4 (2 Isonicotinoyl­hydrazino) 4 oxo­butanoic acid

Download (0)

Full text

(1)

organic papers

o288

Antonio C. Doriguettoet al. C10H11N3O4 DOI: 10.1107/S1600536803002435 Acta Cryst.(2003). E59, o288±o289 Acta Crystallographica Section E

Structure Reports

Online ISSN 1600-5368

4-(2-Isonicotinoylhydrazino)-4-oxobutanoic acid

Antonio C. Doriguetto,a* Carlos H. T. de Paula Silva,a Daniela G. Rando,bElizabeth I. Ferreiraband Javier A. Ellenaa

aInstituto de FõÂsica de SaÄo Carlos, Universidade

de SaÄo Paulo, Caixa Postal 369 ± CEP 13560-970, SaÄo Carlos, SP, Brazil, and bDepartamento de FarmaÂcia, Faculdade de

CieÃncias FarmaceÃuticas, Universidade de SaÄo Paulo, Av. Prof. Lineu Prestes, 580 ± Bloco 13 ± CEP 05508-900, SaÄo Paulo, SP, Brazil

Correspondence e-mail: dorigue@if.sc.usp.br

Key indicators

Single-crystal X-ray study T= 120 K

Mean(C±C) = 0.003 AÊ Rfactor = 0.055 wRfactor = 0.159

Data-to-parameter ratio = 11.4

For details of how these key indicators were automatically derived from the article, see http://journals.iucr.org/e.

#2003 International Union of Crystallography Printed in Great Britain ± all rights reserved

The title compound, C10H11N3O4, was synthesized by reacting isoniazid with succinic anhydride. The structure reveals an in®nite two-dimensional network in the (011) plane, stabilized by intermolecular hydrogen bonds. Three of these hydrogen bonds are symmetrically independent.

Comment

In the last decade, tuberculosis (TB) has reemerged as one of the leading causes of death in the world, reaching nearly three million deaths annually (Bloom & Murray, 1992). Therefore, the search for new drugs for tuberculosis is of the utmost importance. Treatment regimens are based on long-term and combined chemotherapy. The most used ®rst-choice drug is isoniazid, (I), a bactericidal drug that acts both intracellularly in the macrophages and extracellularly in the necrotic tissue (Loenhout-Rooyackers & Veen, 1998).

The success of the drug depends signi®cantly on patient compliance, since the interruption of the treatment is considered the main cause of bacterial resistance (World Health Organization, 1997). From this perspective, succinyl derivatives are good synthetic intermediates in design of prodrugs with prolonged action, which could improve the patient compliance by decreasing the doses to be taken. Once in the blood, the drug is expected to be slowly released from the prodrug (unpublished data).

Fig. 1 shows anORTEP-3 (Farrugia, 1997) view of the title compound, (II). The main geometrical parameters are given in Table 1. As expected, the pyridine ring is planar and shows nearly equal CÐC distances [mean distance 1.389 (5) AÊ]. The CÐN bond lengths in the pyridine ring are slightly shorter than the CÐC bond lengths [C2ÐN1 = 1.342 (2) AÊ and C3Ð N1 = 1.333 (2) AÊ]. The mean bond angle in the ring is 120 (3).

The observed geometry of the ring agrees well with similar pyridine geometries (e.g.Bhatet al., 1974). The group bound to the aromatic ring exhibits an extended conformation, in which the mean CÐC and CÐN bond lengths are 1.51 (1) and 1.344 (4) AÊ, respectively. The NÐN bond length is 1.390 (2) AÊ. These distances are in good agreement with the expected values for formal CÐC, CÐN and NÐN single bonds.

The crystal packing is governed by an in®nite two-dimen-sional network in the (011) plane, stabilized by intermolecular hydrogen bonds (see Fig. 2). The compound exhibits three

(2)

independent intermolecular hydrogen bonds (Fig. 2 and Table 2). One of them is between the pyridine N atom and the terminal carboxylic acid group (O4ÐH7 N1iii, symmetry code as in Table 2), and gives rise to an in®nite chain along the [011] direction. The other two hydrogen bonds, which involve the carbonyl and amino groups (N2ÐH5 O1i and N3Ð H6 O2ii, symmetry codes as in Table 2), form another chain along the [100] direction.

Experimental

Succinyl isoniazid, (II), was obtained from the reaction of succinic anhydride with isoniazid, (I), in chloroform, at 343 K for 4 h. Pale yellow crystals were obtained by recrystallization from ethanol/H2O (1:1).

