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The isoxazole proton is sufficiently acidic to give the title salt, hydroxy­l­ammonium 4-(ethyl­oxy­carbonyl)-5-oxo-2,5-di­hydro­isoxazolide, NH3OH+·C6H6NO4-, in the presence of hydroxyl­amine. The deprotonation of the heterocyclic ring has a profound effect on its geometry, notably increasing the N-O distance by 0.05 Å to 1.433 (2) Å.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536803018828/bt6333sup1.cif
Contains datablocks I, global

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S1600536803018828/bt6333Isup2.hkl
Contains datablock I

CCDC reference: 222912

Key indicators

  • Single-crystal X-ray study
  • T = 150 K
  • Mean [sigma](C-C) = 0.002 Å
  • R factor = 0.038
  • wR factor = 0.088
  • Data-to-parameter ratio = 12.0

checkCIF/PLATON results

No syntax errors found



Alert level C PLAT042_ALERT_1_C Calc. and Rep. MoietyFormula Strings Differ .... ? PLAT125_ALERT_4_C No _symmetry_space_group_name_Hall Given ....... ?
0 ALERT level A = In general: serious problem 0 ALERT level B = Potentially serious problem 2 ALERT level C = Check and explain 0 ALERT level G = General alerts; check 1 ALERT type 1 CIF construction/syntax error, inconsistent or missing data 0 ALERT type 2 Indicator that the structure model may be wrong or deficient 0 ALERT type 3 Indicator that the structure quality may be low 1 ALERT type 4 Improvement, methodology, query or suggestion

Comment top

As part of a search for biologically active heterocyclic compounds, the title compound, (I), was prepared. Isoxazoles have a plethora of biological activities, for instance antibacterial and antifungal activity (Kang et al., 2000; Tsubotani et al., 1991) and anti-inflammatory activity (Pathak el al., 1998). They are also known to suppress the immune system (Millan et al., 2000). Heterocyclic compounds of this sort are also incorporated in the synthesis of DNA minor-groove binders, such as analogues of the well known anticancer and antibiotic drugs distamycin and netropsin (Khalaf et al., 2002).

The vicinal O atom and double bond of (I) appears to make the amine proton more acidic than in other isoxazoles and so the compound isolated is a salt with the proton found on the hydroxylamine group. We know of no other crystal structure of a deprotonated isoxazole. The loss of a proton has a major effect on the bonding within the planar heterocycle. Compared to its closest relative (a neutral amide substituted isoxazole; Tsubotani et al., 1991), (I) has lengthened N1—O2, C2C3 and C1O1 bonds [1.433 (2), 1.409 (2) and 1.257 (2) Å in (I) compared with 1.385, 1.385 and 1.226 Å in the neutral compound] and shortened N1—C2, C1—C3 and C1—O2 distances [compare 1.302 (2), 1.394 (2) and 1.370 (2) Å with 1.346, 1.402 and 1.404 Å]. The longer N—O bond must be due to repulsion from the increased negative charge on N1, whilst the other changes can be rationalized by resonance effects caused by the extra electron pushing ability of N1. The NH3OH cation utilizes all four protons in acting as a hydrogen-bond donor to all the possible acceptor atoms of the anion with the exception of O4. The shortest, most linear and hence presumably the strongest of these interactions is between the hydroxy proton and O1.

