The crystal structure of the title compound, C
16H
23N
3O
4·CH
3CN, was refined using a multipolar atom model transferred from an experimental electron-density database. The refinement showed some improvement in crystallographic statistical indices compared with the independent atom model. The triazepane ring adopts a twist-boat conformation. In the crystal structure, the molecule forms intermolecular contacts with 14 different neighbours. There are two N—H
O and one C—H
O intermolecular hydrogen bond.
Supporting information
CCDC reference: 782535
The title compound was prepared starting from benzyl bromoacetate. Reaction
with veratrylamine gave the corresponding N-alkylated aminobenzyl ester
in 71% yield. Coupling with Boc-L-Tic-OH followed by hydrogenolysis
afforded the corresponding N-Boc protected dipeptide in 90% yield. The
dipeptide was then engaged in a four-step procedure as described previously
(Lena et al., 2006), to give the title triazepandione in 50%
yield.
Compound (I) was recrystallized by slow evaporation of a 1:1 mixture of
methanol and acetonitrile.
Least-squares refinements, based on |F|, were carried out using the
program MoPro (Guillot et al., 2001; Jelsch et
al., 2005)
using the ELMAM electron-density database (Zarychta et al.,
2007).
According to Wilson (1976), a refinement versus F is equivalent
to
obtaining a least-squares fit between the calculated electron density and that
obtained from a Fourier series based on the observed structure factors. A
refinement versus I is equivalent to obtaining a least-squares fit for
the Patterson syntheses. Both refinements versus F and I are
valid, and are very close for good quality structures. The diffraction data
set had no negative intensity and the refinement versus |F| was
carried out using all reflections. The weighted R factor wR and
goodness of fit S are based on F, and conventional R
factors are based on F. The threshold expression of F2 >
2σ(F2) is used only for calculating R factors and is not
relevant to the choice of reflections for refinement. The reflection weights
were set equal to 7.29/σ2(Fo). The Uiso(H) values were
constrained to be 1.2Ueq of the parent atom, except for the CH3
group, where the ratio was 1.5.
Data collection: CrysAlis CCD (Oxford Diffraction, 2008); cell refinement: CrysAlis RED (Oxford Diffraction, 2008); data reduction: CrysAlis RED (Oxford Diffraction, 2008); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: MoPro (Guillot et al., 2001; Jelsch et al.,
2005); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: MoPro (Guillot et al., 2001; Jelsch et al.,
2005).
