3-(1-Ethyl-1H-pyrrole-2-carboxamido)propionic acid monohydrate

Abstract

The title compound, C₁₀H₁₄N₂O₃·H₂O, was synthesized by alkyl­ation of methyl 3-(1H-pyrrole-2-carboxamido)­propion­ate with ethyl bromide, followed by saponification and acidification. In the crystal structure, inter­molecular O—H⋯O and N—H⋯O hydrogen bonds link the mol­ecules, forming layers parallel to the ac plane.

Related literature

For pyrroles sourced from marine organisms, see: Liu et al. (2005 ▶). For the bioactivity of pyrrole derivatives, see: Banwell et al. (2006 ▶); Sosa et al. (2002 ▶). For related structures, see: Zeng et al. (2005 ▶); Liu et al. (2006 ▶); Tang et al. (2008 ▶).

Experimental

Crystal data

• C₁₀H₁₄N₂O₃·H₂O

• M _r = 228.25

• Monoclinic,

• a = 5.2814 (12) Å

• b = 31.795 (7) Å

• c = 7.0226 (16) Å

• β = 106.392 (4)°

• V = 1131.3 (4) ų

• Z = 4

• Mo Kα radiation

• μ = 0.10 mm⁻¹

• T = 173 K

• 0.47 × 0.44 × 0.15 mm

Data collection

• Bruker SMART 1K CCD area-detector diffractometer

• Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.953, T _max = 0.985

• 5260 measured reflections

• 2215 independent reflections

• 1772 reflections with I > 2σ(I)

• R _int = 0.028

Refinement

• R[F ² > 2σ(F ²)] = 0.052

• wR(F ²) = 0.163

• S = 1.14

• 2215 reflections

• 155 parameters

• H atoms treated by a mixture of independent and constrained refinement

• Δρ_max = 0.30 e Å⁻³

• Δρ_min = −0.26 e Å⁻³

Data collection: SMART (Bruker,1999 ▶); cell refinement: SAINT-Plus (Bruker, 1999 ▶); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H3⋯O4i	0.84	1.83	2.669 (3)	173
N2—H2⋯O4ii	0.88	2.28	3.091 (3)	154
O4—H4A⋯O1iii	0.96 (3)	1.79 (3)	2.737 (2)	170 (3)
O4—H4B⋯O2iv	0.81 (3)	2.08 (4)	2.863 (3)	164 (3)

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) .

supplementary crystallographic information

Comment

Pyrrole derivatives are well known constituents of many marine organisms (Liu et al., 2005), and some of them show important bioactivities, such as antitumor (Banwell et al., 2006) and protein kinase inhibiting (Sosa et al., 2002) activities. As a continuation of our studies in this field, which have recently resulted in the communication of the crystal structure of 3-(4-bromo-1H-pyrrole-2-carboxamido)propanoic acid (Zeng et al., 2005), 3-(1-methyl-1H-pyrrole-2-carboxamido)propanoic acid (Liu et al., 2006) and methyl 2-(1H-pyrrole-2-carboxamido)acetate (Tang et al., 2008), we report herein the synthesis and crystal structure of the title compound.

In the molecule of the title compound (Fig. 1), bond lengths and angles are unexceptional. In the crystal structure, molecules are linked by intermolecular O—H···O and N—H···O hydrogen bonds (Table 1) involving water molecules to form two-dimensional layers parallel to the ac plane (Fig. 2, Fig. 3)

Experimental

A suspension of potassium carbonate (2.10 mg, 15.0 mmol), ethyl bromide (1.87 ml, 25.0 mmol) and methyl 3-(1H-pyrrole-2-carbonyl)aminopropionate (0.98 g, 5.0 mmol) in acetonitrile (12 ml) was refluxed for 40 h. After evaporation of the solvent, the residue was dissolved in ethyl acetate (15 ml) and washed twice with water. The organic layer was dried over sodium sulfate and evaporated in vacuo. Then the alkylated product was added to a solution of 10% aqueous sodium hydroxide (10 ml) and ethanol (2 ml), and the mixture was stirred at room temperature for 24 h. The hydrolyzed mixture was made acidic with 10% hydrochloric acid to pH 2–3. After filtration, the precipitate was collected as a yellow solid (m.p. 320 K, 92.3% yield). Pale yellow crystals suitable for X-ray analysis were obtained over a period of one week by slow evaporation at room temperature of an ethanol/water solution (3:2 v/v).

