Crystal structure of rac-3-hy­droxy-2-(p-tol­yl)-2,3,3a,4,7,7a-hexa­hydro-1H-4,7-methano­isoindol-1-one

In the title compound, C₁₆H₁₇NO₂, the cyclo­hexene ring adopts a boat conformation, and the five-membered rings have envelope conformations with the bridging atom as the flap. Their mean planes are oriented at a dihedral angle of 86.51 (7)°. The mol­ecular structure is stabilized by a short intra­molecular C—H...O contact. In the crystal, mol­ecules are linked by O—H...O hydrogen bonds forming chains propagating along [100]. The chains are linked by C—H...π inter­actions, forming slabs parallel to (001).

Key indicators

• Single-crystal X-ray study
• T = 296 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.063
• wR factor = 0.180
• Data-to-parameter ratio = 27.9

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT906_ALERT_3_C Large K value in the Analysis of Variance ......      4.684 Check
PLAT910_ALERT_3_C Missing # of FCF Reflection(s) Below Th(Min) ...          5 Report
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.600         19 Report

Alert level G
PLAT005_ALERT_5_G No _iucr_refine_instructions_details  in the CIF     Please Do !
PLAT007_ALERT_5_G Number of Unrefined Donor-H Atoms ..............          1 Report
PLAT066_ALERT_1_G Predicted and Reported Tmin&Tmax Range Identical          ? Check
PLAT380_ALERT_4_G Incorrectly? Oriented X(sp2)-Methyl Moiety .....         C1 Check
PLAT793_ALERT_4_G The Model has Chirality at C9      (Centro SPGR)          R Verify
PLAT793_ALERT_4_G The Model has Chirality at C10     (Centro SPGR)          S Verify
PLAT793_ALERT_4_G The Model has Chirality at C11     (Centro SPGR)          R Verify
PLAT793_ALERT_4_G The Model has Chirality at C12     (Centro SPGR)          S Verify
PLAT793_ALERT_4_G The Model has Chirality at C15     (Centro SPGR)          R Verify
PLAT912_ALERT_4_G Missing # of FCF Reflections Above STh/L=  0.600          7 Note

   0 ALERT level A = Most likely a serious problem - resolve or explain
   0 ALERT level B = A potentially serious problem, consider carefully
   3 ALERT level C = Check. Ensure it is not caused by an omission or oversight
  10 ALERT level G = General information/check it is not something unexpected

   1 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   3 ALERT type 3 Indicator that the structure quality may be low
   7 ALERT type 4 Improvement, methodology, query or suggestion
   2 ALERT type 5 Informative message, check

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S1. Comment

Chiral tricyclic compounds in heterocyclic chemistry are important in medicinal and pharmaceutical fields (Abel et al., 1996; Salvati et al., 2005). We report herein on the synthesis and crystal structure of the title compound, prepared by reduction of 2-(p-tolyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione, using NaBH₄.

The bond lengths and angles in the title compound, Fig. 1, are close to those reported for two similar chiral structures (Takebayashi et al., 2010). The cyclohexene ring (C9/C190/C12-C15) has a normal boat conformation [puckering parameters: θ₂ = 0.9587 (3) Å and ϕ₂ = 169.02 (14)°]. The main bridge angle, C12—C16—C15, which connects the two bridgeheads on the cyclohexene ring, is 93.78 (12) °. The two five-membered rings, A(C9/C10/C15/C16/C12) and B(C12-C16) have envelope conformations with the flap atom C16 deviating from their mean planes by 0.5131 (2) and 0.4027 (2) Å, respectively. The dihedral angle between their mean planes, [A/B], is 86.51 (7)°. The whole molecule is non-planar with the dihedral angle between the benzene (C2-C7) and imide (N1/C8-C11) rings being 26.12 (5)°. This is much smaller than the same dihedral angle of ca.57.22 ° in the 2-phenyl derivative (Takebayashi et al., 2010) or ca. 61.37 ° in the 2-(4-fluorophenyl) derivative (Takebayashi et al., 2010). In the molecule there is a strong C—H···O intra-molecular contact present (Table 1).

In the crystal, molecules are linked by O—H···O hydrogen bonds forming chains along [100]; see Table 1 and Fig. 2. The chains are linked by C-H···π interactions forming slabs parallel to (001); see Table 1.