Crystal data

C10H11N3O4

Mr= 237.22

Triclinic,P1

a= 4.8140 (2) AÊ

b= 8.9168 (4) AÊ

c= 12.4943 (6) AÊ

= 83.797 (2) = 79.735 (2) = 81.035 (2)

V= 519.51 (4) AÊ3

Z= 2

Dx= 1.516 Mg mÿ3

MoKradiation Cell parameters from 1004

re¯ections

= 1±25 = 0.12 mmÿ1

T= 120 (2) K Needle, pale yellow 0.400.060.06 mm

Data collection

Nonius KappaCCD diffractometer

'and!scans withoffsets Rmaxint= 0.104= 25

Re®nement

Re®nement onF2

R[F2> 2(F2)] = 0.055

wR(F2) = 0.159

S= 1.08 1753 re¯ections 154 parameters

H-atom parameters constrained

w= 1/[2(F

o2) + (0.1004P)2

+ 0.0903P]

whereP= (Fo2+ 2Fc2)/3

(/)max<max= 0.25 e AÊÿ3 min=ÿ0.28 e AÊÿ3 Table 1

Selected geometric parameters (AÊ,).

C2ÐN1 1.342 (2) C3ÐN1 1.333 (2) C6ÐO1 1.237 (2) C6ÐN2 1.341 (2) C7ÐO2 1.231 (2)

C7ÐN3 1.347 (2) C10ÐO3 1.204 (2) C10ÐO4 1.321 (2) N2ÐN3 1.390 (2) N1ÐC2ÐC1 122.97 (16)

N1ÐC3ÐC4 123.39 (16) O1ÐC6ÐN2 121.40 (16) O1ÐC6ÐC5 121.95 (15) N2ÐC6ÐC5 116.59 (15) O2ÐC7ÐN3 121.07 (16) O2ÐC7ÐC8 124.41 (15)

N3ÐC7ÐC8 114.49 (15) O3ÐC10ÐO4 123.07 (16) O3ÐC10ÐC9 124.51 (15) O4ÐC10ÐC9 112.42 (14) C3ÐN1ÐC2 117.80 (15) C6ÐN2ÐN3 118.20 (14) C7ÐN3ÐN2 119.21 (15)

Table 2

Hydrogen-bonding geometry (AÊ,).

DÐH A DÐH H A D A DÐH A

N2ÐH5 O1i 0.88 1.99 2.842 (2) 162

N3ÐH6 O2ii 0.88 2.11 2.906 (2) 150

O4ÐH7 N1iii 0.84 1.84 2.673 (2) 173

Symmetry codes: (i)xÿ1;y;z; (ii) 1‡x;y;z; (iii)x;yÿ1;1‡z.

The H atoms were positioned stereochemically and were treated using theSHELXL97 default riding models. All H atoms were set isotropically, with displacement parameters 20% greater than the equivalent isotropic displacement parameters of the bonded atoms.

Data collection:COLLECT(Nonius, 1998); cell re®nement:HKL SCALEPACK(Otwinowski & Minor, 1997); data reduction: HKL DENZO (Otwinowski & Minor, 1997) and SCALEPACK; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to re®ne structure:SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); soft-ware used to prepare material for publication: WinGX (Farrugia, 1999).

This work was supported by Brazilian agencies FAPESP (98/12151-1), CNPq, and CAPES. ACD and CHTPS thank FAPESP for a postdoctoral fellowship. DGR thanks CAPES for a PhD fellowship.

References

Bhat, T. N., Singh, T. P. & Vijayan, M. (1974).Acta Cryst.B30, 2921±2922. Bloom, B. R. & Murray, C. J. (1992).Science,21, 1055±1064.

Farrugia, L. J. (1997).J. Appl. Cryst.30, 565. Farrugia, L. J. (1999).J. Appl. Cryst.32, 837±838.

Loenhout-Rooyackers, J. H. & Veen, J. (1998).Netherlands J. Med.53, 7±14. Nonius (1998).COLLECT. Nonius BV, Delft, The Netherlands.

Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276,

Macromolecular Crystallography, Part A, edited by C. W. Carter Jr and R. M. Sweet, pp. 307±326. New York: Academic Press.

Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of GoÈttingen, Germany.

Figure 2

Packing of the title compound, showing the in®nite two-dimensional network in the (011) plane. Hydrogen bonds are indicated by dashed lines.

Figure 1

(3)

supporting information

sup-1 Acta Cryst. (2003). E59, o288–o289

supporting information

Acta Cryst. (2003). E59, o288–o289 [https://doi.org/10.1107/S1600536803002435]

4-(2-Isonicotinoylhydrazino)-4-oxobutanoic acid

Antonio C. Doriguetto, Carlos H. T. de Paula Silva, Daniela G. Rando, Elizabeth I. Ferreira and

Javier A. Ellena

4-(2-isonicotinoylhydrazino)-4-oxobutanoic acid

Crystal data

C10H11N3O4 Mr = 237.22 Triclinic, P1 Hall symbol: -P 1 a = 4.8140 (2) Å b = 8.9168 (4) Å c = 12.4943 (6) Å α = 83.797 (2)° β = 79.735 (2)° γ = 81.035 (2)° V = 519.51 (4) Å3

Z = 2 F(000) = 248 Dx = 1.516 Mg m−3

Mo radiation, λ = 0.71073 Å Cell parameters from 1004 reflections θ = 1–25°

µ = 0.12 mm−1 T = 120 K

Needle, light yellow 0.4 × 0.06 × 0.06 mm

Data collection

Nonius KappaCCD diffractometer

Radiation source: fine-focus sealed tube Horizonally mounted graphite crystal

monochromator

Detector resolution: 9 pixels mm-1 φ and ω scans with κ offsets 6740 measured reflections

