4-[(1RS,5RS,7SR)-5-Methyl-2,4-dioxo-3,6-diaza­bicyclo­[3.2.1]octan-7-yl]benzonitrile

Kudryavtsev, K.V.; Churakov, A.V.

doi:10.1107/S1600536812020156

organic compounds

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Volume 68| Part 6| June 2012| Page o1718

doi:10.1107/S1600536812020156

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4-[(1RS,5RS,7SR)-5-Methyl-2,4-dioxo-3,6-diazabicyclo[3.2.1]octan-7-yl]benzonitrile

Konstantin V. Kudryavtsev ^a,^b ^* and Andrei V. Churakov ^c

^aDepartment of Chemistry, M.V. Lomonosov Moscow State University, Leninskie Gory 1/3, Moscow 119991, Russian Federation, ^bInstitute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka 142432, Moscow region, Russian Federation, and ^cInstitute of General and Inorganic Chemistry, Russian Academy of Sciences, Leninskii prosp. 31, Moscow 119991, Russian Federation
^*Correspondence e-mail: kudr@org.chem.msu.ru

(Received 28 April 2012; accepted 4 May 2012; online 16 May 2012)

In the title compound, C₁₄H₁₃N₃O₂, the relative stereochemistry of the three stereogenic C atoms has been determined. In the crystal, N—H⋯O hydrogen bonds link the molecules into chains of inversion dimers running along the b axis.

Related literature

For general background to chemistry affording a bridged 3,6-diazabicyclo[3.2.1]octane scaffold, substituted at the 3, 5, 6, and 7 positions, and the biological activity of this class of compounds, see: Kudryavtsev (2010 ).

Experimental

Crystal data

C₁₄H₁₃N₃O₂
M_r = 255.27
Monoclinic, P 2₁ /c
a = 14.8572 (13) Å
b = 6.2269 (6) Å
c = 13.1215 (12) Å
β = 95.568 (1)°
V = 1208.20 (19) Å³
Z = 4
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 150 K
0.40 × 0.15 × 0.10 mm

Data collection

Bruker SMART APEXII diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2008 ) T_min = 0.962, T_max = 0.990
11909 measured reflections
2924 independent reflections
2601 reflections with I > 2σ(I)
R_int = 0.019

Refinement

R[F² > 2σ(F²)] = 0.040
wR(F²) = 0.110
S = 1.06
2924 reflections
224 parameters
All H-atom parameters refined
Δρ_max = 0.35 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2⋯O2ⁱ	0.899 (18)	2.368 (19)	3.2377 (14)	162.8 (15)
N1—H1⋯O1ⁱⁱ	0.877 (17)	2.032 (17)	2.9019 (14)	171.3 (15)
Symmetry codes: (i) x, y+1, z; (ii) -x, -y+1, -z+1.

Data collection: APEX2 (Bruker, 2008); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536812020156/ff2066sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536812020156/ff2066Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536812020156/ff2066Isup3.cml

checkCIF report

Comment top

In the title compound, 4-cyanophenyl substituent occupies endo position (Fig. 1). The –C(=O)NHC(=O)- system is planar within 0.046 (3) Å. The adjacent molecules are combined into double centrosymmetric chains along b-axis by N—H···O=C hydrogen bonds (Fig. 2). These chains are linked by weak van der Waals interactions.

3,6-Diazabicyclo[3.2.1]octanes are of interest as a structural motif for enzymes inhibitors. Synthesis of substituted 3,6-diazabicyclo[3.2.1]octane is based on copper(I) catalyzed intramolecular imide formation (Kudryavtsev (2010), Fig. 3).

Related literature top

For general background to chemistry affording bridged a 3,6-diazabicyclo[3.2.1]octane scaffold, substituted at the 3, 5, 6, and 7 positions, and the biological activity of this class of compounds, see: Kudryavtsev (2010).

