Z. Kristallogr.

NCS 2020; aop

Ignez Caracelli*, Julio Zukerman-Schpector, Ariel L. Llanes Garcia, Edson R. Costenaro,

Carlos Roque D. Correia and Edward R.T. Tiekink*

Crystal structure of tert-butyl 2-(hydroxymethyl)-

5-{4-[(methoxycarbonyl)amino]phenyl}-2,5-
dihydro-1H-pyrrole-1-carboxylate, C18H24N2O5
Table 1: Data collection and handling.

Crystal: Colourless irregular

Size: 0.33 × 0.19 × 0.16 mm
Wavelength: Mo Kα radiation (0.71073 Å)
µ: 0.09 mm−1
Diffractometer, scan mode: Enraf Nonius TurboCAD4, ω
θmax , completeness: 27.4°, >99%
N(hkl)measured , N(hkl)unique , Rint : 4328, 4192, 0.029
Criterion for Iobs , N(hkl)gt : Iobs > 2 σ(Iobs ), 1916
N(param)refined : 236
Programs: CAD4 [1, 2], SIR2014 [3], SHELX
[4], WinGX/ORTEP [5]

https://doi.org/10.1515/ncrs-2020-0305 the atoms including atomic coordinates and displacement

Received June 21, 2020; accepted July 10, 2020; available online July
parameters.
18, 2020

Source of material
Abstract
The synthesis and characterisation of (I) are as described in
C18 H24 N2 O5 , monoclinic, P21 /c (no. 14), a = 11.4784(7) Å,
ref. [6], with crystals for the X-ray study being obtained from
b = 9.0180(8) Å, c = 17.9483(17) Å, β = 92.823(7)°,
recrystallisation from an ethanol solution of (I).
V = 1855.6(3) Å3 , Z = 4, Rgt (F) = 0.0505, wRref (F 2 ) = 0.1611,
T = 293 K.
Experimental details
CCDC no.: 2015454 The C-bound H atoms were geometrically placed
(C—H = 0.93–0.98 Å) and refined as riding with U iso (H) = 1.2–
The molecular structure is shown in the figure. Table 1 con-
1.5U eq (C). The O- and N-bound H atoms were refined with
tains crystallographic data and Table 2 contains the list of
O—H = 0.82 ± 0.01 Å and N—H = 0.86 ± 0.01 Å, and with
U iso (H) = 1.5U eq (O) or 1.2U eq (N).

*Corresponding authors: Ignez Caracelli, BioMat, Departamento de Comment

Física, Universidade Federal de São Carlos, C.P. 676, São Carlos, The Heck-Matsuda arylation reaction is a valuable and
SP, 13565-905, Brazil, e-mail: [email protected]; and Edward
versatile synthetic procedure for carbon-carbon bond for-
R.T. Tiekink, Research Centre for Crystalline Materials, School of
mation, being based on the coupling of an olefin with
Science and Technology, Sunway University, 47500 Bandar Sunway,
Selangor Darul Ehsan, Malaysia, e-mail: [email protected]. an arenediazonium salt in the presence of a zerovalent
https://orcid.org/0000-0003-1401-1520 organopalladium species [7]. This technology was employed
Julio Zukerman-Schpector: Laboratório de Cristalografia, [6] to synthesise molecules containing an α-aryl hetero-
Estereodinâmica e Modelagem Molecular, Departamento de cyclic framework in the core structure as precursors to
Química, Universidade Federal de São Carlos, C.P. 676, São Carlos,
pharmacologically-important species such as Schramm’s
SP, 13565-905, Brazil
Ariel L. Llanes Garcia, Edson R. Costenaro and Carlos Roque potent antiprotozoan C-azanucleoside [8] and the non-
D. Correia: Instituto de Química, Universidade Estadual de peptide cholecystokinin antagonist (+)-RP 66803 [9]. The title
Campinas, UNICAMP, CP 6154, CEP 13084-917 Campinas, Brazil compound (I) was investigated crystallographically in the

