rac-5-Diphenyl­acetyl-2,2,4-trimethyl-2,3,4,5-tetra­hydro-1,5-benzothia­zepine and rac-5-formyl-2,2,4-tri­methyl-2,3,4,5-tetra­hydro-1,5-benzo­thia­zepine

rac-5-Diphenyl­acetyl-2,2,4-trimethyl-2,3,4,5-tetra­hydro-1,5-benzothia­zepine, C₂₆H₂₇NOS, (I), and rac-5-formyl-2,2,4-tri­methyl-2,3,4,5-tetra­hydro-1,5-benzothia­zepine, C₁₃H₁₇NOS, (II), are both characterized by a planar configuration around the heterocyclic N atom. In contrast with the chair conformation of the parent benzothia­zepine, which has no substituents at the heterocyclic N atom, the seven-membered ring adopts a boat conformation in (I) and a conformation inter­mediate between boat and twist-boat in (II). The mol­ecules lack a symmetry plane, indicating distortions from the perfect boat or twist-boat conformations. The supra­molecular architectures are significantly different, depending in (I) on C—H...O inter­actions and inter­molecular S...S contacts, and in (II) on a single aromatic π–π stacking inter­action.

S1. Comment

1,5-Benzothiazepine is a versatile pharmacophore found in a number of drugs used clinically. The biological function of such drugs is quite varied, and ranges from calcium antagonist activity observed for diltiazem, (+)-cis-3-(acetyloxy)-5-(2,2-dimethylaminoethyl)-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepine-4(5H)-one and clentiazem, (+)-cis-3-(acetyloxy)-8-chloro-5-(2,2-dimethylaminoethyl)-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepine-4(5H)-one, to CNS-depressant behaviour observed for thiazesim, (+)-5-(2,2-dimethylaminoethyl)-2,3-dihydro-2-phenyl-1,5-benzothiazepin-4(5H)-one. Replacement of the 3-acetyl group of diltiazem with a methyl group gives a more potent analogue of diltiazem. Further, TA 933, which has an inverted stereochemistry with respect to the substituents at the 2 and 3 positions of diltiazem, is a more active vasorelaxant (Bariwal et al., 2008). Dihydro-1,5-benzothiazepines containing phenyl substituents at the 2 and 4 positions are potent antibacterial agents (Micheli et al., 2001). Therefore, the configuration and conformation of 1,5-benzothiazepines are of interest and importance.

The conformational effects of substituents in the seven-membered ring are pronounced as indicated by the existence of the chair conformation in 2,3,4,5-tetrahydro-2,2,4-trimethyl-1,5-benzothiazepine (III) (Muthukumar et al., 2004) and the twist-boat conformation in 2,3,4,5-tetrahydro-2,4-diphenylbenzothiazepine (Laavanya et al., 2002). Subtle electronic effects can introduce distortions in the ideal conformations viz. chair, twist-chair, boat and twist-boat. In the solid state, the conformation of rac-5-diphenylacetyl-2,3,4,5-tetrahydro-2,2,4-trimethyl-1,5- benzothiazepine, (I), is a distorted twist-boat and that of rac-5-formyl-2,3,4,5-tetrahydro-2,2,4-trimethyl-1,5-benzothiazepine, (II), is intermediate between boat and twist-boat forms. The molecules of compounds (I)–(III) are all chiral, raising the possibility that they could crystallise in non-centrosymmetric space groups, as required for non-linear optical properties (Long, 1995). In fact, only (III) crystallizes in a non-centrosymmetric space group, P2₁ (Muthukumar et al., 2004).

The molecules of these compounds could, in principle, be linked by one or more non-covalent forces viz. C—H···X, N—H···X (X = O or S), S···S, C—H···π and π···π interactions. The presence or absence of these interactions can affect the molecular conformation and supramolecular structure of these crystals. Here, we report the crystal and molecular structures of (I) and (II) and compare them with those of (III). Analysis of the Cambridge Structural Database (CSD, Version 5.29; Allen, 2002) reveals 75 reported crystal structures of 1,5-benzothiazepine derivatives, six of which belong to the diltiazem family, and 11 1,5-benzothiazepines which contain neither ring oxo groups nor extra fused rings, which are akin to compounds (I)–(III).

Compounds (I) and (II) crystallize as racemates and for each compound the reference molecules were selected to have an R configuration at C4 (Figs. 1 and 2). The bond lengths and angles of (I) and (II) are unexceptional. As expected, the C—S bond lengths in (I) are unequal [1.7603 (16) and 1.8518 (18) Å], also in (II) [1.7577 (15) and 1.8536 (13) Å]. The means of the bond angles around N are 119.98 (8) and 119.82 (6)° [to which compound do these values relate?], signifying planarity of the heterocyclic N, as expected. The C4—C3—C2—C12 and C4—C3—C2—C13 torsion angles of (I) are -177.45 (19) and -55.2 (2)°, respectively, and the same torsion angles for (II) are -173.65 (12)° and -50.89 (17)°, respectively; indicating in both molecules that the two methyl groups are not isoclinal but assume equatorial and axial orientations. The C2—C3—C4—C14 torsion angles of (I) and (II) are 178.41 (15) and -179.07 (11)°, respectively, confirming the equatorial orientations of the methyl group bonded to C4. The selected torsion angles of (I)–(III) are listed in Table 1.