Experimental top

(2SR,4SR,5RS)-Methyl 4-carbamoyl-5-(4-cyanophenyl)-2-methylpyrrolidine-2-carboxylate (0.862 g, 3.0 mmol) was dissolved in 30 ml of DMF, 0.054 g (0.6 mmol) of CuCN were added, and the mixture was stirred under argon at 413 K during 6 h. The solvent was distilled off under reduced pressure, and the residue was dissolved in 20 ml of AcOEt, washed with saturated solution of NaHCO₃ (2 x 7 ml). Organic phase was dried under Na₂SO₄, concentrated and recrystallized from hexane–ethyl acetate. 4-((1RS,5RS,7SR- 5-methyl-2,4-dioxo-3,6-diazabicyclo[3.2.1]octan-7-yl)benzonitrile. Yield 0.490 g (64%), colourless crystals, m.p. 497–499 K. ¹H NMR (400 MHz, DMSO-d₆): δ 1.38 (s, 3H, CH₃), 2.00 (dd, J 11.8, 4.0, 1H, H-8a), 2.31 (d, J 11.8, 1H, H-8 b), 3.37 (br.s, 1H, H-1), 3.59 (d, J 7.8, 1H, N(6)H), 4.93 (dd, J 7.8, 5.8, 1H, H-7), 7.55 (d, J 8.3, 2H, Ar), 7.73 (d, J 8.3, 2H, Ar), 10.42(s, 1H, N(3)H). ¹³C NMR (100 MHz, DMSO-d₆): δ 18.73, 40.82, 52.78, 62.73, 63.09, 109.99, 119.42, 128.01 (2 C), 132.33 (2 C), 147.52, 174.04, 176.39. Anal. Calcd. for C₁₄H₁₃N₃O₂: C, 65.87; H, 5.13; N, 16.46. Found: C, 65.92; H, 5.17; N,16.63. The crystals were obtained by slow evaporation of saturated solution in hexane–ethyl acetate (2:3) mixture at ambient temperature.

Computing details top

Data collection: APEX2 (Bruker, 2008); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top

	Fig. 1. The molecular structure of the title compound, showing the numbering scheme adopted. Displacement ellipsoids are shown at the 50% probability level.
	Fig. 2. Hydrogen-bonded chains along b-axis in the structure of the title compound. H-bonds are shown as dashed lines.
	Fig. 3. Synthetic scheme.

4-[(1RS,5RS,7SR)-5-Methyl-2,4-dioxo-3,6- diazabicyclo[3.2.1]octan-7-yl]benzonitrile top

Crystal data top

C₁₄H₁₃N₃O₂	F(000) = 536
M_r = 255.27	D_x = 1.403 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 5466 reflections
a = 14.8572 (13) Å	θ = 2.3–31.0°
b = 6.2269 (6) Å	µ = 0.10 mm⁻¹
c = 13.1215 (12) Å	T = 150 K
β = 95.568 (1)°	Block, colourless
V = 1208.20 (19) Å³	0.40 × 0.15 × 0.10 mm
Z = 4

Data collection top

Bruker SMART APEXII diffractometer	2924 independent reflections
Radiation source: fine-focus sealed tube	2601 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.019
ω scans	θ_max = 28.0°, θ_min = 2.8°
Absorption correction: multi-scan (SADABS; Bruker, 2008)	h = −19→19
T_min = 0.962, T_max = 0.990	k = −8→8
11909 measured reflections	l = −17→17

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)] = 0.040	Hydrogen site location: difference Fourier map
wR(F²) = 0.110	All H-atom parameters refined
S = 1.06	w = 1/[σ²(F_o²) + (0.0568P)² + 0.4568P] where P = (F_o² + 2F_c²)/3
2924 reflections	(Δ/σ)_max < 0.001
224 parameters	Δρ_max = 0.35 e Å⁻³
0 restraints	Δρ_min = −0.21 e Å⁻³

Crystal data top

C₁₄H₁₃N₃O₂	V = 1208.20 (19) Å³
M_r = 255.27	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 14.8572 (13) Å	µ = 0.10 mm⁻¹
b = 6.2269 (6) Å	T = 150 K
c = 13.1215 (12) Å	0.40 × 0.15 × 0.10 mm
β = 95.568 (1)°

Data collection top

Bruker SMART APEXII diffractometer	2924 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2008)	2601 reflections with I > 2σ(I)
T_min = 0.962, T_max = 0.990	R_int = 0.019
11909 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.040	0 restraints
wR(F²) = 0.110	All H-atom parameters refined
S = 1.06	Δρ_max = 0.35 e Å⁻³
2924 reflections	Δρ_min = −0.21 e Å⁻³
224 parameters

Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s 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 > σ(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.