Related literature

For medical and pharmaceutical applications of chiral tricyclic compounds, see: Abel et al. (1996); Salvati et al. (2005). For the synthesis of the starting reagent, 2-(p-tolyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione, see: Andrade & Evilazio (2004). For the reduction reaction used to synthesise the title compound, see: Hubert et al. (1975). For the crystal structure of a similar compound, see: Takebayashi et al. (2010).

S2. Experimental

The starting reagent, 2-(p-tolyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione (L), is a known compound and was prepared from nadic anhydride and 4-toluidine (Andrade & Evilazio, 2004). The title compound was prepared by a reduction reaction following a modification of a literature procedure (Hubert et al., 1975). NaBH₄ (0.94 g) was added in small portions at 298 K over a period of 2 h to L (0.72 g, 2.84 mmol) dissolved in ethanol (250 ml). The excess of NaBH₄ was consumed in 15 min at 278 K by adding aqueous HCl (2 mol dm^-3) until the pH reached 3. The mixture was stirred for an additional 1 h at the same temperature then poured into water and extracted with dichloromethane. The organic layer was separated, dried over Na₂SO₄, filtered and evaporated to yield a white solid that was purified by silica gel chromatography [ethyl acetate/n-hexane (3:2 v/v)] which on slow evaporation of the solvent gave colourless crystals (yield: 65%; m.p.: 475–477 K). NMR (DMSO): δ(H) 1.38–1.42 (dd, 2H, CH₂), 2.24 (s, 3H, CH₃), 2.59–2.60 (d, H, CH), 2.61–2.62 (d, H, CH), 3.11–3.13 (m, H, CH), 3.18–3.21 (dd, H, CH), 4.81 (s, H, CH—OH), 6.03–6.05 (dd, H, ═CH), 6.16–6.18 (dd, H, ═CH), 7.09–7.11 (d, 2H, aromatic), 7.25–7.27 (d, 2H, aromatic); δ(C) 20.96 (CH₃), 45.08 (CH), 45.62 (CH), 46.56 (CH), 49.58 (CH), 51.06 (CH₂), 86.17 (CH—OH), 124.07 (Cm), 129.33 (Co), 134.37 (CH═CH), 134.93 (Cq—N), 135.87 (C—CH₃), 174.39 (C═O) p.p.m.. FT—IR (ATR): 3211 (OH), 2972, 2943, 1646 (C═O), 1613 and 1515 (aromatic, C═C), 1422, 1403, 1065 (C—N), 819 cm^-1.

S3. Refinement

H atoms attached to bridging atom C16 were located in a difference Fourier map and freely refined. The other H atoms were placed in geometrically idealized positions (C—H = 0.93–0.98 Å and O—H= 0.82 Å) and treated as riding, with U_iso(H) = 1.5U_eq(O,C) for hydroxyl and methyl H atoms and = 1.2U_eq(C) for other H atoms.

Computing details

Data collection: APEX2 (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: WinGX publication routines (Farrugia, 2012).

Figures

	Fig. 1. The molecular structure of the title compound, with atom labelling. Displacement ellipsoids are drawn at the 30% probability level.
	Fig. 2. A partial view along the b axis of the crystal packing of the title compound. Dashed lines indicate the O—H···O hydrogen bonds (see Table 1 for details).

rac-3-Hydroxy-2-(p-tolyl)-2,3,3a,4,7,7a-hexahydro-1H-4,7-methanoisoindol-1-one

Crystal data

C16H17NO2	F(000) = 544
Mr = 255.31	Dx = 1.280 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 5019 reflections
a = 6.5067 (2) Å	θ = 3.6–33.2°
b = 9.7385 (2) Å	µ = 0.08 mm^−1
c = 21.0780 (5) Å	T = 296 K
β = 97.154 (1)°	Prism, colourless
V = 1325.22 (6) Å^3	0.45 × 0.25 × 0.15 mm
Z = 4

Data collection

Bruker APEXII diffractometer	5019 independent reflections
Radiation source: fine-focus sealed tube	3930 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.023
ϕ and ω scans	θmax = 33.2°, θmin = 3.6°
Absorption correction: multi-scan (Blessing, 1995)	h = −5→9
Tmin = 0.963, Tmax = 0.988	k = −14→15
28760 measured reflections	l = −32→32

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.063	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.180	H atoms treated by a mixture of independent and constrained refinement
S = 1.09	w = 1/[σ^2(Fo^2) + (0.0762P)^2 + 0.4345P] where P = (Fo^2 + 2Fc^2)/3
5019 reflections	(Δ/σ)max < 0.001
180 parameters	Δρmax = 0.40 e Å^−3
0 restraints	Δρmin = −0.38 e Å^−3

