Ethyl 2-amino­oxazole-5-carboxyl­ate

The crystal structure of ethyl 2-amino­oxazole-5-carboxyl­ate, C₆H₈N₂O₃, consists of planar sheets internally connected by intermolecular hydrogen bonding running parallel to the (120) plane. Interactions between the sheets are limited to dipole-dipole interactions between antiparallel carbonyl groups.

Key indicators

• Single-crystal X-ray study
• T = 150 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.050
• wR factor = 0.126
• Data-to-parameter ratio = 11.9

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry


 Alert Level C:



WEIGH_01  Alert C Extra text has been found in the
          _refine_ls_weighting_scheme field. This should be in the
          _refine_ls_weighting_details field.
          Weighting scheme given as calc w = 1/[\s^2^(Fo^2^)+(0.0599P)^2^+0.040
          Weighting scheme identified as calc


 0 Alert Level A = Potentially serious problem

 0 Alert Level B = Potential problem

 1 Alert Level C = Please check

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S1. Comment

Ethyl 2-aminooxazole-5-carboxylate, (I), was prepared as part of an ongoing investigation of anticancer antibiotic drugs such as distamycin and netropsin (lexitropsins; see Khalaf et al., 2000). Since these drugs exhibit biological activity by binding to specific (A/T)₄ sequences in the minor groove of DNA, several analogues with subtly differing binding sites were prepared and tested for activity (Fishleigh et al., 2000). The antiviral activity of (I) was tested in vitro by inhibition of plaque formation in cell cultures infected with several RNA and DNA viruses, including Newcastle-Disease and Psuedorabiesvirus (Ulbricht, 1987).

The molecular structure of (I) is essentially planar with only the atoms of the ethyl tail showing any significant deviation from the plane defined by the atoms of the five-membered ring [C5 0.163 (6) Å and C6 0.326 (8) Å]. Sheets of coplanar molecules lie parallel to the (120) plane. These sheets are held together internally by in-plane intermolecular hydrogen bonding involving the amine H atoms and all other available acceptor atoms [N2—H2···N1ⁱ 2.09 (3), N2—H1···O2ⁱⁱ 2.14 (3) and N2—H1···O1ⁱⁱ 2.63 (3) Å for the H···A distances; symmetry codes: (i) -x, -y, -z + 2; (ii) -x, -y, -z + 1]. There are dipole–dipole interactions along the b direction and thus between these sheets involving the carbonyl group [O2···C4ⁱⁱⁱ 3.545 (3) Å; symmetry code: (iii) -x + 1, -y, -z + 1], but no short π interactions involving the ring atoms.

A search of the Cambridge Structural Database (Allen & Kennard, 1993) found no primary amine analogues to (I) but did find a series of secondary and tertiary amines which had been synthesized as aldose reductase inhibitors (Shibata et al., 1982; Ishida et al., 1991). (I) shows several differences in intra-ring bond distances as compared to these compounds. Most notable is the considerable lengthening of the C1—N1 bond [1.316 (3) Å ca a range of 1.263–1.294 Å for the five related fragments found] and a shortening of the C2—N1 bond [1.378 (3) Å ca 1.385–1.410 Å]. The bond lengths appear to show that the N2 amine lone pair is considerably conjugated through the ring.

S2. Experimental

Sodium ethoxide (2.44 g, 0.33 mol) was added to diethyl ether (500 ml) and cooled to 273 K with stirring. Ethyl chloroacetate (40.5 g, 0.33 mole) and ethyl formate (24.3 g, 0.33 mol) were added to the reaction mixture over 2 h. The stirring continued overnight at room temperature. The reaction mixture was diluted with ice/water (500 ml) until the sodium salt dissolved. The diethyl ether layer was separated and the water layer was acidified with concentrated HCl and cooled. The precipitated ester was filtered off. After work up, 43.70 g of crude product was distilled at 5 m mH g (333–338 K). The product, ethyl 2-chloro-3-oxopropanoate C₅H₇ClO₃, recrystallized on standing (22.44 g, 45%) as white needles (m.p. 288–293 K). To the above starting material, urea (8.95 g, 0.149 mol) was added followed by 100 ml of ethanol. This mixture was refluxed for 2 h. Ethanol was removed under reduced pressure and then a sodium bicarbonate solution (10%) was added until effervescence ceased. Diethyl ether was added and 20.98 g of ethyl (2Z)-3-[(aminocarbonyl)amino]-2-chloro-2-propenoate, C₆H₉ClN₂O₃, was removed by filtration (m.p. 484–487 K). The diethyl ether layer was dried over Na₂SO₄ and then the solvent was removed under reduced pressure to leave a green oil. Purification by flash silica-gel column chromatography using ethyl acetate/n-hexane (1:2, R_f = 1/5) afforded crystalline (I) (1.72 g, 7.4% yield), m.p. 425–428 K (literature m.p. 428 K; Dornow et al., 1953). ¹H NMR (CDCl₃): 1.35–1.36 (3H, t, CH₃); 4.31–4.36 (2H, q, CH₂); 5.33 (2H, s, NH₂); 7.48 (1H, oxazole); IR (KBr): 3387, 3119, 1715, 1676, 1568, 1408, 1376, 1325, 1261, 1178, 1146 cm^-1.

