Thia­mine dichloride monohydrate: vitamin B1 (form III)

Two different forms of the title compound, C₁₂H₁₈N₄OS²⁺·2Cl⁻·H₂O, have already been reported [Kraut & Reed (1962). Acta Cryst. 15, 747–757; Suh et al. (1982). J. Korean Phys. Soc. 15, 114–121]. In this third form, in which the H atoms were located, a different conformation is observed. The planes of the pyrimidine and thia­zolium rings are at a dihedral angle of 79 (15)°. The structure contains two weak O—H...Cl hydrogen bonds.

Key indicators

• Single-crystal X-ray study
• T = 173 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.033
• wR factor = 0.081
• Data-to-parameter ratio = 17.5

checkCIF/PLATON results

No syntax errors found



Alert level A
PLAT222_ALERT_3_A Large Non-Solvent    H     Ueq(max)/Ueq(min) ...       5.50 Ratio

Author Response: This may be due to the presence of two Chlorine atoms in the anion Part of the structure.

PLAT772_ALERT_2_A Suspect O-H Bond in CIF:      O2     -H1O1    ..       1.95 Ang.

Author Response: This hydrogen bond is caught up using SHELXL program. The unusual hydrogen bonding is novel and found to be very weak.

Alert level C
PLAT042_ALERT_1_C Calc. and Rep. MoietyFormula Strings Differ ....          ?
PLAT066_ALERT_1_C Predicted and Reported Transmissions Identical .          ?
PLAT720_ALERT_4_C Number of Unusual/Non-Standard Label(s) ........          6
PLAT790_ALERT_4_C Centre of Gravity not Within Unit Cell: Resd.  #          4
              Cl

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

   2 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 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
   2 ALERT type 4 Improvement, methodology, query or suggestion

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S1. Comment

Thiamine, as its pyrophosphate ester, is a coenzyme in a number of important metabolic processes such as the decarboxylation of α-keto acids and the transfer of aldehyde or acyl groups (Krampitz, 1969). In the present work, the H atoms being located by difference map leads to the better understanding of the hydrogen-bonding pattern in vitamin B1. The molecular diagram of the title compound, (I), is given in Fig. 1. Bond angles within the pyrimidine ring are all close to 120°. The small difference between the angle of 120.93 (12)° at N4 and 118.76 (12)° at N3 is some what surprising in view of the fact that N4 is externally bonded to an H atom whereas N3 is not. It has already been pointed out that one would expect the angle at the ring N atom in pyrimidines to approach 125° for the externally bonded case or 106° for the non-bonded case (Pauling & Corey, 1956).

The bond lengths and bond angles in this structure are similar to those of the two different forms reported previously [forms I (Kraut & Reed, 1962) and II (Suh et al., 1982) {please check assignment of references}]. Both of the aromatic rings in this molecule are virtually planar with small deviations from strict planarity. The conformation of the thiamine molecule is described by two torsion angles, ϕ_T and ϕ_P, centering the methylene atom C7 to the respective rings ϕ_T [C2—N1—C7—C8] and ϕ_P [N1—C7—C8—C9] (Pletcher & Sax, 1972). Basically three kinds of conformers have been observed in the thiamine molecule, namely F, S and V conformations. The value of ϕ_T and ϕ_P decides the conformation whether belongs to F, S and V conformation. The torsion angle of ϕ_T is 0° for F, ±100° for S and ±90° for V (Shin et al., 1977). The value of ϕ_P is ±90° for F, ±150° for S and ±90° for V (Shin et al., 1977). Among them, the F conformation has been most frequently found in thiamine derivatives. The present structure in which the torsion angle of ϕ_T = 179.18 (11)°, and ϕ_P = −79.27 (15)° also belongs to the F conformation. Thus the F conformation is the predominant one of the free thiamine molecules.

