5 Nitro 2 furaldehyde N (hy­droxy­methyl)semicarbazone

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Acta Cryst.(2005). E61, o2099–o2101 doi:10.1107/S1600536805017721 Doriguettoet al. C

7H8N4O5

o2099

Acta Crystallographica Section E

Structure Reports

Online

ISSN 1600-5368

5-Nitro-2-furaldehyde

N

-(hydroxymethyl)-semicarbazone

Antonio C. Doriguetto,a* Carlos H. T. de Paula Silva,b Javier Ellena,cGustavo H. G. Trossini,dChung Man Chineand Elizabeth I. Ferreirad

aEscola de Farma´cia e Odontologia de Alfenas,

Efoa/Ceufe, Rua Gabriel Monteiro da Silva, 714, CEP 37130-000, Alfenas - MG, Brazil,

b

Faculdade de Cieˆncias Farmaceˆuticas de Ribeira˜o Preto, USP, Avenida do Cafe´ s/n, CEP 14040-903, Ribeira˜o Preto - SP, Brazil,cInstituto de Fı´sica de Sa˜o Carlos, USP, Caixa Postal 369, CEP 13560-970, Sa˜o Carlos - SP, Brazil,

dDepartamento de Farma´cia, Faculdade de

Cieˆncias Farmaceˆuticas, USP, Avenida Professor Lineu Prestes, 580 - Bloco 13, CEP 05508-900, Sa˜o Paulo - SP, Brazil, andeDepartamento de Fa´rmacos e Me´dicamentos, FCFA, UNESP, Rodovia Araraquara-Jau´ Km 1, CEP 14801-902, Araraquara - SP, Brazil

Correspondence e-mail: doriguetto@int.efoa.br

Key indicators

Single-crystal X-ray study

T= 298 K

Mean(C–C) = 0.003 A˚ Disorder in main residue

Rfactor = 0.039

wRfactor = 0.111

Data-to-parameter ratio = 10.3

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

#2005 International Union of Crystallography Printed in Great Britain – all rights reserved

The title compound, C7H8N4O5, which is a potential

anti-Chagas’ derivative, was synthesized using a simple hydroxy-methylation method in a basic medium with formaldehyde. The structure reveals two infinite two-dimensional networks in the (102) and (001) planes, stabilized by intermolecular hydrogen bonds.

Comment

Chagas’ disease has re-emerged as an important medico–social problem for people living in the Americas (Moncayo, 1992; World Health Organization, 2003). It is endemic in 21 coun-tries, with approximately 16 to 18 million individuals infected withTrypanosoma cruziand about 100 million people at risk of contracting the parasitosis. Among many compounds that are active againstT. cruzi, aromatic nitroheterocyclic deriva-tives are, generally, very active (Cerecetto & Gonzalez, 2002; Maya et al., 2003). Despite their toxicity, this class of compounds has been considered as important leads for mol-ecular modification.

Nitrofurazone (1) is a 5-nitro-2-furfurylidenesemicarbazone and is primarily an antimicrobial agent active against Gram-positive microorganisms (Korolkovas, 2004). It has been used as a precursor to obtain potential anti-Chagas’ derivatives (Chung & Ferreira, 1999). An intermediate compound in this synthesis is the title hydroxymethylnitrofurazone, (2), which has been shown to be active against the trypomastigote or amastigote forms ofT. cruzi, as well as being about four times less mutagenic than nitrofurazone (Chunget al., 2003).

Fig. 1 shows an ORTEP-3 (Farrugia, 1997) view of (2). Relevant geometric parameters are given in Table 1. The molecule is essentially planar except for the hydroxyl group. Atom O5 deviates by 1.106 (7) A˚ from the least-squares plane through the furan ring. The C6—N4—C7—O5 torsion angle is

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113.39 (18). Due to the disorder observed in the nitro group, the O atoms linked to atom N1 are also slightly displaced from the overall molecular plane. Atoms O11, O12, O21 and O22 deviate by 0.24 (1), 0.21 (1), 0.12 (1) and

0.30 (2) A˚ , respectively, from the best lequares plane through the furan ring.

