1,3(R):4,6(R)-Di-O-benzyl­idene-D-mannitol

The title compound, C₂₀H₂₂O₆, has crystallographic twofold symmetry. The central six-C-atom chain has an extended conformation similar to that of D-mannitol, with two independent C-C-C-C torsion angles of 165.69 (14) and 177.60 (12)°. The 1,3-dioxane ring has a chair conformation. All chiral centers have the R configuration.

S1. Comment

The use of carbohydrates as inexpensive starting materials and building blocks is of great interest (Bols, 1996). For example, D-mannitol, which has C₂ symmetry, offers unique synthetic approaches to chiral auxiliaries (Defoin et al., 1991; Masaki et al., 1992) and chiral drugs (Poitout et al., 1994). Benzylidene acetal is a commonly used temporary protective group for D-mannitol because of its stability to most reaction conditions and high-yielding deprotection step (Greene & Wuts, 1991). The title compound, (I), is a benzylidene-protected mannitol. The elucidation of its structure was carried out to study the effect of the two six-membered 1,3-dioxane rings on the conformation of the central six-C-atom mannitol core. \scheme

Fig. 1 shows the atomic numbering scheme and conformationof (I). The molecule lies on a crystallographic twofold axis. The chiral centers C2, C3 and C7 all have the R configuration. The six-membered benzylidene acetal 1,3-dioxane ring adopts a chair conformation, with endocyclic torsion angles in the range 44.54 (14)–68.55 (13)°. All substituents are in equatorial positions. The torsion angles formed by the six central C atoms of (I) are comparable with those in DL-mannitol (Kanters et al., 1977), D-mannitol (Berman et al., 1968; Kim et al., 1968) and hexaacetal-D-mannitol (Stein et al., 1992), despite the presence of the 1,3-dioxane ring. While in all these cases the conformation is anti-anti-anti, deviations from 180° vary by up to about 20°. In (I), there are only two such independent torsion angles, as a result of the molecular symmetry. These are C1—C2—C3—C3ⁱ [165.69 (14)°; symmetry code: (i) 1 - x, y, -z] and C2—C3—C3ⁱ—C2ⁱ [177.60 (12)°]. None of the other mannitols retain their C₂ symmetry in the crystal, and thus have three independent torsion angles. In DL-mannitol (Kanters et al., 1977) they are -175.9 (4), -176.5 (4) and 174.8 (4)°, in β-D-mannitol (Berman et al., 1968) they are -175.3 (6), 175.8 (6) and -179.8 (6)°, in K—D-mannitol (Kim et al., 1968) they are -174.8 (3), 175.8 (3) and -176.5 (3)°, and in hexaacetal-D-mannitol (Stein et al., 1992) they are -175.3 (5), 159.8 (5) and -173.2 (5)°. The main difference in conformation between (I) and the cited acyclic mannitols is the torsion angle involving vicinal O atoms, O1—C1—C2—O2 [-169.52 (11)°]. Cyclization forces the O atoms to be antiperiplanar, while they are gauche [torsion angle magnitudes 58.0 (3)–65.6 (7)°] in the acyclic mannitols.

The phenyl ring in (I) is planar, with a maximum deviation of 0.006 (2) Å for C11. Molecules form weakly hydrogen-bonded chains in the symmetry direction, via pairs of O2—H···O1ⁱⁱ interactions [symmetry code: (ii) x, y - 1, z]. Both OH groups of each molecule donate to 1,3-dioxane O atoms of the same translation-related adjacent molecule. The O···O distance in this interaction is 3.183 (2) Å and the angle about the H atom is 158 (3)°.

S2. Experimental

Compound (I) was prepared by acetalization of D-mannitol with benzaldehyde (Baggett & Stribblehill, 1977). A suitable crystal used for data collection was obtained by slow evaporation of an ethanol solution at room temperature.

S3. Refinement

The absolute structure of (I) was determined by refinement of the Flack (1983) parameter, based on 713 Friedel pairs. The hydroxyl-H atom was refined isotropically. Other H atoms were placed in calculated positions with C—H bond distances 0.93 (phenyl) and 0.97 Å (sp³) and U_iso = 1.2U_eq of the attached C atom, and thereafter treated as riding.

Computing details

Data collection: CAD-4 EXPRESS (Enraf-Nonius, 1994); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1996); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 1997); software used to prepare material for publication: SHELXTL.

