Ethyl 1-formamido-4-oxo-2,6-diphenyl-cyclo-hexa-necarboxyl-ate.

In the title compound, C(22)H(23)NO(4), the central six-membered ring is in a twist-boat conformation, the two aryl groups are in equatorial positions and the dihedral angle between the two aromatic rings is 75.98 (12)°.

Related literature

For the synthesis, see: Tan et al. (2009 ▶); Zhang et al. (2010 ▶). For related structures, see: Rowland & Gill (1988 ▶); Rowland et al. (1998 ▶); Aleman et al. (2009 ▶). Cyclic constrained analogues of phenyl­alanine (Phe) are of particular inter­est in the construction of peptide analogues with controlled folds in the backbone because they play an important role in both restricting the χ1 torsion angle and in peptide receptor recognition processes, see: Cativiela & Díaz-de-Villegas (1998 ▶, 2000 ▶, 2007 ▶); Cativiela & Ordóñez (2009 ▶); Lasa & Cativiela (2006 ▶).

Experimental

Crystal data

C22H23NO4

M = 365.41

Monoclinic,

a = 11.3240 (12) Å

b = 13.5100 (15) Å

c = 12.5870 (14) Å

β = 99.149 (2)°

V = 1901.2 (4) Å3

Z = 4

Mo Kα radiation

μ = 0.09 mm−1

T = 293 K

0.21 × 0.16 × 0.14 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer

Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T min = 0.982, T max = 0.988

11361 measured reflections

4439 independent reflections

3120 reflections with I > 2σ(I)

R int = 0.021

Refinement

R[F 2 > 2σ(F 2)] = 0.042

wR(F 2) = 0.116

S = 1.02

4439 reflections

244 parameters

H-atom parameters constrained

Δρmax = 0.22 e Å−3

Δρmin = −0.19 e Å−3

Data collection: APEX2 (Bruker, 2007 ▶); cell refinement: SAINT (Bruker, 2007 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811000985/nc2214sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811000985/nc2214Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C22H23NO4	F(000) = 776
Mr = 365.41	Dx = 1.277 Mg m−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71069 Å
a = 11.3240 (12) Å	Cell parameters from 132 reflections
b = 13.5100 (15) Å	θ = 1.3–26.0°
c = 12.5870 (14) Å	µ = 0.09 mm−1
β = 99.149 (2)°	T = 293 K
V = 1901.2 (4) Å3	Block, colorless
Z = 4	0.21 × 0.16 × 0.14 mm

Bruker SMART APEXII CCD area-detector diffractometer	4439 independent reflections
Radiation source: fine-focus sealed tube	3120 reflections with I > 2σ(I)
graphite	Rint = 0.021
ω scans	θmax = 28.3°, θmin = 2.2°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −15→14
Tmin = 0.982, Tmax = 0.988	k = −16→17
11361 measured reflections	l = −14→16

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.042	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.116	H-atom parameters constrained
S = 1.02	w = 1/[σ2(Fo2) + (0.0534P)2 + 0.306P] where P = (Fo2 + 2Fc2)/3
4439 reflections	(Δ/σ)max < 0.001
244 parameters	Δρmax = 0.22 e Å−3
0 restraints	Δρmin = −0.19 e Å−3

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.

