Crystal structure of 2-chloro-5-(3-hy­droxy-3-methyl­but-1-yn-1-yl)pyrimidine

Hübscher, J.; Seichter, W.; Weber, E.

doi:10.1107/S2056989017010027

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Volume 73| Part 8| August 2017| Pages 1172-1174

https://doi.org/10.1107/S2056989017010027

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Crystal structure of 2-chloro-5-(3-hydroxy-3-methylbut-1-yn-1-yl)pyrimidine

Jörg Hübscher,^a Wilhelm Seichter ^a and Edwin Weber ^a ^*

^aInstitut für Organische Chemie, TU Bergakademie Freiberg, Leipziger Strasse 29, D-09596 Freiberg/Sachsen, Germany
^*Correspondence e-mail: edwin.weber@chemie.tu-freiberg.de

Edited by O. Blacque, University of Zürich, Switzerland (Received 30 June 2017; accepted 6 July 2017; online 13 July 2017)

In the title compound, C₉H₉ClN₂O, the ethynylpyrimidine moiety displays an almost planar geometry. In the crystal, molecules are linked by O—H⋯N and C—H_pyrimidine⋯O hydrogen bonds, forming a three-dimensional supramolecular architecture.

Keywords: crystal structure; 5-ethynylpyrimidine derivative; O—H⋯N hydrogen bonding; C—H⋯O contact.

CCDC reference: 1560599

1. Chemical context

The title compound, featuring a blocked acetylenic group and a chloro-substituted pyrimidine ring, is an interesting synthetic intermediate for the preparation of application-oriented solid materials including both porous coordination polymers (MacGillivray, 2010 ) and metal-organic frameworks (Noro & Kitagawa, 2010 ). Deprotection of the acetylenic functional group and transformation of the chloro substituent, e.g. into thiol or amino groups, should result in molecular building blocks for the formation of corresponding aggregate structures (Hübscher et al., 2015 ; Günthel et al., 2015 ; Hübscher et al., 2017 ). Aside from this experimental preparative relevance, substituted 3-hydroxyalkynes are also of considerable interest due to their structural capacity in supramolecular interactions, giving rise to particular modes of aggregation and behavior in the solid state (Toda et al., 1983 , 1985 ; Bourne et al., 1994 ). In combination with heterocyclic nitrogen donors and chlorine substitution, as in the present title compound, a structural study involving competition aspects with regard to hydrogen bonding (Wang & Zheng, 2015 ) and potential halogen (Mukherjee et al., 2014 ) or π-electron assisted (Tiekink & Zukerman-Schpector, 2012 ) interactions should be a promising field of inquiry for crystal engineering (Desiraju et al., 2012 ) being subject to the contacts emanating from a variety of functional groups. Thus, in this respect, the title compound could serve as a worthwhile test substance.

2. Structural commentary

A perspective view of the molecular structure of the title compound is depicted in Fig. 1. The ethynylpyrimidine moiety of the molecule is almost planar with the largest atomic distances from the mean plane being 0.015 (1) Å for atom C1 and 0.013 (1) Å for atom C4. The OH group adopts a staggered arrangement with respect to the ethynyl unit and the methyl group C9, the C6—C7—O1–H1 torsion angle being 57.0°.

Figure 1
Perspective view of the molecular structure of the title compound including the atom-numbering scheme. Displacement parameters are drawn at the 50% probability level.

3. Supramolecular features

An O—H⋯π_C≡C hydrogen-bond type intermolecular interaction mode typical of 3-hydroxyalkyne structure units (Desiraju & Steiner, 1999 ) is not present here, apparently in favor of a stronger O—H⋯N hydrogen bond involving the hydroxy group and a pyrimidine nitrogen atom (N2). Aside from this, C—H_pyrimidine⋯O hydrogen bonds are found to yield a three-dimensional supramolecular architecture (Table 1, Fig. 2). No other types of directed intermolecular contacts, including those involving the Cl atom or π–arene stacking, are observed. Hence, this shows that in the presence of a strong donor center such as a nitrogen atom, competing with the acetylenic moiety, the common O—H⋯π_C≡C hydrogen bonding is suppressed, which could be a useful finding in relation to aspects of crystal engineering.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C8—H8A⋯Cl1ⁱ	0.98	2.99	3.7911 (14)	140
C4—H4⋯O1ⁱⁱ	0.95	2.45	3.1963 (15)	136
C2—H2⋯O1ⁱⁱⁱ	0.95	2.60	3.2816 (14)	129
O1—H1⋯N2^iv	0.84	2.05	2.8881 (13)	172
Symmetry codes: (i) $[-x+{\script{1\over 2}}, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (ii) -x+1, -y, -z+1; (iii) $[-x+{\script{1\over 2}}, y+{\script{1\over 2}}, -z+{\script{3\over 2}}]$ ; (iv) $[x+{\script{1\over 2}}, -y+{\script{1\over 2}}, z+{\script{1\over 2}}]$ .

