Home Crystal structure of 2-tert-butyl 1-methyl 5-{4-[(methoxycarbonyl)amino]phenyl}-2,5-dihydro-1H-pyrrole-1,2-dicarboxylate, C19H24N2O6
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Crystal structure of 2-tert-butyl 1-methyl 5-{4-[(methoxycarbonyl)amino]phenyl}-2,5-dihydro-1H-pyrrole-1,2-dicarboxylate, C19H24N2O6

  • Ignez Caracelli EMAIL logo , Julio Zukerman-Schpector , Ariel L. Llanes Garcia , Carlos Roque D. Correia and Edward R.T. Tiekink ORCID logo EMAIL logo
Published/Copyright: July 18, 2020

Abstract

C19H24N2O6, monoclinic, P21 (no. 4), a = 8.3611(7) Å, b = 9.0521(8) Å, c = 13.8988(8) Å, β = 106.710(5)°, V = 1007.52(14) Å3, Z = 2, Rgt(F) = 0.0428, wRref(F2) = 0.1174, T = 293(2) K.

CCDC no.: 2014879

The molecular structure is shown in the figure. Table 1 contains crystallographic data and Table 2 contains the list of the atoms including atomic coordinates and displacement parameters.

Table 1:

Data collection and handling.

Crystal:Colourless irregular
Size:0.40 × 0.32 × 0.30 mm
Wavelength:Mo Kα radiation (0.71073 Å)
μ:0.09 mm−1
Diffractometer, scan mode:Enraf Nonius TurboCAD4, ω
θmax, completeness:30.0°, >99%
N(hkl)measured, N(hkl)unique, Rint:3294, 3105, 0.025
Criterion for Iobs, N(hkl)gt:Iobs > 2 σ(Iobs), 1902
N(param)refined:252
Programs:Absorption correction [1], CAD4 [2], [3], SIR2014 [3], SHELX [4], WinGX/ORTEP [5], [6]
Table 2:

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2).

AtomxyzUiso*/Ueq
O10.8580(3)0.2321(3)0.83858(15)0.0741(7)
O20.9732(2)0.1773(3)1.00129(15)0.0619(6)
O30.2235(2)0.8167(2)0.82843(12)0.0528(5)
O40.1395(2)0.9078(2)0.67070(12)0.0467(4)
O5−0.2428(3)0.7926(3)0.49100(13)0.0712(7)
O6−0.2030(2)0.7842(2)0.65798(12)0.0506(5)
N10.1019(2)0.6687(2)0.69561(14)0.0383(5)
N20.7240(3)0.2746(3)0.95713(15)0.0472(5)
H2N0.744(4)0.268(4)1.0207(8)0.057*
C20.0947(3)0.5385(3)0.75698(18)0.0424(6)
H20.0381320.5641330.8074650.051*
C3−0.0151(3)0.4382(3)0.6794(2)0.0525(7)
H3−0.0433060.3425340.6927770.063*
C4−0.0667(3)0.5012(3)0.5903(2)0.0526(7)
H4−0.1304110.4538360.5325970.063*
C5−0.0102(3)0.6580(3)0.59370(17)0.0432(6)
H50.0499660.6759810.5438500.052*
C60.2642(3)0.4717(3)0.80829(17)0.0401(6)
C70.3145(3)0.4508(3)0.91076(19)0.0507(7)
H70.2448040.4801450.9487150.061*
C80.4675(4)0.3866(4)0.95817(18)0.0521(7)
H80.4999650.3741171.0275150.062*
C90.5718(3)0.3411(3)0.90275(17)0.0410(6)
C100.5229(3)0.3608(3)0.79963(18)0.0478(6)
H100.5924100.3311570.7616320.057*
C110.3689(3)0.4252(3)0.75330(18)0.0488(7)
H110.3357160.4371740.6839170.059*
C120.8510(3)0.2300(3)0.92356(19)0.0442(6)
C131.1159(4)0.1162(5)0.9779(3)0.0795(11)
H13A1.1575050.1861150.9389820.119*
H13B1.0841930.0268990.9399080.119*
H13C1.2013810.0947351.0389890.119*
C140.1593(3)0.7982(3)0.73947(17)0.0402(5)
C150.1852(5)1.0529(4)0.7103(2)0.0657(9)
H15A0.2944751.0499170.7575500.099*
H15B0.1059331.0868560.7434430.099*
H15C0.1858251.1190810.6564520.099*
C16−0.1659(3)0.7561(3)0.57373(17)0.0445(6)
C17−0.3580(4)0.8624(4)0.6599(2)0.0630(8)
C18−0.3480(6)0.8569(7)0.7699(3)0.1032(16)
H18A−0.2437490.8983920.8087470.155*
H18B−0.3553520.7561090.7897840.155*
H18C−0.4385460.9126110.7813280.155*
C19−0.3512(7)1.0175(5)0.6252(4)0.1066(16)
H19A−0.3525711.0174690.5559060.160*
H19B−0.2506201.0637840.6649830.160*
H19C−0.4461951.0711290.6323980.160*
C20−0.5075(4)0.7776(7)0.5956(3)0.1069(16)
H20A−0.4953200.6747010.6128350.160*
H20B−0.5140280.7897440.5259810.160*
H20C−0.6077200.8148410.6074530.160*