	x	y	z	Uiso*/Ueq
O2	1.03050 (10)	0.14890 (8)	0.47576 (8)	0.0541 (3)
O1	0.94334 (8)	0.26361 (7)	0.36180 (7)	0.0426 (2)
C19	0.98394 (11)	0.17327 (10)	0.38744 (10)	0.0364 (3)
N1	1.01302 (10)	0.00919 (8)	0.33120 (9)	0.0401 (3)
C8	0.95919 (11)	0.10312 (9)	0.29070 (10)	0.0339 (3)
C1	0.75462 (12)	0.08726 (11)	0.35380 (11)	0.0416 (3)
O4	0.95020 (11)	−0.09967 (8)	0.19437 (10)	0.0637 (3)
O3	0.76178 (11)	0.15572 (10)	−0.01954 (9)	0.0699 (4)
C7	0.81977 (11)	0.09052 (10)	0.25754 (10)	0.0366 (3)
H7	0.8083	0.0251	0.2239	0.044*
C10	0.94777 (13)	0.11160 (11)	0.08583 (11)	0.0443 (3)
H10A	0.9870	0.1368	0.0283	0.053*
H10B	0.9497	0.0399	0.0832	0.053*
C13	1.14993 (12)	0.13184 (11)	0.20876 (11)	0.0408 (3)
C9	1.01555 (12)	0.14705 (10)	0.19429 (10)	0.0378 (3)
H9	1.0031	0.2188	0.1961	0.045*
C12	0.76820 (13)	0.16456 (11)	0.17030 (11)	0.0448 (3)
H12A	0.6819	0.1579	0.1554	0.054*
H12B	0.7870	0.2315	0.1955	0.054*
C20	0.94851 (15)	0.33379 (11)	0.45037 (13)	0.0534 (4)
H20A	1.0308	0.3516	0.4773	0.064*
H20B	0.9137	0.3050	0.5088	0.064*
C11	0.81977 (13)	0.14617 (11)	0.06898 (11)	0.0456 (3)
C18	1.20075 (13)	0.04802 (12)	0.17129 (12)	0.0510 (4)
H18	1.1518	0.0000	0.1342	0.061*
C14	1.22578 (14)	0.20301 (12)	0.26263 (12)	0.0496 (4)
H14	1.1936	0.2601	0.2878	0.060*
C2	0.70022 (14)	0.16996 (13)	0.38990 (13)	0.0550 (4)
H2	0.7006	0.2295	0.3528	0.066*
C6	0.74950 (14)	−0.00068 (14)	0.40968 (14)	0.0563 (4)
H6	0.7837	−0.0576	0.3861	0.068*
C22	1.00363 (14)	−0.07956 (11)	0.28331 (14)	0.0500 (4)
H22	1.0424	−0.1318	0.3225	0.060*
C15	1.34882 (15)	0.18981 (14)	0.27916 (14)	0.0610 (5)
H15	1.3985	0.2380	0.3152	0.073*
C17	1.32359 (15)	0.03502 (15)	0.18842 (14)	0.0621 (5)
H17	1.3564	−0.0218	0.1633	0.075*
C16	1.39736 (15)	0.10596 (16)	0.24257 (14)	0.0648 (5)
H16	1.4798	0.0970	0.2542	0.078*
C3	0.64542 (17)	0.16480 (18)	0.48052 (17)	0.0773 (6)
H3	0.6105	0.2212	0.5044	0.093*
C5	0.69387 (18)	−0.00491 (19)	0.50051 (17)	0.0799 (6)
H5	0.6919	−0.0642	0.5378	0.096*
C21	0.87950 (17)	0.42237 (12)	0.40695 (16)	0.0659 (5)
H21A	0.8803	0.4706	0.4631	0.099*
H21B	0.7984	0.4036	0.3803	0.099*
H21C	0.9151	0.4502	0.3494	0.099*
C4	0.64203 (19)	0.0781 (2)	0.53508 (17)	0.0882 (7)
H4	0.6046	0.0753	0.5957	0.106*
H1N	1.0524	0.0128	0.3939	0.106*