Refinement

All non-H atoms were refined with anisotropic displacement parameters. The water H atoms were located in a difference Fourier map and refined freely. All other H atoms were positioned geometrically and refined using a riding model, with C—H = 0.95-0.99Å, N—H = 0.88 Å, O—H = 0.84 Å, and with U_iso = 1.2 U_eq(C, N) or 1.5 U_eq(C, O) for methyl and hydroxy H atoms.

Figures

Fig. 1.

The molecular structure of the title compound, with the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level.

Fig. 2.

Crystal packing of the title compound viewed along the a axis. Dashed lines indicate hydrogen bonds.

Fig. 3.

Crystal packing of the title compound viewed along the c axis. Dashed lines indicate hydrogen bonds.

Crystal data

C10H14N2O3·H2O	F(000) = 488
Mr = 228.25	Dx = 1.340 Mg m−3
Monoclinic, P21/c	Melting point: 320 K
Hall symbol: -P 2ybc	Mo Kα radiation, λ = 0.71073 Å
a = 5.2814 (12) Å	Cell parameters from 2595 reflections
b = 31.795 (7) Å	θ = 2.6–28.0°
c = 7.0226 (16) Å	µ = 0.10 mm−1
β = 106.392 (4)°	T = 173 K
V = 1131.3 (4) Å3	Plate, pale yellow
Z = 4	0.47 × 0.44 × 0.15 mm

Data collection

Bruker SMART 1K CCD area-detector diffractometer	2215 independent reflections
Radiation source: fine-focus sealed tube	1772 reflections with I > 2σ(I)
graphite	Rint = 0.028
φ and ω scans	θmax = 26.0°, θmin = 1.3°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −6→4
Tmin = 0.953, Tmax = 0.985	k = −39→33
5260 measured reflections	l = −8→8

Refinement

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.052	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.163	H atoms treated by a mixture of independent and constrained refinement
S = 1.14	w = 1/[σ2(Fo2) + (0.087P)2 + 0.3989P] where P = (Fo2 + 2Fc2)/3
2215 reflections	(Δ/σ)max = 0.001
155 parameters	Δρmax = 0.30 e Å−3
0 restraints	Δρmin = −0.26 e Å−3

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 (Ų)