1753 independent reflections 1511 reflections with I > 2σ(I) Rint = 0.104

θmax = 25°, θmin = 2.7° h = −5→4

k = −10→10 l = −14→14

Refinement

Refinement on F2

Least-squares matrix: full R[F2 > 2σ(F2)] = 0.055 wR(F2) = 0.159 S = 1.08 1753 reflections 154 parameters

0 restraints

H-atom parameters constrained w = 1/[σ2(F

o2) + (0.1004P)2 + 0.0903P]

where P = (Fo2 + 2Fc2)/3

(Δ/σ)max < 0.001

Δρmax = 0.25 e Å−3

Δρmin = −0.28 e Å−3

Special details

(4)

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

x y z Uiso*/Ueq

C1 0.3792 (4) 0.49229 (19) −0.13616 (14) 0.0261 (5) H1 0.2598 0.4842 −0.0671 0.031* C2 0.3046 (4) 0.6031 (2) −0.21654 (15) 0.0289 (5) H2 0.1322 0.6708 −0.2009 0.035* C3 0.7058 (4) 0.5234 (2) −0.33620 (15) 0.0330 (5) H3 0.8192 0.5332 −0.4064 0.04* C4 0.7998 (4) 0.4100 (2) −0.26058 (14) 0.0289 (5) H4 0.9749 0.3452 −0.2781 0.035* C5 0.6310 (4) 0.3932 (2) −0.15798 (14) 0.0249 (5) C6 0.7359 (4) 0.2769 (2) −0.07343 (14) 0.0245 (5) C7 0.4268 (4) 0.05865 (19) 0.16140 (14) 0.0248 (4) C8 0.5465 (4) −0.0410 (2) 0.25235 (14) 0.0277 (5) H8A 0.7088 0.0025 0.2697 0.033* H8B 0.6204 −0.1434 0.2271 0.033* C9 0.3276 (4) −0.0571 (2) 0.35575 (14) 0.0290 (5) H9A 0.2708 0.0431 0.3864 0.035* H9B 0.1555 −0.0894 0.3373 0.035* C10 0.4435 (4) −0.1716 (2) 0.44035 (14) 0.0287 (5) N1 0.4647 (3) 0.61917 (18) −0.31551 (12) 0.0317 (4) N2 0.5370 (3) 0.21225 (16) −0.00228 (11) 0.0247 (4) H5 0.3558 0.2327 −0.009 0.03* N3 0.6248 (3) 0.11208 (16) 0.08232 (11) 0.0261 (4) H6 0.8074 0.0839 0.0842 0.031* O1 0.9919 (2) 0.24573 (14) −0.06653 (10) 0.0297 (4) O2 0.1713 (2) 0.08798 (15) 0.15559 (10) 0.0300 (4) O3 0.6600 (3) −0.25941 (16) 0.42301 (11) 0.0408 (4) O4 0.2780 (3) −0.16703 (16) 0.53674 (10) 0.0391 (4) H7 0.3495 −0.2324 0.5814 0.059*

Atomic displacement parameters (Å2)

U11 U22 U33 U12 U13 U23

(5)

supporting information

sup-3 Acta Cryst. (2003). E59, o288–o289

O1 0.0239 (7) 0.0349 (8) 0.0285 (7) −0.0035 (6) −0.0046 (5) 0.0053 (5) O2 0.0231 (7) 0.0381 (8) 0.0261 (7) −0.0019 (6) −0.0037 (5) 0.0049 (6) O3 0.0373 (8) 0.0426 (9) 0.0322 (8) 0.0109 (7) 0.0008 (6) 0.0081 (6) O4 0.0387 (8) 0.0439 (9) 0.0254 (8) 0.0075 (6) 0.0013 (6) 0.0088 (6)

Geometric parameters (Å, º)

C1—C2 1.385 (3) C7—N3 1.347 (2) C1—C5 1.387 (2) C7—C8 1.506 (2) C1—H1 0.95 C8—C9 1.524 (2) C2—N1 1.342 (2) C8—H8A 0.99 C2—H2 0.95 C8—H8B 0.99 C3—N1 1.333 (2) C9—C10 1.507 (3) C3—C4 1.387 (3) C9—H9A 0.99 C3—H3 0.95 C9—H9B 0.99 C4—C5 1.397 (2) C10—O3 1.204 (2) C4—H4 0.95 C10—O4 1.321 (2) C5—C6 1.496 (2) N2—N3 1.390 (2) C6—O1 1.237 (2) N2—H5 0.88 C6—N2 1.341 (2) N3—H6 0.88 C7—O2 1.231 (2) O4—H7 0.84

(6)

Hydrogen-bond geometry (Å, º)

D—H···A D—H H···A D···A D—H···A

N2—H5···O1i 0.88 1.99 2.842 (2) 162

N3—H6···O2ii 0.88 2.11 2.906 (2) 150

O4—H7···N1iii 0.84 1.84 2.673 (2) 173

Figure

Updating...

References