	U11	U22	U33	U12	U13	U23
O2	0.0651 (7)	0.0600 (7)	0.0331 (5)	0.0161 (5)	−0.0045 (5)	−0.0018 (5)
O1	0.0489 (6)	0.0382 (5)	0.0375 (5)	0.0043 (4)	−0.0026 (4)	−0.0064 (4)
C19	0.0337 (6)	0.0409 (7)	0.0339 (7)	0.0032 (5)	0.0027 (5)	−0.0003 (5)
N1	0.0411 (6)	0.0377 (6)	0.0415 (6)	0.0070 (5)	0.0065 (5)	0.0038 (5)
C8	0.0345 (6)	0.0335 (6)	0.0333 (7)	0.0026 (5)	0.0039 (5)	0.0012 (5)
C1	0.0298 (6)	0.0528 (8)	0.0411 (8)	0.0000 (6)	0.0021 (5)	0.0003 (6)
O4	0.0742 (8)	0.0462 (6)	0.0687 (8)	0.0036 (5)	0.0055 (6)	−0.0131 (6)
O3	0.0697 (8)	0.0954 (9)	0.0387 (6)	0.0093 (7)	−0.0093 (5)	0.0077 (6)
C7	0.0346 (7)	0.0372 (7)	0.0367 (7)	−0.0003 (5)	0.0015 (5)	−0.0011 (5)
C10	0.0484 (8)	0.0517 (8)	0.0321 (7)	−0.0063 (6)	0.0044 (6)	−0.0016 (6)
C13	0.0413 (7)	0.0501 (8)	0.0318 (7)	−0.0082 (6)	0.0078 (5)	0.0002 (6)
C9	0.0419 (7)	0.0388 (7)	0.0323 (7)	−0.0032 (6)	0.0052 (5)	−0.0006 (5)
C12	0.0406 (7)	0.0484 (8)	0.0424 (8)	0.0039 (6)	−0.0030 (6)	0.0016 (6)
C20	0.0587 (9)	0.0488 (9)	0.0482 (9)	0.0065 (7)	−0.0051 (7)	−0.0169 (7)
C11	0.0518 (8)	0.0444 (8)	0.0374 (8)	−0.0036 (6)	−0.0032 (6)	0.0040 (6)
C18	0.0436 (8)	0.0646 (10)	0.0463 (8)	−0.0092 (7)	0.0120 (7)	−0.0124 (7)
C14	0.0524 (9)	0.0514 (9)	0.0445 (8)	−0.0142 (7)	0.0065 (7)	−0.0011 (7)
C2	0.0445 (8)	0.0649 (10)	0.0566 (10)	0.0045 (7)	0.0109 (7)	−0.0073 (8)
C6	0.0443 (8)	0.0663 (10)	0.0599 (10)	0.0038 (7)	0.0127 (7)	0.0158 (8)
C22	0.0538 (9)	0.0384 (8)	0.0602 (10)	0.0095 (6)	0.0166 (8)	0.0050 (7)
C15	0.0517 (9)	0.0753 (12)	0.0542 (10)	−0.0266 (9)	0.0026 (8)	0.0007 (9)
C17	0.0460 (9)	0.0851 (13)	0.0588 (10)	−0.0002 (8)	0.0195 (8)	−0.0123 (9)
C16	0.0389 (8)	0.0963 (14)	0.0615 (11)	−0.0126 (9)	0.0150 (8)	−0.0043 (10)
C3	0.0604 (11)	0.1077 (17)	0.0673 (12)	0.0159 (11)	0.0212 (9)	−0.0169 (12)
C5	0.0580 (11)	0.1129 (17)	0.0710 (13)	0.0032 (11)	0.0172 (10)	0.0370 (12)
C21	0.0682 (11)	0.0490 (10)	0.0774 (12)	0.0083 (8)	0.0022 (9)	−0.0117 (8)
C4	0.0616 (12)	0.148 (2)	0.0601 (12)	0.0153 (13)	0.0267 (10)	0.0114 (14)