Special details

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 (Ų)

	x	y	z	Uiso*/Ueq
O1	0.45122 (14)	1.12217 (12)	0.27036 (6)	0.0443 (3)
H2	0.5256	1.0905	0.3011	0.066*
O2	−0.18121 (15)	0.99108 (14)	0.30186 (6)	0.0498 (3)
C16	−0.0698 (3)	1.0387 (2)	0.09543 (8)	0.0528 (4)
C1	0.4966 (4)	0.7713 (3)	0.53749 (9)	0.0695 (6)
H1A	0.4064	0.7943	0.5686	0.104*
H1B	0.6307	0.8110	0.5498	0.104*
H1C	0.5094	0.6733	0.5350	0.104*
H16A	−0.073 (3)	1.138 (2)	0.0867 (10)	0.057 (6)*
H16B	−0.110 (4)	0.990 (2)	0.0570 (12)	0.066 (6)*
N1	0.16608 (15)	0.98524 (11)	0.29178 (5)	0.0303 (2)
C11	0.30916 (17)	1.02207 (13)	0.24528 (6)	0.0323 (2)
H11	0.3825	0.9402	0.2330	0.039*
C5	0.24201 (17)	0.92979 (12)	0.35282 (6)	0.0303 (2)
C8	−0.03527 (18)	1.01463 (13)	0.27142 (7)	0.0337 (2)
C9	−0.05367 (19)	1.07927 (14)	0.20645 (7)	0.0363 (3)
H9	−0.1068	1.1733	0.2075	0.044*
C10	0.16740 (19)	1.07774 (14)	0.18773 (6)	0.0351 (3)
H10	0.2096	1.1710	0.1777	0.042*
C6	0.4272 (2)	0.85725 (15)	0.36000 (7)	0.0387 (3)
H6	0.4973	0.8419	0.3248	0.046*
C2	0.4079 (2)	0.82658 (16)	0.47322 (7)	0.0440 (3)
C7	0.5078 (2)	0.80753 (17)	0.41974 (7)	0.0455 (3)
H7	0.6327	0.7600	0.4239	0.055*
C12	−0.1801 (2)	0.99380 (17)	0.15201 (8)	0.0470 (3)
H12	−0.3307	1.0066	0.1470	0.056*
C15	0.1436 (3)	0.98780 (17)	0.12617 (7)	0.0448 (3)
H15	0.2563	0.9944	0.0995	0.054*
C4	0.1392 (2)	0.94992 (18)	0.40597 (7)	0.0459 (3)
H4	0.0148	0.9981	0.4021	0.055*
C13	−0.1047 (3)	0.84754 (17)	0.16019 (8)	0.0530 (4)
H13	−0.1791	0.7734	0.1733	0.064*
C3	0.2228 (3)	0.8979 (2)	0.46493 (8)	0.0534 (4)
H3	0.1517	0.9115	0.5001	0.064*
C14	0.0870 (3)	0.84423 (17)	0.14533 (8)	0.0520 (4)
H14	0.1720	0.7672	0.1465	0.062*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0241 (4)	0.0503 (6)	0.0575 (6)	−0.0066 (4)	0.0005 (4)	0.0026 (5)
O2	0.0203 (4)	0.0751 (8)	0.0549 (6)	0.0010 (4)	0.0079 (4)	0.0096 (5)
C16	0.0568 (9)	0.0558 (9)	0.0421 (8)	−0.0040 (8)	−0.0091 (7)	0.0114 (7)
C1	0.0762 (14)	0.0834 (14)	0.0453 (9)	−0.0020 (11)	−0.0064 (9)	0.0202 (9)
N1	0.0193 (4)	0.0366 (5)	0.0347 (5)	0.0025 (3)	0.0030 (3)	0.0021 (4)
C11	0.0218 (4)	0.0375 (6)	0.0380 (6)	0.0015 (4)	0.0058 (4)	0.0020 (5)
C5	0.0244 (5)	0.0332 (5)	0.0328 (5)	0.0007 (4)	0.0022 (4)	−0.0013 (4)
C8	0.0204 (4)	0.0377 (6)	0.0424 (6)	0.0021 (4)	0.0019 (4)	0.0008 (5)
C9	0.0254 (5)	0.0377 (6)	0.0444 (7)	0.0034 (4)	−0.0011 (4)	0.0061 (5)
C10	0.0300 (5)	0.0356 (6)	0.0395 (6)	−0.0011 (4)	0.0037 (4)	0.0071 (5)
C6	0.0287 (5)	0.0496 (7)	0.0379 (6)	0.0092 (5)	0.0050 (5)	0.0037 (5)
C2	0.0466 (7)	0.0473 (8)	0.0361 (6)	−0.0043 (6)	−0.0026 (5)	0.0045 (5)
C7	0.0358 (6)	0.0540 (8)	0.0450 (7)	0.0090 (6)	−0.0013 (5)	0.0087 (6)
C12	0.0351 (6)	0.0562 (9)	0.0464 (8)	−0.0055 (6)	−0.0089 (6)	0.0091 (6)
C15	0.0477 (8)	0.0496 (8)	0.0372 (7)	0.0010 (6)	0.0063 (6)	0.0052 (6)
C4	0.0422 (7)	0.0590 (9)	0.0377 (7)	0.0157 (6)	0.0093 (5)	−0.0018 (6)
C13	0.0641 (10)	0.0452 (8)	0.0459 (8)	−0.0178 (7)	−0.0079 (7)	0.0030 (6)
C3	0.0587 (9)	0.0672 (10)	0.0358 (7)	0.0103 (8)	0.0121 (6)	−0.0004 (7)
C14	0.0711 (11)	0.0396 (7)	0.0436 (8)	0.0024 (7)	−0.0003 (7)	−0.0026 (6)

