(7R)-6-Methyl-7,9-bis­(prop-2-yn-1-yl)-7H,8H,9H-1,2,4-triazolo[4,3-b][1,2,4]triazepin-8-one

El Bakri, Y.; Harmaoui, A.; Sebhaoui, J.; Ramli, Y.; Essassi, E.M.; Mague, J.T.

doi:10.1107/S2414314616012451

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 1| Part 8| August 2016| x161245

doi:10.1107/S2414314616012451

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(7R)-6-Methyl-7,9-bis(prop-2-yn-1-yl)-7H,8H,9H-1,2,4-triazolo[4,3-b][1,2,4]triazepin-8-one

Youness El Bakri,^a ^* Abdallah Harmaoui,^a Jihad Sebhaoui,^a Youssef Ramli,^b El Mokhtar Essassi ^a and Joel T. Mague ^c

^aLaboratoire de Chimie Organique Hétérocyclique, URAC 21, Pôle de Compétence Pharmacochimie, Av Ibn Battouta, BP 1014, Faculté des Sciences, Mohammed V University, Rabat, Morocco, ^bMedicinal Chemistry Laboratory, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, 10170 Rabat, Morocco, and ^cDepartment of Chemistry, Tulane University, New Orleans, LA 70118, USA
^*Correspondence e-mail: youness.chimie14@gmail.com

Edited by S. Bernès, Benemérita Universidad Autónoma de Puebla, México (Received 27 July 2016; accepted 2 August 2016; online 5 August 2016)

In the title molecule, C₁₂H₁₁N₅O, the seven-membered ring derived from triazepine adopts a boat conformation. Intermolecular C—H⋯N hydrogen bonds and C—H⋯π-ring interactions form columns of molecules parallel to the a axis, which are further associated into the three-dimensional crystal structure by additional C—H⋯O hydrogen bonds.

Keywords: crystal structure; hydrogen bonds; alkyne; triazepine.

CCDC reference: 1497249

Structure description

Fused triazepines with a bridged nitrogen atom in heterocyclic systems exhibit interesting biological properties (Groszkowski & Wrona, 1978 ; Lenman et al., 1997 ). Triazepine derivatives have also been reported to possess antifungal activity (Gupta et al., 2011 ). As a continuation of our previous studies on the synthesis and reactivity of fused triazepines (Essassi et al., 1977 ; Zemama et al., 2009 ; Harmaoui et al., 2015 ), we report the synthesis and crystal structure of the title compound (Fig. 1). A puckering analysis of the seven-membered ring yielded the parameters q₂ = 0.847 (1) Å, φ₂ = 228.47 (8)°, q₃ = 0.235 (1) Å, and φ₃ = 79.7 (3)°. These metrics indicate that the ring adopts a boat conformation.

Figure 1
The title molecule with 30% probability ellipsoids for non-H atoms. Only one orientation of the disordered propynyl group C12/C13/C14 is shown.

The molecules are stacked parallel to the a axis through the action of intermolecular C7—H7⋯N4ⁱ hydrogen bonds [symmetry code: (i) 1 − x, 1 − y, 1 − z; Table 1] and C12—H12B⋯π(Cgⁱⁱ) interactions [symmetry code: (ii) 2 − x, 1 − y, 1 − z; Cg is the centroid of the C1/C4/N1/N4/N5 ring], characterized by H12B⋯Cgⁱⁱ = 3.217 Å and C12—H12B⋯Cgⁱⁱ = 138°. Finally, intermolecular C4—H4⋯O1ⁱⁱⁱ hydrogen bonds [symmetry code: (iii) 1 − x, $[{1\over 2}]$ + y, $[{1\over 2}]$ − z; Table 1] tie the columns together to form the full three-dimensional structure (Fig. 2).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C7—H7⋯N4ⁱ	0.98	2.40	3.164 (2)	135
C4—H4⋯O1ⁱⁱ	0.93	2.23	3.147 (2)	167
Symmetry codes: (i) -x+1, -y+1, -z+1; (ii) $[-x+1, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]$ .

Figure 2
Packing viewed along the a axis with C—H⋯O hydrogen bonds shown as dotted lines.