5-(3,4-Dimethoxybenzyl)-7-isopropyl-1,3,5-triazepane-2,6-dione acetonitrile
solvate
top
Crystal data top
C16H23N3O4·C2H3N | F(000) = 776 |
Mr = 362.41 | Dx = 1.279 Mg m−3 |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 3551 reflections |
a = 7.0090 (2) Å | θ = 3.0–32.6° |
b = 10.5040 (3) Å | µ = 0.09 mm−1 |
c = 25.5620 (9) Å | T = 100 K |
V = 1881.9 (1) Å3 | Prism, colourless |
Z = 4 | 0.3 × 0.1 × 0.1 mm |
Data collection top
Oxford Xcalibur diffractometer | 2881 reflections with I > 2σ(I) |
Radiation source: Enhance (Mo) X-ray Source | Rint = 0.013 |
Graphite monochromator | θmax = 32.6°, θmin = 3.0° |
Detector resolution: 10.4508 pixels mm-1 | h = 0→9 |
ω scans | k = 0→15 |
6144 measured reflections | l = 0→38 |
3421 independent reflections | |
Refinement top
Refinement on F | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.036 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.027 | H-atom parameters constrained |
S = 1.65 | Weighting scheme based on measured s.u.'s |
3421 reflections | (Δ/σ)max < 0.001 |
235 parameters | Δρmax = 0.05 e Å−3 |
0 restraints | Δρmin = −0.04 e Å−3 |
Crystal data top
C16H23N3O4·C2H3N | V = 1881.9 (1) Å3 |
Mr = 362.41 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 7.0090 (2) Å | µ = 0.09 mm−1 |
b = 10.5040 (3) Å | T = 100 K |
c = 25.5620 (9) Å | 0.3 × 0.1 × 0.1 mm |
Data collection top
Oxford Xcalibur diffractometer | 2881 reflections with I > 2σ(I) |
6144 measured reflections | Rint = 0.013 |
3421 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.036 | 0 restraints |
wR(F2) = 0.027 | H-atom parameters constrained |
S = 1.65 | Δρmax = 0.05 e Å−3 |
3421 reflections | Δρmin = −0.04 e Å−3 |
235 parameters | |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
N1 | 0.5167 (1) | 0.1744 (1) | 0.43969 (4) | 0.0149 (1) | |
H1 | 0.39785 | 0.19795 | 0.45973 | 0.01783* | |
C2 | 0.4867 (2) | 0.1417 (1) | 0.38466 (5) | 0.0126 (2) | |
H2 | 0.59613 | 0.07148 | 0.37391 | 0.01514* | |
C3 | 0.5053 (2) | 0.2666 (1) | 0.35430 (5) | 0.0148 (2) | |
O1 | 0.3677 (1) | 0.3255 (1) | 0.33679 (4) | 0.0216 (1) | |
N4 | 0.6868 (2) | 0.3118 (1) | 0.35200 (4) | 0.0175 (2) | |
C5 | 0.8458 (2) | 0.2383 (1) | 0.37343 (5) | 0.0153 (2) | |
H5A | 0.97750 | 0.28733 | 0.36265 | 0.01835* | |
H5B | 0.85171 | 0.14313 | 0.35634 | 0.01835* | |
N6 | 0.8404 (1) | 0.2296 (1) | 0.43058 (4) | 0.0153 (1) | |
H6 | 0.96107 | 0.25554 | 0.44926 | 0.01831* | |
C7 | 0.6827 (2) | 0.2149 (1) | 0.46079 (5) | 0.0138 (2) | |
O2 | 0.6904 (1) | 0.23765 (10) | 0.50913 (3) | 0.0184 (1) | |
C8 | 0.2912 (2) | 0.0795 (1) | 0.37831 (5) | 0.0166 (2) | |
H8 | 0.18405 | 0.15038 | 0.38998 | 0.01986* | |