The crystal packing of (2) is formed by two infinite two-dimensional networks. One of them, which is stabilized by several intermolecular hydrogen bonds (Fig. 2), is parallel to the (102) plane. The networks parallel to the (102) plane are themselves hydrogen-bonded via O5—H5A O4 associa-tions, forming another infinite two-dimensional network parallel to the (001) plane (Fig. 3). Details of all hydrogen-bond contacts involved in the networks are given in Table 2.

Experimental

5-Nitro-2-furfurylidenesemicarbazone, (1) (0.99 g, 5 mmol), was mixed with potassium carbonate (0.69 g, 5 mmol) and suspended in water (10 ml). Formaldehyde solution (37%, 18 ml) was added in two steps, half at the start of the reaction and the other half 2.5 h later. The reaction was stirred at room temperature for 5 h and then

filtered. The filtrate was evaporated under low pressure. The product, (2), was crystallized from methanol–water (6:0.1) and yellow crystals were obtained (yield 61.4%). The compound was identified as (2) by IR,1H and13C NMR and mass spectrometry.1H NMR spectroscopic data (300 MHz, DMSO-d6,, p.p.m.): 11.02 (s, 1H, H8), 7.81 (d,J=

3.9 Hz, 1H, H4)*, 7.80 (s, 1H, H6)*, 7.64 (t,J= 6.3 Hz, 1H, H12), 7.25

(d,J= 3.9 Hz, 1H, H3), 5.57 (t,J= 6.9 Hz, 1H, H14), 4.61 (t,J= 6.6 Hz,

2H, H13) (* denotes superimposed signals); 13

C NMR spectroscopic data (75 MHz, DMSO-d6,, p.p.m.): 154.47 (C9), 152.42 (C5), 151.25

(C2), 127.82 (C6), 115.11 (C4), 112.63 (C3), 63.07 (C13); IR data (KBr,

, cm1): 3410 (O—H), 3334 and 3162 (N—H), 2980 and 2860 (C—H),

1674 (C O), 1522 and 1359 (NO2). Mass spectrometry: m/z: 228

[M+], 210, 198, 155.

Crystal data

C7H8N4O5 Mr= 228.17

Monoclinic,C2=c a= 10.3757 (5) A˚ b= 10.8125 (5) A˚ c= 16.9455 (8) A˚ = 92.095 (3)

V= 1899.8 (2) A˚3 Z= 8

Dx= 1.596 Mg m 3

MoKradiation

Cell parameters from 16323 reflections

= 2.9–27.5

= 0.14 mm1 T= 298 (2) K Block, yellow 0.20.10.1 mm

Data collection

Nonius KappaCCD area-detector diffractometer

’scans, and!scans withoffsets Absorption correction: none 13352 measured reflections 1755 independent reflections

1367 reflections withI> 2(I) Rint= 0.036

max= 25.5 h=12!12 k=13!13 l=20!20

Refinement

Refinement onF2 R[F2> 2(F2)] = 0.039 wR(F2) = 0.111 S= 1.07 1755 reflections 170 parameters

H atoms treated by a mixture of independent and constrained refinement

w= 1/[2(F

o2) + (0.0609P)2

+ 0.6344P]

whereP= (Fo2+ 2Fc2)/3

(/)max< 0.001 max= 0.18 e A˚

3

min=0.17 e A˚ 3

Extinction correction:SHELXL97 (Sheldrick, 1997)

Extinction coefficient: 0.013 (2)

organic papers

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Doriguettoet al. C

7H8N4O5 Acta Cryst.(2005). E61, o2099–o2101

Figure 1

A view of (2), with displacement ellipsoids for shown at the 50% probability level. Both disorder components are shown.

Figure 2

The packing of (2), showing the infinite two-dimensional network along the (102) plane. [Symmetry codes: (i)1

2x, 3

2y,-z; (ii) 1 2x,

1 2y,z;

(iii)3 2x,y

1 2,

1 2z; (iv)

3 2x,

1 2+y,

1

2z.] Both disorder components

are shown.

Figure 3

Part of the packing of (2), showing the infinite two-dimensional network parallel to the (001) plane. Both disorder components are shown. [Symmetry codes: (v)x, 1y,z; (vi)1

2x, 1

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Table 1

Selected geometric parameters (A˚ ,).

N1—C1 1.415 (2) N2—C5 1.274 (2) N2—N3 1.354 (2) N3—C6 1.369 (2) N4—C6 1.335 (2)

N4—C7 1.436 (2) O3—C1 1.355 (2) O3—C4 1.373 (2) O4—C6 1.240 (2) O5—C7 1.400 (2)

C7—O5—H5A 109 (2) O5—C7—N4 112.6 (1)

Table 2

Hydrogen-bond geometry (A˚ ,).