	x	y	z	Uiso*/Ueq
O2	−0.2174 (3)	0.48016 (5)	0.1312 (3)	0.0377 (4)
O1	0.4540 (3)	0.36651 (5)	0.1693 (2)	0.0350 (4)
N1	0.9087 (4)	0.32234 (6)	0.4136 (3)	0.0281 (5)
O3	0.0271 (4)	0.53444 (5)	0.2775 (3)	0.0370 (5)
H3	−0.1105	0.5479	0.2213	0.055*
N2	0.3901 (4)	0.39704 (6)	0.4423 (3)	0.0307 (5)
H2	0.4458	0.3994	0.5723	0.037*
C4	0.7462 (4)	0.34863 (6)	0.4836 (3)	0.0254 (5)
C6	0.1614 (4)	0.42138 (7)	0.3356 (3)	0.0295 (5)
H6A	0.0205	0.4183	0.4023	0.035*
H6B	0.0936	0.4103	0.1990	0.035*
C5	0.5200 (4)	0.37122 (6)	0.3528 (3)	0.0250 (5)
C7	0.2283 (4)	0.46754 (7)	0.3265 (3)	0.0277 (5)
H7A	0.3132	0.4778	0.4627	0.033*
H7B	0.3567	0.4707	0.2485	0.033*
C8	−0.0108 (5)	0.49402 (7)	0.2343 (3)	0.0267 (5)
C3	0.8518 (5)	0.35132 (7)	0.6881 (3)	0.0319 (6)
H3A	0.7824	0.3673	0.7761	0.038*
C9	0.8797 (5)	0.30933 (8)	0.2082 (3)	0.0361 (6)
H9A	1.0516	0.2987	0.1980	0.043*
H9B	0.8319	0.3342	0.1206	0.043*
C1	1.1074 (5)	0.30880 (8)	0.5705 (4)	0.0350 (6)
H1	1.2446	0.2901	0.5629	0.042*
C10	0.6725 (6)	0.27552 (8)	0.1358 (4)	0.0407 (6)
H10A	0.7317	0.2493	0.2084	0.061*
H10B	0.6457	0.2708	−0.0065	0.061*
H10C	0.5060	0.2846	0.1585	0.061*
C2	1.0782 (5)	0.32635 (8)	0.7411 (4)	0.0366 (6)
H2A	1.1912	0.3223	0.8715	0.044*
O4	0.5768 (4)	0.57638 (6)	0.1280 (3)	0.0343 (4)
H4A	0.584 (6)	0.5980 (10)	0.034 (5)	0.057 (9)*
H4B	0.465 (7)	0.5596 (10)	0.074 (5)	0.051 (9)*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
O2	0.0288 (9)	0.0372 (9)	0.0415 (10)	0.0021 (7)	0.0009 (8)	−0.0031 (7)
O1	0.0450 (10)	0.0355 (9)	0.0196 (8)	0.0068 (8)	0.0013 (7)	−0.0001 (6)
N1	0.0253 (10)	0.0322 (10)	0.0270 (10)	−0.0003 (8)	0.0077 (8)	0.0016 (7)
O3	0.0413 (11)	0.0273 (8)	0.0404 (10)	0.0022 (7)	0.0087 (8)	−0.0014 (7)
N2	0.0350 (11)	0.0324 (10)	0.0220 (9)	0.0048 (8)	0.0038 (8)	0.0004 (8)
C4	0.0285 (12)	0.0239 (10)	0.0227 (11)	−0.0027 (9)	0.0057 (9)	0.0011 (8)
C6	0.0255 (12)	0.0301 (12)	0.0309 (12)	0.0011 (9)	0.0048 (9)	−0.0013 (9)
C5	0.0290 (11)	0.0225 (10)	0.0222 (11)	−0.0043 (9)	0.0049 (9)	0.0010 (8)
C7	0.0255 (11)	0.0311 (12)	0.0265 (11)	−0.0032 (9)	0.0076 (9)	−0.0026 (9)
C8	0.0311 (12)	0.0292 (11)	0.0219 (10)	−0.0009 (9)	0.0110 (9)	−0.0003 (8)
C3	0.0376 (13)	0.0312 (12)	0.0235 (11)	−0.0002 (10)	0.0029 (10)	0.0005 (9)
C9	0.0368 (14)	0.0459 (14)	0.0306 (12)	0.0049 (11)	0.0179 (11)	0.0016 (10)
C1	0.0258 (12)	0.0371 (13)	0.0393 (13)	0.0020 (10)	0.0044 (10)	0.0052 (10)
C10	0.0506 (16)	0.0392 (14)	0.0304 (13)	0.0054 (12)	0.0082 (12)	−0.0061 (10)
C2	0.0341 (13)	0.0394 (14)	0.0282 (12)	−0.0038 (11)	−0.0044 (10)	0.0039 (10)
O4	0.0431 (11)	0.0282 (9)	0.0289 (9)	−0.0011 (8)	0.0058 (8)	0.0009 (7)

Geometric parameters (Å, °)

