(2R,4R)-3-(tert-But­oxy­carbon­yl)-2-(3-chloro­phen­yl)-1,3-thia­zolidine-4-carb­oxy­lic acid monohydrate

In the title compound, C₁₅H₁₈ClNO₄S·H₂O, the thia­zolidine ring displays a half-chair conformation. In the crystal, the water mol­ecules are linked to the organic acid mol­ecules via inter­molecular O—H...O hydrogen bonds.

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.009 Å
• R factor = 0.068
• wR factor = 0.167
• Data-to-parameter ratio = 15.3

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT242_ALERT_2_C Check Low       Ueq as Compared to Neighbors for        C12
PLAT340_ALERT_3_C Low Bond Precision on  C-C Bonds (x 1000) Ang ..          9
PLAT417_ALERT_2_C Short Inter D-H..H-D       H2C    ..  H5B     ..       2.12 Ang.
PLAT912_ALERT_4_C Missing # of FCF Reflections Above STh/L=  0.600          4

Alert level G
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           25.31
           From the CIF: _reflns_number_total               3182
           Count of symmetry unique reflns         1767
           Completeness (_total/calc)            180.08%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured      1415
           Fraction of Friedel pairs measured     0.801
           Are heavy atom types Z>Si present        yes
PLAT916_ALERT_2_G Hooft y and Flack x Parameter values differ by .       0.11
PLAT199_ALERT_1_G Check the Reported _cell_measurement_temperature        293 K
PLAT200_ALERT_1_G Check the Reported   _diffrn_ambient_temperature        293 K
PLAT791_ALERT_4_G Note: The Model has Chirality at C1     (Verify)          R
PLAT791_ALERT_4_G Note: The Model has Chirality at C3     (Verify)          R

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   4 ALERT level C = Check and explain
   6 ALERT level G = General alerts; check

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

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S1. Comment

The steric course of the reaction between L-cysteine and aldehydes deserved much attention because this reaction had been implicated in several biochemical processes (Kallen, 1971). An analogous condensation reaction constituted the first step in the syntheses of important natural products, such as penicillin and biotin (Seki et al., 2004). Therefore, thiazolidine derivatives have become especially noteworthy in recent years (Song et al. 2009). In the present work, the structure of the title new compound is reported.

The compound consists of a (2R,4R)-3-(tert-butoxycarbonyl)-2-(3-chlorophenyl)thiazolidine-4-carboxylic acid molecule and a water molecule of crystallization (Fig. 1). The torsion angles C12—O4—C11—O3, C12—O4—C11—N1, and N1—C1—C2—S1 are 3.2 (5), 5.5 (5), and 37.1 (5)°, respectively. The S1 atom is located 0.762 (6)Å from the least-squares plane defined by C2/C1/N1/C3. In the crystal structure, the (2R,4R)-3-(tert-butoxycarbonyl)-2- (3-chlorophenyl)thiazolidine-4-carboxylic acid molecules are linked by water molecules through intermolecular O–H···O hydrogen bonds (Table 1), forming chains running along the b axis (Fig. 2).

Related literature

For applications of thiazolidine derivatives, see: Kallen (1971); Seki et al. (2004); Song et al. (2009).

S2. Experimental

Cysteine (0.121 g, 1.0 mmol) and appropriate aldehyde (1.0 mmol) in ethanol (25 ml) was stirred at room temperature for 8 h, and the solid separated was collected, washed with diethyl ether and dried to obtain (2RS,4R)-2-(3-chlorophenyl)thiazolidine-4-carboxylic acid (TCA). A mixture of TCA (1.0 mmol) and appropriate NaOH (10%, 1.0 mmol) in dioxane (25 ml) was stirred at ice-water temperature for 2 h. BOC₂O (1.0 mmol) was added and stirred at ice-water temperature for 1 h and then at room temperature for 5 h. Most of the solvent was extracted and appropriate amount of water was added to adjust to neutral pH value. Ethyl acetate was added and extracted (50 ml), and washed with appropriate saturated aqueous solution of common salt, and dried with anhydrous magnesium sulfate. Solvent was extracted to dry to obtain whiter solids (2R,4R)-3-(tert-butoxycarbonyl)-2-(3-chlorophenyl)thiazolidine-4-carboxylic acid hydrate

