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Acta Crystallogr Sect E Struct Rep Online. 2008 June 1; 64(Pt 6): o1160.
Published online 2008 May 30. doi:  10.1107/S1600536808015341
PMCID: PMC2961379

Diisoprop­yl{2-[2-(2-oxopyrrolidin-1-yl)acetamido]eth­yl}ammonium hydrogen sulfate

Abstract

The structure of the title compound, C14H28N3O2 +·HSO4 , a nootropic drug (pramiracetam) investigated for cognition-enhancing properties, is closely similar to that of the previously determined acetonitrile solvate, both structures being characterized by the presence of ribbons of hydrogen-bonded ions. The pyrrolidine ring adopts an envelope conformation.

Related literature

For related literature, see: Claus et al. (1991 [triangle]); Gouliaev & Senning (1994 [triangle]); Mondadori et al. (1991 [triangle]); Pugsley et al. (1983 [triangle]). For a related structure, see: Bandoli et al. (1987 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-64-o1160-scheme1.jpg

Experimental

Crystal data

  • C14H28N3O2 +·HSO4
  • M r = 367.46
  • Triclinic, An external file that holds a picture, illustration, etc.
Object name is e-64-o1160-efi1.jpg
  • a = 6.7834 (3) Å
  • b = 11.1755 (4) Å
  • c = 12.9012 (6) Å
  • α = 72.165 (4)°
  • β = 89.394 (4)°
  • γ = 89.509 (3)°
  • V = 930.95 (7) Å3
  • Z = 2
  • Cu Kα radiation
  • μ = 1.85 mm−1
  • T = 170 (2) K
  • 0.50 × 0.25 × 0.10 mm

Data collection

  • Oxford Diffraction Xcalibur PX Ultra CCD diffractometer
  • Absorption correction: multi-scan (ABSPACK in CrysAlisPro RED; Oxford Diffraction, 2006 [triangle]) T min = 0.762, T max = 1.000 (expected range = 0.634–0.831)
  • 7656 measured reflections
  • 3356 independent reflections
  • 3253 reflections with I > 2σ(I)
  • R int = 0.018

Refinement

  • R[F 2 > 2σ(F 2)] = 0.046
  • wR(F 2) = 0.132
  • S = 1.06
  • 3356 reflections
  • 230 parameters
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.45 e Å−3
  • Δρmin = −0.57 e Å−3

Data collection: CrysAlisPro CCD (Oxford Diffraction, 2006 [triangle]); cell refinement: CrysAlisPro CCD; data reduction: CrysAlisPro RED (Oxford Diffraction, 2006 [triangle]); program(s) used to solve structure: SIR97 (Altomare et al., 1999 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEP-3 (Farrugia, 1997 [triangle]) and PLATON (Spek, 2003 [triangle]); software used to prepare material for publication: SHELXL97.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808015341/pv2084sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808015341/pv2084Isup2.hkl

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

Acknowledgments

The authors acknowledge financial support from the Italian Ministero dell’Istruzione, dell’Universitá e della Ricerca.

supplementary crystallographic information

Comment

Pramiracetam is a nootropic drug (Gouliaev & Senning, 1994) whose neurochemical properties have been investigated (Pugsley et al., 1983) also in view of possible applications as a memory aid (Mondadori et al., 1991) and for symptomatic treatment of Alzheimer's desease (Claus et al., 1991).

The contents of the asymmetric unit of the title compound (I) are shown in Fig 1. The atomic labelling is consistent with that previously adopted for the CH3CN solvate (Bandoli et al., 1987) with which (I) is isomorphous and substantially isostructural, although the present conventional choice of labels for the axes does not match that of the previous report. There is a 3.8% reduction in the cell volume going from the solvated form to the present one, due to contraction of the two longest cell axes. The packing (Fig. 2) is controlled by a network of hydrogen bonds. The HSO4- anion behaves as a hydrogen bond donor towards a carbonylic oxygen and acts as acceptor of two hydrogen bonds from the aminic and ammonium N atoms (details of hydrogen-bonding geometry have been provided in Table 1). In this way two centrosymmetric and adjacent loops, consisting of 14 and 18 non-hydrogen atoms, respectively, are formed. Each loop has contributions from parts of two anions and two cations and each of these ions contributes to two contiguous loops which share the N2—H2···O3—S strand. Such arrangement, combined with the operation of the c translation, generates ribbons in the structure (these were parallel to the a direction in the previously reported structure of the solvated form, due to the different labelling of cell axes). In the case of the CH3CN solvate the solvent molecules occupy large voids among the ribbons and are not involved in the network of hydrogen bonds. The largest difference in the conformation of the cation between the two structures is found for the C1—N1—C5—C6 torsion angle, whose value of -94.6 (2)° for (I) is significantly smaller than that, of -105.4(1.2)°, found for the structure of the solvate. The structure of (I) is stabilized by non-classical intermolecular and intramolecular hydrogen bonds of the type C—H···O (Table 1).