S3. Refinement

The H1 and H2 atoms of the amine group were placed as found in difference syntheses and refined isotropically. All other H atoms were placed in calculated positions and refined in riding modes.

Computing details

Data collection: DENZO (Otwinowski & Minor, 1997) and COLLECT (Hooft, 1988); cell refinement: DENZO and COLLECT; data reduction: DENZO and COLLECT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: SHELXL97.

Figures

Fig. 1. ORTEPII (Johnson, 1976) view of (I) with non-H atoms as 50% ellipsoids and H atoms as small spheres of arbitary size.

(I)

Crystal data

C6H8N2O3	Z = 2
Mr = 156.14	F(000) = 164
Triclinic, P1	Dx = 1.422 Mg m^−3
a = 6.1295 (6) Å	Mo Kα radiation, λ = 0.71073 Å
b = 7.8227 (6) Å	Cell parameters from 1086 reflections
c = 8.3961 (8) Å	θ = 1.0–26.0°
α = 113.592 (7)°	µ = 0.12 mm^−1
β = 93.831 (4)°	T = 150 K
γ = 95.557 (4)°	Cut needle, colourless
V = 364.74 (6) Å^3	0.20 × 0.15 × 0.08 mm

Data collection

Nonius KappaCCD diffractometer	905 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.064
Graphite monochromator	θmax = 25.3°, θmin = 2.7°
ϕ and ω scans to fill Ewald sphere	h = −7→7
3501 measured reflections	k = −9→9
1300 independent reflections	l = −10→9

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.050	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.126	H atoms treated by a mixture of independent and constrained refinement
S = 1.06	Calculated w = 1/[σ^2(Fo^2) + (0.0599P)^2 + 0.0404P] where P = (Fo^2 + 2Fc^2)/3
1300 reflections	(Δ/σ)max = 0.001
109 parameters	Δρmax = 0.21 e Å^−3
0 restraints	Δρmin = −0.20 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
O1	0.1957 (2)	0.0855 (2)	0.6651 (2)	0.0328 (5)
O2	0.4822 (3)	0.2378 (2)	0.4979 (2)	0.0421 (5)
O3	0.7277 (2)	0.3524 (2)	0.7411 (2)	0.0375 (5)
N1	0.2431 (3)	0.0900 (3)	0.9343 (3)	0.0367 (6)
N2	−0.0923 (3)	−0.0567 (3)	0.7513 (3)	0.0379 (6)
H1	−0.177 (4)	−0.081 (3)	0.650 (4)	0.044 (7)*
H2	−0.154 (4)	−0.078 (4)	0.833 (4)	0.053 (9)*
C1	0.1110 (4)	0.0373 (3)	0.7880 (3)	0.0318 (6)
C2	0.4295 (4)	0.1815 (3)	0.9050 (3)	0.0350 (6)
H3	0.5576	0.2374	0.9870	0.042*
C3	0.4056 (4)	0.1810 (3)	0.7453 (3)	0.0321 (6)
C4	0.5378 (4)	0.2567 (3)	0.6467 (3)	0.0330 (6)
C5	0.8751 (4)	0.4369 (3)	0.6566 (3)	0.0372 (6)
H4	0.7990	0.5214	0.6171	0.045*
H5	0.9237	0.3380	0.5535	0.045*
C6	1.0705 (4)	0.5467 (3)	0.7889 (3)	0.0383 (7)
H6	1.0213	0.6483	0.8874	0.057*
H7	1.1774	0.6005	0.7341	0.057*
H8	1.1400	0.4627	0.8313	0.057*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0256 (9)	0.0362 (10)	0.0330 (10)	−0.0055 (7)	−0.0047 (7)	0.0138 (8)
O2	0.0380 (10)	0.0526 (12)	0.0329 (11)	−0.0065 (8)	−0.0061 (8)	0.0188 (9)
O3	0.0302 (9)	0.0463 (11)	0.0328 (10)	−0.0108 (8)	−0.0054 (8)	0.0180 (9)
N1	0.0269 (11)	0.0463 (13)	0.0331 (12)	−0.0052 (10)	−0.0066 (9)	0.0162 (11)
N2	0.0296 (13)	0.0458 (14)	0.0365 (14)	−0.0070 (10)	−0.0060 (11)	0.0193 (12)
C1	0.0280 (13)	0.0317 (14)	0.0365 (14)	0.0001 (11)	0.0001 (11)	0.0165 (12)
C2	0.0242 (13)	0.0412 (15)	0.0349 (15)	−0.0055 (11)	−0.0074 (11)	0.0146 (13)
C3	0.0251 (13)	0.0326 (14)	0.0337 (14)	−0.0025 (11)	−0.0042 (10)	0.0113 (12)
C4	0.0264 (13)	0.0305 (14)	0.0364 (15)	−0.0021 (11)	−0.0063 (11)	0.0108 (12)
C5	0.0313 (14)	0.0420 (15)	0.0353 (14)	−0.0078 (12)	−0.0016 (11)	0.0164 (12)
C6	0.0344 (14)	0.0387 (15)	0.0402 (15)	−0.0001 (12)	0.0002 (12)	0.0164 (13)