Synthesis and crystallization

To a solution of 6-methyl-7H-[1,2,4]triazolo[4,3-b][1,2,4]triazepin-8(9H)-one (0.3 g, 1.82 mmol) in N,N-dimethylformamide (10 ml), was added potassium carbonate (0.25 g, 1.82 mmol), propargyl bromide (0.14 ml, 1.82 mmol) and a catalytic amount of tetra-n-butylammonium bromide. The reaction mixture was stirred for 12 h. The solution was then taken to dryness under reduced pressure and the residue was extracted with dichloromethane. The precipitate formed under cooling was filtered off and recrystallized from ethanol solutionto give colourless crystals in 30% yield.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. The propynyl substituent attached to N3 is disordered over two sites, modelled with C12/C13/C14 [occupancy: 0.610 (15)] and C12A/C13A/C14A [occupancy:0.390 (15)]. The components of the disorder were refined with restraints on both the geometry and displacement parameters.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₂H₁₁N₅O
M_r	241.26
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	296
a, b, c (Å)	7.5436 (3), 15.6498 (6), 10.9701 (4)
β (°)	108.334 (1)
V (Å³)	1229.34 (8)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.09
Crystal size (mm)	0.42 × 0.42 × 0.31

Data collection
Diffractometer	Bruker SMART APEX CCD
Absorption correction	Multi-scan (SADABS; Bruker, 2016 )
T_min, T_max	0.89, 0.97
No. of measured, independent and observed [I > 2σ(I)] reflections	23271, 3313, 2701
R_int	0.031
(sin θ/λ)_max (Å⁻¹)	0.686

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.047, 0.143, 1.05
No. of reflections	3313
No. of parameters	174
No. of restraints	28
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.49, −0.18
Computer programs: APEX3 and SAINT (Bruker, 2016), SHELXT (Sheldrick, 2015a ), SHELXL2014 (Sheldrick, 2015b ), DIAMOND (Brandenburg & Putz, 2012 ) and SHELXTL (Sheldrick, 2008 ).

Structural data

CCDC reference: 1497249

Crystal structure: contains datablocks global, I. DOI: 10.1107/S2414314616012451/bh4010sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S2414314616012451/bh4010Isup2.hkl

Supporting information file. DOI: 10.1107/S2414314616012451/bh4010Isup3.cdx

Supporting information file. DOI: 10.1107/S2414314616012451/bh4010Isup4.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: DIAMOND (Brandenburg & Putz, 2012); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

(7R)-6-Methyl-7,9-bis(prop-2-yn-1-yl)-7H,8H,9H-1,2,4-triazolo[4,3-b][1,2,4]triazepin-8-one top

Crystal data top

C₁₂H₁₁N₅O	F(000) = 504
M_r = 241.26	D_x = 1.304 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
a = 7.5436 (3) Å	Cell parameters from 9984 reflections
b = 15.6498 (6) Å	θ = 2.4–29.1°
c = 10.9701 (4) Å	µ = 0.09 mm⁻¹
β = 108.334 (1)°	T = 296 K
V = 1229.34 (8) Å³	Block, colourless
Z = 4	0.42 × 0.42 × 0.31 mm

Data collection top

Bruker SMART APEX CCD diffractometer	3313 independent reflections
Radiation source: fine-focus sealed tube	2701 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.031
Detector resolution: 8.3333 pixels mm^-1	θ_max = 29.2°, θ_min = 2.4°
φ and ω scans	h = −10→10
Absorption correction: multi-scan (SADABS; Bruker, 2016)	k = −21→21
T_min = 0.89, T_max = 0.97	l = −15→14
23271 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)] = 0.047	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.143	H-atom parameters constrained
S = 1.05	w = 1/[σ²(F_o²) + (0.0829P)² + 0.1647P] where P = (F_o² + 2F_c²)/3
3313 reflections	(Δ/σ)_max < 0.001
174 parameters	Δρ_max = 0.49 e Å⁻³
28 restraints	Δρ_min = −0.18 e Å⁻³

Special details top

Experimental. The diffraction data were obtained from 3 sets of 400 frames, each of width 0.5° in ω, colllected at φ = 0.00, 90.00 and 180.00° and 2 sets of 800 frames, each of width 0.45° in φ, collected at ω = –30.00 and 210.00°. The scan time was 7 sec/frame.

