Coca­ethyl­ene, the in vivo product of cocaine and ethanol, is a narcotic more potent than its precursors

The molecular conformation and supramolecular architecture of cocaethylene [systematic name: eth­yl (1R,2R,3S,5S)-3-benzo­yloxy-8-methyl-8-aza­bicyclo­[3.2.1]octane-2-carboxyl­ate], C₁₈H₂₃NO₄, have been determined for the first time. Cocaethylene is a narcotic produced in vivo when cocaine and ethanol are administered concomitantly. The intra- and inter­molecular features of coca­ethyl­ene and its less potent narcotic precursor cocaine are very similar. The only mol­ecular difference is in the conformation of the methyl group of the ethoxycarbonyl group. Similar to cocaine, the carboxyl­ate atoms and the α-C atom are coplanar in coca­ethyl­ene, but the methyl C atom of the ethyl group is bent by ca 90° away from this plane in the narcotic reported here. The main supra­molecular motif is a one-dimensional chain stabilized by weak C—H...O contacts.

Computing details

Data collection: APEX2 (Bruker, 2003); cell refinement: SAINT (Bruker, 2003); data reduction: SAINT (Bruker, 2003); program(s) used to solve structure: SIR92 (Altomare et al., 1993); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997), Mercury (Macrae et al., 2006); software used to prepare material for publication: WinGX publication routines (Farrugia, 1999).

ethyl (1R,2R,3S,5S)-3-(benzoyloxy)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate

Crystal data

C18H23NO4	F(000) = 340
Mr = 317.37	Dx = 1.248 Mg m^−3
Monoclinic, P21	Cu Kα radiation, λ = 1.54178 Å
a = 8.4533 (2) Å	Cell parameters from 2631 reflections
b = 10.2380 (3) Å	θ = 6.0–66.1°
c = 10.2552 (2) Å	µ = 0.72 mm^−1
β = 107.881 (1)°	T = 296 K
V = 844.66 (4) Å^3	Needle, colourless
Z = 2	0.35 × 0.15 × 0.10 mm

Data collection

Bruker APEXII CCD area-detector diffractometer	2026 reflections with I > 2σ(I)
CCD scans	Rint = 0.024
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	θmax = 66.5°, θmin = 6.0°
Tmin = 0.725, Tmax = 0.931	h = −9→9
3969 measured reflections	k = −9→12
2133 independent reflections	l = −12→11

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.036	w = 1/[σ^2(Fo^2) + (0.0631P)^2 + 0.0701P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.101	(Δ/σ)max < 0.001
S = 1.03	Δρmax = 0.15 e Å^−3
2133 reflections	Δρmin = −0.17 e Å^−3
208 parameters	Absolute structure: Flack x parameter determined using 568 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013).
1 restraint	Absolute structure parameter: −0.03 (14)