C9 | 0.2729 (2) | −0.0375 (2) | 0.41346 (6) | 0.0281 (2) | |
H9A | 0.28855 | −0.01203 | 0.45331 | 0.04217* | |
H9B | 0.38428 | −0.10177 | 0.40415 | 0.04217* | |
H9C | 0.13732 | −0.07989 | 0.40792 | 0.04217* | |
C10 | 0.2587 (2) | 0.0419 (2) | 0.32119 (6) | 0.0279 (2) | |
H10A | 0.12374 | −0.00226 | 0.31695 | 0.04190* | |
H10B | 0.36905 | −0.02227 | 0.31091 | 0.04190* | |
H10C | 0.26258 | 0.12408 | 0.29722 | 0.04190* | |
C11 | 0.7255 (2) | 0.4308 (1) | 0.32415 (5) | 0.0192 (2) | |
H11A | 0.61681 | 0.44042 | 0.29381 | 0.02300* | |
H11B | 0.85956 | 0.42003 | 0.30282 | 0.02300* | |
C12 | 0.7342 (2) | 0.5492 (1) | 0.35801 (5) | 0.0139 (2) | |
C13 | 0.7327 (2) | 0.5492 (1) | 0.41200 (5) | 0.0168 (2) | |
H13 | 0.71220 | 0.46067 | 0.43295 | 0.02020* | |
C14 | 0.7439 (2) | 0.6650 (1) | 0.43970 (5) | 0.0162 (2) | |
H14 | 0.74561 | 0.66391 | 0.48206 | 0.01945* | |
C15 | 0.7567 (2) | 0.7798 (1) | 0.41354 (5) | 0.0135 (2) | |
C16 | 0.7576 (2) | 0.7800 (1) | 0.35820 (5) | 0.0142 (2) | |
C17 | 0.7469 (2) | 0.6659 (1) | 0.33117 (5) | 0.0148 (2) | |
H17 | 0.74146 | 0.66491 | 0.28883 | 0.01773* | |
O3 | 0.7673 (1) | 0.89640 (9) | 0.43676 (3) | 0.0182 (1) | |
C18 | 0.7617 (2) | 0.8996 (1) | 0.49213 (5) | 0.0234 (2) | |
H18A | 0.77073 | 0.99700 | 0.50352 | 0.03504* | |
H18B | 0.87447 | 0.84508 | 0.50892 | 0.03504* | |
H18C | 0.63064 | 0.86042 | 0.50589 | 0.03504* | |
O4 | 0.7691 (1) | 0.89669 (9) | 0.33514 (3) | 0.0177 (1) | |
C19 | 0.7616 (2) | 0.8994 (1) | 0.27939 (5) | 0.0245 (2) | |
H19A | 0.76710 | 0.99723 | 0.26847 | 0.03679* | |
H19B | 0.63226 | 0.85770 | 0.26564 | 0.03679* | |
H19C | 0.88371 | 0.85242 | 0.26371 | 0.03679* | |
C20 | 0.2425 (2) | 0.6211 (1) | 0.36536 (6) | 0.0253 (2) | |
C21 | 0.2392 (2) | 0.6753 (1) | 0.31330 (6) | 0.0253 (2) | |
N7 | 0.2361 (2) | 0.7173 (1) | 0.27192 (5) | 0.0425 (2) | |
H20B | 0.36428 | 0.66009 | 0.38395 | 0.03794* | |
H20C | 0.25989 | 0.52153 | 0.36104 | 0.03794* | |
H20A | 0.11151 | 0.64242 | 0.38404 | 0.03794* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
N1 | 0.0128 (5) | 0.0205 (6) | 0.0113 (6) | −0.0001 (5) | −0.0016 (4) | −0.0023 (5) |
C2 | 0.0166 (6) | 0.0127 (6) | 0.0085 (6) | −0.0001 (5) | −0.0014 (6) | −0.0012 (5) |
C3 | 0.0175 (7) | 0.0140 (7) | 0.0129 (6) | 0.0013 (6) | −0.0013 (5) | 0.0001 (5) |
O1 | 0.0237 (5) | 0.0190 (6) | 0.0221 (6) | 0.0048 (5) | −0.0074 (4) | 0.0015 (5) |
N4 | 0.0247 (6) | 0.0144 (6) | 0.0134 (6) | −0.0009 (5) | −0.0020 (5) | 0.0012 (5) |
C5 | 0.0157 (6) | 0.0200 (8) | 0.0102 (7) | −0.0003 (6) | 0.0008 (5) | −0.0008 (5) |
N6 | 0.0129 (6) | 0.0208 (7) | 0.0120 (6) | −0.0007 (5) | 0.0001 (4) | −0.0006 (5) |
