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(S) Synthesis and structural characterization of tetrahydropyrrole - [1,2, C] - imidazole-1,3-dione

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  • Save International Journal of M aterials and Chemistry 2012, 2(4): 141-144 DOI: 10.5923/j.ijmc.20120204.05 Synthesis and Structural Characterization of (S)-Tetrahydro-Pyrrol-[1,2,c]-Imidazole-1,3-Dione Gerzon E. Delgado*, Jines E. Contreras Laboratorio de Cristalografía, Departamento de Química, Facultad de Ciencias, Universidad de Los Andes, M érida, 5101, Venezuela Abstract In this wo rk we present the synthesis and X-ray single crystal structural characterization of the heterocyclic compound (S)-tetrahydro-pyrrol-[1,2,c]-imidazole-1,3-dione. Th is material crystallize in the orthorhombic system with space group P212121 (Nº19), Z=4, and unit cell parameters a = 7.136(1) Å, b = 8.009(2) Å, c = 11.378(2) Å. The molecular structure shows a hydantoin and pyrrolidine ring coupling forming a bicyclohydantoin. The crystal pac king is governed by N--H···O hydrogen bond-type intermolecu lar interactions, forming infinite one-d imensional chains. Keywords Hydantoin, Hydrogen Bonding, X-ray Crystal Structure 1. Introduction The imidazolidine-2,4-d ione, or hydantoin, is a co mmon 5-member ring containing a reactive cyclic urea core[1,2]. This heterocycle represents a significant molecu lar template in comb inatorial chemistry libraries[3-5], due principally to the four possible points of substitutions. The biological activities of hydantoin derivatives has been known for a long time, and are responsible for a wide variety of b iological behavior[6], due principally to its wide range of therapeutic properties. For instance, several applications have been re port ed for h yd antoins: antia rrh yth mic a n d antihypertensive[ 7], antiviral[8], antineoplastic[9], antitu moral[10] and anticonvulsant agents[11]. The best knwon hydantoin, phenytoin, is the most widely used antiepileptic drug[12]. In addition, these compounds are used as herbicides[13] and fungicides agents[14]. On the other hand, the b iocatalytic conversion of 5-subtituted hydantoins to amino acids has received considerable attention recently for their potential applications in the industrial productions of optically pure amino acids[15,16]. For these reasons, there has been much interest in the search of new synthetic routes for hydantoin via solution[17], or solid state reactions[18-21]. In our laboratory we are interested in the study of N-carbamoyl and hydantoin natural amino acids derivative compounds[22-26], therefore we report here the structure of (S)-tetrahydro-pyrrol-[1,2,c]-imidazole-1,3-d ione, the hydantoin derivative of the natural amino acid L-pro line. The analysis of the hydrogen bond patterns is also discussed. * Corresponding author: gerzon@ul (Gerzon E. Delgado) Published online at Copyright © 2012 Scientific & Academic Publishing. All Rights Reserved 2. Experimental 2.1. Synthesis The title co mpound was synthesized fro m L-pro line using a methodology previously reported[22,23]. 500 mg (4.3 mmo l) of L-proline was disolved in 20 mL of water and the solution was acidified with concentrated HCl (37 % v/v) to pH = 5. Then, 1050 mg (12.9 mmo l) of KOCN was added to this solution. The mixture was warmed up, with agitation, to 60 °C, during 4 h. The resultant solution was acidified with HCl to pH = 2 and agitated during 4 h, until the precipitation of a white solid. (see scheme 1). The solid was filtered and washed with cool water. Colorless crystals of 1 suitable for X-ray diffraction analysis were grown by slow evaporation in a 1:1 methanol-water solution (m.p.: 210-212 °C). FT-IR 1757.6 cm-1 [t, C=O], 1708.7 cm-1 [t, C=O]. 1H NM R (400 MHz, DMSO-d 6) δ =7.27 (H3), 4.07 (t, H5), 3.43 (q, H6A), 3.02 (q, H6B), 2.03 (s, H8A), 1.60 (s, H8B), 1.90 (m, H7A), 1.93 (H7B). 13C NM R (100.6 MHz, DMSO-d6) δ =161.0 (C2), 174.5 (C4), 64.0 (C5), 44.9 (C6), 26.7 (C8), 26.6 (C7). S cheme 1. Synthesis of (S)-t etrahydro-pyrrol-[1,2,c]-imidazole-1,3-dione 2.2. X-ray crystallography Colorless rectangular crystal (0.4, 0.2, 0.1 mm) was used for data collection. Diffraction data were collected at 298(2) K by ω-scan technique on a Rigaku AFC7S Mercury diffracto meter [27] equipped with graphite- monochromat iz ed MoKα radiation (λ = 0.71073 Å). The data were corrected for Lorentz-polarizat ion and absorption effects[28]. The 142 Gerzon E. Delgado et al.: Synthesis and Structural Characterization of (S)-Tet rahy dro-Py rrol-[1,2,c]-Imidaz ole-1,3-Dione structure was solved by direct methods using the SHELXS program[29] and refined by a full-mat rix least-squares calculation on F2 using SHELXL[28]. The absolute structure was assigned from the known configuration of L-pro line. All H ato ms were placed at calculated positions and treated using a riding model, with C-H distances 0.96-0.98 Å and Uiso(H) = 1.2Ueq(C)], N-H 0.86 Å and Uiso(H) = 1.2Ueq(N)]. 