Experimental top

A mixture of triethyl orthoformate (44.5 g, 0.300 mol), acetic anhydride (68.0 g, 0.666 mmol), ethyl malonate (50.6 g, 0.316 mmol) and zinc chloride (0.200 g) was placed in a three-necked flask equipped with a thermometer and a (30 cm) column. The column was attached to a still head and a condenser. The reaction mixture was well stirred and then heated as follows: 375–388 K for 2.5 h, 388–400 K for 12 h, 400–418 K for 2 h, and 418–428 K for 2 h, after which time, acetic anhydride (13.5 g, 0.123 mol) and triethyl orthoformate (8.9 g, 0.060 mol) were added. The mixture was cooled to room temperature, filtered and distilled under reduced pressure. 2-(Ethoxymethylene)malonate was boiled at 383–391 K at 1.0 m mH g and was collected as a colourless oil (31.1 g, 46% yield) [literature 381–383 K at 0.25 m mH g (Fuson et al., 1946)]. Hydroxylamine hydrochloride (0.965 g, 13.8 mmol) was dissolved in a mixture of water (5 ml) and ethanol (5 ml). Potassium hydroxide (0.776 g, 13.8 mmol) was dissolved in ethanol (10 ml). These were then added to the hydroxylamine hydrochloride solution with stirring. Potassium chloride precipitated and was filtered off. The filtrate was added to diethyl 2-(ethoxymethylene)malonate (Fuson et al., 1946) (1.004 g, 4.629 mmol). The reaction mixture was left stirring at room temperature overnight. The resultant mixture was heated on water bath for 2 h, then the solvents were removed under reduced pressure. The product so obtained was re-crystallized from acetone/n-hexane to give a white crystalline solid (0.705 g, 97% yield), m.p. > 503 K [literature m.p. 433–438 K; (Claisen, 1893) and 473–478 K (Claisen, 1897)]. 1H NMR (DMSO-d6): 1.13–1.16 (3H, t, J = 7.0 Hz, CH3); 3.95–4.01 (2H, q, J = 7.0 Hz, CH2); 7.93 (1H, s, CH); 9.83 (1H, broad); 10.08 (3H, broad); IR (KBr): 3097, 2998, 2702, 1686, 1647, 1544, 1499, 1210, 1170, 1070 cm−1.

Refinement top

All H atoms were refined isotropically.

Computing details top

Data collection: DENZO and COLLECT (Otwinowski & Minor, 1997; Nonius, 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 top
[Figure 1] Fig. 1. The molecular structure of (I), with 50% probability ellipsoids.
(I) top
Crystal data top
NH4O+·C6H6NO4F(000) = 400
Mr = 190.16Dx = 1.508 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 4.6788 (2) ÅCell parameters from 1706 reflections
b = 13.3277 (6) Åθ = 1.0–27.5°
c = 13.5380 (7) ŵ = 0.13 mm1
β = 97.212 (2)°T = 150 K
V = 837.52 (7) Å3Needle, colourless
Z = 40.55 × 0.20 × 0.10 mm
Data collection top
Nonius KappaCCD
diffractometer
1536 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.027
Graphite monochromatorθmax = 27.4°, θmin = 3.0°
ϕ and ω scansh = 06
5375 measured reflectionsk = 1716
1894 independent reflectionsl = 1717
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.038Hydrogen site location: difference Fourier map
wR(F2) = 0.088All H-atom parameters refined
S = 1.05 w = 1/[σ2(Fo2) + (0.0278P)2 + 0.4766P]
where P = (Fo2 + 2Fc2)/3
1894 reflections(Δ/σ)max < 0.001
158 parametersΔρmax = 0.26 e Å3
0 restraintsΔρmin = 0.21 e Å3
Crystal data top
NH4O+·C6H6NO4V = 837.52 (7) Å3
Mr = 190.16Z = 4
Monoclinic, P21/cMo Kα radiation
a = 4.6788 (2) ŵ = 0.13 mm1
b = 13.3277 (6) ÅT = 150 K
c = 13.5380 (7) Å0.55 × 0.20 × 0.10 mm
β = 97.212 (2)°
Data collection top
Nonius KappaCCD
diffractometer
1536 reflections with I > 2σ(I)
5375 measured reflectionsRint = 0.027
1894 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0380 restraints
wR(F2) = 0.088All H-atom parameters refined
S = 1.05Δρmax = 0.26 e Å3
1894 reflectionsΔρmin = 0.21 e Å3
158 parameters
Special details top