C7 | 0.0123 (6) | 0.0158 (7) | 0.0132 (7) | 0.0004 (5) | 0.0002 (6) | −0.0013 (5) |
O2 | 0.0160 (5) | 0.0276 (6) | 0.0117 (5) | −0.0006 (4) | −0.0007 (4) | −0.0030 (4) |
C8 | 0.0161 (7) | 0.0188 (7) | 0.0147 (7) | −0.0021 (5) | −0.0009 (6) | −0.0026 (5) |
C9 | 0.0272 (9) | 0.0265 (9) | 0.0306 (9) | −0.0115 (8) | −0.0052 (7) | 0.0071 (6) |
C10 | 0.0295 (9) | 0.0331 (9) | 0.0212 (8) | −0.0078 (8) | −0.0036 (7) | −0.0093 (6) |
C11 | 0.0328 (9) | 0.0127 (7) | 0.0120 (7) | −0.0046 (7) | 0.0020 (6) | −0.0004 (5) |
C12 | 0.0190 (7) | 0.0116 (6) | 0.0111 (6) | −0.0011 (6) | −0.0001 (6) | −0.0004 (5) |
C13 | 0.0247 (8) | 0.0143 (7) | 0.0115 (7) | 0.0003 (7) | 0.0012 (6) | 0.0001 (5) |
C14 | 0.0231 (7) | 0.0136 (7) | 0.0119 (7) | 0.0007 (7) | −0.0006 (6) | 0.0004 (5) |
C15 | 0.0183 (6) | 0.0117 (6) | 0.0106 (6) | 0.0006 (6) | −0.0003 (6) | 0.0002 (5) |
C16 | 0.0185 (6) | 0.0126 (6) | 0.0114 (6) | 0.0001 (6) | −0.0004 (6) | 0.0012 (5) |
C17 | 0.0189 (6) | 0.0134 (7) | 0.0120 (7) | 0.0004 (6) | 0.0004 (6) | 0.0003 (5) |
O3 | 0.0257 (5) | 0.0129 (5) | 0.0159 (5) | 0.0012 (5) | −0.0008 (5) | −0.0026 (4) |
C18 | 0.0333 (8) | 0.0181 (7) | 0.0186 (7) | 0.0033 (7) | −0.0061 (7) | −0.0038 (6) |
O4 | 0.0258 (6) | 0.0129 (5) | 0.0144 (5) | −0.0004 (5) | 0.0010 (5) | 0.0031 (4) |
C19 | 0.0377 (9) | 0.0175 (7) | 0.0184 (7) | 0.0014 (8) | 0.0005 (7) | 0.0042 (6) |
C20 | 0.0218 (7) | 0.0263 (8) | 0.0278 (8) | 0.0008 (7) | −0.0009 (7) | −0.0015 (6) |
C21 | 0.0315 (8) | 0.0185 (7) | 0.0258 (8) | −0.0017 (8) | 0.0028 (7) | −0.0043 (6) |
N7 | 0.0700 (10) | 0.0299 (8) | 0.0277 (8) | 0.0006 (9) | 0.0044 (8) | 0.0024 (6) |
Geometric parameters (Å, º) top
N1—C7 | 1.351 (2) | C11—H11B | 1.092 |
N1—C2 | 1.463 (2) | C11—H11A | 1.092 |
N1—H1 | 1.009 | C12—C13 | 1.380 (2) |
C2—C3 | 1.530 (2) | C12—C17 | 1.407 (2) |
C2—C8 | 1.527 (2) | C13—C14 | 1.409 (2) |
C2—H2 | 1.099 | C13—H13 | 1.083 |
C3—O1 | 1.230 (2) | C14—C15 | 1.382 (2) |
C3—N4 | 1.359 (2) | C14—H14 | 1.083 |
N4—C11 | 1.464 (2) | C15—O3 | 1.363 (2) |
N4—C5 | 1.462 (2) | C15—C16 | 1.415 (2) |
C5—N6 | 1.464 (2) | C16—O4 | 1.363 (2) |
C5—H5A | 1.092 | C16—C17 | 1.385 (2) |
C5—H5B | 1.092 | C17—H17 | 1.083 |
N6—C7 | 1.357 (2) | O3—C18 | 1.416 (2) |
N6—H6 | 1.009 | C18—H18B | 1.066 |
C7—O2 | 1.260 (1) | C18—H18A | 1.066 |
C8—C9 | 1.528 (2) | C18—H18C | 1.066 |
C8—C10 | 1.530 (2) | O4—C19 | 1.426 (2) |
C8—H8 | 1.099 | C19—H19C | 1.066 |
C9—H9A | 1.059 | C19—H19A | 1.066 |
C9—H9B | 1.059 | C19—H19B | 1.066 |
C9—H9C | 1.059 | C20—C21 | 1.447 (2) |
C10—H10B | 1.059 | C20—H20C | 1.059 |
C10—H10A | 1.059 | C20—H20B | 1.059 |
C10—H10C | 1.059 | C20—H20A | 1.059 |