Source of material

To a solution of 2-tert-butyl 1-methyl (2S)-2,3-dihydro-1H-pyrrole-1,2-dicarboxylate (91 mg, 0.40 mol) in dry acetonitrile (2.5 mL), under an inert atmosphere, were added quickly and consecutively anhydrous NaOAc (98 mg, 1.195 mmol), [4-MeOCONHC6H4N2]BF4 (106 mg, 0.40 mmol, M.pt = 415–416 K; recrystallised from acetone/ether) and Pd2(dba)3⋅dba (5.0 mg, 0.0043 mmol; dba = dibenzylideneacetone). The mixture was stirred at room temperature for 45 min; the progress of the reaction was followed by the release of nitrogen. Then, EtOAc (5.0 mL) and a saturated solution (3.0 mL) of NaHCO3 were added. The mixture was stirred for 5 min and the phases were separated. The organic phase was washed with water and then with a saturated solution of NaCl. The solution was then dried with anhydrous Na2SO4, filtered and the solvent was removed in a rotary evaporator. The residue was purified by filtration through a layer of silica gel, using a mixture of EtOAc/n-hexane (2:8) as the eluent. Yield: 148 mg (98%) of Heck products. The products were not separable by flash column chromatography on silica gel, produced a single “spot” by thin layer chromatography and a single signal by capillary gas chromatography. Therefore, the product was dissolved in DMSO and allowed to crystallize slowly. The trans diastereoisomer, (I), precipitated; the cis diastereoisomer remained in solution.

Suitable crystals for the X-ray diffraction analysis were obtained by slow evaporation from a MeOH solution. M. pt: 453–456 K.

The 1H and 13C NMR spectra reflect the presence of conformational rotamers in solution. 1H NMR (300 MHz, DMSO-d6 r.t.): δ = 9.62 and 9.61 (2 br s, 1H); 7.39 (d, J = 8.1 Hz, 1H); 7.37 (d, J = 8.4 Hz, 1H); 7.15 (d, J = 8.4 Hz, 1H); 7.13 (d, J = 8.4 Hz, 1H); 5.95 and 5.93 and 5.91 [(t, J = 1.9 Hz) + (t, J = 1.9 Hz) + (t, J = 1.6 Hz), 1H]; 5.88 and 5.86 (2q, J = 2.2 Hz, 1H); 5.53–5.44 (m, 1H); 5.07 and 5.05 [(t, J = 2.2 or 1.6 Hz) + (t, J = 1.9 Hz), 1H]; 3.65 (s, 3H); 3.48 and 3.39 (2s, 3H); 1.422 and 1.415 (2s, 9H). 1H NMR (300 MHz, DMSO-d6, T = 393 K): δ = 9.05 (br s, 1H); 7.39 (d, J = 8.4 Hz, 2H); 7.14 (d, J = 8.4 Hz, 2H); 5.93 and 5.91 (2t, J = 2.2 or 1.5 Hz, 1H); 5.86 and 5.84 (2t, J = 2.2 or 1.8 Hz, 1H); 5.55-5.48 (m, 1H); 5.05 and 5.03 (2t, J = 2.2 or 1.8 Hz, 1H); 3.68 (s, 3H); 3.49 (s, 3H); 1.46 (s, 9H). 13C NMR (75 MHz, DMSO-d6, T = 393 K): δ = 167.9; 153.4; 137.6; 134.2; 133.4; 126.2; 122.8; 118.1; 80.5; 67.4; 67.2; 51.0; 50.6; 27.0. HRMS (Electron Impact Ionisation) calculated for C19H24N2O6: 376.16344; found: 376.16320.