Experimental

Samples of pramiracetam were kindly provided by SIMS (SIMS srl, Reggello Firenze, Italy). Crystals of (I), suitable for X-ray diffraction analysis, were obtained by slow evaporation from 1:3 2-propanol:acetone solutions.

Refinement

A small fraction of data is missing from completeness because the structure appeared to be monoclinic at the time of data collection. It was impossible to collect a new set of data due to extreme difficulty to obtain suitable material for diffraction. Also, since crystals did not diffract strongly, it was deemed that collecting data at θ higher than 72° would not yield significant improvement. H atoms bound to carbon atoms were in geometrically generated positions, riding; the coordinates of those bound to N and O atoms were refined freely. The constraint U(H) = 1.2Ueq(C,N) was applied [U(H) = 1.5Ueq(C) for methyl group H atoms]. Bond distances involving refined hydrogen atoms: N2—H2 0.86 (3) Å, N3—H3 0.97 (3) Å, O6—H6 0.90 (4) Å. The only residual electron density of any numerical, but not chemical significance is in close proximity of the O and S atoms of the counterion. The existence of voids (57.0 Å3) in the structure is likely due to the stability of the hydrogen-bonds framework, as the solvents used for crystallization could not fit into the available spacing.

Figures

Fig. 1.
A view of the content of the asymmetric unit of (I). Displacement ellipsoids are drawn at the 50% probability level.
Fig. 2.
A view of the crystal packing in the structure of (I), showing the presence of ribbons formed by hydrogen–bonded ions. Hydrogen bonds are denoted by dashed lines. Only hydrogen atoms involved in the formation of hydrogen bonds are shown.

Crystal data

C14H28N3O2+·HSO4Z = 2
Mr = 367.46F000 = 396
Triclinic, P1Dx = 1.311 Mg m3
Hall symbol: -P 1Cu Kα radiation λ = 1.54180 Å
a = 6.7834 (3) ÅCell parameters from 6722 reflections
b = 11.1755 (4) Åθ = 4.6–72.4º
c = 12.9012 (6) ŵ = 1.85 mm1
α = 72.165 (4)ºT = 170 (2) K
β = 89.394 (4)ºPrism, pale yellow
γ = 89.509 (3)º0.50 × 0.25 × 0.10 mm
V = 930.95 (7) Å3

Data collection

Oxford Diffraction Xcalibur PX Ultra CCD diffractometer3356 independent reflections
Radiation source: fine-focus sealed tube3253 reflections with I > 2σ(I)
Monochromator: Oxford Diffraction Enhance ULTRA assemblyRint = 0.018
Detector resolution: 8.1241 pixels mm-1θmax = 72.7º
T = 170(2) Kθmin = 4.6º
ω scansh = −8→8
Absorption correction: multi-scan(ABSPACK in CrysAlisPro RED; Oxford Diffraction, 2006)k = −13→13
Tmin = 0.762, Tmax = 1.000l = −15→15
7656 measured reflections

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.046H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.132  w = 1/[σ2(Fo2) + (0.0779P)2 + 0.7081P] where P = (Fo2 + 2Fc2)/3
S = 1.06(Δ/σ)max < 0.001
3356 reflectionsΔρmax = 0.45 e Å3
230 parametersΔρmin = −0.57 e Å3
Primary atom site location: structure-invariant direct methodsExtinction correction: none

Special details

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.