C11—C12 | 1.517 (2) | C21—N7 | 1.146 (2) |
| | | |
N1—C7—O2 | 119.2 (1) | H10A—C10—H10B | 110.4 |
N1—C7—N6 | 120.66 (10) | H10A—C10—H10C | 108.7 |
N1—C2—C3 | 105.9 (1) | H10B—C10—H10C | 110.9 |
N1—C2—C8 | 109.4 (1) | C11—C12—C13 | 124.8 (1) |
N1—C2—H2 | 107.3 | C11—C12—C17 | 116.02 (10) |
H1—N1—C7 | 115.5 | H11A—C11—C12 | 110.9 |
H1—N1—C2 | 115.3 | H11A—C11—H11B | 104.8 |
C2—N1—C7 | 125.5 (1) | H11B—C11—C12 | 109.6 |
C2—C3—O1 | 123.3 (1) | C12—C13—C14 | 120.1 (1) |
C2—C3—N4 | 113.6 (1) | C12—C13—H13 | 119.7 |
C2—C8—C9 | 110.9 (1) | C12—C17—C16 | 120.9 (1) |
C2—C8—C10 | 110.2 (1) | C12—C17—H17 | 118.5 |
C2—C8—H8 | 107.1 | C13—C14—C15 | 120.9 (1) |
H2—C2—C3 | 112.9 | C13—C14—H14 | 119.6 |
H2—C2—C8 | 108.2 | C13—C12—C17 | 119.2 (1) |
C3—N4—C11 | 119.5 (1) | H13—C13—C14 | 120.0 |
C3—N4—C5 | 120.9 (1) | C14—C15—O3 | 125.3 (1) |
C3—C2—C8 | 112.9 (1) | C14—C15—C16 | 119.0 (1) |
O1—C3—N4 | 122.9 (1) | H14—C14—C15 | 119.5 |
N4—C11—C12 | 115.5 (1) | C15—O3—C18 | 117.1 (1) |
N4—C11—H11B | 108.3 | C15—C16—O4 | 115.7 (1) |
N4—C11—H11A | 107.2 | C15—C16—C17 | 119.8 (1) |
N4—C5—N6 | 112.76 (10) | C16—O4—C19 | 116.6 (1) |
N4—C5—H5A | 107.5 | C16—C17—H17 | 120.6 |
N4—C5—H5B | 111.2 | C16—C15—O3 | 115.7 (1) |
C5—N6—C7 | 126.6 (1) | C17—C16—O4 | 124.4 (1) |
C5—N6—H6 | 115.7 | O3—C18—H18B | 111.7 |
C5—N4—C11 | 119.4 (1) | O3—C18—H18A | 107.1 |
H5A—C5—N6 | 107.7 | O3—C18—H18C | 110.2 |
H5A—C5—H5B | 107.4 | H18A—C18—H18B | 111.2 |
H5B—C5—N6 | 110.0 | H18A—C18—H18C | 109.4 |
N6—C7—O2 | 120.1 (1) | H18B—C18—H18C | 107.4 |
H6—N6—C7 | 116.4 | O4—C19—H19C | 109.7 |
C8—C9—H9A | 110.7 | O4—C19—H19A | 106.2 |
C8—C9—H9B | 108.6 | O4—C19—H19B | 110.7 |
C8—C9—H9C | 109.6 | H19A—C19—H19C | 108.6 |
C8—C10—H10B | 107.0 | H19A—C19—H19B | 109.9 |
C8—C10—H10A | 110.1 | H19B—C19—H19C | 111.7 |
C8—C10—H10C | 109.7 | C20—C21—N7 | 179.4 (2) |
H8—C8—C9 | 109.1 | C21—C20—H20C | 107.1 |
H8—C8—C10 | 109.4 | C21—C20—H20B | 105.9 |
C9—C8—C10 | 109.9 (1) | C21—C20—H20A | 108.5 |
H9A—C9—H9B | 107.5 | H20B—C20—H20C | 109.6 |
H9A—C9—H9C | 109.1 | H20B—C20—H20A | 114.5 |
H9B—C9—H9C | 111.3 | H20C—C20—H20A | 110.8 |
| | | |
N1—C7—N6—C5 | 17.1 (1) | H5B—C5—N4—C11 | −119.7 |
N1—C7—N6—H6 | −176.8 | N6—C5—N4—C11 | 116.1 (1) |
N1—C2—C3—O1 | −104.0 (1) | H6—N6—C7—O2 | 2.4 |
N1—C2—C3—N4 | 71.15 (9) | C7—N1—C2—C8 | 170.6 (1) |
N1—C2—C8—C9 | −56.7 (1) | H8—C8—C9—H9A | −57.3 |
N1—C2—C8—C10 | −178.8 (1) | H8—C8—C9—H9B | −175.1 |
N1—C2—C8—H8 | 62.3 | H8—C8—C9—H9C | 63.1 |
H1—N1—C7—O2 | 23.9 | H8—C8—C10—H10B | 176.9 |
H1—N1—C7—N6 | −156.9 | H8—C8—C10—H10A | −63.1 |
H1—N1—C2—C3 | 90.0 | H8—C8—C10—H10C | 56.5 |
H1—N1—C2—C8 | −32.0 | C9—C8—C10—H10B | −63.3 |
