Chemical and spectroscopic characterization data of 'cannabidibutol', a novel cannabidiol butyl analog

Abstract

Cannabidibutol (CBDB), a novel butyl analog of cannabidiol, was identified as impurity of commercial cannabidiol (CBD) extracted from hemp (for full data and results interpretation see "Analysis of impurities of cannabidiol from hemp. Isolation, characterization and synthesis of cannabidibutol, the novel cannabidiol butyl analog" Citti et al, 2019). The compound was isolated from a CBD sample and subject to a full characterization. First, a complete spectroscopic characterization was performed by Nuclear Magnetic Resonance (NMR): in particular, ¹H-NMR, ¹³C-NMR, COSY, HSQC and HMBC, which were followed by UV absorption and circular dichroism (CD) spectra. In order to confirm the structural identity and stereochemistry of the compound, a stereoselective synthesis of the trans isomer (1R,6R) was carried out and all the chemical and spectroscopic properties were analyzed. The synthesized compound was characterized by NMR (¹H-NMR, ¹³C-NMR, COSY, HSQC and HMBC), Infra-Red spectroscopy (IR), UV and CD absorption, matching the results obtained for the natural isolated compound. With the analytical standard in hand, a simple high-performance liquid chromatography method coupled to UV detection (HPLC-UV) was developed and validated in house in terms of linearity, accuracy, precision, dilution integrity and stability. The present data might be useful to any researcher or industry that may run into a very common impurity of CBD extracted from hemp, so it can be easily compared with their own experimental data.

Keywords: Cannabidiol-C4; Chemical and spectroscopic characterization of cannabidibutol; Circular dichroism; HPLC-UV method validation; NMR spectra; UV absorption.

Fig. 1

a: ¹H-NMR of synthetic CBDB. b: ¹H-NMR of synthetic CBDB from 3 to 5 ppm. c: ¹H-NMR of synthetic CBDB from 0 to 3 ppm.

Fig. 2

a: ¹³C-NMR of synthetic CBDB. b: ¹³C-NMR of synthetic CBDB from 100 to 160 ppm. c: ¹³C-NMR of synthetic CBDB from 0 to 70 ppm.

Fig. 3

COSY of synthetic CBDB.

Fig. 4

HSQC of synthetic CBDB.

Fig. 5

HMBC of synthetic CBDB.

Fig. 6

IR of synthetic CBDB.

Fig. 7

¹H-NMR of isolated CBDB.

Fig. 8

¹³C-NMR of isolated CBDB.

Fig. 9

COSY of isolated CBDB.

Fig. 10

HSQC of isolated CBDB.

Fig. 11

HMBC of isolated CBDB.

Fig. 12

Circular Dichroism (CD) of isolated (green) and synthesized (blue) CBDB. Solvent: acetonitrile, path length: 1 cm; concentration: 10 µg/mL.

Fig. 13

HPLC-UV chromatograms of a blank sample (acetonitrile), an internal standard (IS) working solution, a standard mixture of cannabidivarin (CBDV) and cannabidibutol (CBDB) in IS working solution at the limit of detection (LOD, 0.10 µg/mL for CBDV and 0.04 µg/mL for CBDB), a standard mixture at the lower limit of quantification (LLOQ, 0.28 µg/mL for CBDV and 0.12 µg/mL for CBDB), a standard mixture at three quality control (QC) levels, low (LQC, 0.56 µg/mL for CBDV and 0.24 µg/mL for CBDB), medium (MQC, 18.8 µg/mL for CBDV and 8.00 µg/mL for CBDB) and high (HQC, 45.1 µg/mL for CBDV and 19.2 µg/mL for CBDB), and an authentic cannabidiol (CBD) sample in IS working solution (the peak of CBD is not entirely visible as the chromatogram is zoomed in to highlight the impurities).