Comparison of polarimetry and crown ether-based HPLC chiral stationary phase method to determine (L)-amino acid optical purity.

Although various pharmacopoeias provide titration methods to assay (L)-amino acid content, none of these methods distinguish between (L)- and (D)-amino acids and do not consider the presence of enantiomeric impurities. Consequently, these methods are limited in scope to describe the relationship between content and specific rotation, [α]. In this study, the US Pharmacopoeia method was compared with the crown ether-based high performance liquid chromatographic (HPLC) chiral stationary phase (CSP) method to determine (L)-amino acid content and specific rotation. The (L)-amino acid content specified by the US Pharmacopoeia method was not consistent with the specific rotation in the presence of enantiomeric impurities, whereas the HPLC-CSP method was very effective for determining the (L)-amino acid content and the optical purity. The other advantage is that the HPLC-CSP method requires amino acid samples of quite low concentration (as low as 1 µg/mL), whereas the pharmacopoeia method requires higher concentrations (20-110 mg/mL).

2-Chloro-8-methyl-3-[(pyrimidin-4-yl-oxy)meth-yl]quinoline.

In the title compound, C(15)H(12)ClN(3)O, the quinoline ring system is essentially planar, with a maximum deviation of 0.017 (1) Å. The crystal packing is stabilized by π-π stacking inter-actions between the quinoline rings of adjacent mol-ecule, with a centroid-centroid distance of 3.5913 (8) Å. A weak C-H⋯π contact is also observed between mol-ecules.

1-[(2-Chloro-8-methyl-quinolin-3-yl)-meth-yl]pyridin-2(1H)-one.

In the title compound, C(16)H(13)ClN(2)O, the quinoline ring system is approximately planar [maximum deviation 0.021 (2) Å] and forms a dihedral angle of 85.93 (6)° with the pyridone ring. Inter-molecular C-H⋯O hydrogen bonding, together with weak C-H⋯π and π-π inter-actions [centroid-to-centroid distances 3.5533 (9) and 3.7793 (9) Å], characterize the crystal structure.

5-(4-Chloro-phen-yl)-3-(2,4-dimethyl-thiazol-5-yl)-1,2,4-triazolo[3,4-a]isoquinoline.

In the title mol-ecule, C(21)H(15)ClN(4)S, the triazoloisoquinoline ring system is approximately planar, with an r.m.s. deviation of 0.054 (2) Šand a maximum deviation of 0.098 (2) Šfrom the mean plane for the triazole ring C atom that is bonded to the thia-zole ring. The thia-zole and benzene rings are twisted by 66.36 (7) and 56.32 (7)°, respectively, with respect to the mean plane of the triazoloisoquinoline ring system. In the crystal structure, mol-ecules are linked by inter-molecular C-H⋯N inter-actions along the a axis. The mol-ecular conformation is stabilized by a weak intra-molecular π-π inter-action involving the thia-zole and benzene rings, with a centroid-centroid distance of 3.6546 (11) Å. In addition, two other intermolecular π-π stacking inter-actions are observed, between the triazole and benzene rings and between the dihydro-pyridine and benzene rings [centroid-centroid distances = 3.6489 (11) and 3.5967 (10) Å, respectively].

5-(4-Chloro-phen-yl)-3-(2-fur-yl)-1,2,4-triazolo[3,4-a]isoquinoline.

In the title mol-ecule, C(20)H(12)ClN(3)O, the triazoloisoquinoline ring system is nearly planar, with an r.m.s. deviation of 0.018 (3) Šand a maximum deviation of 0.034 (3) Šfrom the mean plane for the triazole ring C atom which is bonded to the benzene ring. The furan and benzene rings are twisted by 59.71 (14) and 66.95 (10)°, respectively, with respect to the mean plane of the triazoloisoquinoline ring system. The mol-ecular conformation is stabilized by an intra-molecular π-π inter-action [centroid-to-centroid distance = 3.5262 (18) Å]. The crystal packing is stabilized by weak C-H⋯π inter-actions and weak π-π inter-actions [centroid-to-centroid distance = 3.9431 (17) Å].

4-(5-Phenyl-1,2,4-triazolo[3,4-a]isoquinolin-3-yl)benzonitrile.

