organic papers
Acta Cryst.(2005). E61, o1203–o1204 doi:10.1107/S1600536805009074 Christopher L. Brownet al. C
16H18N2O6
o1203
Acta Crystallographica Section EStructure Reports
Online
ISSN 1600-5368
Succinimido 4-(
N
-maleimidomethyl)cyclo-hexanecarboxylate
Christopher L. Brown,* Sarah J. Atkinson and Peter C. Healy
Chemical Biology Program, Eskitis Institute, Griffith University, Nathan, Brisbane 4111, Australia
Correspondence e-mail: c.l.brown@griffith.edu.au
Key indicators
Single-crystal X-ray study T= 295 K
Mean(C–C) = 0.003 A˚ Rfactor = 0.043 wRfactor = 0.132
Data-to-parameter ratio = 17.6
For details of how these key indicators were automatically derived from the article, see http://journals.iucr.org/e.
#2005 International Union of Crystallography Printed in Great Britain – all rights reserved
The title compound {alternative name: 2,5-dioxo-3-pyrrolidin-1-yl 4-[(2,5-dioxo-3-pyrrolin-2,5-dioxo-3-pyrrolidin-1-yl)methyl]cyclohexanecarbox- 4-[(2,5-dioxo-3-pyrrolin-1-yl)methyl]cyclohexanecarbox-ylate}, C16H18N2O6, crystallizes as discrete molecules sepa-rated by normal van der Waals interactions. The succinimide ester and maleimide subunits occupy equatorial positions on the cyclohexane ring.
Comment
The title compound (SMCC), (I), is a heterobifunctional linking reagent that finds considerable utility for the biocon-jugation of chemical and biological species and is reactive to reagents possessing both amine and sulfhydryl functional groups (Bieniarzet al., 1996). We have used a simple two-step procedure to synthesize the target material in reasonable yields (41%). Recrystallization yielded highly pure crystalline material suitable for single-crystal X-ray diffraction studies. The structure of (I) consists of discrete molecules (Fig. 1). Bond lengths are in accord with conventional values (Allenet al., 1987). The succinimide ester and maleimide subunits occupy equatorial positions on the cyclohexane ring.
Experimental
trans -4-{[(3-Carboxy-1-oxo-2-propenyl)amino]methyl}cyclohexane-carboxylic acid (7.402 g, 29 mmol) and N-hydroxysuccinimide (3.696 g, 32 mmol) were dissolved in dry dimethylformamide (50 ml) and cooled to 273 K under an atmosphere of nitrogen. N,N -Di-cyclohexylcarbodiimide (DCC) (10.542 g, 51 mmol) was added to the solution and the reaction stirred for a further hour at 273 K. After warming to room temperature (296 K), the reaction was stirred for an additional 48 h. Precipitated dicyclohexylurea (DCU) was removed by filtration. Water (200 ml) was added to the filtrate and the solution was extracted with CHCl3(4250 ml). The combined
organic layers were dried (MgSO4), filtered and the solvent removed
in vacuoto yield a red oil. The oil was dissolved in dichloromethane (200 ml) and subsequently precipitated by the careful addition of
hexane to yield a white solid that was collected by filtration and characterized as succinimido 4-(N -maleimidomethyl)cyclohexane-carboxylate (4.03 g, 12 mmol, 41%). A small quantity of the product was recrystallized from (CH3)2CO/CH3OH to yield crystals suitable
for single-crystal X-ray diffraction studies (m.p. 444–447 K). ESMS+: 357 (MNa+, 50%), 341 (MLi+, 30%).1H NMR (400 MHz, DMSO-d6):
7.01 (s, 2H), 3.26 (d, 2H), 2.80 (s, 4H), 2.68 (tt, 1H), 1.99 (m, 2H), 1.67 (m, 2H), 1.59 (m, 1H), 1.38 (dddd, 2H), 1.04 (dddd, 2H).13C NMR (100 MHz, DMSO-d6):171.24, 170.85, 170.19, 134.37, 42.73,
39.39, 35.65, 28.55, 27.78, 25.41.