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
O4	0.5751 (2)	0.4990 (2)	−0.13426 (17)	0.0664 (6)
O1	0.65669 (18)	0.5018 (2)	0.27718 (16)	0.0563 (5)
O3	0.6899 (2)	0.6327 (3)	0.0426 (2)	0.0703 (6)
N1	0.2831 (2)	0.6666 (2)	−0.0355 (2)	0.0519 (5)
C17	0.5764 (6)	0.6617 (5)	−0.2996 (4)	0.1061 (14)
H17A	0.642	0.6992	−0.3516	0.159*
H17B	0.4754	0.627	−0.3609	0.159*
H17C	0.5503	0.7277	−0.243	0.159*
C16	0.6698 (4)	0.5572 (5)	−0.2134 (3)	0.0863 (12)
H16A	0.6977	0.4911	−0.2705	0.104*
H16B	0.7727	0.592	−0.1524	0.104*
C15	0.5920 (3)	0.5498 (3)	−0.0097 (2)	0.0500 (6)
C2	0.4677 (3)	0.4846 (3)	0.0482 (2)	0.0467 (5)
H2	0.4796	0.3896	0.0436	0.056*
C3	0.4847 (3)	0.5233 (3)	0.1952 (2)	0.0487 (6)
H3	0.4143	0.4648	0.2291	0.058*
C8	0.6854 (3)	0.4519 (3)	0.4018 (2)	0.0523 (6)
C9	0.8662 (3)	0.4243 (3)	0.4680 (2)	0.0507 (6)
C14	0.9159 (4)	0.3499 (3)	0.5864 (3)	0.0677 (8)
H14	0.837	0.3186	0.625	0.081*
C13	1.0819 (5)	0.3221 (4)	0.6474 (3)	0.0780 (9)
H13	1.1148	0.271	0.7261	0.094*
C12	1.1978 (4)	0.3697 (4)	0.5917 (3)	0.0831 (11)
H12	1.3097	0.3517	0.6337	0.1*
C10	0.9846 (3)	0.4709 (3)	0.4126 (3)	0.0626 (7)
H10	0.9527	0.5209	0.333	0.075*
C11	1.1512 (4)	0.4433 (5)	0.4756 (3)	0.0825 (10)
H11	1.2312	0.4751	0.4386	0.099*
C4	0.4298 (3)	0.6621 (3)	0.2072 (2)	0.0552 (6)
H4A	0.5113	0.7227	0.1932	0.066*
H4B	0.4207	0.6766	0.2981	0.066*
C5	0.2607 (3)	0.6856 (3)	0.0992 (3)	0.0561 (6)
H5	0.2202	0.7739	0.1075	0.067*
C18	0.1473 (4)	0.7238 (4)	−0.1467 (3)	0.0772 (10)
H18A	0.1483	0.817	−0.1365	0.116*
H18B	0.1618	0.7019	−0.2333	0.116*
H18C	0.0429	0.6899	−0.1428	0.116*
C1	0.2916 (3)	0.5243 (3)	−0.0423 (2)	0.0511 (6)
H1	0.2727	0.4956	−0.1371	0.061*
C7	0.1534 (3)	0.4726 (3)	0.0128 (3)	0.0659 (8)
H7A	0.0516	0.4574	−0.0613	0.079*
H7B	0.187	0.392	0.0634	0.079*
C6	0.1309 (3)	0.5823 (4)	0.1068 (3)	0.0694 (8)
H6A	0.152	0.551	0.1999	0.083*
H6B	0.0193	0.6179	0.0746	0.083*
O2	0.5794 (3)	0.4319 (3)	0.45504 (19)	0.0812 (8)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O4	0.0741 (11)	0.0762 (15)	0.0519 (9)	0.0089 (11)	0.0238 (9)	−0.0017 (10)
O1	0.0401 (8)	0.0775 (13)	0.0467 (8)	0.0054 (8)	0.0066 (6)	0.0137 (9)
O3	0.0495 (9)	0.0973 (18)	0.0612 (11)	−0.0194 (10)	0.0129 (8)	−0.0028 (10)
N1	0.0381 (9)	0.0570 (13)	0.0533 (11)	0.0001 (9)	0.0031 (8)	0.0101 (10)
C17	0.148 (4)	0.081 (3)	0.091 (3)	−0.004 (3)	0.039 (3)	0.010 (2)
C16	0.0776 (19)	0.127 (4)	0.0625 (17)	0.017 (2)	0.0336 (15)	0.0166 (19)
C15	0.0386 (11)	0.0581 (16)	0.0491 (12)	0.0082 (11)	0.0076 (10)	0.0042 (11)
C2	0.0445 (11)	0.0451 (13)	0.0475 (11)	0.0018 (9)	0.0095 (9)	−0.0012 (10)
C3	0.0360 (10)	0.0625 (16)	0.0431 (11)	−0.0004 (10)	0.0057 (9)	0.0045 (11)
C8	0.0524 (13)	0.0618 (16)	0.0396 (11)	−0.0022 (12)	0.0097 (10)	0.0005 (11)
C9	0.0560 (13)	0.0515 (15)	0.0371 (10)	0.0033 (11)	0.0034 (10)	−0.0004 (10)
C14	0.0776 (18)	0.070 (2)	0.0447 (13)	0.0009 (15)	0.0035 (13)	0.0063 (13)
C13	0.092 (2)	0.070 (2)	0.0501 (14)	0.0138 (19)	−0.0109 (15)	0.0072 (14)
C12	0.0645 (17)	0.093 (3)	0.0682 (19)	0.0173 (18)	−0.0145 (15)	0.0024 (19)
C10	0.0512 (13)	0.080 (2)	0.0485 (12)	0.0065 (13)	0.0028 (10)	0.0136 (13)
C11	0.0534 (15)	0.112 (3)	0.0719 (18)	0.0078 (18)	0.0046 (13)	0.0153 (19)
C4	0.0485 (12)	0.0642 (17)	0.0500 (12)	0.0018 (12)	0.0110 (10)	−0.0096 (12)
C5	0.0456 (12)	0.0595 (17)	0.0614 (14)	0.0089 (11)	0.0139 (11)	−0.0031 (12)
C18	0.0526 (15)	0.093 (3)	0.0732 (19)	0.0075 (16)	0.0009 (13)	0.0305 (18)
C1	0.0406 (11)	0.0598 (16)	0.0477 (12)	−0.0054 (10)	0.0058 (9)	−0.0045 (11)
C7	0.0422 (12)	0.070 (2)	0.0772 (16)	−0.0127 (12)	0.0063 (11)	0.0089 (15)
C6	0.0391 (12)	0.101 (2)	0.0691 (16)	0.0041 (14)	0.0180 (12)	0.0147 (16)
O2	0.0612 (11)	0.129 (2)	0.0524 (10)	−0.0048 (13)	0.0163 (9)	0.0109 (12)