In the title mol-ecule, C(23)H(14)N(4), the triazoloisoquinoline ring system is nearly planar, with an r.m.s. deviation of 0.038 (2) Šand a maximum deviation of -0.030 (2) Šfrom the mean plane of the triazole ring C atom which is bonded to the benzene ring. The benzene and phenyl rings are twisted by 57.65 (8) and 53.60 (9)°, respectively, with respect to the mean plane of the triazoloisoquinoline ring system. In the crystal structure, mol-ecules are linked by weak aromatic π-π inter-actions [centroid-centroid distance = 3.8074 (12) Å]. In addition, the crystal structure exhibits a nonclassical inter-molecular C-H⋯N hydrogen bond.

3-(4-Chloro-phen-yl)-5-phenyl-1,2,4-triazolo[3,4-a]isoquinoline.

In the title mol-ecule, C(22)H(14)ClN(3), the triazoloisoquinoline ring system is approximately planar, with an r.m.s. deviation of 0.033 (2) Šand a maximum departure from the mean plane of 0.062 (1) Šfor the triazole ring C atom, bonded to the benzene ring. The benzene and phenyl rings are twisted by 57.02 (6) and 62.16 (6)°, respectively, to the mean plane of the triazoloisoquinoline ring system. The mol-ecule is stabilized by a weak intra-molecular π-π inter-action [centroid-centroid distance = 3.7089 (10) Å] between the benzene and phenyl rings. In the crystal structure, weak inter-molecular C-H⋯N hydrogen bonds and C-H⋯π inter-actions link the mol-ecules.

1-[(2-Chloro-3-quinol-yl)meth-yl]indoline-2,3-dione.

In the title compound, C(18)H(11)ClN(2)O(2), the isatin and 2-chloro-3-methyl-quinoline units are both almost planar, with r.m.s. deviations of 0.0075 and 0.0086 Å, respectively, and the dihedral angle between the mean planes of the two units is 83.13 (7)°. In the crystal, a weak inter-molecular C-H⋯ O inter-action links the mol-ecules into chains along the c axis.

N-[4-Chloro-2-(2-chlorobenzoyl)phenyl]acetamide.

In the title compound, C(15)H(11)Cl(2)NO(2), the dihedral angle between the two benzene rings is 74.83 (5)°. The N-bound and terminal benzene rings are inclined at dihedral angles of 4.09 (10) and 78.38 (9)°, respectively, to the mean plane through the acetamide group. Intra-molecular C-H⋯O and N-H⋯O hydrogen bonds both generate S(6) rings.

Methyl 1-methyl-1H-1,2,3-triazole-4-carboxyl-ate.

The title mol-ecule, C(5)H(7)N(3)O(2), has an almost planar conformation, with a maximum deviation of 0.043 (3) Å, except for the methyl H atoms. In the crystal structure, inter-molecular C-H⋯O hydrogen bonds link the mol-ecules into layers parallel to the bc plane. Inter-molecular π-π stacking inter-actions [centroid-centroid distances = 3.685 (2) and 3.697 (2) Å] are observed between the parallel triazole rings.

3-tert-Butyl-1H-isochromene-1-thione.

The title compound, C(13)H(14)OS, crystallizes with two independent mol-ecules in the asymmetric unit. The unit cell contains three voids of 197 Å(3), but the residual electron density (highest peak = 0.24 e Å(-3) and deepest hole = -0.18 e Å(-3)) in the difference Fourier map suggests no solvent mol-ecule occupies this void. The crystal structure is stabilized by π-π inter-actions between the isocoumarin ring systems, with centroid-centroid distances of 3.6793 (14) and 3.6566 (15) Å.

3-Methyl-5-phenyl-1-(3-phenyl-isoquinolin-1-yl)-1H-pyrazole.

The title compound, C(25)H(19)N(3), is composed of an aryl-substituted pyrazole ring connected to an aryl-substituted isoquinoline ring system with a dihedral angle of 52.7 (1)° between the pyrazole ring and the isoquinoline ring system. The dihedral angle between the pyrazole ring and the phenyl ring attached to it is 27.4 (1)° and the dihedral angle between the isoquinoline ring system and the phenyl ring attached to it is 19.6 (1)°.