In each of (I) and (II) the –CO group is exo oriented with respect to the N5—C6 bond and the benzene ring. The S and N atoms are coplanar with the benzene ring in molecule (I); these atoms are oppositely oriented with respect to the benzene ring in (II) and (III). Table 1 indicates the absence of a mirror plane in all the molecules and the considerable distortion from the four distinct conformations of the seven-membered ring. Comparison of the standard values of all the four forms (Hendrickson, 1967) revealed that the conformations of (I) and (II) are clearly non-chair and that of (III) is chair. A transition from chair to boat form occurs as a result of N-acylation.

Ring-puckering parameters can be used to infer the conformational preferences of the molecules (Cremer & Pople, 1975). The four ring-puckering parameters required to discern the conformation of the seven-membered ring for each of the molecules are given in Table 2. Detailed puckering analysis of the seven-membered ring on the basis of the four puckering parameters indicates six conformations derived from the four fundamental conformations discussed above. They are contained in three pseudo-rotational manifolds viz. chair–twist-chair; boat–twist-boat and sofa–twist-sofa–sofa-boat forms. The puckering amplitudes q2 and q3 for (I) and (II) are close to 1.15 and 0, respectively, which are the values ascribed to both boat and twist-boat forms (Boessenkool & Boeyens, 1980) of the seven-membered ring. From the puckering angles ϕ2 and ϕ3 (Table 2), the conformation of (I) is found to be twist-boat, and that of (II) is intermediate between the twist-boat and boat forms.

In (I) the molecules are linked by a C—H···O hydrogen bond (Table 3), forming a chain parallel to the [010] axis (Fig. 3). There are short S···S contacts, 3.376 (2) Å, between adjacent antiparallel chains, involving the S atoms at (x, y, z) and (1 - x, 1 - y, 1 - z) (Fig. 4). The pair of bonds around the S are uneclipsed with respect to those of the other S, signifying a non-parallel orientation (Fig. 5) of S p-type lone pairs, promoting close contacts between the s-type lone pairs of S (Ozturk et al., 1994).

The structure of (II) contains neither S···S nor C—H···O interactions; instead, the molecules are linked by an aromatic π–π interaction. The aryl rings in the molecules at (x,y,z) and (1 - x,1 - y, -z) are parallel with an interplanar spacing of 3.5390 (6) Å. The ring–centroid distance is 3.8597 (9) Å. These parameters are comparable with the corresponding values reported for similar interactions (Portilla et al., 2005; Delgado et al., 2006). This interaction generates a centrosymmetric dimer (Fig. 6). By contrast, the molecules of (III) are linked by an N—H···S hydrogen bond (Muthukumar et al., 2004). It is noted that the three molecules are in different conformations and exhibit differences in intermolecular interactions. The packing indices (%) follow the order (III) 68.6 > (II) 67.2 > (I) 64.5, signifying a lack of close packing in (I) compared with the other two. This is substantiated by the lowest density for (I) despite its high molecular weight; the density order is (II) 1.255 g cm^-3 > (III) 1.219 g cm^-3 > (I) 1.182 g cm^-3. The melting points (K), which depend upon crystal packing forces, follow the order (I) 398 > (III) 358 > (II) 337. The melting point of (II) is low, much lower than (III), indicating weaker intermolecular interactions in the former. As shown by AM1 calculations, the stable conformations of isolated molecules of (I)–(III) are similar to those established through X-ray analysis. We conclude that the molecular conformations of the three benzothiazepines are inherent and crystal packing effects cause subtle distortions in conformation. We further conclude that in the structures of the crystals studied here the packing interactions are determined by the molecular conformations.

S2. Experimental

Compound (I) was obtained by the acetylation of the parent 2,3,4,5-tetrahydro-2,2,4-trimethylbenzothiazepine, (III), using diphenylacetyl chloride in a 1:1 molar ratio in the presence of triethylamine in a benzene medium.The product was isolated as single crystals by recrystallization from a solution in 95% ethanol (yield 54%, m.p. 398–400 K). Compound (II) was prepared by the formylation of (III) in a benzene medium using the same base and acetic formic anhydride as formylating agent, adopting the reported procedure of Muthukumar (2001). The latter was prepared in situ by warming a mixture of acetic anhydride and 85% formic acid in a 1:1 molar ratio. Repeated recrystallization from a solution in petroleum ether afforded colourless single crystals (yield 89%, m.p. 337–339 K).

S3. Refinement

The formyl H atom in (II) was located in a difference map and then freely refined, giving a C—H distance of 1.009 (18) Å. All other H atoms were treated as riding atoms, with C—H = 0.95 (aromatic), 0.98 (CH₃), 0.99 (CH₂) or 1.00 Å (aliphatic CH) and with U_iso(H) = kU_eq(C), where k = 1.5 for the methyl groups and 1.2 for all other H atoms.

Computing details

For both compounds, data collection: APEX2 (Bruker, 2004); cell refinement: APEX2 (Bruker, 2004) and SAINT (Bruker, 2004); data reduction: SAINT (Bruker, 2004) and XPREP (Bruker, 2004); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: PLATON (Spek, 2009).