Experimental details

The C-bound H atoms were geometrically placed (C—H = 0.93–0.98 Å) and refined as riding with Uiso(H) = 1.2–1.5Ueq(C). The N-bound H atom was refined with N—H = 0.86 ± 0.01 Å, and with 1.2Ueq(N). The absolute structure was not determined in the X-ray experiment but, the assignment of stereochemistry at the chiral centres is based on the chirality of the synthetic precursor employed in the synthesis.

Comment

Recent reports have detailed the crystal structure determinations of pyrrole [7] and pyrrolidine [8], [9] derivatives having rare or even unprecented substitution patterns. These are crucial intermediates for the synthesis of pharmacologically-relevant molecules via Heck-Matsuda arylation reactions, namely the coupling of an olefin with an arenediazonium salt mediated by a catalytic palladium complex [10]. In the present case, the title compound, (I), is an intermediate in the enantioselective synthesis of polyhydroxylated pyrrolidines such as analogues of Schramm’s antiprotozoan C-azanucleoside [11], which may display anti-viral, anti-cancer and anti-microbial activities [12], [13]. Herein, the crystal and molecular structures of (I) are described along with an additional analysis of the molecular packing via calculated Hirshfeld surfaces.

The molecular structure of (I) is illustrated in the figure (35% displacement ellipsoids) and features a five-membered ring which is twisted about the N1—C5 bond. The geometry about the N1 atom is close to trigonal with the sum of the angles subtended at N1 = 356.2°. The ring is tri-substituted, with a N1-bound methyloxycarbonyl group flanked on either side by a C2-bound [(methoxycarbonyl)amino]phenyl substituent and a C5-bound tert-butyloxycarbonyl group. The configuration at each of the C2 and C5 atoms is S. The dihedral angle between the N1-substituent and the best plane through the pyrrole ring is 14.91(14)°, being indicative of a twist between the residues. As indicated above, the C2- and C5-bound substituents lie to the opposite side of the pyrrole ring. In fact, they have approximately orthogonal dispositions to the pyrrole ring, forming dihedral angles of 87.83(9) and 83.42(13)°, respectively, with the former. The [(methoxycarbonyl)amino]phenyl is close to planar with the C6/C2NO2 dihedral angle being 2.97(15)°.

There is a single, direct literature precedent for pyrrole (I) which has only been recently described [7]. Here, the N1 atom carries a tert-butyloxycarbonyl group and is flanked by C-bound methylhydroxyl and [(methoxycarbonyl)amino]phenyl groups.

In the crystal, amide-N—H⋯O(carbonyl) hydrogen bonding [N2—H2n⋯O3i: H2n⋯O3i = 2.083(14) Å, N2n⋯O3i = 2.910(3) Å with angle at H2n = 163(3)° for symmetry operation (i): 1 − x, −1/2 + y, 2 − z] connect molecules into a helical supramolecular chain along the b-axis. The presence of methine-C—H⋯O(amide) [C3—H3⋯O1ii: H3⋯O1ii = 2.60 Å, C3⋯O1ii = 3.294(4) Å with angle at H3 = 132° for (ii) −1 + x, y, z] interactions link the chains into a supramolecular layer in the ab-plane. The layers stack without directional interactions between them. In order to understand more fully the nature of the intermolecular contacts in the crystal, an analysis of the Hirshfeld surfaces along with two-dimensional fingerprint plots was undertaken with the aid of Crystal Explorer 17 [14] and literature protocols [15].

The fingerprint plot delineated into H⋯O/O⋯H contacts showed the distinctive spikes due to the N—H⋯O hydrogen bonds and overall, contributed 24.5% of all contacts, with H⋯H contacts being most dominant, at 57.9%. The next most significant contribution to the calculated surface contacts is from H⋯C/C⋯H contacts [11.6%] with smaller contibutions from N⋯C/C⋯N [2.9%] and H⋯N/N⋯H [2.7%] contacts.

Acknowledgements

The Brazilian agencies Coordination for the Improvement of Higher Education Personnel, CAPES, Finance Code 001 and the National Council for Scientific and Technological Development (CNPq) are acknowledged for grants (312210/2019–1, 433957/2018–2 and 406273/2015–4) to IC and for a fellowship (303207/2017–5) to JZS. Sunway University Sdn Bhd is thanked for financial support of this work through Grant No. STR-RCTR-RCCM-001–2019.