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

	x	y	z	U_iso*/U_eq
O1	0.01850 (6)	0.66158 (14)	0.61099 (7)	0.0262 (2)
O2	0.17560 (6)	0.06107 (15)	0.54975 (7)	0.0271 (2)
N1	0.10075 (7)	0.36899 (17)	0.57715 (8)	0.0213 (2)
N2	0.23232 (7)	0.66162 (17)	0.70043 (8)	0.0218 (2)
N3	0.47535 (9)	0.5189 (2)	0.21483 (9)	0.0350 (3)
C1	0.08167 (7)	0.54263 (19)	0.63735 (9)	0.0205 (2)
C2	0.16886 (8)	0.22065 (19)	0.60194 (9)	0.0203 (2)
C3	0.23153 (8)	0.27578 (19)	0.69563 (9)	0.0208 (2)
C4	0.28953 (8)	0.47800 (19)	0.67574 (8)	0.0202 (2)
C5	0.14651 (8)	0.5781 (2)	0.73407 (9)	0.0218 (2)
C6	0.17531 (8)	0.3600 (2)	0.77908 (9)	0.0237 (3)
C7	0.10602 (9)	0.7300 (2)	0.80748 (11)	0.0302 (3)
C8	0.44462 (9)	0.5099 (2)	0.29149 (9)	0.0262 (3)
C10	0.32690 (7)	0.48798 (19)	0.57236 (8)	0.0193 (2)
C11	0.32273 (10)	0.6744 (2)	0.51302 (11)	0.0326 (3)
C12	0.36129 (10)	0.6806 (2)	0.42077 (11)	0.0340 (3)
C13	0.40462 (8)	0.5001 (2)	0.38726 (9)	0.0227 (3)
C14	0.41036 (9)	0.3136 (2)	0.44601 (10)	0.0257 (3)
C15	0.37150 (9)	0.3091 (2)	0.53770 (10)	0.0251 (3)
H4	0.3428 (10)	0.470 (2)	0.7280 (12)	0.023 (4)*
H62	0.2141 (10)	0.378 (3)	0.8439 (12)	0.027 (4)*
H3	0.2689 (11)	0.147 (3)	0.7158 (12)	0.029 (4)*
H1	0.0636 (11)	0.346 (3)	0.5222 (13)	0.027 (4)*
H61	0.1244 (10)	0.265 (2)	0.7877 (11)	0.021 (3)*
H14	0.4399 (11)	0.192 (3)	0.4254 (13)	0.031 (4)*
H73	0.0524 (12)	0.658 (3)	0.8305 (14)	0.039 (5)*
H15	0.3758 (12)	0.181 (3)	0.5765 (13)	0.038 (4)*
H2	0.2219 (11)	0.755 (3)	0.6484 (14)	0.035 (4)*
H72	0.0885 (11)	0.867 (3)	0.7734 (13)	0.035 (4)*
H71	0.1509 (12)	0.751 (3)	0.8687 (15)	0.042 (5)*
H12	0.3569 (14)	0.814 (3)	0.3768 (16)	0.055 (6)*
H11	0.2931 (13)	0.803 (3)	0.5349 (14)	0.043 (5)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0212 (4)	0.0265 (5)	0.0309 (5)	0.0070 (3)	0.0025 (3)	−0.0009 (4)
O2	0.0292 (5)	0.0226 (4)	0.0297 (5)	0.0053 (4)	0.0045 (4)	−0.0035 (4)
N1	0.0191 (5)	0.0226 (5)	0.0221 (5)	0.0035 (4)	0.0016 (4)	−0.0014 (4)
N2	0.0200 (5)	0.0243 (5)	0.0219 (5)	0.0024 (4)	0.0064 (4)	−0.0021 (4)
N3	0.0419 (7)	0.0385 (7)	0.0266 (6)	−0.0124 (5)	0.0137 (5)	−0.0029 (5)
C1	0.0175 (5)	0.0220 (5)	0.0231 (5)	0.0011 (4)	0.0072 (4)	0.0012 (4)
C2	0.0198 (5)	0.0200 (5)	0.0219 (5)	0.0018 (4)	0.0070 (4)	0.0037 (4)
C3	0.0198 (5)	0.0238 (6)	0.0193 (5)	0.0054 (4)	0.0049 (4)	0.0031 (4)
C4	0.0175 (5)	0.0259 (6)	0.0174 (5)	0.0035 (4)	0.0029 (4)	−0.0009 (4)
C5	0.0200 (5)	0.0262 (6)	0.0200 (5)	0.0033 (4)	0.0062 (4)	−0.0016 (4)
C6	0.0240 (6)	0.0293 (6)	0.0189 (5)	0.0042 (5)	0.0079 (4)	0.0026 (5)
C7	0.0281 (6)	0.0365 (7)	0.0275 (6)	0.0063 (6)	0.0101 (5)	−0.0071 (6)
C8	0.0272 (6)	0.0288 (6)	0.0234 (6)	−0.0068 (5)	0.0055 (5)	−0.0021 (5)
C10	0.0160 (5)	0.0249 (6)	0.0172 (5)	0.0012 (4)	0.0027 (4)	−0.0008 (4)
C11	0.0405 (7)	0.0283 (7)	0.0311 (7)	0.0127 (6)	0.0146 (6)	0.0055 (5)
C12	0.0424 (8)	0.0315 (7)	0.0301 (7)	0.0107 (6)	0.0130 (6)	0.0108 (6)
C13	0.0204 (5)	0.0297 (6)	0.0184 (5)	−0.0040 (5)	0.0041 (4)	−0.0008 (5)
C14	0.0283 (6)	0.0246 (6)	0.0256 (6)	0.0024 (5)	0.0103 (5)	−0.0021 (5)
C15	0.0296 (6)	0.0234 (6)	0.0238 (6)	0.0053 (5)	0.0093 (5)	0.0032 (5)

