2-(2-Amino-5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7-yl)acetohydrazide monohydrate

Lahmidi, S.; Sebbar, N.K.; Boulhaoua, M.; Essassi, E.M.; Mague, J.T.; Zouihri, H.

doi:10.1107/S2414314616008701

organic compounds

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doi:10.1107/S2414314616008701

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2-(2-Amino-5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7-yl)acetohydrazide monohydrate

Sanae Lahmidi,^a ^* Nada Kheira Sebbar,^a Mohammed Boulhaoua,^a El Mokhtar Essassi,^a Joel T. Mague ^b and Hafid Zouihri ^c

^aLaboratoire de Chimie Organique Hétérocyclique, Pôle de Compétences Pharmacochimie, Mohammed V University in Rabat, BP 1014, Avenue Ibn Batouta, Rabat, Morocco, ^bDepartment of Chemistry, Tulane University, New Orleans, LA 70118, USA, and ^cDépartement de chimie, Faculté des Sciences, Université Ibn Zohr, BP 8106, Cité Dakhla, 80000 Agadir, Morocco
^*Correspondence e-mail: lahmidi_sanae@yahoo.fr

Edited by P. C. Healy, Griffith University, Australia (Received 25 May 2016; accepted 30 May 2016; online 17 June 2016)

In the crystal structure of the title molecule, C₈H₁₁N₇O·H₂O, a network of O—H⋯O, O—H⋯N, N—H⋯O and N—H⋯N hydrogen bonds links the components, forming layers which include the lattice water molecules. The layers are held together by π–π stacking interactions.

Keywords: crystal structure; pyrimidine; hydrogen bonds; layers.

CCDC reference: 1482515

Structure description

Pyrimidine is one of the most important heterocycles that are widely used as a key building unit for the preparation of many pharmaceutical compounds. Fusion of pyrimidine with 1,2,4-triazole gives 1,2,4-triazolo[1,5-a]pyrimidine (Salas et al., 1999 ). These molecules are thermodynamically stable and, thus, the most studied (Fischer et al., 2008 ). Recently, due to their diverse pharmacological activities, such as antitumor potency (Zhang et al., 2007 ) and antimicrobial activity (Luo et al., 2013 ), it is understandable that research on the synthesis of these compounds has intensified.

As part of our ongoing research program on heterocyclic compounds which may serve as leads for designing novel chemotherapeutic agents, we were particularly interested to examined the action of hydrazine hydrate on ethyl 2-(2-amino-5-methyl-1,2,4-triazolo[1,5-a] pyrimidin-7-yl) acetate leading to the corresponding 2-(2-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)acetohydrazide (Fig. 1).

Figure 1
The title molecule with labeling scheme and 50% probability ellipsoids. The O—H⋯O hydrogen bond is shown as a dotted line.

In the crystal, a network of O—H⋯O, O—H⋯N, N—H⋯O and N—H⋯N hydrogen bonds (Table 1) links the components into layers which include the lattice water molecules (Fig. 2). The layers are held together by π–π stacking interactions as shown in Fig. 3. The dihedral angle between the mean planes of the two molecules is 1.48 (8)° and the slippage is 0.89 Å.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2B⋯O1	0.87	2.00	2.8478 (15)	166
O2—H2A⋯N4ⁱ	0.87	2.06	2.9004 (16)	162
N5—H5B⋯N7ⁱⁱ	0.91	2.17	3.0636 (17)	167
N5—H5A⋯N3ⁱⁱⁱ	0.91	2.06	2.9713 (17)	177
N6—H6D⋯O2^iv	0.91	2.02	2.9193 (16)	169
N7—H7D⋯O1^v	0.91	2.15	2.8715 (16)	135
C7—H7A⋯O2^vi	0.99	2.43	3.4215 (18)	175
Symmetry codes: (i) -x+1, -y+1, -z+1; (ii) -x+2, -y+2, -z+1; (iii) -x+2, -y+1, -z; (iv) x+1, y, z; (v) -x+1, -y+2, -z+2; (vi) -x+1, -y+2, -z+1.