Open Access. © 2020 Ignez Caracelli et al., published by De Gruyter. This work is licensed under the Creative Commons Attribution 4.0 Public
License.
2 | Caracelli et al.: C18 H24 N2 O5

Table 2: Fractional atomic coordinates and isotropic or equivalent about a tri-substituted, five-membered pyrrole ring. The
isotropic displacement parameters (Å2 ). latter is approximately planar, exhibiting a r.m.s. devia-
tion = 0.0291 Å with maximum deviations to either side
Atom x y z Uiso */Ueq
of the plane being 0.0391(15) and 0.0387(14) Å for the N1
O1 0.40740(14) 0.4263(2) 0.89707(10) 0.0718(6) and C4 atoms, respectively. The dihedral angle between the
O2 0.22115(13) 0.49783(19) 0.86865(9) 0.0584(5)
five-membered ring and the appended carboxylate (CO2 )
O3 0.57622(14) 0.2889(3) 0.83031(12) 0.0791(6)
H3O 0.534(3) 0.330(4) 0.8605(16) 0.119* residue and phenyl rings are 5.1(5) and 85.09(8)°, indicat-
O4 −0.17268(16) −0.0935(3) 0.95758(12) 0.0842(7) ing almost co-planar and orthogonal dispositions, respec-
O5 −0.36070(14) −0.0287(2) 0.93977(11) 0.0702(6) tively. The O3-hydroxyl group is orientated towards the
N1 0.29677(14) 0.3181(2) 0.80397(11) 0.0480(5) O1-carbonyl atom enabling the formation of an intramolec-
N2 −0.22909(15) 0.1053(2) 0.88628(12) 0.0521(5)
ular hydroxyl-O3—H· · · O1(carbonyl) hydrogen bond [O3—
H2N −0.2897(15) 0.154(3) 0.8705(13) 0.062*
H3o· · · O1: H3o· · · O1 = 1.84(3) Å, O3· · · O1 = 2.637(3) Å with
C1 0.3831(2) 0.2056(3) 0.78279(16) 0.0595(7)
H1 0.391225 0.130030 0.821927 0.071* angle at H3o = 160(3)°] which closes a S(6) loop. The con-
C2 0.3208(3) 0.1408(4) 0.71529(17) 0.0740(9) figurations at the C1 and C4 atoms are each S. However, the
H2 0.352199 0.066317 0.686530 0.089* centrosymmetric structure contains equal numbers of both
C3 0.2191(2) 0.1984(3) 0.70084(14) 0.0642(8) enantiomers. Finally, the terminal (methoxycarbonyl)amino
H3 0.170939 0.173038 0.659603 0.077*
residue is planar (r.m.s. deviation for C2 NO2 = 0.0033 Å) and
C4 0.18744(18) 0.3104(3) 0.75792(13) 0.0492(6)
H4 0.172424 0.406278 0.733638 0.059* forms a dihedral angle of 7.46(16)° with the phenyl ring to
C5 0.3154(2) 0.4160(3) 0.85961(14) 0.0503(6) which it is connected, indicating a small twist between the
C6 0.2129(2) 0.6061(3) 0.93005(16) 0.0672(8) residues.
C7 0.0871(3) 0.6531(4) 0.9217(2) 0.0978(11) There is no direct literature precedent for pyrrole (I) with
H7A 0.070656 0.689850 0.872118 0.147*
the most closely related structure being a salt with a N1-bound
H7B 0.072635 0.729743 0.957184 0.147*
6-methylpyridinium substituent and flanked on either side
H7C 0.037785 0.569528 0.930525 0.147*
C8 0.2918(3) 0.7349(4) 0.9140(2) 0.1128(13) by 2-(1,3-benzodioxol-5-yl) and piperidin-1-ylcarbonyl groups
H8A 0.277816 0.766139 0.863230 0.169* [12]. For the pyrrolidine analogue of (I), the most closely
H8B 0.371696 0.704780 0.921708 0.169* related structure is one where the once double bond of (I)
H8C 0.276038 0.815593 0.946901 0.169* is now saturated with each carbon atom bearing a hydroxyl
C9 0.2398(3) 0.5328(4) 1.00428(17) 0.0999(12)