Figures

Fig. 1. Numbering scheme and ellipsoids at the 50% level. H atoms are shown as spheres of arbitrary radii.

1,3(R):4,6(R)-di-O-benzylidene-D-mannitol

Crystal data

C20H22O6	F(000) = 380
Mr = 358.4	Dx = 1.391 Mg m^−3
Monoclinic, C2	Cu Kα radiation, λ = 1.54184 Å
a = 17.472 (4) Å	Cell parameters from 25 reflections
b = 4.9237 (10) Å	θ = 11.4–44.7°
c = 9.956 (2) Å	µ = 0.85 mm^−1
β = 94.08 (3)°	T = 293 K
V = 854.4 (3) Å^3	Lath, colorless
Z = 2	0.53 × 0.20 × 0.08 mm

Data collection

Enraf-Nonius CAD-4 diffractometer	1669 reflections with I > 2σ (I)
Radiation source: fine-focus sealed tube	Rint = 0.027
Graphite monochromator	θmax = 75.0°, θmin = 4.5°
ω/2θ scans	h = −21→21
Absorption correction: ψ-scan (North et al., 1968)	k = −6→5
Tmin = 0.668, Tmax = 0.934	l = −12→12
4158 measured reflections	3 standard reflections every 60 min
1703 independent reflections	intensity decay: 2.1%

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.033	w = 1/[σ^2(Fo^2) + (0.0677P)^2 + 0.1745P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.093	(Δ/σ)max = 0.002
S = 0.93	Δρmax = 0.24 e Å^−3
1703 reflections	Δρmin = −0.17 e Å^−3
123 parameters	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
1 restraint	Extinction coefficient: 0.0112 (14)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack (1983)
Secondary atom site location: difference Fourier map	Absolute structure parameter: −0.10 (17)

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	0.50423 (6)	0.5698 (2)	0.31592 (10)	0.0511 (3)
O2	0.60265 (7)	0.0003 (2)	0.16337 (12)	0.0591 (3)
O3	0.44908 (5)	0.50526 (18)	0.10141 (8)	0.0418 (2)
C1	0.55167 (9)	0.3333 (4)	0.31024 (15)	0.0538 (4)
H1A	0.5265	0.1813	0.3506	0.065*
H1B	0.5999	0.3654	0.3621	0.065*
C2	0.56748 (8)	0.2617 (3)	0.16613 (14)	0.0456 (3)
H2	0.6031	0.3962	0.1334	0.055*
C3	0.49318 (7)	0.2677 (3)	0.07414 (12)	0.0404 (3)
H3	0.4628	0.1069	0.0933	0.048*
C7	0.43442 (7)	0.5197 (3)	0.23842 (12)	0.0407 (3)
H7	0.4131	0.3460	0.2661	0.049*
C8	0.37759 (7)	0.7419 (3)	0.25995 (12)	0.0406 (3)
C9	0.33215 (8)	0.8487 (4)	0.15345 (14)	0.0499 (3)
H9	0.3389	0.7909	0.0661	0.060*
C10	0.27670 (8)	1.0408 (4)	0.17589 (17)	0.0605 (4)
H10	0.2467	1.1124	0.1034	0.073*
C11	0.26558 (8)	1.1266 (4)	0.30397 (17)	0.0575 (4)
H11	0.2276	1.2535	0.3185	0.069*
C12	0.31099 (9)	1.0238 (3)	0.41129 (14)	0.0539 (4)
H12	0.3040	1.0835	0.4982	0.065*
C13	0.36706 (8)	0.8316 (3)	0.39009 (13)	0.0482 (3)
H13	0.3975	0.7628	0.4626	0.058*
H1O2	0.5664 (18)	−0.080 (8)	0.203 (3)	0.133 (12)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0536 (5)	0.0418 (6)	0.0560 (5)	0.0044 (4)	−0.0084 (4)	−0.0081 (4)
O2	0.0600 (6)	0.0429 (6)	0.0740 (7)	0.0154 (5)	0.0018 (5)	0.0029 (5)
O3	0.0475 (5)	0.0358 (5)	0.0426 (4)	0.0052 (4)	0.0062 (3)	0.0010 (4)
C1	0.0577 (8)	0.0462 (8)	0.0555 (7)	0.0093 (7)	−0.0097 (6)	0.0011 (6)
C2	0.0452 (6)	0.0329 (7)	0.0585 (7)	0.0030 (5)	0.0016 (5)	0.0040 (6)
C3	0.0426 (6)	0.0294 (6)	0.0496 (7)	−0.0007 (4)	0.0055 (5)	0.0020 (5)
C7	0.0464 (6)	0.0336 (6)	0.0423 (6)	−0.0044 (6)	0.0035 (4)	0.0011 (5)
C8	0.0426 (6)	0.0345 (7)	0.0452 (6)	−0.0061 (5)	0.0065 (5)	−0.0003 (5)
C9	0.0453 (6)	0.0557 (9)	0.0482 (7)	0.0015 (7)	−0.0011 (5)	−0.0081 (6)
C10	0.0469 (7)	0.0696 (12)	0.0635 (8)	0.0089 (7)	−0.0066 (6)	−0.0018 (8)
C11	0.0456 (7)	0.0511 (9)	0.0768 (9)	0.0044 (7)	0.0113 (6)	−0.0090 (8)
C12	0.0624 (8)	0.0478 (8)	0.0536 (7)	−0.0052 (7)	0.0187 (6)	−0.0058 (6)
C13	0.0594 (7)	0.0429 (8)	0.0431 (6)	−0.0029 (6)	0.0087 (5)	0.0043 (6)