O2—C19	1.1983 (15)	C12—H12B	0.9700
O1—C19	1.3258 (16)	C20—C21	1.485 (2)
O1—C20	1.4575 (16)	C20—H20A	0.9700
C19—C8	1.5333 (18)	C20—H20B	0.9700
N1—C22	1.3386 (19)	C18—C17	1.384 (2)
N1—C8	1.4639 (16)	C18—H18	0.9300
N1—H1N	0.8440	C14—C15	1.387 (2)
C8—C9	1.5744 (18)	C14—H14	0.9300
C8—C7	1.5768 (17)	C2—C3	1.384 (3)
C1—C6	1.387 (2)	C2—H2	0.9300
C1—C2	1.387 (2)	C6—C5	1.391 (3)
C1—C7	1.5161 (19)	C6—H6	0.9300
O4—C22	1.2157 (19)	C22—H22	0.9300
O3—C11	1.2070 (17)	C15—C16	1.370 (3)
C7—C12	1.5308 (18)	C15—H15	0.9300
C7—H7	0.9800	C17—C16	1.378 (2)
C10—C11	1.505 (2)	C17—H17	0.9300
C10—C9	1.5326 (18)	C16—H16	0.9300
C10—H10A	0.9700	C3—C4	1.361 (3)
C10—H10B	0.9700	C3—H3	0.9300
C13—C18	1.386 (2)	C5—C4	1.369 (3)
C13—C14	1.392 (2)	C5—H5	0.9300
C13—C9	1.5176 (19)	C21—H21A	0.9600
C9—H9	0.9800	C21—H21B	0.9600
C12—C11	1.505 (2)	C21—H21C	0.9600
C12—H12A	0.9700	C4—H4	0.9300
C19—O1—C20	116.26 (10)	O1—C20—H20B	110.4
O2—C19—O1	124.27 (12)	C21—C20—H20B	110.4
O2—C19—C8	124.39 (12)	H20A—C20—H20B	108.6
O1—C19—C8	111.30 (10)	O3—C11—C12	122.48 (14)
C22—N1—C8	128.38 (12)	O3—C11—C10	122.25 (14)
C22—N1—H1N	117.8	C12—C11—C10	115.24 (12)
C8—N1—H1N	113.8	C17—C18—C13	120.78 (15)
N1—C8—C19	104.24 (10)	C17—C18—H18	119.6
N1—C8—C9	113.44 (11)	C13—C18—H18	119.6
C19—C8—C9	109.50 (10)	C15—C14—C13	120.78 (16)
N1—C8—C7	110.03 (10)	C15—C14—H14	119.6
C19—C8—C7	109.02 (10)	C13—C14—H14	119.6
C9—C8—C7	110.37 (10)	C3—C2—C1	120.67 (18)
C6—C1—C2	117.88 (15)	C3—C2—H2	119.7
C6—C1—C7	119.68 (13)	C1—C2—H2	119.7
C2—C1—C7	122.44 (13)	C1—C6—C5	120.85 (18)
C1—C7—C12	114.43 (11)	C1—C6—H6	119.6
C1—C7—C8	112.68 (10)	C5—C6—H6	119.6
C12—C7—C8	111.78 (11)	O4—C22—N1	127.38 (14)
C1—C7—H7	105.7	O4—C22—H22	116.3
C12—C7—H7	105.7	N1—C22—H22	116.3
C8—C7—H7	105.7	C16—C15—C14	120.19 (15)
C11—C10—C9	111.29 (12)	C16—C15—H15	119.9
C11—C10—H10A	109.4	C14—C15—H15	119.9
C9—C10—H10A	109.4	C16—C17—C18	120.25 (17)
C11—C10—H10B	109.4	C16—C17—H17	119.9
C9—C10—H10B	109.4	C18—C17—H17	119.9
H10A—C10—H10B	108.0	C15—C16—C17	119.80 (16)
C18—C13—C14	118.20 (14)	C15—C16—H16	120.1