Crystal data
C16H18N2O6 Mr= 334.32
Orthorhombic,Pbca a= 20.203 (5) A˚
b= 17.021 (6) A˚
c= 9.643 (3) A˚
V= 3316.0 (18) A˚3
Z= 8
Dx= 1.339 Mg m 3
Mo Kradiation Cell parameters from 25
reflections
= 12.7–17.3
= 0.10 mm1
T= 295 K Prism, colorless 0.500.300.30 mm
Data collection
Rigaku AFC-7Rdiffractometer
!scans
Absorption correction: none 4776 measured reflections 3816 independent reflections 1926 reflections withI> 2(I)
Rint= 0.032
max= 27.5
h= 0!26
k=10!22
l=5!12 3 standard reflections
every 150 reflections intensity decay: 0.1%
Refinement
Refinement onF2 R[F2> 2(F2)] = 0.043 wR(F2) = 0.132 S= 1.01 3816 reflections 217 parameters
H-atom parameters constrained
w= 1/[2(F
o2) + (0.0582P)2]
whereP= (Fo2+ 2Fc2)/3
(/)max= 0.001
max= 0.15 e A˚ 3
min=0.23 e A˚ 3
Table 1
Selected geometric parameters (A˚ ,).
O1—C1 1.203 (3) O2—C4 1.206 (2) O3—N1 1.387 (2) O3—C5 1.395 (2) O4—C5 1.187 (3) O5—C13 1.202 (3)
O6—C16 1.206 (3) N1—C1 1.379 (3) N1—C4 1.376 (2) N2—C12 1.463 (2) N2—C13 1.389 (3) N2—C16 1.380 (3) N1—O3—C5 112.53 (14)
O3—N1—C1 121.31 (15) O3—N1—C4 122.07 (15) C1—N1—C4 116.49 (16) C12—N2—C13 125.11 (16) C12—N2—C16 124.65 (16) C13—N2—C16 110.20 (16) O1—C1—N1 124.28 (19) O1—C1—C2 130.10 (19) N1—C1—C2 105.62 (16) O2—C4—N1 124.30 (18) O2—C4—C3 130.14 (18)
N1—C4—C3 105.55 (16) O3—C5—O4 121.40 (18) O3—C5—C6 109.01 (15) O4—C5—C6 129.57 (19) N2—C12—C9 113.96 (15) O5—C13—N2 124.8 (2) O5—C13—C14 129.4 (2) N2—C13—C14 105.81 (18) O6—C16—N2 125.10 (17) O6—C16—C15 128.83 (19) N2—C16—C15 106.06 (18)
Table 2
Hydrogen-bonding geometry (A˚ ,).
D—H A D—H H A D A D—H A
C2—H2A O2i
0.95 2.50 3.381 (3) 154 C2—H2B O6ii
0.95 2.58 3.033 (3) 109 C3—H3A O6iii 0.95 2.52 3.335 (3) 144 C12—H12A O6 0.95 2.60 2.913 (3) 100 C14—H14 O1iv
0.95 2.42 3.330 (3) 160
Symmetry codes: (i) x;1 2y;z
1 2; (ii)
1 2þx;
1
2y;2z; (iii) 1 2þx;y;
3 2z; (iv) 3
2x; 1 2þy;z.
H atoms were constrained in riding-model approximation, with C—H distances set at 0.95 A˚ .Uiso(H) values were set at 1.2Ueqof the
parent atom.
Data collection:MSC/AFC-7 Diffractometer Control Software for Windows(Molecular Structure Corporation, 1999); cell refinement: MSC/AFC-7 Diffractometer Control Software for Windows; data reduction:TEXSAN for Windows(Molecular Structure Corporation, 2001); program(s) used to solve structure:TEXSAN for Windows; program(s) used to refine structure: TEXSAN for Windows and
SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3
(Farrugia, 1997); software used to prepare material for publication: TEXSAN for WindowsandPLATON(Spek, 2003).
We acknowledge financial support of this work by Griffith University, the Eskitis Institute of Cell and Molecular Therapies and the CRC for Microtechnology.
References
Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987).J. Chem. Soc. Perkin Trans.2, pp. S1–19.
Bieniarz, C., Husain, M., Barnes, G., King, C. A. & Welch, C. J. (1996).
Bioconjugate Chem.7, 88–89.
Farrugia, L. J. (1997).J. Appl. Cryst.30, 565.
Molecular Structure Corporation (1999).MSC/AFC-7 Diffractometer Control Software for Windows. Version 1.02. MSC, 9009 New Trails Drive, The Woodlands, TX 77381-5209, USA.
[image:2.610.314.565.73.160.2]Molecular Structure Corporation (2001). TESXAN for Windows. Version 1.06. MSC, 9009 New Trails Drive, The Woodlands, TX 77381-5209, USA. Sheldrick, G. M. (1997).SHELXL97. University of Go¨ttingen, Germany. Spek, A. L. (2003).J. Appl. Cryst.36, 7–13.