Geometric parameters (Å, º) top

O1—C1	1.2190 (14)	C5—C6	1.5257 (17)
O2—C2	1.2164 (15)	C6—H62	0.986 (16)
N1—C1	1.3845 (15)	C6—H61	0.976 (15)
N1—C2	1.3853 (15)	C7—H73	0.986 (19)
N1—H1	0.877 (17)	C7—H72	0.988 (18)
N2—C4	1.4793 (15)	C7—H71	1.002 (19)
N2—C5	1.4831 (15)	C8—C13	1.4426 (16)
N2—H2	0.899 (18)	C10—C15	1.3944 (16)
N3—C8	1.1457 (17)	C10—C11	1.3960 (17)
C1—C5	1.5331 (16)	C11—C12	1.3890 (18)
C2—C3	1.5080 (16)	C11—H11	0.971 (19)
C3—C6	1.5327 (15)	C12—C13	1.3879 (19)
C3—C4	1.5620 (17)	C12—H12	1.01 (2)
C3—H3	0.998 (16)	C13—C14	1.3919 (18)
C4—C10	1.5161 (15)	C14—C15	1.3843 (17)
C4—H4	0.997 (15)	C14—H14	0.931 (17)
C5—C7	1.5155 (16)	C15—H15	0.944 (18)