Figures

	Fig. 1. The molecule of (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 2. The molecule of (II), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 3. Part of the crystal structure of (I), showing the hydrogen-bonded chain along [010]. For clarity, H atoms bonded to C atoms have been omitted.
	Fig. 4. Part of the crystal structure of (I), showing the S···S contacts between the hydrogen-bonded chains. For clarity, H atoms bonded to C atoms have been omitted.
	Fig. 5. Part of the crystal structure of (I), showing the orientation of bonds around S. The S atom marked with an asterisk (*) is at the symmetry position (-x + 1, -y + 1, -z + 1).
	Fig. 6. Part of the crystal structure of (II), showing the formation of a centrosymmetric π-stacked dimer. For clarity, all H atoms have been omitted. The S atom marked with an asterisk (*) is at the symmetry position (1 - x, 1 - y, -z).

(I) rac-5-diphenylacetyl-2,3,4,5-tetrahydro-2,2,4-trimethyl- 1,5-benzothiazepine

Crystal data

C26H27NOS	F(000) = 856
Mr = 401.55	Dx = 1.182 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 5164 reflections
a = 10.2731 (2) Å	θ = 2.0–27.5°
b = 8.5637 (2) Å	µ = 0.16 mm^−1
c = 25.6968 (6) Å	T = 296 K
β = 93.218 (1)°	Block, colourless
V = 2257.13 (9) Å^3	0.30 × 0.02 × 0.02 mm
Z = 4

Data collection

Bruker Kappa APEXII CCD area-detector diffractometer	5164 independent reflections
Radiation source: fine-focus sealed tube	3691 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.031
ω and ϕ scans	θmax = 27.5°, θmin = 2.0°
Absorption correction: multi-scan (SADABS; Bruker, 1999)	h = −13→13
Tmin = 0.954, Tmax = 0.997	k = −11→11
25865 measured reflections	l = −33→33

