5933. Metazocine

Nomenclature

CAS number: 3734-52-9
1,2,3,4,5,6-Hexahydro-3,6,11-trimethyl-2,6-methano-3-benzazocin-8-ol; 2′-hydroxy-2,5,9-trimethyl-6,7-benzomorphan; methobenzmorphan.
C15H21NO; mol wt 231.33.
C 77.88%, H 9.15%, N 6.05%, O 6.92%.

Description and references

Mixed opioid agonist-antagonist; prototype of the benzomorphan analgesics. Prepn of (±)-cis-form by Grewe cyclization of 3,4-lutidine methiodide: E. L. May, E. M. Fry, J. Org. Chem. 22, 1366 (1957). Prepn of α- (cis) and β- (trans) diastereoisomers: E. L. May, J. H. Ager, ibid. 24, 1432 (1959). Optical resolution of α-forms: E. L. May, N. B. Eddy, ibid. 1435; of β-forms: S. E. Fullerton et al., ibid. 27, 2144 (1962). Abs config: A. F. Casy, A. P. Parulkar, J. Med. Chem. 12, 178 (1969). Enantioselective synthesis of cis-()-form: B. M. Trost, W. Tang, J. Am. Chem. Soc. 125, 8744 (2003). Opioid receptor profile: I. Berzetei-Gurske, G. H. Loew, Prog. Clin. Biol. Res. 328, 33 (1990).

Chemical structure

Derivative

(±)-cis-Form.

Nomenclature

CAS number: 25144-79-0

Properties

Plates from dil methanol, mp 232-235°.

Derivative

(±)-cis-Form hydrochloride monohydrate.

Nomenclature

CAS number: 70222-87-6
C15H21NO.HCl.H2O; mol wt 285.81.
C 63.04%, H 8.46%, N 4.90%, O 11.20%, Cl 12.40%.

Properties

Rods from abs alcohol + ether, mp 194-196°. LD50 in mice (mg/kg): 175 s.c. (May, Eddy).

Derivative

(±)-trans-Form.

Nomenclature

CAS number: 25145-09-9

Properties

Prisms from alcohol, mp 215-217.5°.

Derivative

(2R,6R,11R)-Form.

Nomenclature

CAS number: 21286-60-2
α-()-Metazocine; cis-()-metazocine.

Properties

mp 183-184.5°. [α]D20 84.8° (c = 0.09 in abs ethanol).

Derivative

(2S,6S,11S)-Form.

Nomenclature

CAS number: 67009-58-9
α-(+)-Metazocine; cis-(+)-metazocine.

Properties

Crystals from acetone + water, mp 183-184.5°. [α]D20 +84.3° (c = 0.83 in abs ethanol).

Derivative

(2R,6R,11S)-Form.

Nomenclature

CAS number: 21286-57-7
β-()-Metazocine; trans-()-metazocine.

Properties

Oblong prisms from methanol, mp 179-181°. [α]D20 88.5° (c = 0.52 in abs alc).

Derivative

(2S,6S,11R)-Form.

Nomenclature

CAS number: 64023-94-5
β-(+)-Metazocine; trans-(+)-metazocine.

Properties

Rods or needles from aq methanol, mp 180-181.5°. [α]D20 +88.6° (c = 0.35 in abs alc).

Note

This is a controlled substance (opiate): 21 CFR, 1308.12.