Geometric parameters (Å, º)

O1—C11	1.4008 (16)	C9—C12	1.566 (2)
O1—H2	0.8200	C9—H9	0.9800
O2—C8	1.2320 (16)	C10—C15	1.557 (2)
C16—C12	1.531 (2)	C10—H10	0.9800
C16—C15	1.539 (2)	C6—C7	1.3893 (19)
C16—H16A	0.99 (2)	C6—H6	0.9300
C16—H16B	0.95 (2)	C2—C7	1.382 (2)
C1—C2	1.505 (2)	C2—C3	1.383 (2)
C1—H1A	0.9600	C7—H7	0.9300
C1—H1B	0.9600	C12—C13	1.509 (3)
C1—H1C	0.9600	C12—H12	0.9800
N1—C8	1.3574 (14)	C15—C14	1.513 (2)
N1—C5	1.4256 (16)	C15—H15	0.9800
N1—C11	1.4776 (15)	C4—C3	1.389 (2)
C11—C10	1.5290 (18)	C4—H4	0.9300
C11—H11	0.9800	C13—C14	1.324 (3)
C5—C4	1.3884 (18)	C13—H13	0.9300
C5—C6	1.3885 (17)	C3—H3	0.9300
C8—C9	1.4984 (19)	C14—H14	0.9300
C9—C10	1.5383 (18)
C11—O1—H2	109.5	C11—C10—H10	110.0
C12—C16—C15	93.78 (12)	C9—C10—H10	110.0
C12—C16—H16A	115.2 (12)	C15—C10—H10	110.0
C15—C16—H16A	113.0 (13)	C5—C6—C7	120.04 (13)
C12—C16—H16B	114.7 (15)	C5—C6—H6	120.0
C15—C16—H16B	109.9 (15)	C7—C6—H6	120.0
H16A—C16—H16B	109.4 (19)	C7—C2—C3	117.07 (13)
C2—C1—H1A	109.5	C7—C2—C1	121.32 (16)
C2—C1—H1B	109.5	C3—C2—C1	121.61 (16)
H1A—C1—H1B	109.5	C2—C7—C6	121.98 (13)
C2—C1—H1C	109.5	C2—C7—H7	119.0
H1A—C1—H1C	109.5	C6—C7—H7	119.0
H1B—C1—H1C	109.5	C13—C12—C16	100.44 (15)
C8—N1—C5	125.28 (10)	C13—C12—C9	106.51 (11)
C8—N1—C11	113.71 (10)	C16—C12—C9	99.46 (12)
C5—N1—C11	120.96 (9)	C13—C12—H12	116.0
O1—C11—N1	111.06 (11)	C16—C12—H12	116.0
O1—C11—C10	110.93 (11)	C9—C12—H12	116.0
N1—C11—C10	104.17 (9)	C14—C15—C16	99.98 (14)
O1—C11—H11	110.2	C14—C15—C10	107.43 (12)
N1—C11—H11	110.2	C16—C15—C10	99.24 (13)
C10—C11—H11	110.2	C14—C15—H15	115.9
C4—C5—C6	118.85 (12)	C16—C15—H15	115.9
C4—C5—N1	121.80 (11)	C10—C15—H15	115.9
C6—C5—N1	119.32 (11)	C5—C4—C3	119.75 (14)
O2—C8—N1	124.90 (13)	C5—C4—H4	120.1
O2—C8—C9	125.12 (11)	C3—C4—H4	120.1
N1—C8—C9	109.98 (11)	C14—C13—C12	107.37 (14)
C8—C9—C10	105.05 (10)	C14—C13—H13	126.3
C8—C9—C12	114.92 (11)	C12—C13—H13	126.3
C10—C9—C12	103.28 (12)	C2—C3—C4	122.30 (14)