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)] = 0.042	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.117	H-atom parameters constrained
S = 1.03	w = 1/[σ^2(Fo^2) + (0.0492P)^2 + 0.6041P] where P = (Fo^2 + 2Fc^2)/3
5164 reflections	(Δ/σ)max = 0.002
289 parameters	Δρmax = 0.23 e Å^−3
0 restraints	Δρmin = −0.31 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
S1	0.61879 (4)	0.45627 (6)	0.545728 (16)	0.05420 (15)
C2	0.76961 (16)	0.3829 (2)	0.58029 (7)	0.0552 (4)
C3	0.78578 (15)	0.4393 (2)	0.63653 (6)	0.0492 (4)
H3A	0.8726	0.4046	0.6507	0.054 (5)*
H3B	0.7871	0.5549	0.6359	0.049 (5)*
C4	0.68630 (14)	0.38945 (19)	0.67477 (6)	0.0423 (4)
H4	0.6879	0.2729	0.6769	0.053 (5)*
N5	0.55296 (11)	0.43732 (14)	0.65701 (5)	0.0365 (3)
C6	0.53633 (13)	0.58931 (16)	0.63496 (6)	0.0360 (3)
C7	0.56790 (14)	0.61383 (18)	0.58361 (6)	0.0407 (3)
C8	0.54873 (17)	0.7613 (2)	0.56202 (7)	0.0554 (4)
H8	0.5693	0.7799	0.5270	0.060 (5)*
C9	0.50015 (19)	0.8807 (2)	0.59104 (8)	0.0635 (5)
H9	0.4851	0.9803	0.5756	0.082 (7)*
C10	0.47323 (18)	0.8571 (2)	0.64216 (8)	0.0596 (5)
H10	0.4420	0.9410	0.6622	0.075 (6)*
C11	0.49158 (16)	0.71154 (19)	0.66451 (7)	0.0468 (4)
H11	0.4736	0.6952	0.7000	0.049 (5)*
C12	0.8838 (2)	0.4421 (5)	0.55077 (10)	0.1070 (11)
H12A	0.8746	0.4061	0.5145	0.112 (9)*
H12B	0.9654	0.4018	0.5672	0.105 (8)*
H12C	0.8851	0.5565	0.5515	0.100 (10)*
C13	0.7609 (3)	0.2051 (3)	0.57703 (10)	0.0950 (9)
H13A	0.6871	0.1688	0.5964	0.157 (15)*
H13B	0.8417	0.1591	0.5921	0.117 (9)*
H13C	0.7481	0.1734	0.5405	0.114 (9)*
C14	0.72028 (19)	0.4528 (3)	0.72886 (7)	0.0631 (5)
H14A	0.6551	0.4177	0.7527	0.084 (7)*
H14B	0.7213	0.5671	0.7277	0.094 (8)*
H14C	0.8065	0.4144	0.7411	0.084 (7)*
C15	0.45264 (14)	0.33913 (17)	0.66450 (6)	0.0393 (3)
O16	0.46922 (11)	0.21366 (13)	0.68680 (5)	0.0579 (3)
C17	0.31672 (14)	0.39088 (17)	0.64412 (6)	0.0404 (3)
H17	0.3280	0.4755	0.6180	0.040 (4)*
C20	0.24714 (14)	0.25582 (18)	0.61607 (6)	0.0414 (3)
C21	0.24304 (18)	0.2486 (2)	0.56231 (7)	0.0585 (5)
H21	0.2819	0.3295	0.5432	0.074 (6)*
C22	0.1831 (2)	0.1250 (3)	0.53599 (8)	0.0753 (6)
H22	0.1813	0.1214	0.4990	0.084 (7)*
C23	0.1266 (2)	0.0084 (3)	0.56276 (9)	0.0728 (6)
H23	0.0856	−0.0765	0.5446	0.092 (7)*
C24	0.1292 (2)	0.0140 (2)	0.61597 (9)	0.0680 (5)
H24	0.0896	−0.0672	0.6347	0.083 (7)*
C25	0.18908 (17)	0.1372 (2)	0.64277 (7)	0.0528 (4)
H25	0.1902	0.1400	0.6797	0.060 (5)*
C30	0.24044 (15)	0.45891 (18)	0.68774 (7)	0.0458 (4)
C31	0.14080 (17)	0.5628 (2)	0.67532 (9)	0.0664 (5)
H31	0.1224	0.5920	0.6400	0.063 (6)*
