(2R,3S)-3-Hydr­oxy-N,N-dimethyl­proline monohydrate

The absolute stereochemistry of the title compound, C₇H₁₃NO₃·H₂O, was firmly established by X-ray crystallography. The crystal structure exists as O—H...O hydrogen-bonded layers of mol­ecules lying perpendicular to the a axis.

Key indicators

• Single-crystal X-ray study
• T = 150 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.033
• wR factor = 0.038
• Data-to-parameter ratio = 11.5

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PLAT153_ALERT_1_C The su's on the Cell Axes   are Equal (x 100000)         20 Ang.

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REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           71.75
           From the CIF: _reflns_number_total               1452
           Count of symmetry unique reflns          899
           Completeness (_total/calc)            161.51%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured       553
           Fraction of Friedel pairs measured     0.615
           Are heavy atom types Z>Si present         no
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C2     = .          R
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C3     = .          S
PLAT860_ALERT_3_G Note: Number of Least-Squares Restraints .......          1

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Author Response:

 Jenkinson, Sarah F. - Post Doc chemist and crystallographer Cowley,Andrew -
 Crystallographer Kato, Atsushi - collaborator on project Kato, Noriko -
 collaborator on project Hollinshead, Jackie - Industrial collaborator on
 project Nash, Robert J. - Industrial collaborator on project Booth, Kathrine V.
  - trainee crystallographer Fleet, George W. J. - Preparative Group Leader


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S1. Comment

L-N,N-Dimethylproline (L-stachydrine) and the L-2R,3S-3-hydroxy compound have been reported from the plant family Capparidaceae. Cornforth & Henry (1952) first reported the L-2R,3S compound from Capparis tomentosa and then Delaveau et al. (1973) conducted a taxonomic survey suggesting these compounds were ubiquitous in this plant family. The structure of the L-2R,3S form was confirmed by synthesis by Sakiyama et al. (1964). This is the first report of the L-2R,3S form in the genus Baphia (Leguminosae).

Refinement of the Flack enantiopole parameter gave a value of 0.08 (18), which for an enantio-pure material unambiguously shows the crystal to consist of the 2R enantiomer (i.e a derivative of a D amino acid).

The crystal structure of the title compound (Fig. 1) exists as hydrogen bonded layers of molecules lying perpendicular to the a axis (Fig. 2). One of the hydrogen bonds (involving atom O2) is bifurcated.

Related literature

For related literature, see: Cornforth & Henry (1952); Delaveau et al. (1973); Sakiyama et al. (1964); Nash et al. (1986).

S2. Experimental

2.9 g of 2R, 3S 3-hydroxy-N, N-dimethylproline was obtained from the 50% EtOH extract of 2 kg of leaves of the African medicinal tree Baphia confusum (Fabaceae). The compound was isolated by binding it to Amberlite IR-120 (H⁺ form, 2L) and eluting with 2M NH₄OH. The eluate was concentrated to give a brown oil (30.8 g). This oil was applied to an Amberlite CG-50 column (3.6 x 48 cm, NH₄⁺ form) and eluted with distilled water. The concentrated eluate was chromatographed over a Dowex 1-X8 column (2.2 x 42 cm, OH^-, form) with water. The eluate was concentrated to give a colorless oil (3.64 g). This oil was further chromatographed on a Amberlite CG-50 column (3.6 x 48 cm, NH₄⁺ form) with water as an eluant to give 2R, 3S 3-hydroxy-N,N-dimethylproline·The compound was crystallized from 95% aq. EtOH by layering with acetone. The purification was followed using GC—MS of the trimethylsilyl-derivative (Nash et al., 1986) scanning from 100–400 daltons which gave distinctive fragmentation with major ions at 196 (20%), 226 (100%), 270 (20%) and 285 (80%) amu. m.p. crystals decomposed above 495 K, without melting; [α]_D¹⁸ +17.2 (c, 0.21 in water).

S3. Refinement

The use of Cu—Kα radiation enabled the absolute configuration to be determined from the anomalous differences of the Friedel Pairs.

The H atoms were all located in a difference map, but those attached to carbon atoms were repositioned geometrically. The H atoms were initially refined with soft restraints on the bond lengths and angles to regularize their geometry (C—H in the range 0.93–0.98,O—H = 0.82 Å) and U_iso(H) (in the range 1.2–1.5 times U_eq of the parent atom), after which the positions were refined with riding constraints.

Computing details

Data collection: CrysAlis CCD (Oxford Diffraction, 2005)'; cell refinement: CrysAlis CCD (Oxford Diffraction, 2005); data reduction: CrysAlis RED (Oxford Diffraction, 2005); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003); molecular graphics: CAMERON (Watkin et al., 1996); software used to prepare material for publication: CRYSTALS.