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

xyzUiso*/Ueq
S0.38398 (7)0.68601 (4)0.65914 (4)0.02428 (17)
O30.5651 (2)0.65687 (14)0.72078 (13)0.0327 (4)
O40.4059 (2)0.78663 (14)0.55696 (12)0.0308 (3)
O50.2944 (2)0.57503 (15)0.64603 (14)0.0386 (4)
O60.2374 (3)0.74531 (16)0.72349 (14)0.0384 (4)
H60.234 (5)0.703 (3)0.795 (3)0.058*
N11.0351 (2)0.37637 (16)0.93852 (14)0.0254 (4)
C10.9684 (3)0.33125 (18)1.04001 (16)0.0243 (4)
O10.7977 (2)0.34687 (14)1.06959 (12)0.0289 (3)
C21.1312 (3)0.2564 (2)1.11073 (17)0.0287 (4)
H211.10960.16491.12710.034*
H221.14020.27681.18000.034*
C31.3171 (3)0.2979 (2)1.04077 (18)0.0328 (5)
H311.38270.36791.05840.039*
H321.41160.22721.05150.039*
C41.2393 (3)0.3403 (2)0.92434 (18)0.0310 (5)
H411.31510.41260.87790.037*
H421.24510.27100.89160.037*
C50.9126 (3)0.44164 (18)0.84733 (17)0.0267 (4)
H510.99030.50920.79600.032*
H520.80020.48150.87400.032*
C60.8339 (3)0.35436 (18)0.78717 (16)0.0254 (4)
O20.8971 (2)0.24667 (13)0.80310 (13)0.0322 (4)
N20.6967 (3)0.40757 (16)0.71317 (14)0.0268 (4)
H20.649 (4)0.479 (3)0.711 (2)0.032*
C70.6169 (3)0.34383 (19)0.64051 (17)0.0268 (4)
H710.72040.29060.62200.032*
H720.57330.40670.57220.032*
C80.4429 (3)0.26239 (18)0.69493 (16)0.0254 (4)
H810.48310.20790.76780.031*
H820.33400.31730.70520.031*
N30.3696 (2)0.18130 (15)0.62949 (14)0.0236 (4)
H30.449 (4)0.197 (2)0.564 (2)0.028*
C90.3977 (3)0.04104 (18)0.69036 (18)0.0289 (4)
H90.3453−0.00710.64290.035*
C100.2806 (4)0.0020 (2)0.7957 (2)0.0398 (5)
H1010.14180.02540.78060.060*
H1020.33270.04450.84560.060*
H1030.2914−0.08920.82910.060*
C110.6165 (3)0.0111 (2)0.70570 (19)0.0342 (5)
H1110.6351−0.08010.73590.051*
H1120.67080.05250.75590.051*
H1130.68470.04150.63520.051*
C120.1589 (3)0.21577 (18)0.58962 (17)0.0264 (4)
H120.07000.20610.65400.032*
C130.0884 (3)0.1305 (2)0.5264 (2)0.0341 (5)
H131−0.04120.15930.49530.051*
