267 (12)	0.19760 (12)	0.1183 (6)	0.0136 (13)
H13A	1.467166	0.218195	0.120501	0.016*
H13B	1.214093	0.195059	0.107200	0.016*
C14	1.5489 (13)	0.18457 (13)	−0.0170 (6)	0.0185 (14)
H14A	1.527192	0.163716	−0.015586	0.022*
H14B	1.757187	0.189137	−0.014819	0.022*
C15	1.1949 (12)	0.14708 (11)	0.2346 (6)	0.0129 (13)
H15	1.150922	0.150912	0.129933	0.015*
C16	1.0558 (12)	0.12594 (11)	0.3043 (6)	0.0110 (12)
O1W	0.9736 (9)	−0.05941 (8)	0.0273 (5)	0.0204 (10)
H1WA	0.809 (9)	−0.0764 (12)	0.030 (7)	0.031*
H1WB	1.128 (7)	−0.0675 (11)	0.065 (7)	0.031*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl1	0.0179 (8)	0.0213 (8)	0.0141 (8)	−0.0004 (7)	0.0000 (6)	−0.0022 (7)
Cl2	0.0189 (8)	0.0228 (8)	0.0360 (10)	0.0013 (7)	−0.0007 (7)	−0.0152 (8)
Cl3	0.0409 (10)	0.0299 (9)	0.0122 (8)	0.0010 (8)	0.0027 (7)	0.0029 (7)
O1	0.031 (3)	0.014 (2)	0.031 (3)	0.004 (2)	0.016 (2)	−0.003 (2)
O2	0.046 (3)	0.014 (2)	0.043 (3)	0.003 (2)	0.027 (2)	0.008 (2)
N1	0.015 (3)	0.010 (2)	0.010 (2)	0.006 (2)	0.004 (2)	0.004 (2)
N2	0.011 (3)	0.015 (3)	0.012 (3)	0.000 (2)	−0.001 (2)	−0.002 (2)
N3	0.013 (3)	0.011 (2)	0.015 (3)	−0.003 (2)	0.003 (2)	0.001 (2)
C1	0.014 (3)	0.017 (3)	0.022 (3)	−0.001 (3)	0.002 (3)	0.000 (3)
C2	0.013 (3)	0.011 (3)	0.024 (4)	−0.001 (3)	0.003 (3)	−0.002 (3)
C3	0.016 (3)	0.011 (3)	0.020 (3)	0.000 (3)	0.008 (3)	0.001 (3)
C4	0.014 (3)	0.007 (3)	0.015 (3)	−0.001 (2)	0.005 (3)	0.000 (2)
C5	0.011 (3)	0.014 (3)	0.010 (3)	0.002 (2)	0.003 (2)	−0.002 (3)
C6	0.020 (3)	0.020 (3)	0.012 (3)	−0.004 (3)	0.006 (3)	0.006 (3)
C7	0.013 (3)	0.007 (3)	0.018 (3)	0.000 (2)	0.005 (3)	−0.004 (3)
C8	0.015 (3)	0.014 (3)	0.013 (3)	0.004 (3)	0.002 (3)	−0.001 (3)
C9	0.014 (3)	0.011 (3)	0.017 (3)	−0.004 (3)	0.004 (3)	−0.004 (3)
C10	0.010 (3)	0.008 (3)	0.018 (3)	0.004 (2)	0.008 (3)	−0.001 (3)
C11	0.008 (3)	0.016 (3)	0.012 (3)	−0.004 (3)	−0.003 (2)	−0.003 (3)
C12	0.016 (3)	0.013 (3)	0.019 (3)	−0.002 (3)	−0.001 (3)	−0.003 (3)
C13	0.016 (3)	0.010 (3)	0.014 (3)	−0.001 (3)	−0.002 (2)	0.004 (3)
C14	0.022 (3)	0.022 (3)	0.011 (3)	0.002 (3)	0.002 (3)	0.002 (3)
C15	0.017 (3)	0.011 (3)	0.012 (3)	0.002 (3)	0.005 (3)	0.002 (3)
C16	0.018 (3)	0.004 (3)	0.011 (3)	0.002 (2)	−0.001 (3)	−0.003 (2)
O1W	0.025 (3)	0.017 (2)	0.020 (2)	0.004 (2)	0.009 (2)	0.0032 (19)