C8—C9—H9	111.0	C2—C3—H3	118.9
C10—C9—H9	111.0	C4—C3—H3	118.9
C12—C9—H9	111.0	C13—C14—C15	107.95 (15)
C11—C10—C9	106.91 (10)	C13—C14—H14	126.0
C11—C10—C15	116.70 (11)	C15—C14—H14	126.0
C9—C10—C15	102.71 (11)
C8—N1—C11—O1	117.43 (12)	C3—C2—C7—C6	−0.1 (3)
C5—N1—C11—O1	−60.01 (14)	C1—C2—C7—C6	179.60 (17)
C8—N1—C11—C10	−2.04 (14)	C5—C6—C7—C2	0.7 (2)
C5—N1—C11—C10	−179.48 (11)	C15—C16—C12—C13	−50.25 (14)
C8—N1—C5—C4	−26.3 (2)	C15—C16—C12—C9	58.64 (14)
C11—N1—C5—C4	150.86 (14)	C8—C9—C12—C13	−45.60 (17)
C8—N1—C5—C6	155.78 (13)	C10—C9—C12—C13	68.21 (15)
C11—N1—C5—C6	−27.09 (17)	C8—C9—C12—C16	−149.55 (12)
C5—N1—C8—O2	−3.7 (2)	C10—C9—C12—C16	−35.73 (14)
C11—N1—C8—O2	178.96 (13)	C12—C16—C15—C14	49.62 (15)
C5—N1—C8—C9	176.52 (11)	C12—C16—C15—C10	−60.06 (14)
C11—N1—C8—C9	−0.79 (15)	C11—C10—C15—C14	51.45 (17)
O2—C8—C9—C10	−176.50 (14)	C9—C10—C15—C14	−65.11 (15)
N1—C8—C9—C10	3.26 (15)	C11—C10—C15—C16	155.05 (12)
O2—C8—C9—C12	−63.72 (19)	C9—C10—C15—C16	38.49 (13)
N1—C8—C9—C12	116.04 (13)	C6—C5—C4—C3	0.1 (2)
O1—C11—C10—C9	−115.65 (11)	N1—C5—C4—C3	−177.82 (15)
N1—C11—C10—C9	3.91 (13)	C16—C12—C13—C14	33.93 (16)
O1—C11—C10—C15	130.13 (12)	C9—C12—C13—C14	−69.31 (17)
N1—C11—C10—C15	−110.31 (12)	C7—C2—C3—C4	−0.6 (3)
C8—C9—C10—C11	−4.38 (14)	C1—C2—C3—C4	179.80 (19)
C12—C9—C10—C11	−125.16 (11)	C5—C4—C3—C2	0.5 (3)
C8—C9—C10—C15	118.98 (12)	C12—C13—C14—C15	−0.61 (18)
C12—C9—C10—C15	−1.79 (13)	C16—C15—C14—C13	−32.66 (17)
C4—C5—C6—C7	−0.7 (2)	C10—C15—C14—C13	70.41 (17)
N1—C5—C6—C7	177.28 (13)

Hydrogen-bond geometry (Å, º)

Cg1 and Cg4 are the centroids of the N1/C8–C11 and C2–C7 rings, respectively.

D—H···A	D—H	H···A	D···A	D—H···A
C4—H4···O2	0.93	2.33	2.860 (2)	116
O1—H2···O2^i	0.82	2.14	2.7194 (15)	128
C13—H13···Cg1^ii	0.93	2.94	3.6903 (18)	139
C16—H16A···Cg4^iii	0.99 (2)	2.86 (2)	3.692 (2)	143.4 (15)

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