The C5-hydroxyethyl side chain is folded back towards the thiazolium ring from the opposite side to the pyrimidine moiety. The thiazolium ring is described by the two torsion angles ϕ_5a [S1—C1—C4—C5] and ϕ_{5 b} [C1—C4—C5—O1]. In the present work, the values of ϕ_5a and ϕ_{5 b} are 24.2 (20) and −63.35 (18)°, respectively. However, these angles differ widely from those of the two forms reported earlier. We have calculated these angles ϕ_5a and ϕ_{5 b} as 103.4 (6) and 53.76 (7)°, respectively, for form I, and −100.8 (3) and 50.6 (8)°, respectively, for form II. The values of ϕ_5a and ϕ_{5 b} for most of the thiamine derivatives have been observed to lie in the range ±60 to ±90° (Shin et al., 1977) and within 10° from ±60° (Shin et al., 1977). The essential difference occurs in the angle ϕ_5a of the present structure. This difference appears due to the packing specificity required for the hydroxy group participating in hydrogen bonding. The geometries of the hydrogen bonds are given in Table 2. This structure contains two weak but distinct O—H···Cl and N—H···Cl hydrogen bonds. The interatomic distances H1O2···Cl2 and H2O2···Cl1 are 2.40 (3) and 2.32 (3) Å, respectively, which are shorter than the normal van der Waals distance (3.0) Å. These hydrogen bonds must be weaker than N—H···Cl bonds, for which the hydrogen to chloride distances are 2.359 (19), 2.36 (2) and 2.28 (2) Å in this structure. The hydrogen-bond distribution at the alcohol group is well established in this structure. The interatomic distances O2—Cl1 and O2—Cl2 are 3.163 (13) and 3.212 (14) Å, which is in the range of normal van der Waals distance (3.2 Å).

S2. Experimental

Thiamine hydrochloride (660 mg, Sigma) was dissolved in 75 ml of water. The mixture was heated for about 4 h and allowed to cooling. After a week, colorless block-shaped crystals appeared.

S3. Refinement

All H atoms were found in a difference Fourier map and refined isotropically [C—H = 0.89 (3)–1.003 (19) Å]. O2···H101 [1.95 (2) Å] hydrogen bond is caught up using SHELXL program. The unusual hydrogen bonding is novel and found to be very weak.

Computing details

Data collection: SMART (Bruker, 1998); cell refinement: SAINT (Bruker, 1998); data reduction: SAINT; program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ZORTEP (Zsolnai & Pritzkow, 1995); software used to prepare material for publication: SHELXL97.

Figures

Fig. 1. View of (I), with 50% probability displacement ellipsoids.

Thiamine dichloride monohydrate

Crystal data

C12H18N4OS^2+·2Cl^−·H2O	F(000) = 744
Mr = 355.28	Dx = 1.421 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2y bc	Cell parameters from 25 reflections
a = 9.1437 (2) Å	θ = 2–30.8°
b = 7.3438 (2) Å	µ = 0.53 mm^−1
c = 24.7447 (6) Å	T = 173 K
β = 92.112 (1)°	Block, colorless
V = 1660.47 (7) Å^3	0.5 × 0.32 × 0.24 mm
Z = 4

Data collection

Bruker SMART CCD diffractometer	3913 reflections with I > 2σ(I)
ω scans	Rint = 0.026
Absorption correction: empirical (using intensity measurements) (SADABS; Bruker, 1998)	θmax = 30.8°, θmin = 1.7°
Tmin = 0.817, Tmax = 0.881	h = −12→11
11933 measured reflections	k = −10→10
4716 independent reflections	l = −35→29

Refinement

Refinement on F^2	0 restraints
Least-squares matrix: full	All H-atom parameters refined
R[F^2 > 2σ(F^2)] = 0.033	w = 1/[σ^2(Fo^2) + (0.0341P)^2 + 0.5004P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.081	(Δ/σ)max < 0.001
S = 1.05	Δρmax = 0.27 e Å^−3
4716 reflections	Δρmin = −0.27 e Å^−3
270 parameters

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.