Refinement. H-atoms attached to carbon were placed in calculated positions (C—H = 0.95 - 0.99 Å). All were included as riding contributions with isotropic displacement parameters 1.2 - 1.5 times those of the attached atoms. The propynyl substituent attached to N3 is disordered over two sites in a 61/39 ratio. The components of the disorder were refined with restraints that their geometries be comparable.

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

	x	y	z	U_iso*/U_eq	Occ. (<1)
O1	0.53407 (14)	0.26656 (6)	0.38907 (9)	0.0503 (3)
N1	0.54858 (14)	0.52089 (6)	0.27441 (9)	0.0370 (2)
N2	0.46611 (15)	0.48217 (7)	0.15514 (9)	0.0403 (2)
N3	0.66193 (13)	0.39844 (6)	0.41282 (9)	0.0364 (2)
C1	0.64572 (15)	0.48540 (7)	0.38983 (10)	0.0338 (2)
C4	0.5849 (2)	0.60626 (8)	0.29144 (14)	0.0477 (3)
H4	0.5396	0.6474	0.2282	0.057*
N4	0.73180 (15)	0.54449 (7)	0.47134 (10)	0.0434 (3)
C5	0.37243 (15)	0.41413 (8)	0.15763 (10)	0.0366 (3)
N5	0.69043 (17)	0.62237 (7)	0.40691 (12)	0.0508 (3)
C6	0.3048 (2)	0.36453 (11)	0.03514 (13)	0.0561 (4)
H6A	0.1733	0.3540	0.0149	0.084*
H6B	0.3702	0.3111	0.0450	0.084*
H6C	0.3274	0.3967	−0.0330	0.084*
C7	0.33705 (15)	0.38234 (7)	0.27846 (10)	0.0336 (2)
H7	0.3101	0.4323	0.3235	0.040*
C8	0.17263 (17)	0.32044 (9)	0.25592 (14)	0.0477 (3)
H8A	0.1948	0.2706	0.2103	0.057*
H8B	0.1640	0.3016	0.3381	0.057*
C9	−0.00402 (19)	0.36025 (11)	0.18177 (16)	0.0561 (4)
C10	−0.1441 (2)	0.39323 (15)	0.1201 (2)	0.0803 (6)
H10	−0.2545	0.4192	0.0715	0.096*
C11	0.51588 (15)	0.34220 (7)	0.36473 (10)	0.0345 (2)
C12	0.8373 (10)	0.3649 (11)	0.5031 (6)	0.0457 (7)	0.610 (15)
H12A	0.8427	0.3038	0.4902	0.055*	0.610 (15)
H12B	0.9420	0.3908	0.4835	0.055*	0.610 (15)
C13	0.8572 (15)	0.3810 (5)	0.6390 (6)	0.0565 (12)	0.610 (15)
C14	0.8738 (13)	0.3912 (7)	0.7481 (6)	0.0894 (19)	0.610 (15)
H14	0.8870	0.3992	0.8345	0.107*	0.610 (15)