Figure 1
supporting information
sup-1 Acta Cryst. (2005). E61, o1203–o1204
supporting information
Acta Cryst. (2005). E61, o1203–o1204 [https://doi.org/10.1107/S1600536805009074]
Succinimido 4-(
N
-maleimidomethyl)cyclohexanecarboxylate
Christopher L. Brown, Sarah J. Atkinson and Peter C. Healy
2,5-dioxo-3-pyrrolidin-1-yl 4-[(2,5-dioxo-3-pyrrolin-1-yl)methyl]cyclohexanecarboxylate
Crystal data
C16H18N2O6 Mr = 334.32
Orthorhombic, Pbca
Hall symbol: -P 2ac 2ab
a = 20.203 (5) Å
b = 17.021 (6) Å
c = 9.643 (3) Å
V = 3316.0 (18) Å3 Z = 8
F(000) = 1408
Dx = 1.339 Mg m−3
Mo Kα radiation, λ = 0.7107 Å Cell parameters from 25 reflections
θ = 12.7–17.3°
µ = 0.10 mm−1 T = 295 K
Prismatic, colorless 0.50 × 0.30 × 0.30 mm
Data collection
Rigaku AFC-7R diffractometer
Radiation source: Rigaku rotating anode Graphite monochromator
ω scans
4776 measured reflections 3816 independent reflections 1926 reflections with I > 2σ(I)
Rint = 0.032
θmax = 27.5°, θmin = 2.6° h = 0→26
k = −10→22
l = −5→12
3 standard reflections every 150 reflections intensity decay: 0.1%
Refinement
Refinement on F2
Least-squares matrix: full
R[F2 > 2σ(F2)] = 0.043 wR(F2) = 0.132 S = 1.01 3816 reflections 217 parameters 0 restraints
Primary atom site location: structure-invariant direct methods
Secondary atom site location: difference Fourier map
Hydrogen site location: inferred from neighbouring sites
H-atom parameters constrained
w = 1/[σ2(F
o2) + (0.0582P)2]
where P = (Fo2 + 2Fc2)/3
(Δ/σ)max = 0.001
Δρmax = 0.15 e Å−3
Δρmin = −0.23 e Å−3
Special details
Experimental. The scan width was (1.16 + 0.30tanθ)° with an ω scan speed of 16° per minute (up to 4 scans to achieve I/σ(I) > 10). Stationary background counts were recorded at each end of the scan, and the scan time:background time ratio was 2:1.
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 > 2σ(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 (Å2)
x y z Uiso*/Ueq
supporting information
sup-3 Acta Cryst. (2005). E61, o1203–o1204
H14 0.57280 0.58070 0.87200 0.0740* H15 0.54590 0.45340 0.96460 0.0730*
Atomic displacement parameters (Å2)
U11 U22 U33 U12 U13 U23
O1 0.0627 (10) 0.0780 (11) 0.0882 (12) −0.0282 (8) 0.0077 (9) −0.0039 (9) O2 0.0824 (11) 0.0539 (9) 0.0793 (11) −0.0131 (8) 0.0183 (9) −0.0151 (9) O3 0.0379 (7) 0.0711 (9) 0.0515 (8) 0.0163 (6) 0.0061 (6) 0.0025 (7) O4 0.0773 (12) 0.1376 (16) 0.0520 (10) 0.0493 (11) 0.0069 (9) 0.0060 (10) O5 0.0715 (11) 0.0660 (11) 0.1087 (14) 0.0052 (9) 0.0171 (10) 0.0226 (10) O6 0.0672 (10) 0.0668 (10) 0.0829 (12) 0.0049 (8) 0.0221 (9) 0.0184 (9) N1 0.0350 (8) 0.0486 (9) 0.0599 (10) 0.0074 (7) 0.0097 (8) −0.0019 (8) N2 0.0344 (8) 0.0522 (9) 0.0552 (10) 0.0074 (7) 0.0051 (8) 0.0030 (8) C1 0.0432 (11) 0.0526 (12) 0.0525 (12) −0.0026 (10) −0.0040 (10) 0.0038 (10) C2 0.0540 (12) 0.0477 (11) 0.0520 (12) 0.0048 (10) 0.0030 (10) 0.0007 (9) C3 0.0456 (12) 0.0566 (13) 0.0731 (15) 0.0032 (10) 0.0184 (11) −0.0007 (11) C4 0.0418 (11) 0.0495 (11) 0.0515 (12) −0.0002 (9) 0.0051 (9) 0.0015 (9) C5 0.0419 (11) 0.0624 (13) 0.0550 (13) 0.0115 (10) 0.0020 (10) 0.0040 (11) C6 0.0381 (10) 0.0546 (12) 0.0481 (11) 0.0102 (9) 0.0036 (9) 0.0039 (9) C7 0.0300 (9) 0.0639 (13) 0.0646 (13) 0.0032 (9) −0.0048 (9) 0.0012 (11) C8 0.0359 (10) 0.0561 (12) 0.0625 (13) 0.0055 (9) −0.0101 (10) −0.0074 (10) C9 0.0319 (9) 0.0461 (11) 0.0487 (11) 0.0038 (8) −0.0039 (8) 0.0024 (9) C10 0.0327 (9) 0.0523 (11) 0.0629 (13) −0.0013 (8) 0.0000 (10) −0.0043 (10) C11 0.0412 (11) 0.0580 (13) 0.0670 (14) 0.0023 (10) 0.0016 (10) −0.0146 (10) C12 0.0412 (11) 0.0588 (13) 0.0564 (12) 0.0065 (9) −0.0043 (9) −0.0050 (10) C13 0.0490 (12) 0.0594 (13) 0.0565 (13) 0.0121 (10) 0.0121 (10) 0.0019 (11) C14 0.0446 (12) 0.0833 (17) 0.0649 (14) 0.0238 (12) −0.0006 (11) 0.0021 (13) C15 0.0334 (10) 0.0819 (17) 0.0803 (17) 0.0068 (11) 0.0085 (11) −0.0092 (14) C16 0.0422 (11) 0.0621 (14) 0.0529 (13) 0.0077 (10) 0.0134 (9) −0.0006 (10)
Geometric parameters (Å, º)
C5—C6 1.489 (3) C10—H10B 0.9500 C6—C7 1.525 (3) C11—H11A 0.9500 C6—C11 1.530 (3) C11—H11B 0.9500 C7—C8 1.520 (3) C12—H12A 0.9500 C8—C9 1.522 (3) C12—H12B 0.9400 C9—C10 1.521 (3) C14—H14 0.9500 C9—C12 1.523 (3) C15—H15 0.9600
O1···O3 2.784 (2) C2···H8Bix 3.0200
O1···C5 3.344 (3) C3···H10Biv 3.0700
O1···C14i 3.330 (3) C4···H2Aiii 3.0500
O1···C7ii 3.386 (3) C9···H2Bv 3.0000
O2···C2iii 3.381 (3) C13···H11Axi 2.9900
O2···C16iv 3.257 (3) C15···H15xii 3.0300
O2···O3 2.798 (2) C16···H10B 2.8800 O2···C15iv 3.182 (3) H2A···H8Bix 2.5700
O3···O1 2.784 (2) H2A···O2ii 2.5000
O3···O2 2.798 (2) H2A···O3ii 2.8200
O4···N1 2.559 (2) H2A···C4ii 3.0500
O4···C1 3.181 (3) H2B···O6viii 2.5800
O4···C4 3.273 (3) H2B···C9ix 3.0000
O5···C3v 3.338 (3) H2B···H9ix 2.3200
O6···C3vi 3.335 (3) H3A···O6iv 2.5200
O6···N1vii 3.202 (2) H3B···O5ix 2.6600
O6···C10 3.337 (3) H6···H8A 2.5300 O6···C1vii 2.935 (3) H6···H10A 2.5900
O6···C3vii 3.314 (3) H7A···H9 2.5400
O6···C2vii 3.033 (3) H7A···H11A 2.5700
O1···H14i 2.4200 H7B···O3 2.8700
O1···H7Bii 2.6900 H7B···O1iii 2.6900
O2···H2Aiii 2.5000 H8A···H6 2.5300
O2···H10Biv 2.7900 H8A···H10A 2.5600
O3···H2Aiii 2.8200 H8A···H12A 2.5200
O3···H7B 2.8700 H8B···H12B 2.4300 O4···H11A 2.7000 H8B···C2v 3.0200
O5···H12B 2.6900 H8B···H2Av 2.5700
O5···H3Bv 2.6600 H9···H7A 2.5400
O6···H2Bvii 2.5800 H9···H11A 2.5800
O6···H12A 2.6000 H9···H2Bv 2.3200
O6···H3Avi 2.5200 H10A···H6 2.5900