Geometric parameters (Å, º)

Cl2—C12	1.786 (6)	C6—H6A	0.9800
Cl3—C14	1.796 (6)	C6—H6B	0.9800
O1—C1	1.340 (7)	C6—H6C	0.9800
O1—H1O	0.84 (2)	C7—C8	1.372 (8)
O2—C1	1.196 (7)	C7—C16	1.405 (8)
N1—C5	1.340 (7)	C8—C9	1.379 (8)
N1—C7	1.406 (7)	C8—H8	0.9500
N1—C6	1.462 (7)	C9—C10	1.420 (8)
N2—C5	1.337 (7)	C9—H9	0.9500
N2—C16	1.381 (7)	C10—C15	1.403 (8)
N2—H2N	0.85 (2)	C11—C12	1.518 (8)
N3—C10	1.397 (7)	C11—H11A	0.9900
N3—C13	1.460 (7)	C11—H11B	0.9900
N3—C11	1.469 (7)	C12—H12A	0.9900
C1—C2	1.492 (8)	C12—H12B	0.9900
C2—C3	1.533 (7)	C13—C14	1.517 (8)
C2—H2A	0.9900	C13—H13A	0.9900
C2—H2B	0.9900	C13—H13B	0.9900
C3—C4	1.531 (7)	C14—H14A	0.9900
C3—H3A	0.9900	C14—H14B	0.9900
C3—H3B	0.9900	C15—C16	1.373 (7)
C4—C5	1.485 (7)	C15—H15	0.9500
C4—H4A	0.9900	O1W—H1WA	1.11 (5)
C4—H4B	0.9900	O1W—H1WB	0.851 (14)
C1—O1—H1O	113 (4)	C16—C7—N1	106.4 (5)
C5—N1—C7	108.4 (4)	C7—C8—C9	117.2 (5)
C5—N1—C6	127.6 (5)	C7—C8—H8	121.4
C7—N1—C6	123.9 (5)	C9—C8—H8	121.4
C5—N2—C16	110.1 (5)	C8—C9—C10	122.8 (5)
C5—N2—H2N	118 (4)	C8—C9—H9	118.6
C16—N2—H2N	132 (4)	C10—C9—H9	118.6
C10—N3—C13	119.9 (5)	N3—C10—C15	120.1 (5)
C10—N3—C11	121.1 (5)	N3—C10—C9	120.8 (5)
C13—N3—C11	116.5 (4)	C15—C10—C9	119.1 (5)
O2—C1—O1	122.9 (5)	N3—C11—C12	111.6 (4)
O2—C1—C2	124.4 (5)	N3—C11—H11A	109.3
O1—C1—C2	112.7 (5)	C12—C11—H11A	109.3
C1—C2—C3	113.0 (5)	N3—C11—H11B	109.3
C1—C2—H2A	109.0	C12—C11—H11B	109.3
C3—C2—H2A	109.0	H11A—C11—H11B	108.0
C1—C2—H2B	109.0	C11—C12—Cl2	109.4 (4)
C3—C2—H2B	109.0	C11—C12—H12A	109.8
H2A—C2—H2B	107.8	Cl2—C12—H12A	109.8
C2—C3—C4	111.2 (4)	C11—C12—H12B	109.8
C2—C3—H3A	109.4	Cl2—C12—H12B	109.8
C4—C3—H3A	109.4	H12A—C12—H12B	108.2
C2—C3—H3B	109.4	N3—C13—C14	112.4 (4)
C4—C3—H3B	109.4	N3—C13—H13A	109.1
H3A—C3—H3B	108.0	C14—C13—H13A	109.1
C5—C4—C3	111.5 (4)	N3—C13—H13B	109.1
C5—C4—H4A	109.3	C14—C13—H13B	109.1
C3—C4—H4A	109.3	H13A—C13—H13B	107.9
C5—C4—H4B	109.3	C13—C14—Cl3	107.5 (4)
C3—C4—H4B	109.3	C13—C14—H14A	110.2
H4A—C4—H4B	108.0	Cl3—C14—H14A	110.2
N2—C5—N1	109.2 (5)	C13—C14—H14B	110.2
N2—C5—C4	124.4 (5)	Cl3—C14—H14B	110.2
N1—C5—C4	126.3 (5)	H14A—C14—H14B	108.5
N1—C6—H6A	109.5	C16—C15—C10	117.3 (5)
N1—C6—H6B	109.5	C16—C15—H15	121.3
H6A—C6—H6B	109.5	C10—C15—H15	121.3
N1—C6—H6C	109.5	C15—C16—N2	131.5 (5)
H6A—C6—H6C	109.5	C15—C16—C7	122.6 (5)
H6B—C6—H6C	109.5	N2—C16—C7	105.9 (5)
C8—C7—C16	120.9 (5)	H1WA—O1W—H1WB	103 (4)
C8—C7—N1	132.7 (5)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1O···O1W	0.84 (2)	1.82 (2)	2.657 (6)	171 (6)
N2—H2N···Cl1^i	0.85 (2)	2.20 (2)	3.048 (5)	176 (6)
C6—H6A···O2^ii	0.98	2.43	3.383 (7)	164
C6—H6C···O2^iii	0.98	2.45	3.287 (7)	143
C8—H8···Cl1^iii	0.95	2.81	3.747 (6)	167
C12—H12A···Cl3^iv	0.99	2.98	3.882 (6)	152
C13—H13A···Cl2^v	0.99	2.88	3.690 (6)	139
C14—H14A···Cl1^vi	0.99	2.80	3.775 (6)	170
O1W—H1WA···Cl1	1.11 (5)	2.01 (5)	3.114 (4)	172 (5)
O1W—H1WB···Cl1^vii	0.85 (1)	2.49 (3)	3.264 (4)	151 (5)
C6—H6B···Cl1^ii	0.98	2.84	3.646 (6)	140