S3. Refinement

H atoms were positioned geometrically and refined using the riding-model approximation, with C–H = 0.93–0.97 Å, O–H = 0.82–0.85 Å, and U_iso(H) = 1.2U_eq(C,O) or U_iso(H) = 1.5U_eq(methyl C).

Computing details

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994); cell refinement: CAD-4 EXPRESS (Enraf–Nonius, 1994); data reduction: XCAD4 (Harms & Wocadlo, 1995); 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

	Fig. 1. The molecular structure of the title compounds with atom labels and the 30% probability displacement ellipsoids for H atoms.
	Fig. 2. Molecular packing of the title compound, viewed along the a axis. Hydrogen bonds are shown as dashed lines.

(2R,4R)-3-(tert-Butoxycarbonyl)-2-(3-chlorophenyl)- 1,3-thiazolidine-4-carboxylic acid monohydrate

Crystal data

C15H18ClNO4S·H2O	F(000) = 380
Mr = 361.83	Dx = 1.367 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 25 reflections
a = 8.2460 (16) Å	θ = 9–12°
b = 5.9660 (12) Å	µ = 0.36 mm^−1
c = 18.132 (4) Å	T = 293 K
β = 99.81 (3)°	Block, colorless
V = 879.0 (3) Å^3	0.20 × 0.17 × 0.15 mm
Z = 2

Data collection

Enraf–Nonius CAD-4 diffractometer	2169 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.080
Graphite monochromator	θmax = 25.3°, θmin = 1.1°
ω/2θ scans	h = 0→9
Absorption correction: ψ scan (ABSCOR; Higashi, 1995)	k = −7→7
Tmin = 0.932, Tmax = 0.948	l = −21→21
3417 measured reflections	3 standard reflections every 200 reflections
3182 independent reflections	intensity decay: 1%

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.068	H-atom parameters constrained
wR(F^2) = 0.167	w = 1/[σ^2(Fo^2) + (0.0664P)^2 + 0.2379P] where P = (Fo^2 + 2Fc^2)/3
S = 1.03	(Δ/σ)max = 0.001
3182 reflections	Δρmax = 0.19 e Å^−3
208 parameters	Δρmin = −0.28 e Å^−3
1 restraint	Absolute structure: Flack (1983), 1451 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.11 (16)