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

	x	y	z	Uiso*/Ueq
Cl1	0.73143 (4)	0.61805 (5)	−0.093135 (14)	0.02631 (8)
Cl2	−0.13005 (4)	0.87135 (5)	0.087101 (15)	0.02970 (9)
S1	0.60833 (4)	0.53995 (5)	0.197213 (15)	0.03026 (10)
O1	0.75506 (13)	0.42930 (16)	0.29537 (4)	0.0330 (2)
H1O1	0.796 (2)	0.332 (3)	0.3025 (9)	0.055 (7)*
O2	0.91842 (15)	0.13742 (17)	0.33306 (5)	0.0350 (3)
H1O2	0.978 (3)	0.186 (3)	0.3542 (9)	0.056 (7)*
H2O2	0.873 (3)	0.066 (3)	0.3532 (10)	0.064 (7)*
N1	0.55130 (12)	0.82985 (15)	0.14875 (4)	0.0196 (2)
N2	0.58901 (13)	0.75687 (18)	0.01444 (5)	0.0257 (2)
H1N2	0.6531 (19)	0.791 (2)	0.0383 (7)	0.029 (4)*
H2N2	0.618 (2)	0.706 (3)	−0.0133 (8)	0.037 (5)*
N3	0.35590 (12)	0.71385 (16)	−0.01825 (5)	0.0237 (2)
N4	0.15847 (13)	0.81725 (17)	0.02986 (5)	0.0263 (2)
H1N4	0.067 (2)	0.825 (3)	0.0347 (8)	0.043 (5)*
C1	0.68837 (15)	0.73632 (18)	0.22234 (5)	0.0230 (3)
C2	0.64574 (15)	0.88011 (18)	0.19145 (5)	0.0217 (3)
C3	0.52270 (16)	0.65450 (19)	0.14677 (6)	0.0258 (3)
H3	0.4614 (19)	0.603 (2)	0.1201 (7)	0.030 (4)*
C4	0.78891 (19)	0.7385 (2)	0.27160 (7)	0.0337 (3)
H4A	0.733 (2)	0.775 (3)	0.3017 (8)	0.044 (5)*
H4B	0.856 (2)	0.832 (3)	0.2658 (8)	0.045 (5)*
C5	0.86387 (18)	0.5601 (3)	0.28388 (7)	0.0357 (4)
H5A	0.937 (2)	0.578 (3)	0.3136 (8)	0.039 (5)*
H5B	0.919 (2)	0.523 (3)	0.2514 (8)	0.040 (5)*
C6	0.6878 (2)	1.0741 (2)	0.19913 (7)	0.0327 (3)
H6A	0.737 (2)	1.119 (3)	0.1689 (9)	0.051 (6)*
H6B	0.603 (2)	1.152 (3)	0.2053 (8)	0.052 (6)*
H6C	0.749 (2)	1.089 (3)	0.2314 (9)	0.052 (6)*
C7	0.49062 (15)	0.96432 (18)	0.10890 (6)	0.0224 (3)
H7A	0.5733 (17)	1.025 (2)	0.0934 (6)	0.020 (4)*
H7B	0.4346 (18)	1.049 (2)	0.1290 (7)	0.029 (4)*
C8	0.39391 (14)	0.87760 (17)	0.06647 (5)	0.0209 (2)
C9	0.44822 (14)	0.78210 (17)	0.02089 (5)	0.0203 (2)
C10	0.21472 (15)	0.72945 (19)	−0.01256 (6)	0.0249 (3)