Figure 2
Packing excerpt of the title compound. Hydrogen bonds are shown as dashed lines.

4. Database survey

The title compound represents the first example of a 5-(3-hydroxy-3-methylbut-1-yn-1-yl)pyrimidine. A search in the Cambridge Structural Database (CSD, Version 5.38, update February 2017; Groom et al., 2016 ) for compounds containing the 4-ethynylpyrimidine fragment excluding metal complexes and co-crystals revealed nine hits. Of particular interest is the crystal structure of 5,5′-ethyne-1,2-diylbis(2-chloropyrimidine) (refcode: PUMHIQ; Hübscher et al., 2015). In this case, the absence of a strongly coordinating donor/acceptor substituent results in poor molecular association, which is restricted to π_pyrimidine⋯π_ethyne stacking interactions.

5. Synthesis and crystallization

The title compound was prepared from 2-hydroxy-5-iodopyrimidine (Pérez-Palado et al., 2007 ) and 2-methyl-3-butyn-2-ol (MEBYNOL) via a Shonogashira–Hagihara cross-coupling reaction (Sonogashira et al., 1975 ) as follows. 2-Chloro-5-iodopyrimidine (2.0 g, 8.4 mmol) and MEBYNOL (0.7 g, 8.7 mmol) were dissolved in a degassed mixture of dry diisopropylamine and THF (60 ml each). To this solution, the catalyst being composed of triphenylphosphine (2 mol%), copper(I) and iodide (3 mol-%) and trans-dichlorobis(triphenylphosphine)palladium(II) (2 mol%) was added. The mixture was stirred at room temperature away from light for 12 h, then filtered over Celite and evaporated. Crystallization from n-hexane gave colourless crystals of the title compound on slow evaporation of the solvent (yield 1.1 g, 70%; m.p. 455 K). ¹H NMR (CDCl₃): δ_H 8.64 (2H, s, pyr-H), 2.67 (1H, s, OH), 1.64 (6H, s, Me). ¹³C NMR (CDCl₃): δ_C 161.1 (pyrC-4), 159.4 (pyrC-2), 117.8 (pyrC-5), 102.4 (pyr-C≡C), 74.1 (pyr-C≡C), 65.5 (C_quat.), 31.1 (CH₃). IR (KBr) ν_max. 2240 (C≡C). GC–MS: calculated for C₉H₉N₂OCl (196.04), found 196 [M]⁺. Analysis calculated for C₉H₉N₂OCl: C, 54.97; H, 4.61; N, 14.25; found: C, 54.81; H, 4.56; N, 14.05%. Colourless crystals suitable for X-ray diffraction were obtained by slow evaporation of solvent from a chloroform solution.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. H atoms were included in calculated positions (C—H = 0.95, 0.98 Å; O—H = 0.84 Å) and allowed to ride on their parent atoms with U_iso(H) = 1.5U_eq(C,O) for methyl and hydroxy H atoms and 1.2U_eq(C) for aryl H atoms.

Table 2
Experimental details

Crystal data
Chemical formula	C₉H₉ClN₂O
M_r	196.63
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	153
a, b, c (Å)	7.5555 (3), 13.0278 (7), 9.7397 (5)
β (°)	91.767 (2)
V (Å³)	958.24 (8)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.36
Crystal size (mm)	0.60 × 0.60 × 0.20

Data collection
Diffractometer	Bruker X8 APEX2 CCD detector
Absorption correction	Multi-scan (SADABS; Bruker, 2008 )
T_min, T_max	0.814, 0.932
No. of measured, independent and observed [I > 2σ(I)] reflections	8464, 1988, 1795
R_int	0.021
(sin θ/λ)_max (Å⁻¹)	0.628

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.027, 0.074, 1.07
No. of reflections	1988
No. of parameters	121
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.22, −0.26
Computer programs: APEX2 and SAINT (Bruker, 2008), SHELXS97 and SHELXTL (Sheldrick, 2008 ), SHELXL2015 (Sheldrick, 2015 ) and ORTEP-3 for Windows (Farrugia, 2012 ).