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
S1	−0.27417 (18)	0.2513 (3)	0.65551 (8)	0.0556 (4)
Cl	0.2514 (3)	0.2819 (5)	0.47181 (11)	0.1051 (8)
N1	−0.0494 (5)	0.1770 (7)	0.7725 (2)	0.0353 (10)
O1	−0.0704 (5)	−0.2937 (7)	0.8136 (2)	0.0621 (12)
C1	−0.1971 (6)	0.0662 (9)	0.7899 (3)	0.0379 (13)
H1A	−0.2563	0.1677	0.8185	0.045*
O2	−0.2241 (5)	−0.1623 (7)	0.8928 (2)	0.0531 (11)
H2C	−0.1984	−0.2805	0.9148	0.080*
C2	−0.3015 (7)	0.0154 (11)	0.7147 (3)	0.0519 (16)
H2A	−0.4163	−0.0005	0.7195	0.062*
H2B	−0.2653	−0.1222	0.6940	0.062*
O3	0.0636 (4)	0.1875 (6)	0.89459 (18)	0.0422 (9)
C3	−0.0548 (6)	0.2640 (10)	0.6970 (3)	0.0415 (12)
H3A	−0.0212	0.4217	0.7007	0.050*
O4	0.1931 (4)	0.3384 (6)	0.80485 (18)	0.0407 (9)
C4	0.0541 (7)	0.1417 (9)	0.6516 (3)	0.0395 (13)
C5	0.0950 (7)	0.2482 (12)	0.5896 (3)	0.0505 (14)
H5C	0.0531	0.3897	0.5759	0.061*
C6	0.1987 (8)	0.1427 (12)	0.5482 (3)	0.0592 (17)
C7	0.2659 (8)	−0.0660 (13)	0.5677 (4)	0.0651 (19)
H7A	0.3366	−0.1334	0.5394	0.078*
C8	0.2260 (8)	−0.1720 (11)	0.6297 (3)	0.0590 (17)
H8A	0.2689	−0.3131	0.6433	0.071*
C9	0.1218 (7)	−0.0688 (10)	0.6721 (3)	0.0487 (15)
H9A	0.0970	−0.1402	0.7144	0.058*
C10	−0.1541 (6)	−0.1503 (10)	0.8333 (3)	0.0390 (13)
C11	0.0700 (6)	0.2343 (9)	0.8296 (3)	0.0366 (11)
C12	0.3466 (7)	0.4010 (9)	0.8560 (3)	0.0424 (14)
C13	0.4314 (7)	0.1879 (12)	0.8896 (4)	0.0663 (19)
H13A	0.3687	0.1236	0.9243	0.099*
H13B	0.5400	0.2238	0.9152	0.099*
H13C	0.4388	0.0823	0.8504	0.099*
C14	0.4440 (8)	0.5092 (12)	0.8017 (4)	0.0635 (19)
H14A	0.3894	0.6438	0.7819	0.095*
H14B	0.4516	0.4071	0.7615	0.095*
H14C	0.5525	0.5451	0.8274	0.095*
C15	0.3093 (9)	0.5670 (12)	0.9141 (4)	0.073 (2)
H15A	0.2574	0.6973	0.8894	0.110*
H15B	0.4099	0.6100	0.9457	0.110*
H15C	0.2369	0.4989	0.9438	0.110*
O5	0.8493 (5)	0.4638 (7)	0.9669 (2)	0.0585 (12)
H5B	0.7943	0.4847	1.0019	0.070*
H5A	0.9053	0.3446	0.9659	0.070*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0481 (8)	0.0689 (11)	0.0474 (8)	0.0106 (9)	0.0013 (6)	0.0065 (8)
Cl	0.1239 (18)	0.130 (2)	0.0752 (12)	0.0239 (16)	0.0570 (12)	0.0417 (14)
N1	0.041 (2)	0.034 (2)	0.030 (2)	−0.003 (2)	0.0042 (19)	−0.0031 (19)
O1	0.076 (3)	0.049 (3)	0.069 (3)	0.013 (2)	0.031 (2)	0.005 (2)
C1	0.037 (3)	0.038 (3)	0.040 (3)	−0.002 (2)	0.011 (2)	−0.004 (2)
O2	0.061 (3)	0.048 (3)	0.055 (2)	0.005 (2)	0.021 (2)	0.012 (2)
C2	0.042 (3)	0.061 (4)	0.052 (4)	−0.007 (3)	0.005 (3)	−0.006 (3)
O3	0.047 (2)	0.046 (2)	0.034 (2)	−0.0027 (18)	0.0101 (16)	0.0039 (17)
C3	0.046 (3)	0.035 (3)	0.041 (3)	−0.001 (3)	0.001 (2)	−0.001 (3)
O4	0.042 (2)	0.041 (2)	0.0399 (19)	−0.0063 (18)	0.0093 (16)	−0.0023 (18)
C4	0.042 (3)	0.040 (3)	0.035 (3)	−0.001 (3)	0.002 (2)	−0.002 (3)
C5	0.061 (4)	0.046 (3)	0.047 (3)	0.001 (3)	0.017 (3)	0.003 (3)
C6	0.064 (4)	0.070 (5)	0.045 (4)	0.000 (4)	0.014 (3)	0.006 (3)
C7	0.063 (4)	0.082 (5)	0.054 (4)	0.011 (4)	0.023 (3)	−0.008 (4)
C8	0.077 (4)	0.049 (4)	0.055 (4)	0.015 (3)	0.023 (3)	0.000 (3)
C9	0.059 (4)	0.051 (4)	0.039 (3)	0.003 (3)	0.016 (3)	0.006 (3)
C10	0.035 (3)	0.041 (3)	0.042 (3)	−0.003 (3)	0.006 (2)	−0.002 (3)
C11	0.044 (3)	0.027 (3)	0.041 (3)	0.006 (3)	0.012 (2)	0.000 (2)
C12	0.037 (3)	0.039 (3)	0.051 (3)	−0.010 (3)	0.004 (3)	−0.001 (3)
C13	0.044 (3)	0.066 (5)	0.086 (5)	0.003 (3)	0.004 (3)	0.023 (4)
C14	0.052 (4)	0.059 (4)	0.080 (5)	−0.014 (3)	0.009 (4)	0.017 (4)
C15	0.079 (5)	0.067 (5)	0.071 (5)	−0.021 (4)	0.004 (4)	−0.021 (4)
O5	0.079 (3)	0.047 (3)	0.054 (3)	0.008 (2)	0.024 (2)	0.006 (2)