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

y-[l-methyl-5-bis-([3-chloroethyl)-aminobenzimidazolo-(2)]-butyryl chloride (III)

Crystal data

C16H22Cl2N3O2·Cl	F(000) = 824
Mr = 394.71	Dx = 1.394 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 4.722 (4) Å	Cell parameters from 1149 reflections
b = 45.671 (19) Å	θ = 0.4–29.6°
c = 8.798 (7) Å	µ = 0.50 mm^−1
β = 97.66 (6)°	T = 150 K
V = 1880 (2) Å^3	Needle, colourless
Z = 4	0.48 × 0.18 × 0.14 mm

Data collection

CCD Oxford Diffraction Xcalibur, Eos, Gemini diffractometer	2612 reflections with I > 2σ(I)
Radiation source: Enhance (Mo) X-ray Source	Rint = 0.131
thick slices scans	θmax = 25.3°, θmin = 2.3°
Absorption correction: multi-scan CrysAlisPro (Oxford Diffraction, 2009)	h = −5→5
Tmin = 0.84, Tmax = 0.94	k = −54→52
34373 measured reflections	l = −10→10
3384 independent reflections

Refinement

Refinement on F^2	23 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F^2 > 2σ(F^2)] = 0.171	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.379	w = 1/[σ^2(Fo^2) + 62.7847P] where P = (Fo^2 + 2Fc^2)/3
S = 1.24	(Δ/σ)max < 0.001
3384 reflections	Δρmax = 0.71 e Å^−3
225 parameters	Δρmin = −0.81 e Å^−3

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.

Refinement. Refined as a 2-component twin.