1-[3-(4-Chloro-phen-yl)isoquinolin-1-yl]-3,5-diphenyl-1H-pyrazole.

The title compound, C(30)H(20)ClN(3), is composed of a diaryl-substituted pyrazole ring connected to an aryl-substituted isoquinoline ring system with a dihedral angle of 65.1 (1)° between the pyrazole ring and the isoquinoline ring system. The 3-phenyl and 4-phenyl substitutents are twisted by 8.1 (1) and 43.0 (1)°, respectively, with respect to the pyrazole ring. The chloro-phenyl ring and the isoquinoline ring system are twisted by 21.2 (1)° with respect to each other.

1-[3-(4-Chloro-phen-yl)isoquinolin-1-yl]-3,5-diethyl-1H-pyrazole.

The title compound, C(22)H(20)ClN(3), is composed of a dialkyl-substituted pyrazole ring connected to an aryl-substituted isoquinoline ring system with a dihedral angle of 55.8 (1)° between the pyrazole ring and and the isoquinoline ring system. The dihedral angle between the chloro-phenyl ring and the isoquinoline ring system is 28.3 (1)°.

2-[2-(Hydroxy-meth-yl)phen-yl]-1-(1-naphth-yl)ethanol.

The mol-ecular conformation of the title compound, C(19)H(18)O(2), is stabilized by an intra-molecular O-H-O hydrogen bond. In addition, inter-molecular O-H-O inter-actions link the mol-ecules into zigzag chains running along the c axis.

1,3,6-Trimethyl-pyrano[4,3-b]pyrrol-4(1H)-one.

All the non-H atoms of the title compound, C(10)H(11)NO(2), are almost coplanar [maximum deviation = 0.040 (3) Å]. The crystal structure is stabilized by C-H⋯O hydrogen bonds.

5-Phenyl-3-(2-thien-yl)-1,2,4-triazolo[3,4-a]isoquinoline.

In the title mol-ecule, C(20)H(13)N(3)S, the triazoloisoquinoline ring system is approximately planar, with an r.m.s. deviation of 0.045 Šand a maximum deviation of 0.090 (2) Šfrom the mean plane for the triazole ring C atom which is bonded to the thio-phene ring. The phenyl ring is twisted by 52.0 (1)° with respect to the mean plane of the triazoloisoquinoline ring system. The thio-phene ring is rotationally disordered by approximately 180° over two sites, the ratio of refined occupancies being 0.73 (1):0.27 (1).

1-[(2-Chloro-7,8-dimethyl-quinolin-3-yl)meth-yl]pyridin-2(1H)-one.

In the title compound, C(17)H(15)ClN(2)O, the quinoline ring system is nearly planar, with a maximum deviation from the mean plane of 0.074 (2) Å, and makes a dihedral angle of 81.03 (7)° with the pyridone ring. The crystal packing is stabilized by π-π stacking inter-actions between the pyridone and benzene rings of the quinoline ring system [centroid-centroid distance = 3.6754 (10) Å]. Furthermore, weak inter-molecular C-H⋯O hydrogen bonding links mol-ecules into supra-molecular chains along [001].

(2-Chloro-benzo[h]quinolin-3-yl)methanol.

In the title mol-ecule, C(14)H(10)ClNO, all non-H atoms are coplanar (r.m.s deviation = 0.0266 Å). In the crystal, symmetry-related mol-ecules are hydrogen bonded via inter-molecular O-H⋯O inter-actions, forming chains along the b axis.

1-[(2-Chloro-7-methyl-3-quinol-yl)meth-yl]pyridin-2(1H)-one.

In the title compound, C(16)H(13)ClN(2)O, the quinoline ring system is essentially planar, with a maximum deviation of 0.021 (2) Å. The pyridone ring is oriented at a dihedral angle of 85.93 (6)° with respect to the quinoline ring system. In the crystal structure, inter-molecular C-H⋯O hydrogen bonds link the mol-ecules along the b axis. Weak π-π stacking inter-actions [centroid-centroid distances = 3.7218 (9) and 3.6083 (9) Å] are also observed.