Figures

	Fig. 1. The title compound with displacement ellipsoids drawn at the 50% probability level. H atoms are shown as spheres of arbitary radius.
	Fig. 2. Packing diagram showing the hydrogen bonded (dashed lines) layers lying perpendicular to the a-axis and the hydrogen bonds between each molecule and a molecule of water.

(2R,3S)-3-Hydroxy-N,N-dimethylproline monohydrate

Crystal data

C7H13NO3·H2O	F(000) = 192
Mr = 177.20	Dx = 1.404 Mg m^−3
Monoclinic, P21	Cu Kα radiation, λ = 1.5418 Å
Hall symbol: P 2yb	Cell parameters from 2601 reflections
a = 6.0647 (2) Å	θ = 5–70°
b = 7.1798 (2) Å	µ = 0.97 mm^−1
c = 10.1956 (2) Å	T = 150 K
β = 109.195 (2)°	Fragment, colourless
V = 419.27 (2) Å^3	0.30 × 0.30 × 0.24 mm
Z = 2

Data collection

Oxford Diffraction Gemini area-detector diffractometer	1407 reflections with I > 3σ(I)
Graphite monochromator	Rint = 0.010
ω scans	θmax = 71.8°, θmin = 4.6°
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2005)	h = −7→7
Tmin = 0.75, Tmax = 0.79	k = −8→8
3114 measured reflections	l = −12→12
1452 independent reflections

Refinement

Refinement on F	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	Method, part 1, Chebychev polynomial [Prince (1982). Mathematical Techniques in Crystallography and Materials Science. New York: Springer-Verlag; Watkin (1994). Acta Cryst. A50, 411–437] [weight] = 1.0/[A0*T0(x) + A1*T1(x) ··· + An-1]*Tn-1(x)] where Ai are the Chebychev coefficients listed below and x = F /Fmax Method = Robust Weighting (Prince, 1982) W = [weight] * [1-(deltaF/6*sigmaF)^2]^2 Ai are: 13.0 -4.75 9.02
wR(F^2) = 0.039	(Δ/σ)max = 0.004
S = 1.08	Δρmax = 0.35 e Å^−3
1407 reflections	Δρmin = −0.29 e Å^−3
122 parameters	Absolute structure: Flack (1983), 571 Friedel pairs
1 restraint	Absolute structure parameter: 0.08 (18)
Primary atom site location: structure-invariant direct methods

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
C1	0.1524 (3)	0.2948 (2)	0.27919 (14)	0.0152
C2	0.3289 (2)	0.3724 (2)	0.21421 (13)	0.0140
C3	0.2330 (2)	0.4103 (2)	0.05749 (15)	0.0152
C4	0.4060 (3)	0.5546 (2)	0.03266 (15)	0.0187
C5	0.5849 (3)	0.5926 (2)	0.17550 (16)	0.0188
N1	0.4544 (2)	0.5514 (2)	0.27595 (12)	0.0151
O1	0.11267 (19)	0.38049 (18)	0.37433 (11)	0.0209
O2	0.0669 (2)	0.14086 (17)	0.22910 (11)	0.0212
O3	0.00020 (18)	0.47790 (18)	0.02103 (11)	0.0184
C6	0.2944 (3)	0.7127 (2)	0.27524 (16)	0.0188
C7	0.6228 (3)	0.5226 (2)	0.41945 (15)	0.0203
O4	0.2618 (2)	0.5178 (2)	0.65461 (14)	0.0289
H1	−0.040 (4)	0.524 (3)	−0.056 (2)	0.019 (5)*
H2	0.197 (5)	0.497 (4)	0.574 (3)	0.043 (7)*
H3	0.153 (5)	0.553 (4)	0.682 (2)	0.030 (5)*
H21	0.4398	0.2648	0.2367	0.0168*
H31	0.2230	0.2974	−0.0016	0.0187*
H41	0.3220	0.6718	−0.0078	0.0229*
H42	0.4845	0.5024	−0.0315	0.0229*
H51	0.6375	0.7253	0.1834	0.0235*
H52	0.7233	0.5087	0.1931	0.0235*
H61	0.3898	0.8245	0.3173	0.0228*
H62	0.1911	0.6792	0.3305	0.0228*
H63	0.1963	0.7414	0.1775	0.0228*
H71	0.7012	0.6433	0.4561	0.0233*
H72	0.5366	0.4766	0.4815	0.0233*
H73	0.7429	0.4287	0.4166	0.0233*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0156 (6)	0.0168 (6)	0.0121 (6)	0.0012 (5)	0.0031 (5)	0.0039 (5)
C2	0.0141 (6)	0.0141 (6)	0.0140 (7)	0.0000 (5)	0.0048 (5)	−0.0012 (5)
C3	0.0168 (6)	0.0163 (6)	0.0137 (6)	−0.0002 (5)	0.0068 (5)	0.0000 (5)
C4	0.0210 (7)	0.0204 (7)	0.0159 (7)	−0.0030 (6)	0.0076 (6)	0.0010 (5)
C5	0.0169 (6)	0.0231 (8)	0.0188 (7)	−0.0026 (5)	0.0093 (6)	0.0020 (6)
N1	0.0151 (5)	0.0169 (6)	0.0133 (6)	−0.0006 (4)	0.0047 (5)	0.0006 (4)
O1	0.0249 (5)	0.0226 (5)	0.0189 (5)	−0.0012 (4)	0.0124 (4)	−0.0024 (4)
O2	0.0270 (6)	0.0215 (5)	0.0170 (5)	−0.0080 (5)	0.0096 (4)	−0.0020 (4)
O3	0.0164 (5)	0.0239 (5)	0.0134 (5)	0.0015 (4)	0.0029 (4)	0.0037 (4)
C6	0.0219 (7)	0.0149 (6)	0.0202 (7)	0.0007 (6)	0.0075 (6)	−0.0018 (5)
C7	0.0174 (7)	0.0266 (8)	0.0142 (7)	−0.0034 (6)	0.0015 (6)	−0.0007 (6)
O4	0.0226 (5)	0.0382 (8)	0.0255 (7)	0.0088 (5)	0.0074 (5)	−0.0059 (5)