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Received: 2020-06-24
Accepted: 2020-07-08
Published Online: 2020-07-18
Published in Print: 2020-10-27

©2020 Ignez Caracelli et al., published by De Gruyter, Berlin/Boston

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  39. Crystal structure of chlorido-[(N,N-di-isobutyl)dithiocarbamato-κ2S,S′]-di(4-methylbenzyl-κC)tin(IV), C25H36ClNS2Sn
  40. Crystal structure of chlorido-(η5-pentamethylcyclopentadienyl)-(4-chloro-4-pyridyl-2,2′:6′,2′′-terpyridine-κ2N,N′) rhodium(III) hexaflourophosphate, C31H29Cl2F6N3PRh
  41. The crystal structure of catena-poly[bis-(3,5-dinitro-1,2,4-triazolato-κ2N:O)-(μ2-1,4-bis(1-imidazolyl)benzene-κ2N:N′)copper(II)], C16H10CuN14O8
  42. Crystal structure of poly[triaqua-bis(μ3-3,3′-((5-carboxylato-1,3-phenylene)bis(oxy))dibenzoato)-tris(1,10-phenanthroline)cobalt(II)], C78H46N6O20Co3
  43. The crystal structure of 2,4-dihydroxybenzoic acid–nicotinamide–methanol (1/1/1), C15H18N2O6
  44. The crystal structure of aqua{N,N,N′,N′-tetrakis[(1H-benzimidazol-κN3) methyl]cyclohexane-1,2-diamine}lead(II) diacetate–methanol (1/2), C44H54N10O7Pb
  45. Crystal structure of (2-amino-5-bromo-3-iodophenyl)(3-(4-chlorophenyl)oxiran-2-yl)methanone, C15H10BrClINO2
  46. Synthesis and crystal structure of 3-octyl-5,5-diphenylimidazolidine-2,4-dione, C23H28N2O2
  47. Synthesis and crystal structure of 2-azido-N-(4-nitrophenyl)acetamide, C8H7N5O3
  48. Crystal structure of tert-butyl (1S,2R,5R)-2-(hydroxymethyl)-4-(4-methoxyphenyl)-6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate, C17H23NO5
  49. Crystal structure of 4-[(4-methoxy-2-nitrophenyl)carbamoyl]butanoic acid, C12H14N2O6
  50. Crystal structure of 3-ethyl-1-[(E)-[(2E)-3-phenylprop-2-en-1-ylidene]amino]thiourea, C12H15N3S
  51. Crystal structure of 4,4′-bipyridin-1,1′-dium poly[bis(μ4-benzene-1,3,5-triyltris(hydrogen phosphonato-κ4O:O′:O′′:O′′′))zinc(II)], C11H11NO9P3Zn
  52. Crystal structure of (μ2-1,1′-bis(diphenylphosphino)butane-κ2P,P′)-bis[(Z)-N-(3-fluorophenyl)-O-methylthiocarbamato-κS]-di-gold(I), C44H42Au2F2N2O2P2S2
  53. Crystal structure of (μ2-1,1′-bis(diphenylphosphino)hexane-κ2P,P′)-bis[(Z)-N-(3-fluorophenyl)-O-methylthiocarbamato-κS]digold(I), C46H46Au2F2N2O2P2S2
  54. Crystal structure of tetrakis (N-(2-hydroxyethyl)-N-isopropylcarbamodithioato-κS,S′)-(μ2(2-(pyridin-4-yl)vinyl)pyridine-κN,N′)dicadmium(II), C36H58Cd2N6O4S8
  55. Crystal structure of 4-(2-(benzo[b]thiophen-2-yl)-3,3,4,4,5,5-hexafluorocyclopent-1-en-1-yl)-1,5-dimethyl-1H-pyrrole-2-carbonitrile, C20H12F6N2S
  56. Crystal structure of bis(octahydrocyclopenta[c]pyrrolium)pentachlorobismuthate(III), (C7NH14)2BiCl5
  57. The crystal structure of diaqua-tris(nitrato-κ2O,O′)-bis(4,4,5,5-tetramethyl-2-(p-pyridyl)imidazoline-1-oxyl 3-oxide-κN)samarium(III), C24H36N9O15Sm
  58. Synthesis and crystal structure of methyl 2-(2-((tert-butoxycarbonyl)amino)phenyl)-2-(4-oxo-4H-chromen-3-yl)acetate, C23H23NO6