H1—N1—C2—H2 | −149.1 | C9—C8—C10—H10A | 56.7 |
C2—N1—C7—O2 | −178.7 (1) | C9—C8—C10—H10C | 176.3 |
C2—N1—C7—N6 | 0.5 (1) | H9A—C9—C8—C10 | −177.3 |
C2—C3—N4—C11 | −180.0 (1) | H9B—C9—C8—C10 | 64.9 |
C2—C3—N4—C5 | 4.8 (1) | H9C—C9—C8—C10 | −56.9 |
C2—C8—C9—H9A | 60.5 | C11—C12—C13—C14 | 179.1 (1) |
C2—C8—C9—H9B | −57.3 | C11—C12—C13—H13 | −5.5 |
C2—C8—C9—H9C | −179.0 | C11—C12—C17—C16 | −179.3 (1) |
C2—C8—C10—H10B | 59.3 | C11—C12—C17—H17 | 3.5 |
C2—C8—C10—H10A | 179.3 | H11A—C11—C12—C13 | 130.8 |
C2—C8—C10—H10C | −61.1 | H11A—C11—C12—C17 | −50.0 |
H2—C2—N1—C7 | 53.5 | H11B—C11—C12—C13 | −114.0 |
H2—C2—C3—O1 | 138.8 | H11B—C11—C12—C17 | 65.2 |
H2—C2—C3—N4 | −46.0 | C12—C13—C14—C15 | −0.10 (12) |
H2—C2—C8—C9 | 59.8 | C12—C13—C14—H14 | −178.7 |
H2—C2—C8—C10 | −62.2 | C12—C17—C16—O4 | −179.6 (1) |
H2—C2—C8—H8 | 178.9 | C12—C17—C16—C15 | 0.3 (1) |
C3—N4—C11—C12 | 96.4 (1) | C13—C14—C15—O3 | 179.7 (1) |
C3—N4—C11—H11B | −140.4 | C13—C14—C15—C16 | 0.3 (1) |
C3—N4—C11—H11A | −27.8 | C13—C12—C17—C16 | −0.11 (12) |
C3—N4—C5—N6 | −68.64 (9) | C13—C12—C17—H17 | −177.3 |
C3—N4—C5—H5A | 172.8 | H13—C13—C14—C15 | −175.5 |
C3—N4—C5—H5B | 55.5 | H13—C13—C14—H14 | 5.9 |
C3—C2—N1—C7 | −67.4 (1) | H13—C13—C12—C17 | 175.4 |
C3—C2—C8—C9 | −174.4 (1) | C14—C13—C12—C17 | 0.00 (11) |
C3—C2—C8—C10 | 63.6 (1) | C14—C15—O3—C18 | −1.1 (1) |
C3—C2—C8—H8 | −55.4 | C14—C15—C16—O4 | 179.5 (1) |
O1—C3—N4—C11 | −4.8 (1) | C14—C15—C16—C17 | −0.4 (1) |
O1—C3—N4—C5 | 179.9 (1) | H14—C14—C15—O3 | −1.6 |
O1—C3—C2—C8 | 15.7 (1) | H14—C14—C15—C16 | 178.9 |
N4—C3—C2—C8 | −169.2 (1) | C15—O3—C18—H18B | 58.4 |
N4—C11—C12—C13 | 8.6 (1) | C15—O3—C18—H18A | −179.7 |
N4—C11—C12—C17 | −172.2 (1) | C15—O3—C18—H18C | −60.9 |
N4—C5—N6—C7 | 38.6 (1) | C15—C16—O4—C19 | −177.3 (1) |
N4—C5—N6—H6 | −127.5 | C15—C16—C17—H17 | 177.4 |
C5—N6—C7—O2 | −163.7 (1) | C16—O4—C19—H19C | −64.9 |
C5—N4—C11—C12 | −88.3 (1) | C16—O4—C19—H19A | 177.9 |
C5—N4—C11—H11B | 35.0 | C16—O4—C19—H19B | 58.7 |
C5—N4—C11—H11A | 147.5 | C16—C15—O3—C18 | 178.4 (1) |
H5A—C5—N6—C7 | 157.1 | C17—C16—O4—C19 | 2.6 (1) |
H5A—C5—N6—H6 | −9.1 | C17—C16—C15—O3 | −179.9 (1) |
H5A—C5—N4—C11 | −2.4 | H17—C17—C16—O4 | −2.5 |
H5B—C5—N6—C7 | −86.2 | O3—C15—C16—O4 | 0.03 (10) |
H5B—C5—N6—H6 | 107.7 | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O2i | 1.01 | 1.79 | 2.792 (1) | 172 |
C2—H2···O4ii | 1.10 | 2.41 | 3.485 (2) | 165 |
N6—H6···O2iii | 1.01 | 1.93 | 2.917 (1) | 166 |
Symmetry codes: (i) x−1/2, −y+1/2, −z+1; (ii) x, y−1, z; (iii) x+1/2, −y+1/2, −z+1. |
Experimental details
Crystal data |
Chemical formula | C16H23N3O4·C2H3N |