Supporting information

CCDC reference: 1560599

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989017010027/zq2237sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989017010027/zq2237Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989017010027/zq2237Isup3.cml

checkCIF report

Computing details top

Data collection: APEX2 (Bruker, 2008); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2015 (Sheldrick, 2015); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

2-Chloro-5-(3-hydroxy-3-methylbut-1-yn-1-yl)pyrimidine top

Crystal data top

C₉H₉ClN₂O	F(000) = 408
M_r = 196.63	D_x = 1.363 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
a = 7.5555 (3) Å	Cell parameters from 5586 reflections
b = 13.0278 (7) Å	θ = 2.6–29.2°
c = 9.7397 (5) Å	µ = 0.36 mm⁻¹
β = 91.767 (2)°	T = 153 K
V = 958.24 (8) Å³	Block, colourless
Z = 4	0.60 × 0.60 × 0.20 mm

Data collection top

Bruker X8 APEX2 CCD detector diffractometer	1795 reflections with I > 2σ(I)
φ and ω scans	R_int = 0.021
Absorption correction: multi-scan (SADABS; Bruker, 2008)	θ_max = 26.5°, θ_min = 2.6°
T_min = 0.814, T_max = 0.932	h = −9→9
8464 measured reflections	k = −15→16
1988 independent reflections	l = −10→12

Refinement top

Refinement on F²	0 restraints
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.027	H-atom parameters constrained
wR(F²) = 0.074	w = 1/[σ²(F_o²) + (0.0363P)² + 0.3033P] where P = (F_o² + 2F_c²)/3
S = 1.07	(Δ/σ)_max < 0.001
1988 reflections	Δρ_max = 0.22 e Å⁻³
121 parameters	Δρ_min = −0.26 e Å⁻³

Special details top

Experimental. The melting point was measured using a microscope heating stage (Thermovar, Reichert–Jung). The NMR spectra were obtained on a Bruker Avance 500.1 (¹H) and 125.8 MHz (¹³C) with TMS as internal standard (δ in ppm). The IR spectrum was determined on a Nicolet FT–IR 510 spectrometer as KBr pellet (wavenumber is given in cm^-1). The mass spectrum was recorded on a Hewlett–Packard 5890 Series II/MS 5989A. Elemental analysis was carried out with a Hanau vario MICRO cube.

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
Cl1	0.23192 (4)	0.39748 (3)	0.09166 (3)	0.03135 (12)
O1	0.40922 (11)	−0.02601 (6)	0.82873 (9)	0.0229 (2)
H1	0.4836	0.0217	0.8368	0.034*
N1	0.33701 (13)	0.23553 (8)	0.22655 (10)	0.0237 (2)
N2	0.14057 (13)	0.34952 (8)	0.33846 (10)	0.0227 (2)
C1	0.23671 (15)	0.31831 (9)	0.23470 (12)	0.0205 (2)
C2	0.14420 (15)	0.28822 (9)	0.44881 (12)	0.0219 (3)
H2	0.0768	0.3066	0.5258	0.026*
C3	0.24367 (15)	0.19835 (9)	0.45432 (12)	0.0196 (2)
C4	0.34057 (16)	0.17568 (9)	0.33843 (12)	0.0228 (3)
H4	0.4117	0.1155	0.3389	0.027*
C5	0.24486 (15)	0.13360 (10)	0.57316 (12)	0.0222 (3)
C6	0.24267 (15)	0.08049 (9)	0.67312 (12)	0.0221 (3)
C7	0.23766 (15)	0.01625 (9)	0.79857 (12)	0.0205 (2)
C8	0.11447 (17)	−0.07507 (11)	0.77342 (14)	0.0292 (3)
H8A	0.1610	−0.1182	0.7004	0.044*
H8B	−0.0037	−0.0503	0.7457	0.044*
H8C	0.1070	−0.1154	0.8580	0.044*
C9	0.17864 (17)	0.08197 (11)	0.91878 (13)	0.0281 (3)
H9A	0.1825	0.0408	1.0030	0.042*
H9B	0.0574	0.1062	0.9003	0.042*
H9C	0.2581	0.1410	0.9300	0.042*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.03714 (19)	0.0336 (2)	0.02359 (18)	0.00504 (13)	0.00606 (13)	0.01072 (12)
O1	0.0209 (4)	0.0193 (4)	0.0288 (5)	0.0002 (3)	0.0028 (3)	0.0023 (3)
N1	0.0271 (5)	0.0234 (5)	0.0209 (5)	0.0017 (4)	0.0062 (4)	−0.0002 (4)
N2	0.0255 (5)	0.0229 (5)	0.0197 (5)	0.0039 (4)	0.0020 (4)	0.0003 (4)
C1	0.0221 (5)	0.0213 (6)	0.0180 (6)	−0.0013 (4)	0.0010 (4)	0.0017 (4)
C2	0.0238 (6)	0.0246 (6)	0.0174 (6)	0.0019 (5)	0.0031 (4)	−0.0024 (5)
C3	0.0211 (5)	0.0200 (6)	0.0176 (6)	−0.0021 (4)	0.0003 (4)	−0.0005 (4)
C4	0.0265 (6)	0.0194 (6)	0.0228 (6)	0.0024 (5)	0.0043 (5)	−0.0004 (5)
C5	0.0228 (6)	0.0224 (6)	0.0215 (6)	0.0003 (5)	0.0033 (5)	−0.0015 (5)
C6	0.0231 (6)	0.0222 (6)	0.0213 (6)	0.0007 (5)	0.0041 (5)	−0.0007 (5)
C7	0.0202 (5)	0.0224 (6)	0.0189 (6)	−0.0001 (4)	0.0032 (4)	0.0023 (5)
C8	0.0298 (6)	0.0314 (7)	0.0264 (6)	−0.0090 (5)	0.0016 (5)	0.0032 (5)
C9	0.0287 (6)	0.0330 (7)	0.0230 (6)	0.0040 (5)	0.0075 (5)	0.0000 (5)