N1···O4 2.559 (2) H10A···H8A 2.5600 N1···O6viii 3.202 (2) H10A···H12A 2.5300
N2···H10B 2.7400 H10B···N2 2.7400 C1···O4 3.181 (3) H10B···C16 2.8800 C1···O6viii 2.935 (3) H10B···O2vi 2.7900
C2···O6viii 3.033 (3) H10B···C3vi 3.0700
C2···O2ii 3.381 (3) H11A···O4 2.7000
supporting information
sup-5 Acta Cryst. (2005). E61, o1203–o1204
C3···O6viii 3.314 (3) H11A···H9 2.5800
C3···O6iv 3.335 (3) H11A···C13xiii 2.9900
C4···O4 3.273 (3) H12A···O6 2.6000 C5···O1 3.344 (3) H12A···H8A 2.5200 C7···O1iii 3.386 (3) H12A···H10A 2.5300
C10···C16 3.394 (3) H12B···O5 2.6900 C10···O6 3.337 (3) H12B···H8B 2.4300 C14···O1x 3.330 (3) H14···O1x 2.4200
C15···O2vi 3.182 (3) H15···C15xii 3.0300
C16···C10 3.394 (3) H15···H15xii 2.5300
C16···O2vi 3.257 (3)
N2—C16—C15 106.06 (18) H12A—C12—H12B 110.00 C1—C2—H2A 110.00 C13—C14—H14 126.00 C1—C2—H2B 110.00 C15—C14—H14 125.00 C3—C2—H2A 111.00 C14—C15—H15 126.00 C3—C2—H2B 110.00 C16—C15—H15 125.00
C5—O3—N1—C1 −88.6 (2) C1—C2—C3—C4 −3.8 (2) C5—O3—N1—C4 95.7 (2) C2—C3—C4—O2 −177.9 (2) N1—O3—C5—O4 −1.1 (3) C2—C3—C4—N1 2.2 (2) N1—O3—C5—C6 −179.35 (15) O3—C5—C6—C7 87.80 (19) O3—N1—C1—O1 2.1 (3) O3—C5—C6—C11 −149.79 (16) O3—N1—C1—C2 −178.74 (15) O4—C5—C6—C11 32.1 (3) C4—N1—C1—O1 178.0 (2) O4—C5—C6—C7 −90.3 (3) C4—N1—C1—C2 −2.8 (2) C5—C6—C7—C8 178.92 (15) O3—N1—C4—O2 −3.7 (3) C11—C6—C7—C8 56.3 (2) O3—N1—C4—C3 176.27 (15) C5—C6—C11—C10 −177.11 (16) C1—N1—C4—O2 −179.54 (19) C7—C6—C11—C10 −55.2 (2) C1—N1—C4—C3 0.4 (2) C6—C7—C8—C9 −57.5 (2) C13—N2—C12—C9 −87.4 (2) C7—C8—C9—C12 −178.71 (15) C16—N2—C12—C9 95.3 (2) C7—C8—C9—C10 56.1 (2) C12—N2—C13—O5 2.8 (3) C12—C9—C10—C11 −178.11 (15) C12—N2—C13—C14 −177.76 (17) C8—C9—C12—N2 175.92 (15) C16—N2—C13—O5 −179.6 (2) C8—C9—C10—C11 −54.6 (2) C16—N2—C13—C14 −0.1 (2) C10—C9—C12—N2 −60.5 (2) C12—N2—C16—O6 −0.6 (3) C9—C10—C11—C6 54.9 (2) C12—N2—C16—C15 178.66 (18) O5—C13—C14—C15 178.5 (2) C13—N2—C16—O6 −178.3 (2) N2—C13—C14—C15 −1.0 (2) C13—N2—C16—C15 1.0 (2) C13—C14—C15—C16 1.6 (3) N1—C1—C2—C3 4.0 (2) C14—C15—C16—O6 177.6 (2) O1—C1—C2—C3 −176.9 (2) C14—C15—C16—N2 −1.7 (3)
Symmetry codes: (i) −x+3/2, y−1/2, z; (ii) x, −y+1/2, z−1/2; (iii) x, −y+1/2, z+1/2; (iv) x+1/2, y, −z+3/2; (v) −x+2, y+1/2, −z+3/2; (vi) x−1/2, y, −z+3/2; (vii) x−1/2, −y+1/2, −z+2; (viii) x+1/2, −y+1/2, −z+2; (ix) −x+2, y−1/2, −z+3/2; (x) −x+3/2, y+1/2, z; (xi) −x+3/2, −y+1, z+1/2; (xii) −x+1, −y+1, −z+2; (xiii) −x+3/2, −y+1, z−1/2.
Hydrogen-bond geometry (Å, º)
D—H···A D—H H···A D···A D—H···A
C2—H2A···O2ii 0.95 2.50 3.381 (3) 154
C2—H2B···O6viii 0.95 2.58 3.033 (3) 109
C3—H3A···O6iv 0.95 2.52 3.335 (3) 144
C12—H12A···O6 0.95 2.60 2.913 (3) 100 C14—H14···O1x 0.95 2.42 3.330 (3) 160