C32	0.0671 (2)	0.6250 (3)	0.71412 (13)	0.0884 (8)
H32	−0.0018	0.6957	0.7052	0.103 (8)*
C33	0.0937 (2)	0.5846 (3)	0.76502 (12)	0.0907 (9)
H33	0.0432	0.6274	0.7914	0.114 (9)*
C34	0.1922 (3)	0.4833 (3)	0.77798 (10)	0.0857 (7)
H34	0.2106	0.4555	0.8134	0.141 (12)*
C35	0.2657 (2)	0.4208 (2)	0.73952 (8)	0.0653 (5)
H35	0.3346	0.3505	0.7489	0.081 (7)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0533 (3)	0.0688 (3)	0.0401 (2)	0.0146 (2)	−0.00070 (18)	−0.0113 (2)
C2	0.0441 (9)	0.0723 (12)	0.0499 (10)	0.0150 (8)	0.0079 (7)	−0.0033 (9)
C3	0.0331 (8)	0.0627 (10)	0.0516 (10)	0.0043 (7)	−0.0002 (7)	0.0017 (8)
C4	0.0366 (8)	0.0465 (9)	0.0433 (8)	0.0046 (7)	−0.0014 (6)	0.0002 (7)
N5	0.0329 (6)	0.0360 (6)	0.0408 (7)	0.0018 (5)	0.0030 (5)	0.0013 (5)
C6	0.0317 (7)	0.0347 (7)	0.0417 (8)	−0.0016 (6)	0.0025 (6)	−0.0017 (6)
C7	0.0364 (8)	0.0454 (8)	0.0403 (8)	0.0010 (6)	0.0021 (6)	0.0002 (7)
C8	0.0575 (10)	0.0569 (10)	0.0522 (10)	0.0004 (8)	0.0076 (8)	0.0141 (8)
C9	0.0688 (12)	0.0405 (9)	0.0814 (14)	0.0028 (9)	0.0060 (10)	0.0122 (9)
C10	0.0651 (12)	0.0386 (9)	0.0758 (13)	0.0042 (8)	0.0097 (10)	−0.0083 (9)
C11	0.0486 (9)	0.0427 (8)	0.0498 (10)	0.0000 (7)	0.0092 (7)	−0.0067 (7)
C12	0.0555 (14)	0.193 (4)	0.0747 (18)	0.0125 (16)	0.0233 (12)	0.0151 (19)
C13	0.128 (2)	0.0756 (15)	0.0795 (16)	0.0454 (16)	−0.0089 (17)	−0.0245 (13)
C14	0.0592 (11)	0.0847 (15)	0.0444 (10)	0.0084 (10)	−0.0054 (8)	−0.0043 (9)
C15	0.0405 (8)	0.0351 (7)	0.0423 (8)	0.0001 (6)	0.0041 (6)	−0.0016 (6)
O16	0.0522 (7)	0.0408 (6)	0.0799 (9)	−0.0012 (5)	−0.0035 (6)	0.0160 (6)
C17	0.0363 (7)	0.0378 (8)	0.0472 (9)	−0.0011 (6)	0.0040 (6)	0.0032 (7)
C20	0.0347 (7)	0.0451 (8)	0.0445 (9)	0.0020 (6)	0.0032 (6)	−0.0020 (7)
C21	0.0581 (10)	0.0700 (12)	0.0480 (10)	−0.0030 (9)	0.0080 (8)	−0.0031 (9)
C22	0.0767 (14)	0.0955 (16)	0.0535 (12)	−0.0035 (13)	0.0027 (10)	−0.0241 (12)
C23	0.0632 (12)	0.0735 (13)	0.0810 (15)	−0.0096 (11)	−0.0023 (11)	−0.0319 (12)
C24	0.0652 (12)	0.0560 (11)	0.0828 (15)	−0.0178 (10)	0.0046 (11)	−0.0073 (10)
C25	0.0555 (10)	0.0522 (10)	0.0509 (10)	−0.0112 (8)	0.0029 (8)	−0.0008 (8)
C30	0.0376 (8)	0.0384 (8)	0.0617 (10)	−0.0071 (6)	0.0067 (7)	−0.0091 (7)
C31	0.0462 (10)	0.0635 (12)	0.0890 (16)	0.0047 (9)	−0.0003 (10)	−0.0192 (11)
C32	0.0472 (11)	0.0796 (15)	0.139 (2)	0.0055 (11)	0.0110 (13)	−0.0437 (16)
C33	0.0712 (15)	0.0931 (18)	0.112 (2)	−0.0270 (14)	0.0407 (15)	−0.0535 (17)
C34	0.0990 (18)	0.0853 (16)	0.0759 (17)	−0.0210 (15)	0.0321 (14)	−0.0238 (13)
C35	0.0755 (13)	0.0618 (11)	0.0599 (12)	−0.0007 (10)	0.0161 (10)	−0.0070 (9)