Geometric parameters (Å, º)

O4—C15	1.346 (3)	C14—C13	1.379 (4)
O4—C16	1.434 (4)	C14—H14	0.93
O1—C8	1.328 (3)	C13—C12	1.367 (6)
O1—C3	1.456 (3)	C13—H13	0.93
O3—C15	1.192 (3)	C12—C11	1.361 (5)
N1—C1	1.462 (4)	C12—H12	0.93
N1—C5	1.463 (3)	C10—C11	1.387 (4)
N1—C18	1.468 (3)	C10—H10	0.93
C17—C16	1.456 (7)	C11—H11	0.93
C17—H17A	0.96	C4—C5	1.535 (3)
C17—H17B	0.96	C4—H4A	0.97
C17—H17C	0.96	C4—H4B	0.97
C16—H16A	0.97	C5—C6	1.543 (4)
C16—H16B	0.97	C5—H5	0.98
C15—C2	1.511 (3)	C18—H18A	0.96
C2—C3	1.522 (3)	C18—H18B	0.96
C2—C1	1.548 (3)	C18—H18C	0.96
C2—H2	0.98	C1—C7	1.539 (4)
C3—C4	1.512 (4)	C1—H1	0.98
C3—H3	0.98	C7—C6	1.529 (5)
C8—O2	1.202 (3)	C7—H7A	0.97
C8—C9	1.497 (3)	C7—H7B	0.97
C9—C10	1.379 (4)	C6—H6A	0.97
C9—C14	1.385 (4)	C6—H6B	0.97
C15—O4—C16	117.5 (3)	C11—C12—H12	119.6
C8—O1—C3	117.99 (17)	C13—C12—H12	119.6
C1—N1—C5	101.5 (2)	C9—C10—C11	119.9 (3)
C1—N1—C18	113.5 (2)	C9—C10—H10	120
C5—N1—C18	112.5 (2)	C11—C10—H10	120
C16—C17—H17A	109.5	C12—C11—C10	120.0 (3)
C16—C17—H17B	109.5	C12—C11—H11	120
H17A—C17—H17B	109.5	C10—C11—H11	120
C16—C17—H17C	109.5	C3—C4—C5	109.2 (2)
H17A—C17—H17C	109.5	C3—C4—H4A	109.8
H17B—C17—H17C	109.5	C5—C4—H4A	109.8
O4—C16—C17	110.9 (3)	C3—C4—H4B	109.8
O4—C16—H16A	109.5	C5—C4—H4B	109.8
C17—C16—H16A	109.5	H4A—C4—H4B	108.3
O4—C16—H16B	109.5	N1—C5—C4	107.42 (19)
C17—C16—H16B	109.5	N1—C5—C6	104.9 (2)
H16A—C16—H16B	108.1	C4—C5—C6	112.0 (2)
O3—C15—O4	124.0 (2)	N1—C5—H5	110.8
O3—C15—C2	127.5 (2)	C4—C5—H5	110.8
O4—C15—C2	108.6 (2)	C6—C5—H5	110.8
C15—C2—C3	114.1 (2)	N1—C18—H18A	109.5
C15—C2—C1	107.80 (19)	N1—C18—H18B	109.5
C3—C2—C1	107.85 (18)	H18A—C18—H18B	109.5
C15—C2—H2	109	N1—C18—H18C	109.5
C3—C2—H2	109	H18A—C18—H18C	109.5
C1—C2—H2	109	H18B—C18—H18C	109.5
O1—C3—C4	111.83 (19)	N1—C1—C7	105.7 (2)
O1—C3—C2	107.86 (18)	N1—C1—C2	106.57 (19)