Geometric parameters (Å, º) top

Cl1—C1	1.7329 (12)	C4—H4	0.9500
O1—C7	1.4304 (14)	C5—C6	1.1950 (18)
O1—H1	0.8400	C6—C7	1.4824 (16)
N1—C1	1.3219 (16)	C7—C8	1.5257 (17)
N1—C4	1.3396 (16)	C7—C9	1.5280 (17)
N2—C1	1.3265 (16)	C8—H8A	0.9800
N2—C2	1.3386 (15)	C8—H8B	0.9800
C2—C3	1.3914 (17)	C8—H8C	0.9800
C2—H2	0.9500	C9—H9A	0.9800
C3—C4	1.3958 (17)	C9—H9B	0.9800
C3—C5	1.4320 (16)	C9—H9C	0.9800

C7—O1—H1	109.5	O1—C7—C8	106.10 (10)
C1—N1—C4	115.04 (10)	C6—C7—C8	109.81 (10)
C1—N2—C2	115.51 (10)	O1—C7—C9	110.02 (9)
N1—C1—N2	128.63 (11)	C6—C7—C9	109.31 (10)
N1—C1—Cl1	115.79 (9)	C8—C7—C9	111.65 (10)
N2—C1—Cl1	115.58 (9)	C7—C8—H8A	109.5
N2—C2—C3	122.05 (11)	C7—C8—H8B	109.5
N2—C2—H2	119.0	H8A—C8—H8B	109.5
C3—C2—H2	119.0	C7—C8—H8C	109.5
C2—C3—C4	116.30 (11)	H8A—C8—H8C	109.5
C2—C3—C5	121.11 (11)	H8B—C8—H8C	109.5
C4—C3—C5	122.59 (11)	C7—C9—H9A	109.5
N1—C4—C3	122.47 (11)	C7—C9—H9B	109.5
N1—C4—H4	118.8	H9A—C9—H9B	109.5
C3—C4—H4	118.8	C7—C9—H9C	109.5
C6—C5—C3	178.65 (13)	H9A—C9—H9C	109.5
C5—C6—C7	178.79 (13)	H9B—C9—H9C	109.5
O1—C7—C6	109.91 (9)

C4—N1—C1—N2	0.20 (19)	N2—C2—C3—C4	0.30 (17)
C4—N1—C1—Cl1	179.40 (9)	N2—C2—C3—C5	−179.66 (11)
C2—N2—C1—N1	−0.89 (19)	C1—N1—C4—C3	0.82 (17)
C2—N2—C1—Cl1	179.91 (8)	C2—C3—C4—N1	−1.05 (18)
C1—N2—C2—C3	0.58 (17)	C5—C3—C4—N1	178.91 (11)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C8—H8A···Cl1ⁱ	0.98	2.99	3.7911 (14)	140
C4—H4···O1ⁱⁱ	0.95	2.45	3.1963 (15)	136
C2—H2···O1ⁱⁱⁱ	0.95	2.60	3.2816 (14)	129
O1—H1···N2^iv	0.84	2.05	2.8881 (13)	172

Symmetry codes: (i) −x+1/2, y−1/2, −z+1/2; (ii) −x+1, −y, −z+1; (iii) −x+1/2, y+1/2, −z+3/2; (iv) x+1/2, −y+1/2, z+1/2.

Funding information

This work was supported by the Deutsche Forschungsgemeinschaft (DFG) under the program SPP 1362/1 and by the European Union (European Regional Development Fund) including the Ministry of Science and Art of Saxony (Cluster of Excellence "Structure Design of Novel High-Performance Materials via Atomic Design and Defect Engineering, ADDE").

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