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

	x	y	z	Uiso*/Ueq
Cl1	0.6398 (8)	−0.09912 (7)	0.0915 (4)	0.0308 (8)
Cl2	1.8395 (8)	0.24367 (8)	0.5208 (5)	0.0423 (10)
Cl3	1.2721 (10)	0.19744 (9)	−0.2208 (4)	0.0444 (11)
O1	0.443 (2)	−0.0363 (2)	0.1203 (12)	0.040 (3)
H1O	0.56 (3)	−0.051 (2)	0.137 (19)	0.048*
O2	0.704 (2)	−0.0298 (2)	0.3491 (13)	0.042 (3)
N1	0.828 (2)	0.0941 (2)	0.4566 (11)	0.019 (2)
N2	0.753 (2)	0.1031 (2)	0.2087 (13)	0.025 (2)
H2N	0.64 (2)	0.104 (3)	0.126 (9)	0.030*
N3	1.466 (2)	0.1824 (2)	0.2279 (11)	0.024 (2)
C1	0.526 (3)	−0.0213 (3)	0.2469 (16)	0.033 (3)
C2	0.389 (3)	0.0089 (3)	0.2477 (18)	0.033 (3)
H2A	0.280425	0.012766	0.145420	0.039*
H2B	0.251965	0.009072	0.323668	0.039*
C3	0.607 (3)	0.0327 (3)	0.2862 (18)	0.030 (3)
H3A	0.731785	0.033942	0.204576	0.036*
H3B	0.727724	0.027943	0.383686	0.036*
C4	0.460 (2)	0.0627 (3)	0.3017 (15)	0.020 (2)
H4A	0.323927	0.066525	0.208221	0.023*
H4B	0.350779	0.062093	0.390172	0.023*
C5	0.673 (3)	0.0868 (3)	0.3240 (15)	0.026 (3)
C6	0.803 (3)	0.0822 (3)	0.6097 (17)	0.034 (3)
H6A	0.633500	0.069637	0.603933	0.052*
H6B	0.783664	0.098427	0.680784	0.052*
H6C	0.973580	0.070795	0.646341	0.052*
C7	1.010 (3)	0.1167 (3)	0.4292 (14)	0.024 (3)
C8	1.224 (2)	0.1322 (3)	0.5223 (13)	0.015 (2)
H8	1.267868	0.128258	0.628812	0.018*
C9	1.365 (3)	0.1531 (3)	0.4525 (13)	0.023 (3)
H9	1.505577	0.164263	0.515037	0.027*
C10	1.319 (2)	0.1598 (3)	0.2924 (13)	0.017 (3)
C11	1.685 (3)	0.1998 (3)	0.3224 (13)	0.022 (3)
H11A	1.811742	0.208965	0.255023	0.026*
H11B	1.803068	0.186633	0.394454	0.026*
C12	1.556 (3)	0.2237 (3)	0.4138 (18)	0.031 (3)
H12A	1.433647	0.214807	0.484076	0.037*
H12B	1.437366	0.237049	0.343079	0.037*
C13	1.344 (3)	0.1951 (3)	0.0873 (14)	0.025 (3)
H13A	1.384219	0.216362	0.090201	0.031*
H13B	1.133819	0.192526	0.075814	0.031*
C14	1.455 (3)	0.1820 (3)	−0.0486 (13)	0.026 (3)