Geometric parameters (Å, º)

S1—C7	1.7603 (16)	C14—H14B	0.9800
S1—C2	1.8518 (18)	C14—H14C	0.9800
C2—C12	1.519 (3)	C15—O16	1.2251 (18)
C2—C3	1.524 (2)	C15—C17	1.529 (2)
C2—C13	1.527 (3)	C17—C30	1.519 (2)
C3—C4	1.518 (2)	C17—C20	1.520 (2)
C3—H3A	0.9900	C17—H17	1.0000
C3—H3B	0.9900	C20—C25	1.380 (2)
C4—N5	1.4773 (18)	C20—C21	1.381 (2)
C4—C14	1.514 (2)	C21—C22	1.383 (3)
C4—H4	1.0000	C21—H21	0.9500
N5—C15	1.3522 (19)	C22—C23	1.361 (3)
N5—C6	1.4260 (18)	C22—H22	0.9500
C6—C11	1.387 (2)	C23—C24	1.367 (3)
C6—C7	1.392 (2)	C23—H23	0.9500
C7—C8	1.389 (2)	C24—C25	1.385 (3)
C8—C9	1.375 (3)	C24—H24	0.9500
C8—H8	0.9500	C25—H25	0.9500
C9—C10	1.373 (3)	C30—C31	1.380 (3)
C9—H9	0.9500	C30—C35	1.381 (3)
C10—C11	1.381 (2)	C31—C32	1.391 (3)
C10—H10	0.9500	C31—H31	0.9500
C11—H11	0.9500	C32—C33	1.366 (4)
C12—H12A	0.9800	C32—H32	0.9500
C12—H12B	0.9800	C33—C34	1.360 (4)
C12—H12C	0.9800	C33—H33	0.9500
C13—H13A	0.9800	C34—C35	1.385 (3)
C13—H13B	0.9800	C34—H34	0.9500
C13—H13C	0.9800	C35—H35	0.9500
C14—H14A	0.9800
C7—S1—C2	105.14 (8)	C4—C14—H14A	109.5
C12—C2—C3	108.77 (18)	C4—C14—H14B	109.5
C12—C2—C13	110.5 (2)	H14A—C14—H14B	109.5
C3—C2—C13	111.77 (17)	C4—C14—H14C	109.5
C12—C2—S1	107.23 (15)	H14A—C14—H14C	109.5
C3—C2—S1	113.02 (11)	H14B—C14—H14C	109.5
C13—C2—S1	105.47 (15)	O16—C15—N5	121.66 (14)
C4—C3—C2	118.89 (14)	O16—C15—C17	120.98 (13)
C4—C3—H3A	107.6	N5—C15—C17	117.37 (13)
C2—C3—H3A	107.6	C30—C17—C20	113.16 (12)
C4—C3—H3B	107.6	C30—C17—C15	110.93 (13)
C2—C3—H3B	107.6	C20—C17—C15	109.76 (12)
H3A—C3—H3B	107.0	C30—C17—H17	107.6
N5—C4—C14	110.25 (13)	C20—C17—H17	107.6
N5—C4—C3	111.60 (12)	C15—C17—H17	107.6
C14—C4—C3	111.37 (14)	C25—C20—C21	118.33 (15)
N5—C4—H4	107.8	C25—C20—C17	121.97 (14)
C14—C4—H4	107.8	C21—C20—C17	119.70 (15)
C3—C4—H4	107.8	C20—C21—C22	120.74 (19)
C15—N5—C6	123.29 (12)	C20—C21—H21	119.6
C15—N5—C4	118.97 (12)	C22—C21—H21	119.6
C6—N5—C4	117.66 (12)	C23—C22—C21	120.39 (19)
C11—C6—C7	120.47 (14)	C23—C22—H22	119.8
C11—C6—N5	120.50 (13)	C21—C22—H22	119.8
C7—C6—N5	119.02 (13)	C22—C23—C24	119.65 (19)
C8—C7—C6	118.71 (14)	C22—C23—H23	120.2
C8—C7—S1	121.05 (13)	C24—C23—H23	120.2
C6—C7—S1	120.05 (12)	C23—C24—C25	120.49 (19)
C9—C8—C7	120.44 (16)	C23—C24—H24	119.8
C9—C8—H8	119.8	C25—C24—H24	119.8
C7—C8—H8	119.8	C20—C25—C24	120.40 (17)
C10—C9—C8	120.57 (17)	C20—C25—H25	119.8
C10—C9—H9	119.7	C24—C25—H25	119.8
C8—C9—H9	119.7	C31—C30—C35	118.18 (18)
C9—C10—C11	120.02 (16)	C31—C30—C17	118.89 (17)
C9—C10—H10	120.0	C35—C30—C17	122.93 (16)
C11—C10—H10	120.0	C30—C31—C32	120.5 (2)
C10—C11—C6	119.71 (16)	C30—C31—H31	119.8
C10—C11—H11	120.1	C32—C31—H31	119.8
C6—C11—H11	120.1	C33—C32—C31	120.1 (2)
C2—C12—H12A	109.5	C33—C32—H32	119.9
C2—C12—H12B	109.5	C31—C32—H32	119.9
H12A—C12—H12B	109.5	C34—C33—C32	120.1 (2)
C2—C12—H12C	109.5	C34—C33—H33	119.9
H12A—C12—H12C	109.5	C32—C33—H33	119.9
H12B—C12—H12C	109.5	C33—C34—C35	120.0 (3)
C2—C13—H13A	109.5	C33—C34—H34	120.0
C2—C13—H13B	109.5	C35—C34—H34	120.0
H13A—C13—H13B	109.5	C30—C35—C34	121.1 (2)
C2—C13—H13C	109.5	C30—C35—H35	119.5
H13A—C13—H13C	109.5	C34—C35—H35	119.5
H13B—C13—H13C	109.5
C7—S1—C2—C12	−102.85 (18)	C6—N5—C15—C17	5.0 (2)
C7—S1—C2—C3	17.01 (15)	C4—N5—C15—C17	−178.22 (12)
C7—S1—C2—C13	139.41 (15)	O16—C15—C17—C30	80.76 (18)
C12—C2—C3—C4	−177.45 (19)	N5—C15—C17—C30	−99.09 (15)
C13—C2—C3—C4	−55.2 (2)	O16—C15—C17—C20	−45.02 (19)
S1—C2—C3—C4	63.58 (19)	N5—C15—C17—C20	135.12 (14)
C2—C3—C4—N5	−57.90 (19)	C30—C17—C20—C25	−45.4 (2)
C2—C3—C4—C14	178.41 (15)	C15—C17—C20—C25	79.11 (18)
C14—C4—N5—C15	−94.37 (17)	C30—C17—C20—C21	135.76 (16)
C3—C4—N5—C15	141.30 (14)	C15—C17—C20—C21	−99.73 (17)
C14—C4—N5—C6	82.64 (17)	C25—C20—C21—C22	−0.5 (3)
C3—C4—N5—C6	−41.69 (18)	C17—C20—C21—C22	178.42 (17)
C15—N5—C6—C11	76.69 (19)	C20—C21—C22—C23	0.2 (3)
C4—N5—C6—C11	−100.19 (16)	C21—C22—C23—C24	0.1 (3)
C15—N5—C6—C7	−104.45 (16)	C22—C23—C24—C25	−0.2 (3)
C4—N5—C6—C7	78.68 (17)	C21—C20—C25—C24	0.4 (3)
C11—C6—C7—C8	−2.5 (2)	C17—C20—C25—C24	−178.47 (16)
N5—C6—C7—C8	178.59 (14)	C23—C24—C25—C20	−0.1 (3)
C11—C6—C7—S1	−177.62 (12)	C20—C17—C30—C31	−80.54 (18)
N5—C6—C7—S1	3.51 (19)	C15—C17—C30—C31	155.59 (15)
C2—S1—C7—C8	123.90 (14)	C20—C17—C30—C35	99.04 (18)
C2—S1—C7—C6	−61.14 (14)	C15—C17—C30—C35	−24.8 (2)
C6—C7—C8—C9	0.3 (3)	C35—C30—C31—C32	−0.9 (3)
S1—C7—C8—C9	175.37 (14)	C17—C30—C31—C32	178.69 (17)
C7—C8—C9—C10	1.8 (3)	C30—C31—C32—C33	0.6 (3)
C8—C9—C10—C11	−1.7 (3)	C31—C32—C33—C34	0.0 (4)
C9—C10—C11—C6	−0.5 (3)	C32—C33—C34—C35	−0.1 (4)
C7—C6—C11—C10	2.6 (2)	C31—C30—C35—C34	0.8 (3)
N5—C6—C11—C10	−178.53 (15)	C17—C30—C35—C34	−178.80 (17)
C6—N5—C15—O16	−174.91 (14)	C33—C34—C35—C30	−0.3 (3)
C4—N5—C15—O16	1.9 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C10—H10···O16^i	0.95	2.43	3.263 (2)	146