Figure 2
Packing projected onto (382) showing a portion of the layer structure. O—H⋯O and O—H⋯N hydrogen bonds are shown as red dotted lines while N—H⋯O and N—H⋯N hydrogen bonds are shown as blue dotted lines.

Figure 3
A detail of the π–π stacking interactions between molecules at x, y, z and 2 − x, 1 − y, 1 − z.

Synthesis and crystallization

Ethyl 2-(2-amino-5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7-yl) acetate 1 g (0.004 mol) was refluxed with hydrazine hydrate 0.44 ml (0.008 mol) in absolute ethanol for 4–5 h. On cooling the mixture, white crystals of 2-(2-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)acetohydrazide monohydrate separated out in 80% yield.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	C₈H₁₁N₇O·H₂O
M_r	239.25
Crystal system, space group	Triclinic, P $[\overline{1}]$
Temperature (K)	150
a, b, c (Å)	7.2648 (3), 8.7228 (4), 8.9297 (4)
α, β, γ (°)	82.834 (2), 71.465 (2), 85.478 (1)
V (Å³)	531.87 (4)
Z	2
Radiation type	Cu Kα
μ (mm⁻¹)	0.96
Crystal size (mm)	0.21 × 0.16 × 0.08

Data collection
Diffractometer	Bruker D8 VENTURE PHOTON 100 CMOS
Absorption correction	Multi-scan (SADABS; Bruker, 2016 )
T_min, T_max	0.83, 0.92
No. of measured, independent and observed [I > 2σ(I)] reflections	8613, 2135, 1966
R_int	0.027
(sin θ/λ)_max (Å⁻¹)	0.625

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.039, 0.104, 1.06
No. of reflections	2135
No. of parameters	155
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.30, −0.22
Computer programs: APEX3 (Bruker, 2016), SAINT (Bruker, 2016), SAINT (Bruker, 2016), SHELXT (Sheldrick, 2015a ), SHELXL2014 (Sheldrick, 2015b ), PLATON (Spek, 2009 ), publCIF (Westrip, 2010 ).

Structural data

CCDC reference: 1482515

Crystal structure: contains datablocks global, I. DOI: 10.1107/S2414314616008701/hg4007sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S2414314616008701/hg4007Isup2.hkl

Supporting information file. DOI: 10.1107/S2414314616008701/hg4007Isup3.cml

checkCIF report

Computing details top

Data collection: APEX3 (Bruker, 2016); cell refinement: SAINT (Bruker, 2016); data reduction: SAINT (Bruker, 2016); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: publCIF (Westrip, 2010).

2-(2-Amino-5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7-yl)acetohydrazide monohydrate top

Crystal data top

C₈H₁₁N₇O·H₂O	Z = 2
M_r = 239.25	F(000) = 252
Triclinic, P1	D_x = 1.494 Mg m⁻³
a = 7.2648 (3) Å	Cu Kα radiation, λ = 1.54178 Å
b = 8.7228 (4) Å	Cell parameters from 7288 reflections
c = 8.9297 (4) Å	θ = 5.1–74.4°
α = 82.834 (2)°	µ = 0.96 mm⁻¹
β = 71.465 (2)°	T = 150 K
γ = 85.478 (1)°	Plate, colourless
V = 531.87 (4) Å³	0.21 × 0.16 × 0.08 mm