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) top
xyzUiso*/Ueq
O11.1691 (2)0.08463 (8)0.39923 (8)0.0220 (3)
O21.1901 (2)0.20808 (8)0.28669 (8)0.0214 (2)
O30.7211 (2)0.15399 (8)0.53349 (8)0.0220 (3)
O40.5776 (2)0.31279 (8)0.49485 (8)0.0217 (2)
O50.4513 (2)0.49643 (9)0.19875 (8)0.0258 (3)
N11.0604 (3)0.30382 (10)0.26271 (10)0.0238 (3)
N20.2721 (3)0.44131 (10)0.12622 (10)0.0194 (3)
C11.0782 (3)0.16876 (11)0.36709 (10)0.0171 (3)
C20.8833 (3)0.31791 (11)0.32830 (11)0.0207 (3)
C30.8807 (3)0.23770 (11)0.39600 (11)0.0171 (3)
C40.7226 (3)0.22838 (11)0.48015 (11)0.0173 (3)
C50.4258 (3)0.31709 (12)0.58205 (11)0.0221 (3)
C60.2835 (4)0.41826 (13)0.58026 (13)0.0274 (4)
H10.772 (4)0.3790 (14)0.3243 (13)0.027 (5)*
H20.566 (4)0.3078 (13)0.6433 (14)0.029 (5)*
H30.281 (4)0.2628 (13)0.5771 (12)0.020 (4)*
H40.429 (4)0.4703 (15)0.5854 (15)0.037 (5)*
H50.161 (4)0.4263 (14)0.5173 (15)0.032 (5)*
H60.170 (4)0.4232 (14)0.6349 (15)0.037 (5)*
H70.576 (6)0.535 (2)0.160 (2)0.072 (8)*
H80.184 (4)0.3891 (15)0.1635 (15)0.035 (5)*
H90.127 (4)0.4846 (15)0.0969 (15)0.036 (5)*
H100.378 (4)0.4133 (15)0.0790 (15)0.038 (5)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0217 (5)0.0178 (5)0.0270 (6)0.0036 (4)0.0051 (4)0.0023 (4)
O20.0242 (5)0.0200 (5)0.0214 (5)0.0023 (4)0.0088 (4)0.0011 (4)
O30.0211 (5)0.0211 (5)0.0249 (6)0.0020 (4)0.0074 (4)0.0068 (5)
O40.0263 (6)0.0200 (5)0.0209 (5)0.0053 (4)0.0111 (4)0.0037 (4)
O50.0276 (6)0.0281 (6)0.0211 (6)0.0095 (5)0.0011 (4)0.0022 (5)
N10.0293 (7)0.0196 (7)0.0235 (7)0.0030 (5)0.0077 (5)0.0044 (5)
N20.0212 (6)0.0179 (6)0.0196 (6)0.0030 (5)0.0044 (5)0.0031 (5)
C10.0159 (7)0.0177 (7)0.0177 (7)0.0037 (5)0.0020 (5)0.0006 (6)
C20.0236 (8)0.0176 (7)0.0215 (8)0.0012 (6)0.0057 (6)0.0015 (6)
C30.0167 (7)0.0162 (7)0.0187 (7)0.0000 (5)0.0035 (5)0.0008 (6)
C40.0134 (6)0.0185 (7)0.0198 (7)0.0003 (5)0.0016 (5)0.0001 (6)
C50.0238 (8)0.0245 (8)0.0196 (8)0.0035 (6)0.0093 (6)0.0019 (6)
C60.0350 (9)0.0242 (9)0.0250 (9)0.0051 (7)0.0118 (7)0.0006 (7)
Geometric parameters (Å, º) top
O1—C11.2574 (17)N2—H100.93 (2)
O2—C11.3698 (17)C1—C31.394 (2)
O2—N11.4326 (16)C2—C31.409 (2)
O3—C41.2270 (18)C2—H10.965 (19)
O4—C41.3414 (17)C3—C41.4395 (19)
O4—C51.4533 (17)C5—C61.503 (2)
O5—N21.4143 (16)C5—H20.999 (19)
O5—H70.98 (3)C5—H30.988 (17)
N1—C21.3022 (19)C6—H40.97 (2)
N2—H80.98 (2)C6—H50.97 (2)
N2—H90.94 (2)C6—H60.97 (2)
C1—O2—N1109.12 (10)C1—C3—C4126.16 (13)
C4—O4—C5117.48 (11)C2—C3—C4128.86 (13)
N2—O5—H7104.0 (15)O3—C4—O4123.37 (13)
C2—N1—O2105.17 (12)O3—C4—C3125.23 (13)
O5—N2—H8105.2 (11)O4—C4—C3111.39 (12)
O5—N2—H9107.9 (12)O4—C5—C6106.44 (12)
H8—N2—H9109.1 (16)O4—C5—H2109.3 (11)
O5—N2—H10111.2 (12)C6—C5—H2111.6 (11)
H8—N2—H10111.2 (17)O4—C5—H3108.5 (10)
H9—N2—H10111.9 (17)C6—C5—H3111.0 (9)
O1—C1—O2118.01 (13)H2—C5—H3109.8 (14)
O1—C1—C3134.28 (14)C5—C6—H4109.6 (12)
O2—C1—C3107.70 (12)C5—C6—H5109.0 (11)
N1—C2—C3113.09 (14)H4—C6—H5108.5 (16)
N1—C2—H1118.0 (11)C5—C6—H6109.5 (12)
C3—C2—H1128.9 (11)H4—C6—H6110.3 (16)
C1—C3—C2104.92 (13)H5—C6—H6109.9 (16)
C1—O2—N1—C20.52 (15)N1—C2—C3—C4177.30 (14)
N1—O2—C1—O1179.54 (12)C5—O4—C4—O33.7 (2)
N1—O2—C1—C30.52 (15)C5—O4—C4—C3175.35 (13)
O2—N1—C2—C30.32 (17)C1—C3—C4—O36.7 (2)
O1—C1—C3—C2179.11 (16)C2—C3—C4—O3176.55 (15)
O2—C1—C3—C20.32 (15)C1—C3—C4—O4172.29 (13)
O1—C1—C3—C41.7 (3)C2—C3—C4—O44.5 (2)
O2—C1—C3—C4177.07 (13)C4—O4—C5—C6179.87 (13)
N1—C2—C3—C10.01 (17)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O5—H7···O1i0.98 (3)1.66 (3)2.6244 (15)170 (2)
O5—H7···O2i0.98 (3)2.62 (3)3.2753 (15)124.8 (19)
N2—H8···N1ii0.98 (2)1.90 (2)2.8657 (19)166.2 (17)
N2—H9···O1iii0.94 (2)1.93 (2)2.8019 (17)153.6 (17)
N2—H10···O3iv0.93 (2)2.00 (2)2.8750 (17)154.8 (17)
N2—H10···O1v0.93 (2)2.51 (2)3.0696 (17)118.9 (15)
Symmetry codes: (i) x+2, y+1/2, z+1/2; (ii) x1, y, z; (iii) x+1, y+1/2, z+1/2; (iv) x, y+1/2, z1/2; (v) x1, y+1/2, z1/2.