Symmetry code: (i) x, y+1, z.

(II) rac-5-formyl-2,3,4,5-tetrahydro-2,2,4-trimethyl-1,5-benzothiazepine

Crystal data

C13H17NOS	F(000) = 504
Mr = 235.34	Dx = 1.255 Mg m^−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 4056 reflections
a = 9.6038 (8) Å	θ = 2.3–31.7°
b = 9.9485 (8) Å	µ = 0.24 mm^−1
c = 13.6818 (11) Å	T = 296 K
β = 107.713 (2)°	Block, colourless
V = 1245.23 (18) Å^3	0.29 × 0.12 × 0.10 mm
Z = 4

Data collection

Bruker Kappa APEXII CCD area-detector diffractometer	4056 independent reflections
Radiation source: fine-focus sealed tube	2895 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.024
ω and ϕ scans	θmax = 31.7°, θmin = 2.3°
Absorption correction: multi-scan (SADABS; Bruker, 1999)	h = −14→14
Tmin = 0.934, Tmax = 0.977	k = −14→14
17043 measured reflections	l = −20→20

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)] = 0.041	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.124	H atoms treated by a mixture of independent and constrained refinement
S = 1.06	w = 1/[σ^2(Fo^2) + (0.0565P)^2 + 0.2159P] where P = (Fo^2 + 2Fc^2)/3
4056 reflections	(Δ/σ)max < 0.001
165 parameters	Δρmax = 0.36 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
S1	0.46889 (4)	0.78816 (4)	0.21250 (3)	0.05617 (13)
C2	0.37838 (14)	0.95471 (13)	0.19824 (10)	0.0423 (3)
C3	0.32279 (13)	1.00081 (13)	0.08716 (9)	0.0397 (3)
H3A	0.4057	0.9965	0.0585	0.040 (4)*
H3B	0.2946	1.0965	0.0871	0.051 (4)*
C4	0.19478 (12)	0.92612 (12)	0.01388 (9)	0.0388 (3)
H4	0.1080	0.9384	0.0388	0.044 (4)*
N5	0.22255 (10)	0.78067 (10)	0.01104 (8)	0.0377 (2)
C6	0.36082 (12)	0.73613 (12)	0.00468 (10)	0.0373 (3)
C7	0.48317 (13)	0.74458 (13)	0.09141 (11)	0.0413 (3)
C8	0.61828 (14)	0.70331 (14)	0.08300 (14)	0.0542 (4)
H8	0.7033	0.7107	0.1407	0.069 (5)*
C9	0.62994 (16)	0.65211 (15)	−0.00759 (15)	0.0611 (4)
H9	0.7224	0.6238	−0.0119	0.064 (5)*
C10	0.50840 (18)	0.64191 (16)	−0.09167 (14)	0.0591 (4)
H10	0.5165	0.6049	−0.1537	0.075 (6)*
C11	0.37323 (16)	0.68561 (14)	−0.08648 (12)	0.0480 (3)
H11	0.2897	0.6808	−0.1454	0.071 (5)*
C12	0.4945 (2)	1.05407 (18)	0.25878 (13)	0.0681 (5)
H12A	0.5311	1.0252	0.3306	0.087 (6)*
H12B	0.4511	1.1438	0.2553	0.110 (8)*
H12C	0.5754	1.0568	0.2292	0.102 (8)*
C13	0.25712 (19)	0.9411 (2)	0.24771 (13)	0.0700 (5)
H13A	0.2988	0.9112	0.3189	0.087 (6)*
H13B	0.1853	0.8751	0.2096	0.075 (6)*
H13C	0.2092	1.0283	0.2465	0.101 (7)*
C14	0.15735 (16)	0.98576 (16)	−0.09356 (11)	0.0534 (4)
H14A	0.0747	0.9367	−0.1396	0.077 (6)*
H14B	0.2422	0.9782	−0.1188	0.065 (5)*
H14C	0.1311	1.0807	−0.0914	0.068 (5)*
C15	0.11358 (14)	0.69159 (15)	0.00123 (11)	0.0478 (3)
O16	−0.01107 (11)	0.71988 (13)	−0.00265 (11)	0.0683 (3)
H15	0.1438 (17)	0.5954 (18)	−0.0040 (12)	0.053 (4)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0632 (2)	0.0498 (2)	0.0459 (2)	0.01451 (16)	0.00219 (16)	0.00666 (14)
C2	0.0441 (6)	0.0415 (7)	0.0411 (6)	0.0028 (5)	0.0128 (5)	0.0007 (5)
C3	0.0411 (6)	0.0341 (6)	0.0434 (6)	0.0029 (5)	0.0120 (5)	0.0012 (5)
C4	0.0311 (5)	0.0387 (6)	0.0460 (6)	0.0076 (4)	0.0112 (4)	0.0005 (5)
N5	0.0281 (4)	0.0380 (5)	0.0474 (5)	0.0021 (4)	0.0120 (4)	−0.0012 (4)
C6	0.0318 (5)	0.0317 (5)	0.0506 (7)	0.0029 (4)	0.0159 (5)	0.0024 (5)
C7	0.0333 (5)	0.0325 (6)	0.0569 (7)	0.0057 (4)	0.0120 (5)	0.0040 (5)
C8	0.0316 (6)	0.0407 (7)	0.0882 (11)	0.0077 (5)	0.0153 (6)	0.0097 (7)
C9	0.0476 (7)	0.0422 (8)	0.1071 (13)	0.0129 (6)	0.0437 (9)	0.0120 (8)
C10	0.0692 (9)	0.0451 (8)	0.0804 (11)	0.0079 (7)	0.0487 (9)	0.0024 (7)
C11	0.0507 (7)	0.0422 (7)	0.0555 (8)	0.0018 (5)	0.0228 (6)	−0.0010 (6)
C12	0.0816 (12)	0.0550 (10)	0.0533 (8)	−0.0091 (8)	−0.0011 (8)	−0.0058 (7)
C13	0.0638 (10)	0.0978 (14)	0.0582 (9)	0.0169 (10)	0.0333 (8)	0.0136 (10)
C14	0.0516 (7)	0.0523 (8)	0.0486 (7)	0.0119 (6)	0.0037 (6)	0.0057 (6)
C15	0.0382 (6)	0.0509 (8)	0.0550 (8)	−0.0056 (5)	0.0153 (5)	−0.0033 (6)
O16	0.0357 (5)	0.0789 (8)	0.0937 (9)	−0.0102 (5)	0.0246 (5)	−0.0084 (7)