Geometric parameters (Å, º)

O1—C1	1.350 (3)	C2—C3	1.337 (3)
O1—C3	1.401 (3)	C2—H3	0.9500
O2—C4	1.218 (3)	C3—C4	1.443 (3)
O3—C4	1.333 (3)	C5—C6	1.505 (3)
O3—C5	1.449 (3)	C5—H4	0.9900
N1—C1	1.316 (3)	C5—H5	0.9900
N1—C2	1.378 (3)	C6—H6	0.9800
N2—C1	1.334 (3)	C6—H7	0.9800
N2—H1	0.90 (3)	C6—H8	0.9800
N2—H2	0.87 (3)
C1—O1—C3	103.55 (16)	O2—C4—O3	124.5 (2)
C4—O3—C5	116.24 (17)	O2—C4—C3	124.6 (2)
C1—N1—C2	103.52 (18)	O3—C4—C3	110.9 (2)
C1—N2—H1	121.7 (16)	O3—C5—C6	107.33 (19)
C1—N2—H2	119.1 (18)	O3—C5—H4	110.2
H1—N2—H2	118 (2)	C6—C5—H4	110.2
N1—C1—N2	126.9 (2)	O3—C5—H5	110.2
N1—C1—O1	114.76 (19)	C6—C5—H5	110.2
N2—C1—O1	118.4 (2)	H4—C5—H5	108.5
C3—C2—N1	110.8 (2)	C5—C6—H6	109.5
C3—C2—H3	124.6	C5—C6—H7	109.5
N1—C2—H3	124.6	H6—C6—H7	109.5
C2—C3—O1	107.37 (19)	C5—C6—H8	109.5
C2—C3—C4	135.6 (2)	H6—C6—H8	109.5
O1—C3—C4	117.01 (19)	H7—C6—H8	109.5
C2—N1—C1—N2	−179.7 (2)	C1—O1—C3—C4	−178.2 (2)
C2—N1—C1—O1	0.4 (3)	C5—O3—C4—O2	−0.5 (3)
C3—O1—C1—N1	−0.5 (3)	C5—O3—C4—C3	−179.6 (2)
C3—O1—C1—N2	179.6 (2)	C2—C3—C4—O2	179.6 (3)
C1—N1—C2—C3	−0.2 (3)	O1—C3—C4—O2	−2.5 (4)
N1—C2—C3—O1	−0.1 (3)	C2—C3—C4—O3	−1.3 (4)
N1—C2—C3—C4	178.0 (3)	O1—C3—C4—O3	176.64 (18)
C1—O1—C3—C2	0.3 (2)	C4—O3—C5—C6	176.58 (19)