User:MaFecht93/Sandbox/Pomeranz–Fritsch reaction
The Pomeranz–Fritsch reaction, also named Pomeranz–Fritsch cyclization, is a name reaction in the organic chemistry. It is named after Paul Fritsch (1859–1913) and Cäsar Pomeranz (1860–1926).[1][2] In general it is a synthesis of isoquinoline.[2][3][4]
General Reaction Scheme
[edit]The reaction below shows the acid-promoted synthesis of isoquinoline from benzaldehyde and a 2,2-dialkoxyethylamine.[5]
Various alkyl groups, e.g. methyl and ethyl groups, can be used as substituent R.
In the archetypical reaction sulfuric acid was used as proton donor, but Lewis acids such as trifluoroacetic anhydride and lanthanide triflates have been used occasionally.[1][2][4] Later, a wide range of diverse isoquinolines were succesfully prepared.[4]
Reaction Mechanism
[edit]A possible mechanism is depicted below:[5]
First the benzalaminoacetal 1 is built by the condensation of benzaldehyde and a 2,2-dialkoxyethylamine. After the condensation a hydrogen-atom is added to one of the alkoxy groups. Subsequently an alcohol is removed. Next, the compound 2 is built. After that a second hydrogend-atom is added to the compound. In the last step a second alcohol is removed and the compound is aromatic again.
Applications
[edit]The Pomeranz–Fritsch reaction has general application in the preparation of isoquinoline derivates.
Isoquinolines find many applications, including (but not limited to):[3][4]
- anesthetics; dimethisoquin is one example (shown below).
- antihypertension agents, such as quinapril, quinapirilat, and debrisoquine (all derived from 1,2,3,4-tetrahydroisoquinoline).
- antifungal agents, such as 2,2'Hexadecamethylenediisoquinolinium dichloride, which is also used as a topical antiseptic. This derivative, shown below, is prepared by N-alkylation of isoquinoline with the appropriate dihalide.
- disinfectants, like N-laurylisoquinolinium bromide (shown below), which is prepared by simple N-alkylation of isoquinoline.
- vasodilators, a well-known example, papaverine, shown below.
Bisbenzylisoquinolinium compounds are compounds similar in structure to tubocurarine. They have two isoquinolinium structures, linked by a carbon chain, containing two ester linkages.
References
[edit]- ^ a b Pomeranz, C., Monatsh., 1893, 14, 116. doi:10.1007/BF01517862
- ^ a b c Fritsch, P., Ber. Dtsch. Chem. Ges., 1893, 26, 419. doi:10.1002/cber.18930260191
- ^ a b Zerong Wang (2009), Comprehensive Organic Name Reactions and Reagents (in German), New Jersey: John Wiley & Sons, pp. 2256–2259, ISBN 978-0-471-70450-8
{{citation}}: Check date values in:|year=and|date=(help)CS1 maint: date and year (link) CS1 maint: year (link) - ^ a b c d László Kürti und Barbara Czakó.: Strategic Applications of Named Reactions in Organic Synthesis: Background and Detailed Mechanisms, Elsevier Academic Press, 2005, S. 358–359, ISBN 978-0-12-429785-2.
- ^ a b Jie Jack Li: Name Reactions – A Collection of Detailed Reaction Mechanisms, Springer, 2006, S. 472-474, ISBN 978-3-540-30030-4.