Geometric parameters (Å, º)

O1—C7	1.4179 (15)	C3—C3^i	1.512 (2)
O1—C1	1.4328 (18)	C7—C8	1.5032 (18)
O2—C2	1.4273 (17)	C8—C9	1.382 (2)
O2—H1O2	0.83 (3)	C8—C13	1.3934 (17)
O3—C7	1.4076 (14)	C9—C10	1.384 (2)
O3—C3	1.4370 (15)	C10—C11	1.370 (2)
C1—C2	1.522 (2)	C11—C12	1.381 (2)
C2—C3	1.5349 (18)	C12—C13	1.389 (2)
C7—O1—C1	108.34 (10)	O3—C7—C8	110.03 (10)
C2—O2—H1O2	94 (2)	O1—C7—C8	110.31 (10)
C7—O3—C3	111.17 (9)	C9—C8—C13	119.09 (13)
O1—C1—C2	111.71 (11)	C9—C8—C7	121.10 (11)
O2—C2—C1	109.53 (12)	C13—C8—C7	119.70 (12)
O2—C2—C3	110.67 (11)	C8—C9—C10	120.44 (13)
C1—C2—C3	110.83 (12)	C11—C10—C9	120.55 (15)
O3—C3—C3^i	107.96 (8)	C10—C11—C12	119.70 (15)
O3—C3—C2	110.19 (10)	C11—C12—C13	120.32 (13)
C3^i—C3—C2	113.41 (14)	C12—C13—C8	119.89 (13)
O3—C7—O1	109.11 (10)
C7—O1—C1—C2	58.34 (15)	C1—O1—C7—C8	170.47 (11)
O1—C1—C2—O2	−169.52 (11)	O3—C7—C8—C9	17.58 (16)
O1—C1—C2—C3	−47.14 (16)	O1—C7—C8—C9	138.00 (13)
C7—O3—C3—C3^i	−179.70 (11)	O3—C7—C8—C13	−166.24 (11)
C7—O3—C3—C2	−55.36 (13)	O1—C7—C8—C13	−45.81 (15)
O2—C2—C3—O3	166.27 (11)	C13—C8—C9—C10	−0.3 (2)
C1—C2—C3—O3	44.54 (14)	C7—C8—C9—C10	175.86 (14)
O2—C2—C3—C3^i	−72.58 (11)	C8—C9—C10—C11	−0.5 (3)
C1—C2—C3—C3^i	165.69 (14)	C9—C10—C11—C12	1.1 (3)
C2—C3—C3^i—C2^i	177.60 (12)	C10—C11—C12—C13	−0.9 (3)
C3—O3—C7—O1	68.30 (12)	C11—C12—C13—C8	0.0 (2)
C3—O3—C7—C8	−170.56 (9)	C9—C8—C13—C12	0.6 (2)
C1—O1—C7—O3	−68.55 (13)	C7—C8—C13—C12	−175.66 (12)

Symmetry code: (i) −x+1, y, −z.