Geometric parameters (Å, º)

S1—C2	1.807 (6)	C5—H5C	0.9300
S1—C3	1.838 (5)	C6—C7	1.384 (10)
Cl—C6	1.733 (6)	C7—C8	1.379 (9)
N1—C11	1.346 (6)	C7—H7A	0.9300
N1—C3	1.457 (6)	C8—C9	1.390 (8)
N1—C1	1.466 (6)	C8—H8A	0.9300
O1—C10	1.192 (6)	C9—H9A	0.9300
C1—C2	1.513 (7)	C12—C15	1.515 (8)
C1—C10	1.524 (7)	C12—C14	1.516 (8)
C1—H1A	0.9800	C12—C13	1.527 (8)
O2—C10	1.309 (6)	C13—H13A	0.9600
O2—H2C	0.8200	C13—H13B	0.9600
C2—H2A	0.9700	C13—H13C	0.9600
C2—H2B	0.9700	C14—H14A	0.9600
O3—C11	1.221 (6)	C14—H14B	0.9600
C3—C4	1.505 (7)	C14—H14C	0.9600
C3—H3A	0.9800	C15—H15A	0.9600
O4—C11	1.332 (6)	C15—H15B	0.9600
O4—C12	1.483 (6)	C15—H15C	0.9600
C4—C5	1.383 (8)	O5—H5B	0.8499
C4—C9	1.398 (8)	O5—H5A	0.8500
C5—C6	1.382 (8)
C2—S1—C3	90.2 (3)	C7—C8—H8A	119.9
C11—N1—C3	122.2 (4)	C9—C8—H8A	119.9
C11—N1—C1	118.3 (4)	C8—C9—C4	120.5 (5)
C3—N1—C1	118.0 (4)	C8—C9—H9A	119.7
N1—C1—C2	105.2 (4)	C4—C9—H9A	119.7
N1—C1—C10	111.4 (4)	O1—C10—O2	124.6 (5)
C2—C1—C10	110.0 (5)	O1—C10—C1	123.3 (5)
N1—C1—H1A	110.0	O2—C10—C1	112.1 (5)
C2—C1—H1A	110.0	O3—C11—O4	126.3 (5)
C10—C1—H1A	110.0	O3—C11—N1	122.6 (5)
C10—O2—H2C	109.5	O4—C11—N1	111.1 (4)
C1—C2—S1	105.6 (4)	O4—C12—C15	110.3 (5)
C1—C2—H2A	110.6	O4—C12—C14	101.0 (4)
S1—C2—H2A	110.6	C15—C12—C14	111.5 (5)
C1—C2—H2B	110.6	O4—C12—C13	108.9 (4)
S1—C2—H2B	110.6	C15—C12—C13	113.6 (5)
H2A—C2—H2B	108.7	C14—C12—C13	110.9 (5)
N1—C3—C4	114.5 (4)	C12—C13—H13A	109.5
N1—C3—S1	103.9 (3)	C12—C13—H13B	109.5
C4—C3—S1	113.2 (4)	H13A—C13—H13B	109.5
N1—C3—H3A	108.3	C12—C13—H13C	109.5
C4—C3—H3A	108.3	H13A—C13—H13C	109.5
S1—C3—H3A	108.3	H13B—C13—H13C	109.5
C11—O4—C12	121.7 (4)	C12—C14—H14A	109.5