C11	0.24659 (15)	0.89251 (19)	0.06859 (6)	0.0241 (3)
H11	0.1983 (18)	0.956 (2)	0.0970 (7)	0.025 (4)*
C12	0.11179 (19)	0.6489 (3)	−0.05357 (8)	0.0366 (4)
H12B	0.017 (4)	0.663 (4)	−0.0458 (12)	0.097 (10)*
H12A	0.126 (3)	0.529 (4)	−0.0564 (10)	0.078 (8)*
H12C	0.116 (3)	0.709 (4)	−0.0897 (13)	0.110 (11)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl1	0.02476 (16)	0.02817 (17)	0.02614 (16)	−0.00201 (12)	0.00298 (12)	−0.00412 (13)
Cl2	0.01952 (15)	0.0377 (2)	0.03200 (18)	0.00201 (13)	0.00257 (12)	−0.00273 (15)
S1	0.0424 (2)	0.01704 (16)	0.03040 (19)	−0.00494 (14)	−0.01116 (15)	0.00375 (13)
O1	0.0365 (6)	0.0313 (6)	0.0311 (6)	−0.0021 (5)	−0.0024 (4)	0.0069 (5)
O2	0.0421 (7)	0.0326 (6)	0.0303 (6)	−0.0064 (5)	−0.0001 (5)	0.0036 (5)
N1	0.0210 (5)	0.0164 (5)	0.0216 (5)	0.0003 (4)	0.0027 (4)	0.0004 (4)
N2	0.0197 (5)	0.0321 (6)	0.0255 (6)	0.0023 (5)	0.0029 (5)	−0.0030 (5)
N3	0.0222 (5)	0.0247 (6)	0.0243 (6)	0.0001 (4)	0.0017 (4)	0.0017 (5)
N4	0.0177 (5)	0.0317 (6)	0.0295 (6)	0.0029 (5)	0.0027 (4)	0.0073 (5)
C1	0.0272 (6)	0.0206 (6)	0.0212 (6)	−0.0036 (5)	0.0019 (5)	−0.0012 (5)
C2	0.0257 (6)	0.0190 (6)	0.0206 (6)	−0.0014 (5)	0.0037 (5)	−0.0025 (5)
C3	0.0311 (7)	0.0186 (6)	0.0271 (7)	−0.0039 (5)	−0.0058 (5)	0.0012 (5)
C4	0.0422 (9)	0.0320 (8)	0.0261 (7)	−0.0115 (7)	−0.0082 (6)	0.0029 (6)
C5	0.0304 (8)	0.0462 (9)	0.0301 (8)	−0.0042 (7)	−0.0038 (6)	0.0126 (7)
C6	0.0467 (9)	0.0191 (7)	0.0322 (8)	−0.0067 (6)	−0.0001 (7)	−0.0041 (6)
C7	0.0244 (6)	0.0177 (6)	0.0251 (6)	0.0019 (5)	0.0022 (5)	0.0026 (5)
C8	0.0216 (6)	0.0197 (6)	0.0214 (6)	0.0028 (5)	0.0022 (5)	0.0047 (5)
C9	0.0204 (6)	0.0186 (6)	0.0221 (6)	0.0013 (5)	0.0030 (5)	0.0049 (5)
C10	0.0236 (6)	0.0244 (7)	0.0267 (7)	−0.0010 (5)	−0.0004 (5)	0.0063 (5)
C11	0.0238 (6)	0.0245 (6)	0.0242 (6)	0.0039 (5)	0.0052 (5)	0.0054 (5)
C12	0.0290 (8)	0.0403 (9)	0.0400 (9)	−0.0058 (7)	−0.0073 (7)	0.0006 (8)