Geometric parameters (Å, º)

C1—C2	1.5366 (18)	C5—H51	1.000
C1—O1	1.237 (2)	C5—H52	1.000
C1—O2	1.256 (2)	N1—C6	1.5098 (19)
C2—C3	1.5346 (19)	N1—C7	1.4979 (18)
C2—N1	1.5207 (19)	O3—H1	0.82 (2)
C2—H21	1.000	C6—H61	1.000
C3—C4	1.553 (2)	C6—H62	1.000
C3—O3	1.4217 (18)	C6—H63	1.000
C3—H31	1.000	C7—H71	1.000
C4—C5	1.528 (2)	C7—H72	1.000
C4—H41	1.000	C7—H73	1.000
C4—H42	1.000	O4—H2	0.80 (3)
C5—N1	1.5152 (18)	O4—H3	0.83 (3)
C2—C1—O1	120.05 (13)	C4—C5—H52	110.8
C2—C1—O2	113.37 (12)	N1—C5—H52	110.8
O1—C1—O2	126.54 (14)	H51—C5—H52	109.5
C1—C2—C3	115.71 (11)	C2—N1—C5	100.76 (11)
C1—C2—N1	116.91 (11)	C2—N1—C6	114.40 (11)
C3—C2—N1	104.34 (11)	C5—N1—C6	108.96 (12)
C1—C2—H21	97.6	C2—N1—C7	112.05 (11)
C3—C2—H21	111.9	C5—N1—C7	110.32 (11)
N1—C2—H21	110.5	C6—N1—C7	109.94 (12)
C2—C3—C4	104.06 (12)	C3—O3—H1	110.3 (14)
C2—C3—O3	109.69 (11)	N1—C6—H61	109.5
C4—C3—O3	113.31 (12)	N1—C6—H62	109.5
C2—C3—H31	114.2	H61—C6—H62	109.5
C4—C3—H31	110.7	N1—C6—H63	109.5
O3—C3—H31	105.1	H61—C6—H63	109.5
C3—C4—C5	105.65 (12)	H62—C6—H63	109.5
C3—C4—H41	110.4	N1—C7—H71	109.5
C5—C4—H41	110.4	N1—C7—H72	109.5
C3—C4—H42	110.4	H71—C7—H72	109.5
C5—C4—H42	110.4	N1—C7—H73	109.5
H41—C4—H42	109.5	H71—C7—H73	109.5
C4—C5—N1	104.15 (11)	H72—C7—H73	109.5
C4—C5—H51	110.8	H2—O4—H3	103 (3)
N1—C5—H51	110.8

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O3—H1···O2^i	0.82 (2)	1.91 (3)	2.712 (2)	168 (3)
O4—H3···O2^ii	0.83 (3)	1.95 (3)	2.777 (2)	172 (3)
O4—H2···O1	0.80 (3)	2.10 (3)	2.873 (2)	162 (3)

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