3. Results and discussion Figure 1 shows the molecular structure and the atom-labeling scheme of 1[30], and Table 1 shows the crystallographic data and structure refinement parameters. deviations of -0.049 (2) Å in N1 and 0.049 (2) Å in C2. The pyrrolid ine ring shows maximal deviations to the average plane in the atoms C6 [0.225(2) Ǻ] and C5 [0.189(2) Ǻ]. The N1--C2--O2 bond angle 128.4(2)° is lightly greater than the N3--C2--O2 angle 124.7 (2)° (Table 2). This difference is also observed in the hydantoin molecule[31] and the others hydantoin derivative co mpounds found in the Camb ridge Structural Database, CSD version 5.33 updates (Feb 2012)[32], includ ing the same hydantoin structural report without hydrogen atoms[33]. The asymmetry parameter analysis of the pyrrolid ine ring, [∆Csmax= +47.1(3)°, ∆Cs min= +1.9(4)°, ∆C2max= +62.0(3)°, ∆C2 min= 16.5(3)°, ∆Cs(C8)=1.9(4)°, ∆Cs(C6-N1) = 1.9(4)°], indicates that the same adopt an envelope conformat ion [34]. Figure 1. The molecular structure of 1, showing the atomic numbering scheme. Displacement ellipsoids are drawn at 50% probability level. H atoms are shown as spheres of arbitrary radii Table 2. Select ed geometrical parameters (Å, º) O2-C2 N1-C2 N1-C8 N3-C4 C5-C6 C7-C8 N1-C2-O2 C2-N1-C5 C5-N1-C8 C5-N1-C2-O2 C8-N1-C2-O2 1.215(2) 1.352(2) 1.468(2) 1.356(2) 1.522(2) 1.529(3) 128.4(2) 110.9(1) 111.6(1) -170.6(2) -34.7(3) O4-C4 N1-C5 N3-C2 C4-C5 C6-C7 N1-C2-N3 N3-C2-O2 C2-N1-C8 C2-N3-C4 C4-N3-C2-O2 C2-N3-C4-O4 1.224(2) 1.461(2) 1.408(2) 1.499(2) 1.529(3) 106.9(1) 124.7(2) 123.0(1) 111.9(1) 172.1(2) -177.5(2) Table 1. Crystal data, data collection and structure refinement Chemical formula Formula weight Crystal system Space group a(Å) b(Å) c(Å) V(Å3) Z dx (g cm-3) F(000) µ(mm-1) θ range (°) hkl range Reflect ion s Co llect ed Unique (Rint) With I > 2σ(I) Refinement method Number of parameters R(F2) [I > 2σ(I)] wR(F2) [I > 2σ(I)] Goodness of fit on F2 Max/min ∆ρ (e Å-3) C6H8N2O2 140.14 Ort horhombic P212121 7.136(1) 8.009(2) 11.378(7) 650.3(2) 4 1.431 296 0.110 3.1-28.1 -9 ≤ h ≤ 8, -9 ≤ k ≤ 9, -14 ≤ l ≤ 14 7408 1374 (0.026) 1207 Full-matrix least-squares on F2 93 0.0389 0.1042 1.09 0.17/-0.13 The hydantoin ring is essentially plane with a maximal Figure 2. A portion of the crystal packing viewed in the cb plane. Intermolecular hydrogen bonds, N--H···O, are indicated by dashed lines. H atoms not involved in hydrogen bonding have been omitted for clarity The mo lecular structure and crystal packing of 1 are stabilized by intermolecular N3---3···O4 (-x, ½+y, ½-z) hydrogen bonds (Table 3), forming infin ite one-diment ional zigzag chains that run along (010) direction, which can be described in graph-set notation as C(4)[35] (see Figure 2). These chains that extend along the b axis overlap resulting in a lamellar packing type with mo lecules that pile up along the a direction, with average planes separated 3.57 Å. Table 3. Hydrogen bonds geometry Selected (Å, º) D--H···A N3---H3···O4(i) D--H 0.98 Symmetry codes: (i)-x, ½ + y, ½ - z H···A 1.90 D···A D--H···A 2.881 (2) 174 International Journal of M aterials and Chemistry 2012, 2(4): 141-144 143 4. Conclusions In the crystal structure of (S)-tetrahydro-pyrrol-[1,2,c]imidazo le-1,3-d ione, the mo lecules are lin ked by N---H···O hydrogen bonds, forming infinite one-d imensional zig zag chains, running along [010] plane, with a C(4) graph-set motif. ACKNOWLEDGEMENTS This work was supported by CDCHT-ULA (grant C-1755-11-08-B) and FONA CIT (grant LAB-97000821). REFERENCES [1] C.A. López, G.G. Trigo, “The chemistry of hydantoins”, Adv. Heterocycl. Chem. 38, 177-210, 1985. [2] M . M eusel, M . Gütschow, “Recent developments in hydantoin chemistry. A review”, Org. Prep. Proced. Int. 36, 391-443, 2004. [11] G. Singh, P.H. Driever, J.W. Sander, L. Sander, “Cancer risk in people with epilepsy: The role of antiepileptic drugs”, Brain 128, 7-17, 2005. [12] H.H. M errit, T.J. Putnam, “A new series of anticonvulsant drugs tested by experiments on animals”, Arch. Neurol. Psychiatry 39, 1003-1015, 1938. [13] M . Shiozaki, “Syntheses of hydantocidin and C-2-thioxohydantocidin”, Carbohydr. 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