H1320.07800.04430.57540.051*
H1330.18250.13280.46770.051*
C140.1534 (3)0.35207 (19)0.51788 (18)0.0297 (4)
H1410.01870.37480.49230.045*
H1420.24180.36260.45520.045*
H1430.19630.40670.55990.045*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
S0.0230 (3)0.0252 (3)0.0239 (3)0.00295 (18)−0.0020 (2)−0.00645 (19)
O30.0279 (8)0.0345 (8)0.0357 (8)0.0053 (6)−0.0098 (7)−0.0106 (6)
O40.0319 (7)0.0303 (7)0.0256 (8)0.0063 (6)0.0024 (6)−0.0022 (6)
O50.0385 (9)0.0306 (8)0.0474 (10)−0.0018 (6)−0.0117 (7)−0.0125 (7)
O60.0424 (9)0.0405 (9)0.0283 (8)0.0153 (7)0.0044 (7)−0.0053 (7)
N10.0230 (8)0.0282 (8)0.0241 (9)0.0020 (6)−0.0028 (7)−0.0067 (7)
C10.0241 (9)0.0234 (9)0.0252 (10)−0.0011 (7)−0.0019 (8)−0.0072 (7)
O10.0231 (7)0.0332 (8)0.0289 (8)0.0015 (6)0.0000 (6)−0.0076 (6)
C20.0264 (10)0.0312 (10)0.0266 (10)0.0037 (8)−0.0050 (8)−0.0062 (8)
C30.0243 (10)0.0404 (12)0.0331 (12)0.0042 (8)−0.0041 (9)−0.0104 (9)
C40.0248 (10)0.0379 (11)0.0294 (11)0.0019 (8)0.0013 (9)−0.0091 (9)
C50.0295 (10)0.0252 (9)0.0244 (10)0.0024 (8)−0.0043 (8)−0.0063 (8)
C60.0258 (9)0.0259 (9)0.0232 (10)0.0002 (7)0.0007 (8)−0.0057 (8)
O20.0353 (8)0.0266 (7)0.0358 (8)0.0074 (6)−0.0075 (7)−0.0111 (6)
N20.0289 (9)0.0230 (8)0.0284 (9)0.0009 (7)−0.0062 (7)−0.0073 (7)
C70.0274 (10)0.0274 (10)0.0254 (10)−0.0018 (8)−0.0034 (8)−0.0076 (8)
C80.0256 (9)0.0260 (9)0.0246 (10)0.0001 (7)−0.0019 (8)−0.0076 (8)
N30.0220 (8)0.0221 (8)0.0256 (9)0.0010 (6)−0.0015 (7)−0.0057 (6)
C90.0315 (11)0.0209 (9)0.0314 (11)0.0025 (8)−0.0032 (9)−0.0038 (8)
C100.0436 (13)0.0301 (11)0.0390 (13)0.0002 (9)0.0036 (11)−0.0007 (9)
C110.0336 (11)0.0307 (11)0.0355 (12)0.0085 (9)−0.0063 (9)−0.0062 (9)
C120.0213 (9)0.0265 (10)0.0304 (11)0.0009 (7)−0.0007 (8)−0.0074 (8)
C130.0282 (10)0.0330 (11)0.0430 (13)0.0013 (8)−0.0073 (9)−0.0145 (10)
C140.0262 (10)0.0269 (10)0.0335 (11)0.0043 (8)−0.0033 (9)−0.0056 (8)