C12A	0.8455 (15)	0.3695 (17)	0.4981 (8)	0.0457 (7)	0.390 (15)
H12C	0.8769	0.3151	0.4677	0.055*	0.390 (15)
H12D	0.9406	0.4106	0.4957	0.055*	0.390 (15)
C13A	0.843 (2)	0.3600 (8)	0.6311 (9)	0.0565 (12)	0.390 (15)
C14A	0.853 (2)	0.3561 (9)	0.7398 (9)	0.0894 (19)	0.390 (15)
H14A	0.8603	0.3530	0.8260	0.107*	0.390 (15)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0540 (5)	0.0310 (4)	0.0566 (5)	−0.0013 (4)	0.0044 (4)	0.0021 (4)
N1	0.0419 (5)	0.0323 (5)	0.0368 (5)	−0.0023 (4)	0.0123 (4)	0.0002 (3)
N2	0.0458 (6)	0.0431 (6)	0.0320 (5)	0.0004 (4)	0.0122 (4)	0.0007 (4)
N3	0.0315 (5)	0.0330 (5)	0.0392 (5)	−0.0002 (4)	0.0033 (4)	0.0000 (4)
C1	0.0316 (5)	0.0337 (6)	0.0362 (5)	−0.0023 (4)	0.0108 (4)	−0.0026 (4)
C4	0.0533 (7)	0.0321 (6)	0.0587 (8)	−0.0032 (5)	0.0190 (6)	0.0031 (5)
N4	0.0440 (5)	0.0382 (6)	0.0459 (6)	−0.0079 (4)	0.0109 (4)	−0.0092 (4)
C5	0.0365 (6)	0.0405 (6)	0.0307 (5)	0.0050 (4)	0.0075 (4)	−0.0036 (4)
N5	0.0528 (6)	0.0351 (6)	0.0637 (7)	−0.0073 (5)	0.0173 (6)	−0.0077 (5)
C6	0.0615 (9)	0.0670 (9)	0.0367 (6)	−0.0035 (7)	0.0108 (6)	−0.0162 (6)
C7	0.0320 (5)	0.0339 (5)	0.0328 (5)	−0.0019 (4)	0.0074 (4)	−0.0033 (4)
C8	0.0376 (6)	0.0458 (7)	0.0550 (7)	−0.0094 (5)	0.0078 (5)	−0.0014 (5)
C9	0.0356 (6)	0.0638 (9)	0.0651 (9)	−0.0079 (6)	0.0105 (6)	−0.0065 (7)
C10	0.0416 (8)	0.1020 (16)	0.0906 (14)	0.0074 (9)	0.0111 (8)	−0.0008 (11)
C11	0.0356 (5)	0.0321 (5)	0.0337 (5)	−0.0020 (4)	0.0078 (4)	−0.0024 (4)
C12	0.0305 (8)	0.0461 (15)	0.0528 (8)	0.0049 (9)	0.0024 (6)	−0.0016 (7)
C13	0.0455 (17)	0.058 (4)	0.0515 (11)	0.014 (3)	−0.0054 (11)	−0.0008 (15)
C14	0.088 (3)	0.112 (5)	0.0508 (13)	0.049 (4)	−0.0025 (14)	−0.004 (2)
C12A	0.0305 (8)	0.0461 (15)	0.0528 (8)	0.0049 (9)	0.0024 (6)	−0.0016 (7)
C13A	0.0455 (17)	0.058 (4)	0.0515 (11)	0.014 (3)	−0.0054 (11)	−0.0008 (15)
C14A	0.088 (3)	0.112 (5)	0.0508 (13)	0.049 (4)	−0.0025 (14)	−0.004 (2)