C5—C4—C9	119.1 (5)	C12—C14—H14B	109.5
C5—C4—C3	118.2 (5)	H14A—C14—H14B	109.5
C9—C4—C3	122.6 (5)	C12—C14—H14C	109.5
C6—C5—C4	119.5 (6)	H14A—C14—H14C	109.5
C6—C5—H5C	120.3	H14B—C14—H14C	109.5
C4—C5—H5C	120.3	C12—C15—H15A	109.5
C5—C6—C7	121.9 (6)	C12—C15—H15B	109.5
C5—C6—Cl	118.6 (5)	H15A—C15—H15B	109.5
C7—C6—Cl	119.4 (5)	C12—C15—H15C	109.5
C8—C7—C6	118.6 (6)	H15A—C15—H15C	109.5
C8—C7—H7A	120.7	H15B—C15—H15C	109.5
C6—C7—H7A	120.7	H5B—O5—H5A	120.0
C7—C8—C9	120.3 (6)
C11—N1—C1—C2	−177.5 (5)	C4—C5—C6—Cl	−178.7 (5)
C3—N1—C1—C2	16.0 (6)	C5—C6—C7—C8	0.9 (11)
C11—N1—C1—C10	−58.3 (6)	Cl—C6—C7—C8	178.4 (5)
C3—N1—C1—C10	135.3 (5)	C6—C7—C8—C9	−0.8 (10)
N1—C1—C2—S1	−37.1 (5)	C7—C8—C9—C4	1.1 (10)
C10—C1—C2—S1	−157.2 (4)	C5—C4—C9—C8	−1.5 (9)
C3—S1—C2—C1	39.2 (4)	C3—C4—C9—C8	−177.9 (5)
C11—N1—C3—C4	82.2 (6)	N1—C1—C10—O1	−51.4 (7)
C1—N1—C3—C4	−111.8 (5)	C2—C1—C10—O1	64.9 (7)
C11—N1—C3—S1	−153.8 (4)	N1—C1—C10—O2	130.8 (5)
C1—N1—C3—S1	12.1 (5)	C2—C1—C10—O2	−112.9 (5)
C2—S1—C3—N1	−29.0 (4)	C12—O4—C11—O3	3.2 (8)
C2—S1—C3—C4	95.7 (4)	C12—O4—C11—N1	−174.5 (4)
N1—C3—C4—C5	−161.1 (5)	C3—N1—C11—O3	169.7 (5)
S1—C3—C4—C5	80.0 (6)	C1—N1—C11—O3	3.9 (7)
N1—C3—C4—C9	15.4 (8)	C3—N1—C11—O4	−12.4 (6)
S1—C3—C4—C9	−103.5 (6)	C1—N1—C11—O4	−178.3 (4)
C9—C4—C5—C6	1.5 (9)	C11—O4—C12—C15	−62.5 (6)
C3—C4—C5—C6	178.1 (5)	C11—O4—C12—C14	179.5 (5)
C4—C5—C6—C7	−1.2 (10)	C11—O4—C12—C13	62.7 (6)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2C···O5^i	0.82	1.80	2.620 (6)	177
O5—H5A···O3^ii	0.85	2.20	2.890 (5)	139
O5—H5B···O3^iii	0.85	2.37	2.827 (5)	114

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