substituent [13]; the ring is twisted about the C(OH)—C(OH)
H9A 0.199453 0.439690 1.005960 0.150*
H9B 0.214818 0.595875 1.043518 0.150* bond.
H9C 0.322274 0.516090 1.010698 0.150* The most notable feature of the molecular packing
C10 0.5012(2) 0.2641(4) 0.76614(17) 0.0752(9) is the presence of amino-N2—H· · · .O3(hydroxyl) hydro-
H10A 0.538430 0.194200 0.733800 0.090* gen bonding [N2—H2n· · · O3i : H2n· · · O3i = 2.07(2) Å,
H10B 0.491502 0.356683 0.739053 0.090*
N2· · · O3i = 2.919(3) Å with the angle at H2n = 174(2)° for
C11 0.08093(18) 0.2628(3) 0.79833(13) 0.0451(6)
symmetry operation (i): −1 + x, y, z] which leads to linear
C12 0.08481(19) 0.1542(3) 0.85220(14) 0.0526(6)
H12 0.156805 0.114735 0.867774 0.063* supramolecular chains along the a-axis.
C13 −0.01405(18) 0.1017(3) 0.88400(14) 0.0520(6) In the absence of additional atom-to-atom points of con-
H13 −0.008171 0.029924 0.921204 0.062* tact between chains, additional insight into the molecular
C14 −0.12217(18) 0.1567(3) 0.86006(12) 0.0432(6) packing of (I) was achieved by an analysis of the calcu-
C15 −0.12706(19) 0.2691(3) 0.80824(14) 0.0559(7)
lated Hirshfeld surfaces and of the full and delineated two-
H15 −0.198841 0.309918 0.793247 0.067*
C16 −0.0268(2) 0.3222(3) 0.77818(14) 0.0575(7) dimensional fingerprint plots employing Crystal Explorer 17
H16 −0.031936 0.399319 0.743765 0.069* [14] and literature procedures [15]. This analysis confirms the
C17 −0.2457(2) −0.0129(3) 0.93032(14) 0.0548(7) dominance of H· · · H contacts to the surface, contributing
C18 −0.3915(3) −0.1509(4) 0.9867(2) 0.0932(11) 64.8%. Next most prominent are H· · · O/O· · · H contacts at
H18A −0.388302 −0.241793 0.958990 0.140*
20.2%, with distinctive spikes correlating with the aforemen-
H18B −0.469038 −0.136582 1.003084 0.140*
tioned hydrogen bonding, and then H· · · C/C· · · H contacts
H18C −0.337591 −0.155868 1.029260 0.140*
at 12.2%. The only other contacts of note are H· · · N/N· · · H
contacts, at 2.2%.
context of the characterisation of key intermediates of Heck-
Matsuda arylation reactions [10, 11]. Acknowledgements: The Brazilian agencies Coordination
The molecular structure of (I) is shown in the for the Improvement of Higher Education Personnel, CAPES,
figure (35% displacement ellipsoids) and is constructed Finance Code 001 and the National Council for Scientific
 Caracelli et al.: C18 H24 N2 O5 | 3

and Technological Development (CNPq) are acknowledged 9. Manfré, F.; Pulicani, P.: Enantiospecific synthesis and
for grants (312210/2019–1, 433957/2018–2 and 406273/2015–4) absolute configuration of (+)-RP 66803 a new non-
peptide CCK antagonist. Tetrahedron: Asymmetry 5 (1994)
to IC and for a fellowship (303207/2017–5) to JZS. Sunway Uni-
235–238.
versity Sdn Bhd is thanked for financial support of this work
10. Pedroso, S. D.; Caracelli, I.; Zukerman-Schpector, J.; Soto-
through Grant No. STR-RCTR-RCCM-001–2019. Monsalve, M.; Santos, R. H. De A.; Correia, C. R. D.; Garcia,
A. L. L.; Kwong, C. H.; Tiekink, E. R. T.: 1-Ethyl 2-methyl 3,4-
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