D—H A D—H H A D A D—H A

N3—H3 O4i

0.86 2.08 2.909 (2) 162 N4—H4 O5ii 0.86 2.28 3.047 (2) 148 C2—H2 O21iii

0.93 2.50 3.10 (2) 122 C2—H2 O22iii

0.93 2.47 3.04 (2) 120 C3—H3A O5ii 0.93 2.55 3.446 (2) 162 C5—H5 O11iv

0.93 2.48 3.37 (2) 162 C5—H5 O12iv

0.93 2.51 3.42 (2) 167 O5—H5A O4v

0.90 (2) 1.92 (2) 2.799 (2) 166 (2)

Symmetry codes: (i) xþ1

2;yþ 3

2;z; (ii) xþ 1 2;yþ

1

2;z; (iii) xþ3

2;þy 1 2;zþ

1 2; (iv)xþ

3 2;þyþ

1 2;zþ

1

2; (v)x;yþ1;z.

The hydroxyl H atom, H5A, was located in a difference Fourier synthesis and refined isotropically. The H atoms of the amino and methyl groups were positioned geometrically and were refined using a riding model, with N—H = 0.86 A˚ and C—H = 0.93–0.97 A˚, and with fixed individual displacement parameters of Uiso(H) =

1.2Ueq(C,N). Several least-squares refinements were performed in an

attempt to model the disordered nitro group. The model splitting each O atom of the nitro group over two positions, O11 and O12, and

O21 and O22, with 50% occupancy each, was found to be the best one.

Data collection:COLLECT(Nonius, 1998); cell refinement: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 refine structure:SHELXL97(Sheldrick, 1997); molecular graphics:ORTEP-3for Windows (Farrugia, 1997); soft-ware used to prepare material for publication: WinGX (Farrugia, 1999).

This work was supported by Brazilian agencies FAPESP, CNPq and CAPES.

References

Cerecetto, H. & Gonzalez, M. (2002).Curr. Top. Med. Chem.2, 1187–1213. Chung, M. C. & Ferreira, E. I. (1999).Quim. Nova,22, 75–84.

Chung, M. C., Guido, R. V. C., Martinelli, T. F., Goncalves, M. F., Polli, M. C., Botelho, K. C. A., Varanda, E. A., Colli, W., Miranda, M. T. M. & Ferreira, E. I. (2003).Bioorg. Med. Chem.11, 4779–4783.

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

Korolkovas, A. (2004).Diciona´rio Terapeˆutico 04/05, pp. 18.6–18.7. Guana-bara Koogan: Rio de Janeiro.

Maya, J. D., Bollo, S., Nunez-Vergara, L. J., Squella, J. A., Repetto, Y., Morello, A., Perie, J. & Chauviere, G. (2003).Biochem. Pharmacol.54, 999–1006. Moncayo, A. (1992).World Health Stat. Q.45, 276–279.

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 & R. M. Sweet, pp. 307-326. New York: Academic Press.

Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of Go¨ttingen, Germany.

World Health Organization (2003).Chagas’ Disease, http://www.who.int/tdr/ dw/chagas2003.htm.

organic papers

Acta Cryst.(2005). E61, o2099–o2101 Doriguettoet al. C

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supporting information

sup-1 Acta Cryst. (2005). E61, o2099–o2101

supporting information

Acta Cryst. (2005). E61, o2099–o2101 [https://doi.org/10.1107/S1600536805017721]

5-Nitro-2-furaldehyde

N

-(hydroxymethyl)semicarbazone

Antonio C. Doriguetto, Carlos H. T. de Paula Silva, Javier Ellena, Gustavo H. G. Trossini, Chung