Geometric parameters (Å, º)

S1—C3	1.6753 (15)	C2—C6	1.4863 (19)
S1—C1	1.7229 (14)	C3—H3	0.931 (18)
O1—C5	1.419 (2)	C4—C5	1.504 (2)
O1—H1O1	0.83 (2)	C4—H4A	0.95 (2)
O2—H1O1	1.95 (2)	C4—H4B	0.93 (2)
O2—H1O2	0.82 (2)	C5—H5A	0.984 (19)
O2—H2O2	0.84 (3)	C5—H5B	1.003 (19)
N1—C3	1.3146 (17)	C6—H6A	0.94 (2)
N1—C2	1.3897 (17)	C6—H6B	0.98 (2)
N1—C7	1.4883 (17)	C6—H6C	0.96 (2)
N2—C9	1.3161 (17)	C7—C8	1.4904 (19)
N2—H1N2	0.854 (19)	C7—H7A	0.971 (16)
N2—H2N2	0.83 (2)	C7—H7B	0.958 (17)
N3—C10	1.3087 (17)	C8—C11	1.3544 (18)
N3—C9	1.3570 (17)	C8—C9	1.4325 (18)
N4—C11	1.3477 (19)	C10—C12	1.481 (2)
N4—C10	1.3497 (19)	C11—H11	0.963 (17)
N4—H1N4	0.85 (2)	C12—H12B	0.90 (3)
C1—C2	1.3526 (19)	C12—H12A	0.89 (3)
C1—C4	1.499 (2)	C12—H12C	1.00 (3)
C3—S1—C1	91.68 (7)	O1—C5—H5B	110.5 (11)
C5—O1—H1O1	108.2 (16)	C4—C5—H5B	108.4 (11)
H1O1—O2—H1O2	106.8 (18)	H5A—C5—H5B	106.9 (15)
H1O1—O2—H2O2	113.6 (17)	C2—C6—H6A	111.0 (13)
H1O2—O2—H2O2	103 (2)	C2—C6—H6B	112.0 (12)
C3—N1—C2	113.93 (11)	H6A—C6—H6B	108.8 (18)
C3—N1—C7	123.82 (12)	C2—C6—H6C	110.7 (13)
C2—N1—C7	122.25 (11)	H6A—C6—H6C	110.0 (18)
C9—N2—H1N2	121.6 (12)	H6B—C6—H6C	104.1 (17)
C9—N2—H2N2	120.3 (13)	N1—C7—C8	112.35 (11)
H1N2—N2—H2N2	118.0 (17)	N1—C7—H7A	107.0 (9)
C10—N3—C9	118.76 (12)	C8—C7—H7A	111.7 (9)
C11—N4—C10	120.93 (12)	N1—C7—H7B	106.3 (10)
C11—N4—H1N4	116.0 (13)	C8—C7—H7B	109.2 (10)
C10—N4—H1N4	123.0 (13)	H7A—C7—H7B	110.1 (14)
C2—C1—C4	127.34 (13)	C11—C8—C9	116.36 (13)
C2—C1—S1	109.86 (10)	C11—C8—C7	120.23 (12)
C4—C1—S1	122.80 (11)	C9—C8—C7	123.36 (12)
C1—C2—N1	112.36 (11)	N2—C9—N3	116.55 (12)
C1—C2—C6	127.47 (13)	N2—C9—C8	122.23 (13)
N1—C2—C6	120.17 (13)	N3—C9—C8	121.21 (12)
N1—C3—S1	112.17 (11)	N3—C10—N4	122.08 (13)
N1—C3—H3	122.6 (11)	N3—C10—C12	119.72 (14)
S1—C3—H3	125.2 (11)	N4—C10—C12	118.21 (13)
C1—C4—C5	114.60 (14)	N4—C11—C8	120.59 (13)
C1—C4—H4A	107.9 (12)	N4—C11—H11	116.0 (10)
C5—C4—H4A	109.7 (12)	C8—C11—H11	123.4 (10)
C1—C4—H4B	105.5 (13)	C10—C12—H12B	113.7 (19)
C5—C4—H4B	112.1 (13)	C10—C12—H12A	110.9 (17)
H4A—C4—H4B	106.7 (17)	H12B—C12—H12A	106 (2)
O1—C5—C4	108.20 (13)	C10—C12—H12C	113.1 (18)
O1—C5—H5A	113.6 (11)	H12B—C12—H12C	102 (2)
C4—C5—H5A	109.1 (11)	H12A—C12—H12C	111 (2)
C3—S1—C1—C2	0.35 (11)	C2—N1—C7—C8	179.18 (11)
C3—S1—C1—C4	−179.97 (13)	N1—C7—C8—C11	103.29 (14)
C4—C1—C2—N1	−179.84 (13)	N1—C7—C8—C9	−79.27 (15)
S1—C1—C2—N1	−0.18 (15)	C10—N3—C9—N2	177.41 (13)
C4—C1—C2—C6	−0.3 (2)	C10—N3—C9—C8	−3.04 (19)
S1—C1—C2—C6	179.37 (13)	C11—C8—C9—N2	−179.32 (13)
C3—N1—C2—C1	−0.15 (17)	C7—C8—C9—N2	3.1 (2)
C7—N1—C2—C1	−179.47 (12)	C11—C8—C9—N3	1.15 (18)
C3—N1—C2—C6	−179.74 (14)	C7—C8—C9—N3	−176.39 (12)
C7—N1—C2—C6	0.95 (19)	C9—N3—C10—N4	2.6 (2)
C2—N1—C3—S1	0.42 (16)	C9—N3—C10—C12	−177.33 (13)
C7—N1—C3—S1	179.73 (10)	C11—N4—C10—N3	−0.3 (2)
C1—S1—C3—N1	−0.44 (12)	C11—N4—C10—C12	179.67 (14)
C2—C1—C4—C5	−156.16 (15)	C10—N4—C11—C8	−1.7 (2)
S1—C1—C4—C5	24.2 (2)	C9—C8—C11—N4	1.19 (19)
C1—C4—C5—O1	−63.35 (18)	C7—C8—C11—N4	178.81 (12)
C3—N1—C7—C8	−0.07 (18)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H1O2···Cl2^i	0.82 (2)	2.40 (3)	3.2120 (14)	171 (2)
O2—H2O2···Cl1^ii	0.84 (3)	2.32 (3)	3.1636 (13)	175 (2)
N2—H1N2···Cl2^iii	0.854 (19)	2.359 (19)	3.1934 (14)	165.9 (15)
O1—H1O1···O2	0.83 (2)	1.95 (2)	2.7555 (17)	166 (2)
N2—H2N2···Cl1	0.83 (2)	2.36 (2)	3.1744 (13)	167.8 (18)
N4—H1N4···Cl2	0.85 (2)	2.28 (2)	3.0659 (12)	152.7 (17)

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