Acetyl­hydroxamic acid

Dziuk, B.; Zarychta, B.; Ejsmont, K.; Daszkiewicz, Z.

doi:10.1107/S2414314617013906

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 2| Part 10| October 2017| x171390

https://doi.org/10.1107/S2414314617013906

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Acetylhydroxamic acid

Błażej Dziuk,^a Bartosz Zarychta,^a ^* Krzysztof Ejsmont ^a and Zdzisław Daszkiewicz ^a

^aFaculty of Chemistry, University of Opole, Oleska 48, 45-052 Opole, Poland
^*Correspondence e-mail: bzarychta@uni.opole.pl

Edited by M. Bolte, Goethe-Universität Frankfurt, Germany (Received 23 September 2017; accepted 26 September 2017; online 6 October 2017)

There is one independent molecule in the asymmetric unit of the title compound (alternatively named N-hydroxyacetamide), C₂H₅NO₂. It crystallizes in the noncentrosymmetric space group P4₃. The structure is an anhydrous form of acetylhydroxamic acid with typical geometry that corresponds well with the hydrated structure described by Bracher & Small [Acta Cryst. (1970), B26, 1705–1709]. In the crystal, N—H⋯O and O—H⋯O hydrogen bonds connect the molecules into chains in the c-axis direction.

Keywords: crystal structure; acetylhydroxamic acid; hydrogen bonds.

CCDC reference: 1576592

Structure description

Hydroxamic acids were first described by Lossen (1869 ). Since then, intensive work has been focused on their reactions and structures. Acetylhydroxamic acid can exist in two tautomeric forms, i.e. amide and imide. In addition, each of these forms may be in the form of the Z or E isomer. Hydroxamic acids have the ability to coordinate metal ions and to form complexes, thereby inter alia participating in many biochemical processes. These acids belong to the siderophores and transport iron ions as bioligands in bacteria (Miller, 1989 ; Neilands, 1995 ). Hydroxamic acids are useful reagents with interesting biological and medical applications. This is also the result of their ability to form stable chelates with multiple metal ions (Kaczor & Proniewicz, 2004 ). Compounds containing hydroxamic groups are inhibitors of the activity of various metalloproteinases such as urease (Stemmler et al., 1995 ), oxidase (Ikeda-Saito et al., 1991 ) and zinc proteinases involved in neoplastic diseases (Groneberg et al., 1999 ; Hajduk et al., 1997 ). Enzyme activity is inhibited by urease inhibitors. These inhibitors do not allow the pH of the urine to rise and therefore do not allow the crystallization of calcium and magnesium. The first specific urease inhibitor was acetylhydroxamic acid. Acetylhydroxamic acid in the presence of urease-positive bacteria in vitro and in vivo reduces the pH of the urine and prevents the formation of urinary stones in rats. In higher doses in vitro studies (2–4 mg ml⁻¹) show that it inhibits urease activity and additionally has bacteriostatic effects (Cisowska, 2003 ).

The title compound crystallizes in the non-centrosymmetric space group P4₃ with one independent molecule in the asymmetric unit. The values of bond lengths and valance angles of the acetylhydroxamic acid are typical (Allen, 2002 ). The structure is the imidate of the Z isomer of acetylhydroxamic acid (Fig. 1).

Figure 1
The molecular structure of the title compound, with displacement ellipsoids drawn at the 50% probability level.

In the crystal, there are intermolecular hydrogen bonds (Table 1), two N—H⋯O, one O—H⋯O and one C—H⋯O contact. The strongest hydrogen bond in the crystalline structure of acetylhydroxamic acid is the O1—H5⋯O2 hydrogen bond. This bond creates a twisted string along the c axis. It can be assumed that the next two hydrogen bonds of the type N—H⋯O have comparable strength. In the N1—H4⋯O2 hydrogen bond, the donor and the H atom are closer to the acceptor but form a smaller angle than the N1—H4⋯O1 hydrogen bond. Those bonds form a chain of molecules along the c axis. The weakest hydrogen bond in the crystalline structure of acetylhydroxamic acid is C2—H1⋯O1. This hydrogen bond connects adjacent parallel molecules also along the c axis. The packing is shown in Fig. 2.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C2—H2⋯O1ⁱ	0.96	2.45	3.300 (3)	147
N1—H4⋯O1ⁱⁱ	0.86	2.48	3.246 (3)	149
N1—H4⋯O2ⁱⁱ	0.86	2.26	2.917 (3)	133
O1—H5⋯O2ⁱⁱⁱ	0.82	1.81	2.624 (2)	176
Symmetry codes: (i) x+1, y, z; (ii) $[-y, x, z+{\script{1\over 4}}]$ ; (iii) $[-y, x-1, z+{\script{1\over 4}}]$ .

Figure 2
The crystal packing of the title compound, viewed along the b axis.