Geometric parameters (Å, °)

S—O51.4422 (16)C7—H710.9900
S—O31.4504 (14)C7—H720.9900
S—O41.4543 (15)C8—N31.505 (2)
S—O61.5574 (16)C8—H810.9900
O6—H60.90 (4)C8—H820.9900
N1—C11.327 (3)N3—C121.530 (2)
N1—C51.446 (2)N3—C91.534 (2)
N1—C41.465 (3)N3—H30.97 (3)
C1—O11.243 (2)C9—C101.512 (3)
C1—C21.514 (3)C9—C111.521 (3)
C2—C31.533 (3)C9—H91.0000
C2—H210.9900C10—H1010.9800
C2—H220.9900C10—H1020.9800
C3—C41.528 (3)C10—H1030.9800
C3—H310.9900C11—H1110.9800
C3—H320.9900C11—H1120.9800
C4—H410.9900C11—H1130.9800
C4—H420.9900C12—C131.514 (3)
C5—C61.523 (3)C12—C141.521 (3)
C5—H510.9900C12—H121.0000
C5—H520.9900C13—H1310.9800
C6—O21.231 (2)C13—H1320.9800
C6—N21.339 (3)C13—H1330.9800
N2—C71.451 (2)C14—H1410.9800
N2—H20.86 (3)C14—H1420.9800
C7—C81.525 (3)C14—H1430.9800
O5—S—O3111.94 (9)N3—C8—C7112.54 (16)
O5—S—O4112.97 (10)N3—C8—H81109.1
O3—S—O4113.20 (9)C7—C8—H81109.1
O5—S—O6108.27 (10)N3—C8—H82109.1
O3—S—O6107.71 (9)C7—C8—H82109.1
O4—S—O6102.03 (9)H81—C8—H82107.8
S—O6—H6113 (2)C8—N3—C12112.04 (15)
C1—N1—C5123.65 (17)C8—N3—C9111.57 (15)
C1—N1—C4113.69 (16)C12—N3—C9113.44 (15)
C5—N1—C4122.23 (17)C8—N3—H3108.8 (14)
O1—C1—N1124.46 (18)C12—N3—H3104.9 (14)
O1—C1—C2126.64 (18)C9—N3—H3105.5 (15)
N1—C1—C2108.87 (17)C10—C9—C11113.40 (19)
C1—C2—C3103.44 (17)C10—C9—N3111.46 (18)
C1—C2—H21111.1C11—C9—N3109.53 (16)
C3—C2—H21111.1C10—C9—H9107.4
C1—C2—H22111.1C11—C9—H9107.4
C3—C2—H22111.1N3—C9—H9107.4
H21—C2—H22109.0C9—C10—H101109.5
C4—C3—C2103.68 (16)C9—C10—H102109.5
C4—C3—H31111.0H101—C10—H102109.5
C2—C3—H31111.0C9—C10—H103109.5
C4—C3—H32111.0H101—C10—H103109.5
C2—C3—H32111.0H102—C10—H103109.5
H31—C3—H32109.0C9—C11—H111109.5
N1—C4—C3102.97 (17)C9—C11—H112109.5
N1—C4—H41111.2H111—C11—H112109.5
C3—C4—H41111.2C9—C11—H113109.5
N1—C4—H42111.2H111—C11—H113109.5
C3—C4—H42111.2H112—C11—H113109.5
H41—C4—H42109.1C13—C12—C14110.05 (18)
N1—C5—C6112.43 (16)C13—C12—N3110.61 (16)
N1—C5—H51109.1C14—C12—N3109.11 (16)
C6—C5—H51109.1C13—C12—H12109.0
N1—C5—H52109.1C14—C12—H12109.0
C6—C5—H52109.1N3—C12—H12109.0
H51—C5—H52107.9C12—C13—H131109.5
O2—C6—N2123.75 (18)C12—C13—H132109.5
O2—C6—C5122.51 (18)H131—C13—H132109.5
N2—C6—C5113.70 (17)C12—C13—H133109.5
C6—N2—C7122.02 (17)H131—C13—H133109.5
C6—N2—H2119.3 (17)H132—C13—H133109.5
C7—N2—H2118.6 (17)C12—C14—H141109.5
N2—C7—C8109.99 (17)C12—C14—H142109.5
N2—C7—H71109.7H141—C14—H142109.5
C8—C7—H71109.7C12—C14—H143109.5
N2—C7—H72109.7H141—C14—H143109.5
C8—C7—H72109.7H142—C14—H143109.5
H71—C7—H72108.2
C5—N1—C1—O1−5.0 (3)O2—C6—N2—C7−3.3 (3)
C4—N1—C1—O1−177.65 (18)C5—C6—N2—C7174.22 (18)
C5—N1—C1—C2173.48 (17)C6—N2—C7—C887.1 (2)
C4—N1—C1—C20.8 (2)N2—C7—C8—N3−172.82 (15)
O1—C1—C2—C3−165.6 (2)C7—C8—N3—C12−115.80 (18)
N1—C1—C2—C316.0 (2)C7—C8—N3—C9115.77 (18)
C1—C2—C3—C4−25.4 (2)C8—N3—C9—C1062.2 (2)
C1—N1—C4—C3−17.3 (2)C12—N3—C9—C10−65.5 (2)
C5—N1—C4—C3169.93 (18)C8—N3—C9—C11−64.1 (2)
C2—C3—C4—N125.7 (2)C12—N3—C9—C11168.21 (18)
C1—N1—C5—C6−94.6 (2)C8—N3—C12—C13−178.70 (17)
C4—N1—C5—C677.4 (2)C9—N3—C12—C13−51.3 (2)
N1—C5—C6—O2−12.1 (3)C8—N3—C12—C1460.1 (2)
N1—C5—C6—N2170.35 (18)C9—N3—C12—C14−172.46 (17)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N2—H2···O30.86 (3)2.10 (3)2.948 (2)172 (2)
N3—H3···O4i0.97 (3)1.79 (3)2.764 (2)175 (2)
O6—H6···O1ii0.90 (4)1.68 (4)2.559 (2)167 (3)
C12—H12···O2iii1.002.403.362 (3)162
C13—H131···O4iv0.982.593.559 (2)171
C14—H143···O50.982.563.530 (2)172

Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) −x+1, −y+1, −z+2; (iii) x−1, y, z; (iv) −x, −y+1, −z+1.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: PV2084).

References

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