Mr | 362.41 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 100 |
a, b, c (Å) | 7.0090 (2), 10.5040 (3), 25.5620 (9) |
V (Å3) | 1881.9 (1) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.09 |
Crystal size (mm) | 0.3 × 0.1 × 0.1 |
|
Data collection |
Diffractometer | Oxford Xcalibur diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 6144, 3421, 2881 |
Rint | 0.013 |
(sin θ/λ)max (Å−1) | 0.757 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.036, 0.027, 1.65 |
No. of reflections | 3421 |
No. of parameters | 235 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.05, −0.04 |
Selected geometric parameters (Å, º) topN1—C7 | 1.351 (2) | N4—C5 | 1.462 (2) |
N1—C2 | 1.463 (2) | N6—C7 | 1.357 (2) |
C3—N4 | 1.359 (2) | | |
| | | |
C3—N4—C11 | 119.5 (1) | C5—N4—C11 | 119.4 (1) |
C3—N4—C5 | 120.9 (1) | | |
| | | |
N1—C7—N6—C5 | 17.1 (1) | C3—N4—C5—N6 | −68.64 (9) |
N1—C2—C3—N4 | 71.15 (9) | C3—C2—N1—C7 | −67.4 (1) |
C2—N1—C7—N6 | 0.5 (1) | N4—C5—N6—C7 | 38.6 (1) |
C2—C3—N4—C5 | 4.8 (1) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O2i | 1.01 | 1.79 | 2.792 (1) | 172 |
C2—H2···O4ii | 1.10 | 2.41 | 3.485 (2) | 165 |
N6—H6···O2iii | 1.01 | 1.93 | 2.917 (1) | 166 |
Symmetry codes: (i) x−1/2, −y+1/2, −z+1; (ii) x, y−1, z; (iii) x+1/2, −y+1/2, −z+1. |
1,3,5-Triazepan-2,6-diones are a novel class of dipeptidomimetics (Lena et al. 2006; Lena & Guichard, 2008) whose skeleton can be readily prepared starting from N-protected dipeptides. All five points of diversity can be manipulated using either solution-phase or solid-phase synthesis. Our interest in 1,3,5-triazepan-2,6-diones stems from the identification of several inhibitors of group V and X of secreted phospholipase A2 (Muller et al., 2006). With the aim of improving the potency of the first reported inhibitors, we have started structure–activity relationship studies by systematically varying the nature of the substituents on the ring, and at the amide N3 position in particular. Interestingly, the nature and the number of substitutents on the ring can dramatically affect the overall geometry, with the side chain at C7 adopting a pseudo-equatorial or pseudo-axial orientation. Moreover, 1,3,5-triazepan-2,6-diones can be used in crystal engineering to create helical molecular tapes that can self-assemble to form channel-type structures (Schaffner et al., 2006). Here, we report the structure of the title compound, (I), an analogue of cyclo(L-Val-gSar-CO) (Aubert et al., 2007) in which the methyl group at N3 is replaced by the much bulkier 3,4-dimethoxybenzyl group. This structure has been refined using a multipolar atom model.