Data collection top

Bruker D8 VENTURE PHOTON 100 CMOS diffractometer	2135 independent reflections
Radiation source: INCOATEC IµS micro–focus source	1966 reflections with I > 2σ(I)
Mirror monochromator	R_int = 0.027
Detector resolution: 10.4167 pixels mm^-1	θ_max = 74.4°, θ_min = 5.1°
ω scans	h = −9→9
Absorption correction: multi-scan (SADABS; Bruker, 2016)	k = −10→10
T_min = 0.83, T_max = 0.92	l = −11→11
8613 measured reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.039	Hydrogen site location: mixed
wR(F²) = 0.104	H-atom parameters constrained
S = 1.06	w = 1/[σ²(F_o²) + (0.0511P)² + 0.2766P] where P = (F_o² + 2F_c²)/3
2135 reflections	(Δ/σ)_max < 0.001
155 parameters	Δρ_max = 0.30 e Å⁻³
0 restraints	Δρ_min = −0.22 e Å⁻³

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.

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 > 2sigma(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. H-atoms attached to carbon were placed in calculated positions (C—H = 0.95 - 0.99 Å) while those attached to nitrogen and to oxygen were placed in locations derived from a difference map and their parameters adjusted to give N—H = 0.91 and O—H = 0.87 Å. All were included as riding contributions with isotropic displacement parameters 1.2 - 1.5 times those of the attached atoms.

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

	x	y	z	U_iso*/U_eq
O1	0.56050 (15)	0.88518 (13)	0.82814 (13)	0.0295 (3)
N1	0.85056 (17)	0.64386 (13)	0.42124 (13)	0.0188 (3)
N2	0.96315 (17)	0.73473 (13)	0.29304 (13)	0.0212 (3)
N3	0.91216 (18)	0.50117 (13)	0.22122 (14)	0.0221 (3)
N4	0.71916 (17)	0.39440 (13)	0.48112 (14)	0.0211 (3)
N5	1.1119 (2)	0.68303 (15)	0.02980 (15)	0.0302 (3)
H5B	1.1518	0.7819	0.0107	0.036*
H5A	1.1098	0.6274	−0.0493	0.036*
N6	0.86297 (17)	0.91552 (14)	0.83455 (14)	0.0231 (3)
H6D	0.9931	0.9192	0.7843	0.028*
N7	0.79660 (18)	0.97790 (14)	0.98230 (14)	0.0237 (3)
H7D	0.6648	0.9874	1.0086	0.028*
H7C	0.8283	0.9061	1.0542	0.028*
