2-Butoxy-N-[2-(diethylamino)ethyl]quinoline-4-carboxamide (dibucaine)

The molecular conformation of the title compound, C20H29N3O2, is stabilized by an intramolecular C—H⋯O hydrogen bond. The orientation of the amide group to the ring system is characterized by a C—C—C—O dihedral angle of 137.5 (3)°. In the crystal, intermolecular N—H⋯O hydrogen bonds between the amide groups form C(4) chains running parallel to the a axis.

The molecular conformation of the title compound, C 20 H 29 N 3 O 2 , is stabilized by an intramolecular C-HÁ Á ÁO hydrogen bond. The orientation of the amide group to the ring system is characterized by a C-C-C-O dihedral angle of 137.5 (3) . In the crystal, intermolecular N-HÁ Á ÁO hydrogen bonds between the amide groups form C(4) chains running parallel to the a axis.

Related literature
For a monograph on dibucaine, see: Sweetman (2009). For a comparison of the vasoactivity of dibucaine with other amide and ester local anaesthetics, see: Willatts & Reynolds (1985). For the initial crystal structure determination of dibucaine hydrochloride monohydrate, see: Hayward & Donohue (1977). For the subsequent revision of parameters, bond distances and bond angles, see Donohue & Hayward (1980). Outlier data were removed using a local program based on the method of Prince & Nicholson (1983 Table 1 Hydrogen-bond geometry (Å , ).

Comment
Dibucaine is an amide local anaesthetic that is now generally only used for surface anaesthesia. It is one of the most potent and toxic of the long-acting local anaesthetics and its parenteral use was restricted to spinal anaesthesia (Sweetman, 2009).
Although the single-crystal structure of dibucaine hydrochloride monohydrate has been published (Hayward & Donohue, 1977;Donohue & Hayward, 1980), that of the free base has not been reported.
The molecular structure of the title compound is shown in Figure 1. The molecular conformation is stabilized by an intramolecular C-H···O hydrogen bond (Table 1). In the crystal structure, molecules are linked by intermolecular N-H···O hydrogen bonds into chains running parallel to the a axis. These hydrogen bonds, formed between the carbonyl oxygen and the amide nitrogen, have a O11···N12 distance of 2.857 (3)Å and a N12-H12···O11 angle of 171 (2)°. In the published structure of dibucaine hydrochloride monohydrate, the hydrogen bonds between the amide groups are disrupted due to hydrogen bonding with chloride and water molecules (Hayward & Donohue, 1977;Donohue & Hayward, 1980).

Experimental
A non-saturated solution of the title compound was prepared by dissolving the powder to 20 ml of a 1/1 (v/v) ethanol/water mixture in 20 ml scintillation vials (Research Products International Corp., Mt. Prospect, IL, USA). The open vial was allowed to stand at room temperature to let the liquid slowly evaporate. After one week, the liquid had partly evaporated and crystals of the title compound were obtained. Subsequent to decanting the majority of the remaining liquid and prior to crystal structure determination, the crystals were allowed to dry overnight.

Refinement
The H atom bound to nitrogen N12 was located in a difference Fourier map and refined freely with isotropic displacement parameters. Other H atoms were placed in calculated positions and treated as riding on their parent atoms with C-H = 0.95 Å (aromatic), 0.99 Å (aliphatic CH 2 ), 0.98 Å (aliphatic CH 3 ) and with U iso (H) = 1.2U eq (C). Fig. 1  Refinement. Outlier data were removed using a local program based on the method of Prince and Nicholson (1983).

Figures
Refinement on F 2 for ALL reflections except for 0 with very negative F 2 or flagged by the user for potential systematic errors.
Weighted R-factors wR and all goodnesses of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The observed criterion of F 2 > σ(F 2 ) is used only for calculating R_factor_obs etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.