Geometric parameters (Å, º) top

O1—C11	1.2117 (14)	C7—C11	1.5189 (15)
N1—C4	1.3649 (16)	C7—C8	1.5314 (16)
N1—C1	1.3657 (14)	C7—H7	0.9800
N1—N2	1.3979 (13)	C8—C9	1.4641 (19)
N2—C5	1.2830 (16)	C8—H8A	0.9700
N3—C11	1.3789 (14)	C8—H8B	0.9700
N3—C1	1.3824 (15)	C9—C10	1.179 (2)
N3—C12	1.4773 (18)	C10—H10	0.9300
N3—C12A	1.477 (2)	C12—C13	1.472 (4)
C1—N4	1.3082 (14)	C12—H12A	0.9700
C4—N5	1.2913 (19)	C12—H12B	0.9700
C4—H4	0.9300	C13—C14	1.174 (3)
N4—N5	1.3941 (16)	C14—H14	0.9300
C5—C6	1.4957 (16)	C12A—C13A	1.472 (4)
C5—C7	1.5160 (15)	C12A—H12C	0.9700
C6—H6A	0.9600	C12A—H12D	0.9700
C6—H6B	0.9600	C13A—C14A	1.174 (3)
C6—H6C	0.9600	C14A—H14A	0.9300

C4—N1—C1	104.19 (10)	C11—C7—H7	107.5
C4—N1—N2	124.30 (10)	C8—C7—H7	107.5
C1—N1—N2	129.98 (10)	C9—C8—C7	111.70 (11)
C5—N2—N1	115.21 (9)	C9—C8—H8A	109.3
C11—N3—C1	122.98 (9)	C7—C8—H8A	109.3
C11—N3—C12	118.0 (7)	C9—C8—H8B	109.3
C1—N3—C12	118.8 (7)	C7—C8—H8B	109.3
C11—N3—C12A	121.5 (11)	H8A—C8—H8B	107.9
C1—N3—C12A	115.4 (11)	C10—C9—C8	178.34 (19)
N4—C1—N1	110.63 (10)	C9—C10—H10	180.0
N4—C1—N3	125.09 (11)	O1—C11—N3	121.18 (10)
N1—C1—N3	124.09 (10)	O1—C11—C7	123.93 (10)
N5—C4—N1	111.14 (12)	N3—C11—C7	114.87 (9)
N5—C4—H4	124.4	C13—C12—N3	113.7 (6)
N1—C4—H4	124.4	C13—C12—H12A	108.8
C1—N4—N5	106.72 (10)	N3—C12—H12A	108.8
N2—C5—C6	116.50 (11)	C13—C12—H12B	108.8
N2—C5—C7	122.72 (10)	N3—C12—H12B	108.8
C6—C5—C7	120.73 (11)	H12A—C12—H12B	107.7
C4—N5—N4	107.30 (10)	C14—C13—C12	177.9 (9)
C5—C6—H6A	109.5	C13—C14—H14	180.0
C5—C6—H6B	109.5	C13A—C12A—N3	110.9 (8)
H6A—C6—H6B	109.5	C13A—C12A—H12C	109.5
C5—C6—H6C	109.5	N3—C12A—H12C	109.5
H6A—C6—H6C	109.5	C13A—C12A—H12D	109.5
H6B—C6—H6C	109.5	N3—C12A—H12D	109.5
C5—C7—C11	108.32 (9)	H12C—C12A—H12D	108.0
C5—C7—C8	115.01 (9)	C14A—C13A—C12A	175.1 (17)
C11—C7—C8	110.76 (9)	C13A—C14A—H14A	180.0
C5—C7—H7	107.5

C4—N1—N2—C5	−151.65 (12)	N2—C5—C7—C11	−75.45 (14)
C1—N1—N2—C5	44.75 (17)	C6—C5—C7—C11	102.00 (12)
C4—N1—C1—N4	0.99 (13)	N2—C5—C7—C8	160.04 (11)
N2—N1—C1—N4	167.07 (11)	C6—C5—C7—C8	−22.50 (16)
C4—N1—C1—N3	−174.20 (11)	C5—C7—C8—C9	−61.48 (15)
N2—N1—C1—N3	−8.12 (18)	C11—C7—C8—C9	175.30 (11)
C11—N3—C1—N4	145.40 (12)	C1—N3—C11—O1	−178.44 (11)
C12—N3—C1—N4	−28.4 (3)	C12—N3—C11—O1	−4.6 (3)
C12A—N3—C1—N4	−31.9 (5)	C12A—N3—C11—O1	−1.3 (5)
C11—N3—C1—N1	−40.11 (16)	C1—N3—C11—C7	2.93 (15)
C12—N3—C1—N1	146.1 (3)	C12—N3—C11—C7	176.7 (3)
C12A—N3—C1—N1	142.6 (5)	C12A—N3—C11—C7	−179.9 (5)
C1—N1—C4—N5	−1.42 (15)	C5—C7—C11—O1	−112.30 (13)
N2—N1—C4—N5	−168.53 (11)	C8—C7—C11—O1	14.70 (16)
N1—C1—N4—N5	−0.24 (13)	C5—C7—C11—N3	66.29 (12)
N3—C1—N4—N5	174.88 (11)	C8—C7—C11—N3	−166.71 (10)
N1—N2—C5—C6	−171.81 (11)	C11—N3—C12—C13	−98.7 (11)
N1—N2—C5—C7	5.75 (16)	C1—N3—C12—C13	75.3 (11)
N1—C4—N5—N4	1.31 (16)	C11—N3—C12A—C13A	−80.7 (18)
C1—N4—N5—C4	−0.65 (15)	C1—N3—C12A—C13A	96.7 (17)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C7—H7···N4ⁱ	0.98	2.40	3.164 (2)	135
C4—H4···O1ⁱⁱ	0.93	2.23	3.147 (2)	167

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

Acknowledgements

JTM thanks Tulane University for support of the Tulane Crystallography Laboratory.

References

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