O2—C8	1.210 (3)	C7—H7A	0.9900
O1—C5	1.245 (3)	C7—H7B	0.9900
N1—C1	1.359 (3)	C3—C2	1.395 (4)
N1—C4	1.384 (3)	C3—H3A	0.9500
N1—C9	1.466 (3)	C9—C10	1.516 (4)
O3—C8	1.323 (3)	C9—H9A	0.9900
O3—H3	0.8400	C9—H9B	0.9900
N2—C5	1.335 (3)	C1—C2	1.370 (4)
N2—C6	1.452 (3)	C1—H1	0.9500
N2—H2	0.8800	C10—H10A	0.9800
C4—C3	1.388 (3)	C10—H10B	0.9800
C4—C5	1.473 (3)	C10—H10C	0.9800
C6—C7	1.515 (3)	C2—H2A	0.9500
C6—H6A	0.9900	O4—H4A	0.96 (3)
C6—H6B	0.9900	O4—H4B	0.81 (3)
C7—C8	1.504 (3)
C1—N1—C4	108.54 (19)	O2—C8—O3	123.0 (2)
C1—N1—C9	123.4 (2)	O2—C8—C7	124.0 (2)
C4—N1—C9	128.08 (19)	O3—C8—C7	113.00 (19)
C8—O3—H3	109.5	C4—C3—C2	107.7 (2)
C5—N2—C6	123.23 (18)	C4—C3—H3A	126.1
C5—N2—H2	118.4	C2—C3—H3A	126.1
C6—N2—H2	118.4	N1—C9—C10	113.3 (2)
N1—C4—C3	107.2 (2)	N1—C9—H9A	108.9
N1—C4—C5	123.25 (19)	C10—C9—H9A	108.9
C3—C4—C5	129.3 (2)	N1—C9—H9B	108.9
N2—C6—C7	111.60 (19)	C10—C9—H9B	108.9
N2—C6—H6A	109.3	H9A—C9—H9B	107.7
C7—C6—H6A	109.3	N1—C1—C2	109.2 (2)
N2—C6—H6B	109.3	N1—C1—H1	125.4
C7—C6—H6B	109.3	C2—C1—H1	125.4
H6A—C6—H6B	108.0	C9—C10—H10A	109.5
O1—C5—N2	122.0 (2)	C9—C10—H10B	109.5
O1—C5—C4	121.9 (2)	H10A—C10—H10B	109.5
N2—C5—C4	116.13 (18)	C9—C10—H10C	109.5
C8—C7—C6	112.51 (19)	H10A—C10—H10C	109.5
C8—C7—H7A	109.1	H10B—C10—H10C	109.5
C6—C7—H7A	109.1	C1—C2—C3	107.3 (2)
C8—C7—H7B	109.1	C1—C2—H2A	126.3
C6—C7—H7B	109.1	C3—C2—H2A	126.3
H7A—C7—H7B	107.8	H4A—O4—H4B	108 (3)
C1—N1—C4—C3	0.7 (2)	N2—C6—C7—C8	−174.39 (18)
C9—N1—C4—C3	179.4 (2)	C6—C7—C8—O2	−19.0 (3)
C1—N1—C4—C5	175.90 (19)	C6—C7—C8—O3	161.00 (19)
C9—N1—C4—C5	−5.3 (3)	N1—C4—C3—C2	−0.3 (3)
C5—N2—C6—C7	−106.2 (2)	C5—C4—C3—C2	−175.1 (2)
C6—N2—C5—O1	0.6 (3)	C1—N1—C9—C10	101.2 (3)
C6—N2—C5—C4	−179.44 (19)	C4—N1—C9—C10	−77.4 (3)
N1—C4—C5—O1	3.2 (3)	C4—N1—C1—C2	−0.8 (3)
C3—C4—C5—O1	177.3 (2)	C9—N1—C1—C2	−179.6 (2)
N1—C4—C5—N2	−176.8 (2)	N1—C1—C2—C3	0.6 (3)
C3—C4—C5—N2	−2.6 (3)	C4—C3—C2—C1	−0.2 (3)

Hydrogen-bond geometry (Å, °)

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3···O4i	0.84	1.83	2.669 (3)	173
N2—H2···O4ii	0.88	2.28	3.091 (3)	154
O4—H4A···O1iii	0.96 (3)	1.79 (3)	2.737 (2)	170 (3)
O4—H4B···O2iv	0.81 (3)	2.08 (4)	2.863 (3)	164 (3)

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