C1	0.9968 (2)	0.64125 (16)	0.17728 (16)	0.0218 (3)
C2	0.8213 (2)	0.50413 (15)	0.37634 (16)	0.0195 (3)
C3	0.6465 (2)	0.42573 (16)	0.63186 (17)	0.0216 (3)
C4	0.6719 (2)	0.56896 (16)	0.68086 (17)	0.0221 (3)
H4	0.6155	0.5878	0.7888	0.027*
C5	0.77773 (19)	0.68022 (15)	0.57282 (16)	0.0192 (3)
C6	0.5390 (2)	0.30117 (17)	0.75096 (18)	0.0276 (3)
H6A	0.4841	0.2334	0.6979	0.041*
H6B	0.4339	0.3480	0.8334	0.041*
H6C	0.6286	0.2405	0.7996	0.041*
C7	0.8302 (2)	0.83592 (16)	0.59765 (16)	0.0222 (3)
H7A	0.7896	0.9152	0.5236	0.027*
H7B	0.9732	0.8376	0.5703	0.027*
C8	0.7395 (2)	0.87902 (15)	0.76432 (17)	0.0215 (3)
O2	0.27856 (16)	0.88291 (12)	0.66816 (13)	0.0296 (3)
H2B	0.3787	0.8856	0.7012	0.044*
H2A	0.3067	0.7999	0.6191	0.044*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0224 (5)	0.0370 (6)	0.0313 (6)	−0.0006 (4)	−0.0067 (4)	−0.0172 (5)
N1	0.0234 (6)	0.0169 (5)	0.0185 (6)	−0.0004 (4)	−0.0083 (4)	−0.0057 (4)
N2	0.0278 (6)	0.0185 (6)	0.0179 (6)	−0.0035 (4)	−0.0066 (5)	−0.0035 (4)
N3	0.0296 (6)	0.0192 (6)	0.0198 (6)	−0.0024 (5)	−0.0089 (5)	−0.0059 (4)
N4	0.0246 (6)	0.0190 (6)	0.0223 (6)	−0.0010 (4)	−0.0103 (5)	−0.0040 (4)
N5	0.0475 (8)	0.0251 (6)	0.0188 (6)	−0.0116 (6)	−0.0078 (6)	−0.0056 (5)
N6	0.0222 (6)	0.0259 (6)	0.0225 (6)	−0.0022 (5)	−0.0053 (5)	−0.0108 (5)
N7	0.0250 (6)	0.0260 (6)	0.0214 (6)	−0.0017 (5)	−0.0062 (5)	−0.0097 (5)
C1	0.0274 (7)	0.0201 (6)	0.0204 (7)	−0.0010 (5)	−0.0098 (6)	−0.0054 (5)
C2	0.0237 (7)	0.0165 (6)	0.0223 (7)	0.0008 (5)	−0.0114 (5)	−0.0066 (5)
C3	0.0214 (7)	0.0213 (7)	0.0242 (7)	−0.0003 (5)	−0.0098 (6)	−0.0027 (5)
C4	0.0240 (7)	0.0220 (7)	0.0214 (7)	−0.0001 (5)	−0.0073 (6)	−0.0059 (5)
C5	0.0208 (6)	0.0192 (6)	0.0198 (6)	0.0017 (5)	−0.0081 (5)	−0.0075 (5)
C6	0.0304 (8)	0.0240 (7)	0.0279 (8)	−0.0058 (6)	−0.0084 (6)	0.0004 (6)
C7	0.0259 (7)	0.0200 (7)	0.0213 (7)	−0.0030 (5)	−0.0060 (6)	−0.0076 (5)
C8	0.0237 (7)	0.0170 (6)	0.0249 (7)	−0.0011 (5)	−0.0072 (6)	−0.0070 (5)
O2	0.0307 (6)	0.0266 (5)	0.0366 (6)	0.0024 (4)	−0.0147 (5)	−0.0132 (4)

