Quinisocaine
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| ECHA InfoCard | 100.001.546 |
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| Formula | C17H24N2O |
| Molar mass | 272.392 g·mol−1 |
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Quinisocaine (INN), also known as dimethisoquin (BAN and USAN), is a topical anesthetic used as an antipruritic.[1]
Synthesis
Quinisocaine can be synthesized starting from phthalaldehydic acid.[2][3][4] Patent:[5][6] The Henry reaction between phthalaldehydic acid (1) and 1-nitropentane occurs by a mechanism that involves a hydroxy acid (2). Expulsion of water then gives the lactone 3. Reduction of the nitro group via catalytic hydrogenation leads to the amine 4. Treatment of that amine with sodium hydroxide leads to ring opening of the lactone ring to the intermediary amino acid (5). This cyclizes spontaneously to the lactam to give the isoquinoline derivative 7. Dehydration by means of strong acid gives 3-butylisocarbostyril (8). Phosphorus oxychloride converts the oxygen function to the corresponding chloride via the enol forms 3-butyl-1-chloroisoquinoline (9). Displacement of halogen with the sodium salt from 2-dimethylaminoethanol (10) affords dimethisoquin (11).
References
- ↑ Elks J (1990). "Dimethisoquin". The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Dordrecht: Springer. p. 430. ISBN 978-1-4757-2085-3.
- ↑ Thieme
- ↑ Eloy, F. et al, Chim. Ther., 1969, 4, 469
- ↑ Wilson JW, Dawson ND (March 1949). "Local anesthetics; aminoalkoxyisoquinoline derivatives". Journal of the American Chemical Society. 71 (3): 937. Bibcode:1949JAChS..71..937W. doi:10.1021/ja01171a047. PMID 18129083.
- ↑ Anon., (1952 to Smith Kline and French International Co).
- ↑ Ullyot, US patent 2612503, Ullyot GE, "Basic ether-substituted isoquinolines", published 1952-09-30, issued 1952-09-30, assigned to Smith Kline French Lab and Smith, Kline & French Laboratories (1952 to SK & F).