C1—N1—C2	124.90 (10)	C5—C6—H62	110.7 (9)
C1—N1—H1	116.8 (11)	C3—C6—H62	109.9 (9)
C2—N1—H1	118.0 (11)	C5—C6—H61	113.2 (9)
C4—N2—C5	108.84 (9)	C3—C6—H61	110.9 (9)
C4—N2—H2	113.2 (11)	H62—C6—H61	111.2 (12)
C5—N2—H2	111.3 (11)	C5—C7—H73	107.1 (11)
O1—C1—N1	120.48 (11)	C5—C7—H72	110.8 (10)
O1—C1—C5	123.50 (11)	H73—C7—H72	110.3 (14)
N1—C1—C5	115.97 (10)	C5—C7—H71	108.5 (11)
O2—C2—N1	120.71 (11)	H73—C7—H71	107.9 (15)
O2—C2—C3	124.53 (11)	H72—C7—H71	112.1 (15)
N1—C2—C3	114.76 (10)	N3—C8—C13	179.09 (15)
C2—C3—C6	108.91 (9)	C15—C10—C11	118.62 (11)
C2—C3—C4	110.75 (9)	C15—C10—C4	119.08 (10)
C6—C3—C4	101.02 (9)	C11—C10—C4	122.20 (11)
C2—C3—H3	108.4 (9)	C12—C11—C10	120.64 (12)
C6—C3—H3	114.4 (9)	C12—C11—H11	118.1 (11)
C4—C3—H3	113.1 (9)	C10—C11—H11	121.3 (11)
N2—C4—C10	115.62 (10)	C13—C12—C11	119.78 (12)
N2—C4—C3	104.39 (9)	C13—C12—H12	119.5 (12)
C10—C4—C3	116.00 (9)	C11—C12—H12	120.7 (12)
N2—C4—H4	108.7 (9)	C12—C13—C14	120.37 (11)
C10—C4—H4	106.4 (9)	C12—C13—C8	119.00 (12)
C3—C4—H4	105.1 (9)	C14—C13—C8	120.62 (11)
N2—C5—C7	112.09 (11)	C15—C14—C13	119.33 (11)
N2—C5—C6	102.15 (9)	C15—C14—H14	119.0 (10)
C7—C5—C6	115.05 (10)	C13—C14—H14	121.7 (10)
N2—C5—C1	107.06 (9)	C14—C15—C10	121.25 (12)
C7—C5—C1	111.09 (10)	C14—C15—H15	118.2 (11)
C6—C5—C1	108.79 (10)	C10—C15—H15	120.5 (11)
C5—C6—C3	100.36 (9)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···O2ⁱ	0.899 (18)	2.368 (19)	3.2377 (14)	162.8 (15)
N1—H1···O1ⁱⁱ	0.877 (17)	2.032 (17)	2.9019 (14)	171.3 (15)

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

Experimental details

Crystal data
Chemical formula	C₁₄H₁₃N₃O₂
M_r	255.27
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	150
a, b, c (Å)	14.8572 (13), 6.2269 (6), 13.1215 (12)
β (°)	95.568 (1)
V (Å³)	1208.20 (19)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.10
Crystal size (mm)	0.40 × 0.15 × 0.10

Data collection
Diffractometer	Bruker SMART APEXII diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2008)
T_min, T_max	0.962, 0.990
No. of measured, independent and observed [I > 2σ(I)] reflections	11909, 2924, 2601
R_int	0.019
(sin θ/λ)_max (Å⁻¹)	0.661

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.040, 0.110, 1.06
No. of reflections	2924
No. of parameters	224
H-atom treatment	All H-atom parameters refined
Δρ_max, Δρ_min (e Å⁻³)	0.35, −0.21

Computer programs: APEX2 (Bruker, 2008), SAINT (Bruker, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···O2ⁱ	0.899 (18)	2.368 (19)	3.2377 (14)	162.8 (15)
N1—H1···O1ⁱⁱ	0.877 (17)	2.032 (17)	2.9019 (14)	171.3 (15)

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

Acknowledgements

This study was partially supported by the Russian Foundation for Basic Research (project Nos. 11–03–00630_ a and 11–03–91375-ST_a) and State Contract No. 11.519.11.2032.

References

Bruker (2008). APEX2, SADABS and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Kudryavtsev, K. V. (2010). Russ. J. Org. Chem. 46, 372–379. Web of Science CrossRef CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar

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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

4-[(1RS,5RS,7SR)-5-Methyl-2,4-dioxo-3,6-di­aza­bi­cyclo­[3.2.1]octan-7-yl]benzo­nitrile

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Experimental

Crystal data

Data collection

Refinement

Supporting information

Acknowledgements

References

organic compounds

4-[(1RS,5RS,7SR)-5-Methyl-2,4-dioxo-3,6-diazabicyclo[3.2.1]octan-7-yl]benzonitrile