The geometry of the presented structure corresponds well with the structure described by Bracher & Small (1970 ).

Synthesis and crystallization

In this study, we prepared acetohydroxamic acid by heating equivalent proportions of acetamide and hydroxylamine hydrochloride. Dried ethyl acetate was used as a solvent for extracting and recrystallizing the product (yield 17.9 g; m.p. 354–355 K).

Refinement

All H atoms were found in a difference map but set to idealized positions and treated as riding, with methyl C—H = 0.96 Å and U_iso(H) = 1.5U_eq(C), N—H = 0.86 Å and U_iso(H) = 1.2U_eq(N), and O—H = 0.82 Å and U_iso(H) = 1.5U_eq(O). Crystal data, data collection and structure refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	C₂H₅NO₂
M_r	75.07
Crystal system, space group	Tetragonal, P4₁
Temperature (K)	293
a, c (Å)	5.2344 (6), 13.809 (2)
V (Å³)	378.34 (10)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.12
Crystal size (mm)	0.05 × 0.04 × 0.03

Data collection
Diffractometer	Xcalibur
No. of measured, independent and observed [I > 2σ(I)] reflections	2579, 751, 683
R_int	0.018
(sin θ/λ)_max (Å⁻¹)	0.616

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.028, 0.086, 1.11
No. of reflections	751
No. of parameters	47
No. of restraints	1
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.10, −0.14
Absolute structure	Flack x determined using 307 quotients [(I⁺) − (I⁻)]/[(I⁺) + (I⁻)] (Parsons et al., 2013 )
Absolute structure parameter	0.0 (4)
Computer programs: CrysAlis CCD (Oxford Diffraction, 2008 $[Oxford Diffraction (2008). CrysAlis CCD and CrysAlis RED. Oxford Diffraction Ltd, Abingdon, Oxfordshire, England.]$ ), SHELXS2014 (Sheldrick, 2015a ), SHELXL2014 (Sheldrick, 2015b ) and SHELXTL (Sheldrick, 2008 ).

Structural data

CCDC reference: 1576592

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S2414314617013906/bt4064sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314617013906/bt4064Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314617013906/bt4064Isup3.cml

checkCIF report

Computing details top

Data collection: CrysAlis CCD (Oxford Diffraction, 2008); cell refinement: CrysAlis CCD (Oxford Diffraction, 2008); data reduction: CrysAlis CCD (Oxford Diffraction, 2008); program(s) used to solve structure: SHELXS2014 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015b).

N-Hydroxyacetamide top

Crystal data top

C₂H₅NO₂	D_x = 1.318 Mg m⁻³
M_r = 75.07	Mo Kα radiation, λ = 0.71073 Å
Tetragonal, P4₁	Cell parameters from 2579 reflections
a = 5.2344 (6) Å	θ = 3.9–26.0°
c = 13.809 (2) Å	µ = 0.12 mm⁻¹
V = 378.34 (10) Å³	T = 293 K
Z = 4	Plate, colourless
F(000) = 160	0.05 × 0.04 × 0.03 mm

Data collection top

Xcalibur diffractometer	683 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.018
Detector resolution: 1024 pixels mm^-1	θ_max = 26.0°, θ_min = 3.9°
ω–scan	h = −5→6
2579 measured reflections	k = −6→5
751 independent reflections	l = −16→16

Refinement top

Refinement on F²	H-atom parameters constrained
Least-squares matrix: full	w = 1/[σ²(F_o²) + (0.0584P)² + 0.0038P] where P = (F_o² + 2F_c²)/3
R[F² > 2σ(F²)] = 0.028	(Δ/σ)_max < 0.001
wR(F²) = 0.086	Δρ_max = 0.10 e Å⁻³
S = 1.11	Δρ_min = −0.14 e Å⁻³
751 reflections	Extinction correction: SHELXL2014 (Sheldrick, 2015b), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
47 parameters	Extinction coefficient: 0.24 (4)
1 restraint	Absolute structure: Flack x determined using 307 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
Hydrogen site location: inferred from neighbouring sites	Absolute structure parameter: 0.0 (4)