  59. Crystal structure of O-hexyl benzoylcarbamothioate, C14H19NO2S
  60. Crystal structure of chlorido-(O-methyl phenylcarbamothioamide-κS)-bis(triphenylphosphane-κP)silver(I), C44H39AgClNOP2S
  61. Crystal structure of chlorido-(O-ethyl phenylcarbamothioamide-κS)-bis(triphenylphosphane-κP)-silver(I), C45H41AgClNOP2S
  62. Crystal structure of 4-[(2-methoxyphenyl)carbamoyl]butanoic acid, C12H15NO4
  63. Crystal structure of ethyl 4-methyl-2-oxo-5-phenyl-1,3,4-oxadiazinane-3-carboxylate, C13H16N2O4
  64. Crystal structure of catena-poly[diaqua(μ2-2-(hydroxymethyl)-1H-imidazole-4,5-dicarboxylato)cadmium(II)], C6H8CdN2O7
  65. Crystal structure of (1S)-N-(chloromethyl)-1-((4S,6aR,8aS, 8bR,9aR)-4-methoxy-6a,8a-dimethyl-1,3,4, 5,6,6a,6b,7,8,8a,9a,10,10a,10b-tetradecahydro-8bH-naphtho[2′,1′:4,5] indeno[1,2-b]oxiren-8b-yl)-N-methylethan-1-amine, C24H46ClNO5
  66. Crystal structure of 4-[(3,5-dichlorophenyl)carbamoyl]butanoic acid, C11H11Cl2NO3
  67. Crystal structure of (2Z)-2-amino-3-[(E)-[(2,4-dihydroxyphenyl)methylidene]-amino]but-2-enedinitrile, C11H8N4O2
  68. Crystal structure of 3-methyl-1-[(E)-(4-phenylbutan-2-ylidene)amino]thiourea, C12H17N3S
  69. Crystal structure of carbonyl{hydridotris[3-phenyl-5-methylpyrazol-1-yl]borato-κ3N,N′N′′}copper(I), C31H28BCuN6O
  70. Crystal structure of ethane-1,2-diylbis(diphenylphosphine oxide) – dihydrogenperoxide (1/2), C26H28O6P2
  71. Crystal structure of 2-(pyridin-2-ylamino)pyridinium chloride dibenzyldichlorostannane, [C10H10N3]Cl, C14H14Cl2Sn
  72. Crystal structure of 4-[(3-methoxyphenyl)carbamoyl]butanoic acid, C12H15NO4
  73. Crystal structure of dichlorido-bis(tri-4-tolylphosphane oxide-κO)-di(4-chlorophenyl-κC)tin(IV), C54H50Cl4O2P2Sn
  74. Crystal structure of dichloridodimethylbis(tri-4-tolylphosphane oxide-κO)-tin(IV), C44H48Cl2O2P2Sn
  75. Crystal structure of chlorido(2-methylquinolin-8-olato-κ2N,O)-bis(4-tolyl-κC)tin(IV), C24H22ClNOSn
  76. Crystal structure of (E)-dichloro(1-chloro-3-methoxyprop-1-en-2-yl)(4-methoxyphenyl)-λ4-tellane, C11H13Cl3O2Te
  77. Crystal structure of bis{N-methyl-N′-[3-(4-methoxyphenyl)-1-methylpropane-1-ylidene]carbamohydrazonothioato}zinc(II), C26H36N6O2S2Zn
  78. Crystal structure of (2-carboxy-4-(3-carboxy-5-carboxylatophenoxy)benzoato-κ2O,O′)bis(1,10-phenantroline-κ2N,N′)cobalt(II), C40H24N4O9Co
  79. The crystal structure of (3S,8R,10R,14R)-17-((2S,5S)-5-(2-hydroxypropan-2-yl)-2-methyltetrahydrofuran-2-yl)-4,4,8,10,14-pentamethyl-12-oxohexadecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate, C32H52O5
  80. Crystal structure of (μ2-1,1′-bis(diphenylphosphino)ferrocene-κ2P,P′)-bis[(Z)N-(3-fluorophenyl)-O-methylthiocarbamato-S]digold(I) chloroform solvate, C50H42Au2F2FeN2O2P2S2, CHCl3
  81. Crystal structure of poly[bis(μ2-1,4-di(1H-imidazol-1-yl)benzene-κ2N:N′)-(μ2-tetraoxidomolybdato(VI)-κ2O:O′)cobalt(II)], C24H20N8O4MoCo
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