C4—C3—C2	112.8 (2)	C7—C1—C2	112.9 (2)
O1—C3—H3	108.1	N1—C1—H1	110.5
C4—C3—H3	108.1	C7—C1—H1	110.5
C2—C3—H3	108.1	C2—C1—H1	110.5
O2—C8—O1	124.2 (2)	C6—C7—C1	103.6 (2)
O2—C8—C9	124.2 (2)	C6—C7—H7A	111
O1—C8—C9	111.65 (19)	C1—C7—H7A	111
C10—C9—C14	119.3 (2)	C6—C7—H7B	111
C10—C9—C8	121.1 (2)	C1—C7—H7B	111
C14—C9—C8	119.6 (2)	H7A—C7—H7B	109
C13—C14—C9	120.2 (3)	C7—C6—C5	104.1 (2)
C13—C14—H14	119.9	C7—C6—H6A	110.9
C9—C14—H14	119.9	C5—C6—H6A	110.9
C12—C13—C14	119.8 (3)	C7—C6—H6B	110.9
C12—C13—H13	120.1	C5—C6—H6B	110.9
C14—C13—H13	120.1	H6A—C6—H6B	109
C11—C12—C13	120.8 (3)
C15—O4—C16—C17	−90.5 (4)	C8—C9—C10—C11	−179.6 (3)
C16—O4—C15—O3	−6.1 (4)	C13—C12—C11—C10	0.1 (6)
C16—O4—C15—C2	173.6 (2)	C9—C10—C11—C12	0.3 (6)
O3—C15—C2—C3	−6.0 (4)	O1—C3—C4—C5	169.50 (19)
O4—C15—C2—C3	174.3 (2)	C2—C3—C4—C5	47.7 (3)
O3—C15—C2—C1	113.7 (3)	C1—N1—C5—C4	75.8 (3)
O4—C15—C2—C1	−66.0 (3)	C18—N1—C5—C4	−162.6 (3)
C8—O1—C3—C4	95.5 (3)	C1—N1—C5—C6	−43.6 (2)
C8—O1—C3—C2	−139.9 (2)	C18—N1—C5—C6	78.1 (3)
C15—C2—C3—O1	−53.0 (3)	C3—C4—C5—N1	−61.3 (3)
C1—C2—C3—O1	−172.69 (19)	C3—C4—C5—C6	53.3 (3)
C15—C2—C3—C4	71.1 (2)	C5—N1—C1—C7	43.2 (2)
C1—C2—C3—C4	−48.7 (3)	C18—N1—C1—C7	−77.8 (3)
C3—O1—C8—O2	−5.6 (4)	C5—N1—C1—C2	−77.1 (2)
C3—O1—C8—C9	174.8 (2)	C18—N1—C1—C2	161.9 (2)
O2—C8—C9—C10	−168.0 (3)	C15—C2—C1—N1	−59.9 (2)
O1—C8—C9—C10	11.6 (4)	C3—C2—C1—N1	63.8 (2)
O2—C8—C9—C14	12.5 (4)	C15—C2—C1—C7	−175.5 (2)
O1—C8—C9—C14	−167.9 (3)	C3—C2—C1—C7	−51.8 (3)
C10—C9—C14—C13	−0.5 (5)	N1—C1—C7—C6	−25.7 (3)
C8—C9—C14—C13	179.0 (3)	C2—C1—C7—C6	90.4 (3)
C9—C14—C13—C12	1.0 (5)	C1—C7—C6—C5	−1.1 (3)
C14—C13—C12—C11	−0.8 (6)	N1—C5—C6—C7	27.4 (3)
C14—C9—C10—C11	−0.1 (5)	C4—C5—C6—C7	−88.8 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C6—H6B···O3^i	0.97	2.71	3.618 (3)	157

Symmetry code: (i) x−1, y, z.