Man Chin and Elizabeth I. Ferreira

5-nitro-2-furaldehyde N-(hydroxymethyl)semicarbazone

Crystal data

C7H8N4O5

Mr = 228.17

Monoclinic, C2/c

Hall symbol: -C 2yc

a = 10.3757 (5) Å

b = 10.8125 (5) Å

c = 16.9455 (8) Å

β = 92.095 (3)°

V = 1899.8 (2) Å3

Z = 8

F(000) = 944

Dx = 1.596 Mg m−3

Mo radiation, λ = 0.71073 Å Cell parameters from 16323 reflections

θ = 2.9–27.5°

µ = 0.14 mm−1

T = 298 K Needle, yellow 0.2 × 0.1 × 0.1 mm

Data collection

Nonius KappaCCD area-detector diffractometer

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

monochromator

Detector resolution: 9 pixels mm-1

φ scans, and ω scans with κ offsets 13352 measured reflections

1755 independent reflections 1367 reflections with I > 2σ(I)

Rint = 0.036

θmax = 25.5°, θmin = 3.6°

h = −12→12

k = −13→13

l = −20→20

Refinement

Refinement on F2

Least-squares matrix: full

R[F2 > 2σ(F2)] = 0.039

wR(F2) = 0.111

S = 1.07 1755 reflections 170 parameters 0 restraints

H atoms treated by a mixture of independent and constrained refinement

w = 1/[σ2(F

o2) + (0.0609P)2 + 0.6344P]

where P = (Fo2 + 2Fc2)/3

(Δ/σ)max < 0.001

Δρmax = 0.18 e Å−3

Δρmin = −0.17 e Å−3

Extinction correction: SHELXL97 (Sheldrick, 1997), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4

Extinction coefficient: 0.013 (2)

Special details

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supporting information

sup-2 Acta Cryst. (2005). E61, o2099–o2101

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

x y z Uiso*/Ueq Occ. (<1)

N1 0.85510 (17) 0.46319 (18) 0.30115 (10) 0.0687 (5) N2 0.41500 (12) 0.53080 (12) 0.08495 (8) 0.0481 (4) N3 0.32951 (13) 0.60726 (13) 0.04746 (9) 0.0537 (4) H3 0.3337 0.6859 0.0545 0.064* N4 0.24375 (13) 0.43515 (12) −0.01394 (9) 0.0502 (4) H4 0.3056 0.3951 0.0096 0.06* O3 0.68403 (11) 0.53924 (11) 0.21938 (7) 0.0522 (4) O4 0.15337 (11) 0.62518 (10) −0.03360 (8) 0.0551 (4) O5 0.07951 (12) 0.28440 (11) −0.02165 (8) 0.0587 (4)

O11 0.8972 (16) 0.369 (2) 0.3360 (11) 0.080 (3) 0.5 O12 0.9298 (17) 0.377 (2) 0.3184 (12) 0.087 (3) 0.5 O21 0.8728 (19) 0.5650 (15) 0.3258 (9) 0.073 (2) 0.5 O22 0.896 (2) 0.5726 (18) 0.3076 (10) 0.110 (5) 0.5 C1 0.75064 (17) 0.43960 (17) 0.24722 (10) 0.0535 (5)

C2 0.70584 (19) 0.33386 (18) 0.21729 (11) 0.0634 (5) H2 0.7369 0.2547 0.2279 0.076* C3 0.60162 (19) 0.36677 (17) 0.16629 (11) 0.0597 (5) H3A 0.5499 0.3129 0.1364 0.072* C4 0.59064 (15) 0.49087 (16) 0.16884 (9) 0.0469 (4) C5 0.50308 (15) 0.57706 (15) 0.13029 (10) 0.0490 (4) H5 0.5105 0.6619 0.1381 0.059* C6 0.23621 (14) 0.55693 (15) −0.00192 (10) 0.0450 (4) C7 0.15416 (17) 0.36740 (16) −0.06393 (11) 0.0530 (5) H7A 0.0975 0.4252 −0.0919 0.064* H7B 0.2015 0.322 −0.1029 0.064* H5A 0.012 (2) 0.325 (2) −0.0022 (13) 0.093 (8)*

Atomic displacement parameters (Å2)

U11 U22 U33 U12 U13 U23

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supporting information

sup-3 Acta Cryst. (2005). E61, o2099–o2101

C5 0.0448 (9) 0.0431 (9) 0.0582 (10) −0.0023 (7) −0.0101 (8) 0.0010 (7) C6 0.0361 (8) 0.0402 (9) 0.0581 (9) −0.0001 (6) −0.0053 (7) 0.0050 (7) C7 0.0514 (10) 0.0451 (9) 0.0617 (10) −0.0046 (7) −0.0107 (8) −0.0010 (7)