Geometric parameters (Å, º)

S1—C7	1.7577 (15)	C8—H8	0.9500
S1—C2	1.8536 (13)	C9—C10	1.371 (2)
C2—C3	1.5203 (17)	C9—H9	0.9500
C2—C13	1.521 (2)	C10—C11	1.391 (2)
C2—C12	1.531 (2)	C10—H10	0.9500
C3—C4	1.5227 (17)	C11—H11	0.9500
C3—H3A	0.9900	C12—H12A	0.9800
C3—H3B	0.9900	C12—H12B	0.9800
C4—N5	1.4741 (16)	C12—H12C	0.9800
C4—C14	1.5233 (19)	C13—H13A	0.9800
C4—H4	1.0000	C13—H13B	0.9800
N5—C15	1.3465 (16)	C13—H13C	0.9800
N5—C6	1.4274 (15)	C14—H14A	0.9800
C6—C11	1.383 (2)	C14—H14B	0.9800
C6—C7	1.3955 (17)	C14—H14C	0.9800
C7—C8	1.3987 (18)	C15—O16	1.2151 (17)
C8—C9	1.376 (3)	C15—H15	1.009 (18)
C7—S1—C2	106.85 (6)	C10—C9—C8	120.10 (13)
C3—C2—C13	112.85 (11)	C10—C9—H9	120.0
C3—C2—C12	108.82 (12)	C8—C9—H9	120.0
C13—C2—C12	110.29 (14)	C9—C10—C11	120.24 (15)
C3—C2—S1	112.68 (9)	C9—C10—H10	119.9
C13—C2—S1	105.77 (11)	C11—C10—H10	119.9
C12—C2—S1	106.22 (10)	C6—C11—C10	119.82 (14)
C2—C3—C4	118.59 (11)	C6—C11—H11	120.1
C2—C3—H3A	107.7	C10—C11—H11	120.1
C4—C3—H3A	107.7	C2—C12—H12A	109.5
C2—C3—H3B	107.7	C2—C12—H12B	109.5
C4—C3—H3B	107.7	H12A—C12—H12B	109.5
H3A—C3—H3B	107.1	C2—C12—H12C	109.5
N5—C4—C3	112.34 (9)	H12A—C12—H12C	109.5
N5—C4—C14	110.39 (11)	H12B—C12—H12C	109.5
C3—C4—C14	110.58 (11)	C2—C13—H13A	109.5
N5—C4—H4	107.8	C2—C13—H13B	109.5
C3—C4—H4	107.8	H13A—C13—H13B	109.5
C14—C4—H4	107.8	C2—C13—H13C	109.5
C15—N5—C6	119.92 (11)	H13A—C13—H13C	109.5
C15—N5—C4	120.48 (10)	H13B—C13—H13C	109.5
C6—N5—C4	119.04 (10)	C4—C14—H14A	109.5
C11—C6—C7	120.49 (12)	C4—C14—H14B	109.5
C11—C6—N5	120.31 (11)	H14A—C14—H14B	109.5
C7—C6—N5	119.20 (11)	C4—C14—H14C	109.5
C6—C7—C8	118.33 (13)	H14A—C14—H14C	109.5
C6—C7—S1	121.95 (9)	H14B—C14—H14C	109.5
C8—C7—S1	119.36 (11)	O16—C15—N5	125.27 (14)
C9—C8—C7	120.97 (14)	O16—C15—H15	121.2 (9)
C9—C8—H8	119.5	N5—C15—H15	113.5 (9)
C7—C8—H8	119.5
C7—S1—C2—C3	7.64 (11)	C11—C6—C7—C8	1.25 (19)
C7—S1—C2—C13	131.37 (10)	N5—C6—C7—C8	−178.55 (11)
C7—S1—C2—C12	−111.41 (11)	C11—C6—C7—S1	−171.93 (10)
C13—C2—C3—C4	−50.89 (17)	N5—C6—C7—S1	8.26 (17)
C12—C2—C3—C4	−173.65 (12)	C2—S1—C7—C6	−57.55 (12)
S1—C2—C3—C4	68.82 (13)	C2—S1—C7—C8	129.33 (11)
C2—C3—C4—N5	−55.25 (15)	C6—C7—C8—C9	−1.8 (2)
C2—C3—C4—C14	−179.07 (11)	S1—C7—C8—C9	171.58 (11)
C3—C4—N5—C15	143.57 (12)	C7—C8—C9—C10	0.6 (2)
C14—C4—N5—C15	−92.50 (14)	C8—C9—C10—C11	1.2 (2)
C3—C4—N5—C6	−44.92 (15)	C7—C6—C11—C10	0.5 (2)
C14—C4—N5—C6	79.01 (13)	N5—C6—C11—C10	−179.70 (12)
C15—N5—C6—C11	66.09 (17)	C9—C10—C11—C6	−1.8 (2)
C4—N5—C6—C11	−105.47 (14)	C6—N5—C15—O16	−173.92 (15)
C15—N5—C6—C7	−114.10 (14)	C4—N5—C15—O16	−2.5 (2)
C4—N5—C6—C7	74.34 (15)