C18—C13—C9	122.16 (12)	C17—C16—H16	120.1
C14—C13—C9	119.63 (13)	C4—C3—C2	120.76 (19)
C13—C9—C10	114.53 (11)	C4—C3—H3	119.6
C13—C9—C8	112.22 (11)	C2—C3—H3	119.6
C10—C9—C8	111.21 (11)	C4—C5—C6	120.05 (19)
C13—C9—H9	106.1	C4—C5—H5	120.0
C10—C9—H9	106.1	C6—C5—H5	120.0
C8—C9—H9	106.1	C20—C21—H21A	109.5
C11—C12—C7	110.16 (12)	C20—C21—H21B	109.5
C11—C12—H12A	109.6	H21A—C21—H21B	109.5
C7—C12—H12A	109.6	C20—C21—H21C	109.5
C11—C12—H12B	109.6	H21A—C21—H21C	109.5
C7—C12—H12B	109.6	H21B—C21—H21C	109.5
H12A—C12—H12B	108.1	C3—C4—C5	119.78 (19)
O1—C20—C21	106.74 (12)	C3—C4—H4	120.1
O1—C20—H20A	110.4	C5—C4—H4	120.1
C21—C20—H20A	110.4
C20—O1—C19—O2	−5.0 (2)	C7—C8—C9—C13	−162.62 (11)
C20—O1—C19—C8	172.73 (12)	N1—C8—C9—C10	91.15 (13)
C22—N1—C8—C19	170.75 (13)	C19—C8—C9—C10	−152.88 (11)
C22—N1—C8—C9	−70.21 (17)	C7—C8—C9—C10	−32.86 (15)
C22—N1—C8—C7	53.98 (18)	C1—C7—C12—C11	−167.17 (11)
O2—C19—C8—N1	−4.36 (18)	C8—C7—C12—C11	63.22 (14)
O1—C19—C8—N1	177.89 (10)	C19—O1—C20—C21	−169.98 (13)
O2—C19—C8—C9	−126.04 (14)	C7—C12—C11—O3	143.48 (15)
O1—C19—C8—C9	56.21 (14)	C7—C12—C11—C10	−34.51 (16)
O2—C19—C8—C7	113.11 (14)	C9—C10—C11—O3	155.50 (14)
O1—C19—C8—C7	−64.64 (14)	C9—C10—C11—C12	−26.50 (17)
C6—C1—C7—C12	148.86 (13)	C14—C13—C18—C17	0.9 (2)
C2—C1—C7—C12	−31.95 (18)	C9—C13—C18—C17	−178.16 (15)
C6—C1—C7—C8	−81.98 (16)	C18—C13—C14—C15	−0.6 (2)
C2—C1—C7—C8	97.21 (15)	C9—C13—C14—C15	178.47 (14)
N1—C8—C7—C1	76.19 (13)	C6—C1—C2—C3	1.6 (2)
C19—C8—C7—C1	−37.55 (14)	C7—C1—C2—C3	−177.59 (14)
C9—C8—C7—C1	−157.86 (11)	C2—C1—C6—C5	−1.5 (2)
N1—C8—C7—C12	−153.29 (11)	C7—C1—C6—C5	177.76 (15)
C19—C8—C7—C12	92.97 (13)	C8—N1—C22—O4	2.0 (3)
C9—C8—C7—C12	−27.35 (14)	C13—C14—C15—C16	−0.1 (2)
C18—C13—C9—C10	−38.46 (19)	C13—C18—C17—C16	−0.5 (3)
C14—C13—C9—C10	142.52 (14)	C14—C15—C16—C17	0.5 (3)
C18—C13—C9—C8	89.57 (16)	C18—C17—C16—C15	−0.3 (3)
C14—C13—C9—C8	−89.45 (15)	C1—C2—C3—C4	−1.1 (3)
C11—C10—C9—C13	−169.26 (12)	C1—C6—C5—C4	0.8 (3)
C11—C10—C9—C8	62.20 (15)	C2—C3—C4—C5	0.4 (3)
N1—C8—C9—C13	−38.62 (15)	C6—C5—C4—C3	−0.2 (3)
C19—C8—C9—C13	77.35 (13)