Geometric parameters (Å, º)

N1—O21 1.190 (17) O3—C4 1.373 (2)

N1—O12 1.24 (2) O4—C6 1.240 (2)

N1—O11 1.24 (2) O5—C7 1.400 (2)

N1—O22 1.259 (19) O5—H5A 0.90 (3)

N1—C1 1.415 (2) C1—C2 1.328 (3)

N2—C5 1.274 (2) C2—C3 1.405 (2)

N2—N3 1.354 (2) C2—H2 0.93

N3—C6 1.369 (2) C3—C4 1.347 (2)

N3—H3 0.86 C3—H3A 0.93

N4—C6 1.335 (2) C4—C5 1.441 (2)

N4—C7 1.436 (2) C5—H5 0.93

N4—H4 0.86 C7—H7A 0.97

O3—C1 1.355 (2) C7—H7B 0.97

O21—N1—O12 121.6 (14) C1—C2—C3 105.52 (17) O21—N1—O11 122.7 (13) C1—C2—H2 127.2 O12—N1—O11 21.6 (12) C3—C2—H2 127.2 O21—N1—O22 18.8 (14) C4—C3—C2 107.25 (16) O12—N1—O22 118.7 (14) C4—C3—H3A 126.4 O11—N1—O22 127.9 (13) C2—C3—H3A 126.4 O21—N1—C1 119.9 (9) C3—C4—O3 109.92 (14) O12—N1—C1 118.4 (11) C3—C4—C5 133.01 (16) O11—N1—C1 114.0 (10) O3—C4—C5 117.07 (15) O22—N1—C1 118.1 (9) N2—C5—C4 116.47 (15) C5—N2—N3 119.10 (14) N2—C5—H5 121.8 N2—N3—C6 118.73 (13) C4—C5—H5 121.8

N2—N3—H3 120.6 O4—C6—N4 124.36 (15)

C6—N3—H3 120.6 O4—C6—N3 119.44 (15)

C6—N4—C7 123.58 (14) N4—C6—N3 116.18 (14)

C6—N4—H4 118.2 O5—C7—N4 112.6 (1)

C7—N4—H4 118.2 O5—C7—H7A 109.1

C1—O3—C4 104.69 (13) N4—C7—H7A 109.1

C7—O5—H5A 109 (2) O5—C7—H7B 109.1

C2—C1—O3 112.61 (15) N4—C7—H7B 109.1 C2—C1—N1 130.62 (17) H7A—C7—H7B 107.8 O3—C1—N1 116.76 (16)

Hydrogen-bond geometry (Å, º)

D—H···A D—H H···A D···A D—H···A

N3—H3···O4i 0.86 2.08 2.909 (2) 162

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sup-4 Acta Cryst. (2005). E61, o2099–o2101

C2—H2···O21iii 0.93 2.50 3.10 (2) 122

C2—H2···O22iii 0.93 2.47 3.04 (2) 120

C3—H3A···O5ii 0.93 2.55 3.446 (2) 162

C5—H5···O11iv 0.93 2.48 3.37 (2) 162

C5—H5···O12iv 0.93 2.51 3.42 (2) 167

O5—H5A···O4v 0.90 (2) 1.92 (2) 2.799 (2) 166 (2)

Figure

Fig. 1 shows an ORTEP-3Relevant geometric parameters are given in Table 1. Themolecule is essentially planar except for the hydroxyl group.Atom O5 deviates by 1.106 (7) A (Farrugia, 1997) view of (2).˚ from the least-squares planethrough the furan ring
Fig. 1 shows an ORTEP-3Relevant geometric parameters are given in Table 1. Themolecule is essentially planar except for the hydroxyl group.Atom O5 deviates by 1.106 (7) A (Farrugia, 1997) view of (2).˚ from the least-squares planethrough the furan ring p.1
Figure 3Part of the packing of (2), showing the infinite two-dimensional network

Figure 3Part

of the packing of (2), showing the infinite two-dimensional network p.2
Figure 1

Figure 1

p.2
Figure 2The packing of (2), showing the infinite two-dimensional network alongCrystal data

Figure 2The

packing of (2), showing the infinite two-dimensional network alongCrystal data p.2
Table 2Hydrogen-bond geometry (A˚ , �).

Table 2Hydrogen-bond

geometry (A˚ , �). p.3

References