Experimental details

Crystal data
Chemical formulaNH4O+·C6H6NO4
Mr190.16
Crystal system, space groupMonoclinic, P21/c
Temperature (K)150
a, b, c (Å)4.6788 (2), 13.3277 (6), 13.5380 (7)
β (°) 97.212 (2)
V3)837.52 (7)
Z4
Radiation typeMo Kα
µ (mm1)0.13
Crystal size (mm)0.55 × 0.20 × 0.10
Data collection
DiffractometerNonius KappaCCD
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
5375, 1894, 1536
Rint0.027
(sin θ/λ)max1)0.648
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.038, 0.088, 1.05
No. of reflections1894
No. of parameters158
H-atom treatmentAll H-atom parameters refined
Δρmax, Δρmin (e Å3)0.26, 0.21

Computer programs: DENZO and COLLECT (Otwinowski & Minor, 1997; Nonius, 1988), DENZO and COLLECT, SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), ORTEPII (Johnson, 1976), SHELXL97.

Selected geometric parameters (Å, º) top
O1—C11.2574 (17)O5—N21.4143 (16)
O2—C11.3698 (17)N1—C21.3022 (19)
O2—N11.4326 (16)C1—C31.394 (2)
O3—C41.2270 (18)C2—C31.409 (2)
O4—C41.3414 (17)C3—C41.4395 (19)
O4—C51.4533 (17)
C1—O2—N1109.12 (10)O2—C1—C3107.70 (12)
C2—N1—O2105.17 (12)N1—C2—C3113.09 (14)
O1—C1—O2118.01 (13)C1—C3—C2104.92 (13)
O1—C1—C3134.28 (14)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O5—H7···O1i0.98 (3)1.66 (3)2.6244 (15)170 (2)
O5—H7···O2i0.98 (3)2.62 (3)3.2753 (15)124.8 (19)
N2—H8···N1ii0.98 (2)1.90 (2)2.8657 (19)166.2 (17)
N2—H9···O1iii0.94 (2)1.93 (2)2.8019 (17)153.6 (17)
N2—H10···O3iv0.93 (2)2.00 (2)2.8750 (17)154.8 (17)
N2—H10···O1v0.93 (2)2.51 (2)3.0696 (17)118.9 (15)
Symmetry codes: (i) x+2, y+1/2, z+1/2; (ii) x1, y, z; (iii) x+1, y+1/2, z+1/2; (iv) x, y+1/2, z1/2; (v) x1, y+1/2, z1/2.
 

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