Initially, in the independent atom model (IAM) refinement, a conventional spherical neutral atom model was applied. Scale factors, atomic positions and displacement parameters for all atoms were refined using the MoPro program (Guillot et al., 2001; Jelsch et al., 2005) until convergence. In the experimental library multipolar atom model (ELMAM; Pichon-Pesme et al., 2004; Zarychta et al., 2007) refinement, the same parameters were varied but a multipolar charged atom model was applied. The electron-density parameters were transferred from the ELMAM library and subsequently kept fixed. Riding constraints on H-atom isotropic displacement parameters were applied similarly in both refinements, which were carried out with the same diffraction data using all reflections. The riding was defined with Uiso(H) = 1.5Ueq(C) for methyl groups and Uiso(H) = 1.2Ueq(X) for all other chemical groups. The H—X distances were constrained to standard values from neutron diffraction studies (Allen, 1986) in the IAM and ELMAM refinements. The target distances were 1.059 Å for C—CH3, 1.066 Å for O—CH3, 1.009 Å for amide N—H, 1.083 Å for aromatic >C—H, 1.092 Å for >CH2 groups and 1.099 Å for sp3 C—H groups.
The ELMAM refinement shows a slight improvement in statistical indexes when compared with the IAM refinement. The I > 2σI crystallographic factors are reduced from 5.18 to 3.59% for R(F) and from 3.86 to 2.53% for wR2(F). The minimum and maximum peaks in the residual electron density are -0.050862 and 0.062570 e Å-3 after the IAM refinement, and -0.042279 and 0.053564 e Å-3 after the ELMAM refinement. The largest effect of the multipole transfer on the crystallographic structure is observed on the atomic displacements. The average value of Ueq (geometric mean of eigenvalues Ui) derived from the IAM refinement is 0.0214 Å2, which is slightly higher than the value of 0.0182 Å2 from the ELMAM refinement. With the IAM spherical atom model, the displacement parameters are incorrect as they incorporate some significant deformation electron density, due to improper deconvolution between these two features (Jelsch et al., 1998).
The molecular structure of (I), with the atomic numbering scheme, is presented in Fig. 1. All bond distances and angles are normal (Table 1) and are in good agreement with the geometry of similar 1,3,5-triazepane-2,6-diones (Lena et al., 2006; Lena & Guichard, 2008). The S configuration of the C atom at the 2-position of the seven-membered ring was assumed from the precursor Boc-L-Tic OH compound. The triazepane ring adopts a twist-boat conformation, TB (Boessenkool & Boyens, 1980), similar to those observed in the crystal structures of carbazepine (Hempel et al., 2005; Lisgarten et al., 1989). The seven-membered ring consists of two nearly planar halves. The first is defined by atoms C2/C3/N4/C5, with the largest deviation from this plane not exceeding 0.025 Å. The second half of the ring is composed of atoms C2/N1/C7/N6/C5 and only atom N6 is displaced from the mean plane, by 0.115 Å; for the other atoms, the deviation does not exceed 0.063 Å. The dihedral angle between the two halves is 64.66° and is almost in the range of values found for this group of compounds (57.74–63.93°; Aubert et al., 2007; Lena et al., 2006; Lena & Guichard, 2008; Schaffner et al., 2006). The benzene ring makes angles of 82.05 and 66.90° with these planes, respectively. The amide atom N4 is almost exactly in the plane defined by the three neighbouring C atoms (C3, C5 and C11), at a distance not exceeding 0.03 Å. Therefore, the sum of the valence angles around the N atom is 359.8°, which identifies very clear sp2 hybridization (328° for sp3 and 360° for sp2).
In the crystal structure of (I), the molecules are linked by two C═ O···H—N hydrogen bonds (Table 2 and Fig. 2), exhibiting the graph-set motif C(6) (Bernstein et al., 1995) and forming chains running along the [100] direction. The planes of parallel benzene rings of neighbouring molecules are separated from each other by 7.01 Å. The acetonitrile solvent molecules are in the space between these planes. The distance from the centre of the benzene ring to the nearest H atom of the methyl group of acetonitrile is about 2.6 Å. The third H atom of this group takes part in a weak C20—H20C···O1 hydrogen bond (Table 2). Atom N7 of the acetonitrile does not participate in hydrogen bonds, but forms a significant interaction with the amide atom N4 (3.36 Å), with the N7···N4 direction nearly perpendicular to the amide sp2 plane.