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

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

	x	y	z	U_iso*/U_eq
C1	0.4274 (4)	0.0253 (4)	0.41879 (16)	0.0485 (5)
C2	0.6056 (5)	0.2400 (5)	0.4372 (2)	0.0672 (7)
H1	0.5655	0.3173	0.4984	0.101*
H2	0.7778	0.1769	0.4385	0.101*
H3	0.5888	0.3647	0.3867	0.101*
N1	0.2554 (4)	−0.0170 (4)	0.48604 (13)	0.0600 (6)
H4	0.2639	0.0612	0.5407	0.072*
O1	0.0601 (3)	−0.1893 (3)	0.46796 (13)	0.0663 (5)
H5	0.0673	−0.3064	0.5073	0.099*
O2	0.4385 (3)	−0.1073 (3)	0.34398 (11)	0.0584 (5)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0516 (12)	0.0508 (11)	0.0430 (10)	0.0120 (9)	−0.0098 (9)	−0.0019 (8)
C2	0.0614 (14)	0.0644 (15)	0.0759 (18)	−0.0010 (12)	−0.0132 (12)	−0.0134 (12)
N1	0.0744 (13)	0.0623 (10)	0.0433 (10)	−0.0005 (10)	0.0010 (9)	−0.0117 (8)
O1	0.0715 (11)	0.0685 (9)	0.0589 (10)	−0.0048 (9)	0.0023 (9)	0.0067 (8)
O2	0.0595 (10)	0.0706 (11)	0.0451 (9)	−0.0034 (7)	−0.0005 (6)	−0.0134 (7)

Geometric parameters (Å, º) top

C1—O2	1.246 (3)	C2—H3	0.9600
C1—N1	1.312 (3)	N1—O1	1.386 (3)
C1—C2	1.482 (4)	N1—H4	0.8600
C2—H1	0.9600	O1—H5	0.8200
C2—H2	0.9600

O2—C1—N1	121.6 (2)	H1—C2—H3	109.5
O2—C1—C2	122.4 (2)	H2—C2—H3	109.5
N1—C1—C2	116.0 (2)	C1—N1—O1	119.24 (17)
C1—C2—H1	109.5	C1—N1—H4	120.4
C1—C2—H2	109.5	O1—N1—H4	120.4
H1—C2—H2	109.5	N1—O1—H5	109.5
C1—C2—H3	109.5

O2—C1—N1—O1	−9.0 (3)	C2—C1—N1—O1	170.80 (19)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C2—H2···O1ⁱ	0.96	2.45	3.300 (3)	147
N1—H4···O1ⁱⁱ	0.86	2.48	3.246 (3)	149
N1—H4···O2ⁱⁱ	0.86	2.26	2.917 (3)	133
O1—H5···O2ⁱⁱⁱ	0.82	1.81	2.624 (2)	176

Symmetry codes: (i) x+1, y, z; (ii) −y, x, z+1/4; (iii) −y, x−1, z+1/4.

References

Allen, F. H. (2002). Acta Cryst. B58, 380–388. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Bracher, B. H. & Small, R. W. H. (1970). Acta Cryst. B26, 1705–1709. CSD CrossRef CAS IUCr Journals Web of Science Google Scholar
Cisowska, A. (2003). Postępy Mikrobiol. 42, 3–23. CAS Google Scholar
Groneberg, R. D., Burns, C. J., Morrissette, M. M., Ullrich, J. W., Morris, R. L., Darnbrough, S., Djuric, S. W., Condon, S. M., McGeehan, G. M., Labaudiniere, R., Neuenschwander, K., Scotese, A. C. & Kline, J. A. (1999). J. Med. Chem. 42, 541–544. Web of Science CrossRef PubMed CAS Google Scholar
Hajduk, P. J., Sheppard, G., Nettesheim, D. G., Olejniczak, E. T., Shuker, S. B., Meadows, R. P., Steinman, D. H., Carrera, G. M. Jr, Marcotte, P. A., Severin, J., Walter, K., Smith, H., Gubbins, E., Simmer, R., Holzman, T. F., Morgan, D. W., Davidsen, S. K., Summers, J. B. & Fesik, S. W. (1997). J. Am. Chem. Soc. 119, 5818–5827. CrossRef CAS Web of Science Google Scholar
Ikeda-Saito, M., Shelley, D. A., Lu, L., Booth, K. S., Caughey, W. S. & Kimura, S. (1991). J. Biol. Chem. 266, 3611–3616. PubMed CAS Web of Science Google Scholar
Kaczor, A. & Proniewicz, L. M. (2004). J. Mol. Struct. 704, 189–196. Web of Science CrossRef CAS Google Scholar
Lossen, H. (1869). Justus Liebigs Ann. Chem. 150, 314–316. CrossRef Google Scholar
Miller, M. J. (1989). Chem. Rev. 89, 1563–1579. CrossRef CAS Web of Science Google Scholar
Neilands, J. B. (1995). J. Biol. Chem. 270, 26723–26726. CrossRef CAS PubMed Web of Science Google Scholar
Oxford Diffraction (2008). CrysAlis CCD and CrysAlis RED. Oxford Diffraction Ltd, Abingdon, Oxfordshire, England. Google Scholar
Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249–259. Web of Science CrossRef CAS IUCr Journals Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Stemmler, A. J., Kampf, J. W., Kirk, M. L. & Pecoraro, V. L. (1995). J. Am. Chem. Soc. 117, 6368–6369. CSD CrossRef CAS Web of Science Google Scholar

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