Geometric parameters (Å, º) top

O1—C8	1.2425 (18)	N7—H7D	0.9099
N1—C5	1.3558 (17)	N7—H7C	0.9100
N1—N2	1.3742 (16)	C3—C4	1.4180 (19)
N1—C2	1.3814 (16)	C3—C6	1.496 (2)
N2—C1	1.3458 (17)	C4—C5	1.370 (2)
N3—C2	1.3342 (18)	C4—H4	0.9500
N3—C1	1.3677 (18)	C5—C7	1.4997 (18)
N4—C3	1.3351 (18)	C6—H6A	0.9800
N4—C2	1.3377 (18)	C6—H6B	0.9800
N5—C1	1.3396 (19)	C6—H6C	0.9800
N5—H5B	0.9099	C7—C8	1.5058 (18)
N5—H5A	0.9098	C7—H7A	0.9900
N6—C8	1.3237 (18)	C7—H7B	0.9900
N6—N7	1.4151 (15)	O2—H2B	0.8701
N6—H6D	0.9100	O2—H2A	0.8702

C5—N1—N2	126.59 (11)	C4—C3—C6	120.25 (13)
C5—N1—C2	122.89 (12)	C5—C4—C3	120.14 (13)
N2—N1—C2	110.52 (11)	C5—C4—H4	119.9
C1—N2—N1	101.11 (11)	C3—C4—H4	119.9
C2—N3—C1	103.21 (11)	N1—C5—C4	115.77 (12)
C3—N4—C2	116.98 (12)	N1—C5—C7	114.62 (12)
C1—N5—H5B	115.8	C4—C5—C7	129.60 (12)
C1—N5—H5A	118.1	C3—C6—H6A	109.5
H5B—N5—H5A	122.4	C3—C6—H6B	109.5
C8—N6—N7	121.17 (12)	H6A—C6—H6B	109.5
C8—N6—H6D	122.6	C3—C6—H6C	109.5
N7—N6—H6D	115.3	H6A—C6—H6C	109.5
N6—N7—H7D	106.4	H6B—C6—H6C	109.5
N6—N7—H7C	106.6	C5—C7—C8	114.22 (12)
H7D—N7—H7C	108.5	C5—C7—H7A	108.7
N5—C1—N2	121.12 (13)	C8—C7—H7A	108.7
N5—C1—N3	122.86 (12)	C5—C7—H7B	108.7
N2—C1—N3	115.99 (13)	C8—C7—H7B	108.7
N3—C2—N4	129.03 (12)	H7A—C7—H7B	107.6
N3—C2—N1	109.16 (12)	O1—C8—N6	122.79 (13)
N4—C2—N1	121.79 (12)	O1—C8—C7	121.80 (12)
N4—C3—C4	122.42 (13)	N6—C8—C7	115.36 (12)
N4—C3—C6	117.31 (12)	H2B—O2—H2A	101.3

C5—N1—N2—C1	178.41 (13)	C2—N4—C3—C6	−177.54 (12)
C2—N1—N2—C1	−0.65 (14)	N4—C3—C4—C5	−1.4 (2)
N1—N2—C1—N5	−176.73 (13)	C6—C3—C4—C5	177.09 (13)
N1—N2—C1—N3	1.19 (15)	N2—N1—C5—C4	−178.90 (12)
C2—N3—C1—N5	176.63 (13)	C2—N1—C5—C4	0.05 (19)
C2—N3—C1—N2	−1.25 (16)	N2—N1—C5—C7	−0.43 (19)
C1—N3—C2—N4	−177.86 (14)	C2—N1—C5—C7	178.52 (12)
C1—N3—C2—N1	0.72 (14)	C3—C4—C5—N1	0.81 (19)
C3—N4—C2—N3	178.34 (13)	C3—C4—C5—C7	−177.38 (13)
C3—N4—C2—N1	−0.08 (19)	N1—C5—C7—C8	176.75 (11)
C5—N1—C2—N3	−179.15 (12)	C4—C5—C7—C8	−5.0 (2)
N2—N1—C2—N3	−0.05 (15)	N7—N6—C8—O1	−5.9 (2)
C5—N1—C2—N4	−0.4 (2)	N7—N6—C8—C7	171.46 (12)
N2—N1—C2—N4	178.65 (12)	C5—C7—C8—O1	−58.21 (18)
C2—N4—C3—C4	0.98 (19)	C5—C7—C8—N6	124.40 (13)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2B···O1	0.87	2.00	2.8478 (15)	166
O2—H2A···N4ⁱ	0.87	2.06	2.9004 (16)	162
N5—H5B···N7ⁱⁱ	0.91	2.17	3.0636 (17)	167
N5—H5A···N3ⁱⁱⁱ	0.91	2.06	2.9713 (17)	177
N6—H6D···O2^iv	0.91	2.02	2.9193 (16)	169
N7—H7D···O1^v	0.91	2.15	2.8715 (16)	135
C7—H7A···O2^vi	0.99	2.43	3.4215 (18)	175

Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) −x+2, −y+2, −z+1; (iii) −x+2, −y+1, −z; (iv) x+1, y, z; (v) −x+1, −y+2, −z+2; (vi) −x+1, −y+2, −z+1.

Acknowledgements

The support of NSF–MRI Grant No. 1228232 for the purchase of the diffractometer and Tulane University for support of the Tulane Crystallography Laboratory are gratefully acknowledged.

References

Bruker (2016). APEX3, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

2-(2-Amino-5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7-yl)acetohydrazide monohydrate

Structure description

Synthesis and crystallization

Refinement

Structural data

Acknowledgements

References

organic compounds