H14A	1.426805	0.160504	−0.049073	0.031*
H14B	1.662839	0.185887	−0.042661	0.031*
C15	1.114 (3)	0.1434 (3)	0.1979 (13)	0.020 (3)
H15	1.078567	0.146469	0.090271	0.025*
C16	0.963 (3)	0.1224 (3)	0.2713 (13)	0.018 (3)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl1	0.0373 (19)	0.0329 (18)	0.0206 (16)	−0.0008 (15)	−0.0019 (14)	−0.0079 (14)
Cl2	0.034 (2)	0.035 (2)	0.055 (3)	−0.0003 (16)	−0.0045 (18)	−0.0187 (18)
Cl3	0.067 (3)	0.043 (2)	0.0217 (18)	−0.001 (2)	−0.0004 (18)	0.0010 (16)
O1	0.057 (7)	0.028 (6)	0.032 (6)	0.008 (5)	−0.004 (5)	−0.008 (4)
O2	0.057 (7)	0.023 (5)	0.044 (7)	0.003 (5)	−0.006 (6)	−0.011 (5)
N1	0.023 (6)	0.021 (5)	0.012 (5)	0.002 (4)	0.007 (4)	−0.004 (4)
N2	0.016 (6)	0.025 (6)	0.035 (7)	−0.010 (5)	0.007 (5)	−0.004 (5)
N3	0.038 (7)	0.028 (6)	0.010 (5)	−0.006 (5)	0.011 (5)	0.001 (4)
C1	0.050 (8)	0.034 (5)	0.015 (7)	0.003 (5)	0.004 (6)	−0.002 (5)
C2	0.026 (5)	0.030 (4)	0.040 (8)	−0.006 (4)	0.001 (5)	−0.006 (5)
C3	0.015 (5)	0.024 (4)	0.049 (9)	0.003 (4)	0.003 (5)	−0.008 (4)
C4	0.013 (5)	0.023 (4)	0.023 (7)	0.001 (4)	0.004 (4)	−0.005 (4)
C5	0.025 (6)	0.029 (5)	0.024 (7)	−0.007 (5)	0.002 (5)	−0.007 (5)
C6	0.035 (8)	0.034 (8)	0.037 (9)	0.004 (6)	0.014 (7)	0.007 (6)
C7	0.036 (8)	0.027 (7)	0.010 (6)	−0.004 (6)	0.001 (6)	−0.010 (5)
C8	0.011 (6)	0.025 (6)	0.009 (6)	0.002 (5)	0.002 (5)	0.002 (5)
C9	0.031 (7)	0.028 (7)	0.008 (6)	−0.003 (6)	−0.005 (5)	−0.005 (5)
C10	0.014 (6)	0.025 (7)	0.011 (6)	0.003 (5)	0.004 (5)	0.001 (5)
C11	0.025 (7)	0.034 (7)	0.007 (6)	0.008 (6)	0.005 (5)	0.002 (5)
C12	0.021 (7)	0.023 (7)	0.049 (9)	0.004 (6)	0.012 (6)	−0.003 (6)
C13	0.034 (8)	0.027 (7)	0.017 (6)	0.001 (6)	0.010 (6)	0.002 (5)
C14	0.034 (8)	0.038 (8)	0.009 (6)	0.006 (6)	0.012 (6)	0.000 (5)
C15	0.022 (7)	0.029 (7)	0.008 (6)	0.003 (5)	−0.006 (5)	−0.004 (5)
C16	0.024 (7)	0.024 (7)	0.007 (6)	0.001 (5)	0.003 (5)	−0.004 (5)

Geometric parameters (Å, º)

Cl2—C12	1.780 (15)	C4—H4B	0.9900
Cl3—C14	1.787 (13)	C6—H6A	0.9800
O1—C1	1.324 (17)	C6—H6B	0.9800
O1—H1O	0.85 (2)	C6—H6C	0.9800
O2—C1	1.210 (18)	C7—C16	1.402 (17)
N1—C5	1.334 (16)	C7—C8	1.406 (17)
N1—C7	1.384 (16)	C8—C9	1.359 (17)
N1—C6	1.470 (17)	C8—H8	0.9500
N2—C5	1.352 (17)	C9—C10	1.428 (17)
N2—C16	1.385 (16)	C9—H9	0.9500
N2—H2N	0.85 (2)	C10—C15	1.405 (17)
N3—C10	1.403 (16)	C11—C12	1.529 (17)
N3—C13	1.418 (17)	C11—H11A	0.9900
N3—C11	1.472 (17)	C11—H11B	0.9900
C1—C2	1.52 (2)	C12—H12A	0.9900
C2—C3	1.507 (18)	C12—H12B	0.9900
C2—H2A	0.9900	C13—C14	1.495 (16)
C2—H2B	0.9900	C13—H13A	0.9900
C3—C4	1.547 (17)	C13—H13B	0.9900
C3—H3A	0.9900	C14—H14A	0.9900
C3—H3B	0.9900	C14—H14B	0.9900
C4—C5	1.486 (17)	C15—C16	1.403 (17)
C4—H4A	0.9900	C15—H15	0.9500
C1—O1—H1O	99 (10)	N1—C7—C8	133.7 (11)
C5—N1—C7	108.3 (10)	C16—C7—C8	119.2 (12)
C5—N1—C6	127.5 (11)	C9—C8—C7	116.8 (11)
C7—N1—C6	124.1 (11)	C9—C8—H8	121.6
C5—N2—C16	108.0 (11)	C7—C8—H8	121.6
C5—N2—H2N	117 (10)	C8—C9—C10	125.1 (12)
C16—N2—H2N	131 (10)	C8—C9—H9	117.4
C10—N3—C13	119.3 (11)	C10—C9—H9	117.4
C10—N3—C11	121.1 (10)	C15—C10—N3	119.4 (11)
C13—N3—C11	116.4 (10)	C15—C10—C9	118.2 (11)
O2—C1—O1	123.9 (13)	N3—C10—C9	122.4 (11)
O2—C1—C2	122.8 (13)	N3—C11—C12	112.6 (11)
O1—C1—C2	113.2 (13)	N3—C11—H11A	109.1
C3—C2—C1	112.2 (12)	C12—C11—H11A	109.1
C3—C2—H2A	109.2	N3—C11—H11B	109.1
C1—C2—H2A	109.2	C12—C11—H11B	109.1
C3—C2—H2B	109.2	H11A—C11—H11B	107.8
C1—C2—H2B	109.2	C11—C12—Cl2	108.7 (9)
H2A—C2—H2B	107.9	C11—C12—H12A	109.9
C2—C3—C4	111.1 (11)	Cl2—C12—H12A	109.9
C2—C3—H3A	109.4	C11—C12—H12B	109.9
C4—C3—H3A	109.4	Cl2—C12—H12B	109.9
C2—C3—H3B	109.4	H12A—C12—H12B	108.3
C4—C3—H3B	109.4	N3—C13—C14	112.8 (11)
H3A—C3—H3B	108.0	N3—C13—H13A	109.0
C5—C4—C3	111.4 (10)	C14—C13—H13A	109.0
C5—C4—H4A	109.4	N3—C13—H13B	109.0
C3—C4—H4A	109.4	C14—C13—H13B	109.0
C5—C4—H4B	109.4	H13A—C13—H13B	107.8
C3—C4—H4B	109.4	C13—C14—Cl3	109.7 (9)
H4A—C4—H4B	108.0	C13—C14—H14A	109.7
N1—C5—N2	110.1 (11)	Cl3—C14—H14A	109.7
N1—C5—C4	125.6 (12)	C13—C14—H14B	109.7
N2—C5—C4	124.2 (11)	Cl3—C14—H14B	109.7
N1—C6—H6A	109.5	H14A—C14—H14B	108.2
N1—C6—H6B	109.5	C10—C15—C16	116.4 (11)
H6A—C6—H6B	109.5	C10—C15—H15	121.8
N1—C6—H6C	109.5	C16—C15—H15	121.8
H6A—C6—H6C	109.5	N2—C16—C15	129.2 (11)
H6B—C6—H6C	109.5	N2—C16—C7	106.5 (11)
N1—C7—C16	107.0 (10)	C15—C16—C7	124.2 (11)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1O···Cl1	0.85 (2)	2.29 (9)	3.036 (10)	147 (15)
N2—H2N···Cl1^i	0.85 (2)	2.18 (3)	3.024 (12)	171 (14)
C6—H6A···O2^ii	0.98	2.49	3.438 (18)	163
C6—H6C···O2^iii	0.98	2.41	3.329 (18)	156
C8—H8···Cl1^iii	0.95	2.78	3.696 (12)	162
C12—H12A···Cl3^iv	0.99	2.91	3.838 (16)	156
C13—H13A···Cl2^v	0.99	2.95	3.743 (14)	138
C14—H14A···Cl1^vi	0.99	2.84	3.824 (15)	172

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