Preparation of Phenethylamines, Part 1: By Aminomethylation

This video is about the significance of phenethylamines, and about their preparation by aminomethylation of benzylic electrophiles or nucleophiles. This includes formation and reduction of nitrostyrenes, acyl cyanides, cyanohydrins, and nitro ketones. You'll find here many specific examples with complete experimental details. I've also included a discussion of potential side reactions and other problems of these reactions.
Further examples (patents are available at worldwide.espa...
Org. Syn. 2009, 86, 18 (Neber); 1997, 74, 257 (Willgerodt Kindler); 1986, 64, 19 (Neber); 1984, 62, 196 (cyanohydrin); 1981, 60, 14 (cyanohydrin); 1972, 52, 96 (cyanohydrin); 1963, 43, 49 (hydantoin); 25 (aminonitrile); 1961, 41, 82 (Neber); 1953, 33, 7 (cyanohydrin); 1944, 24, 9 (aminonitrile); 1943, 23, 71 (hydrogenation RCN); 1942, 22, 89; 23 (aminonitrile); 1939, 19, 1 (azlactone);
J. Org. Chem. 2024, 89, 2294-2305 (ylides); ACS Central Sci. 2023, 9, 1775-1783; Chem. Sci. 2022, 13, 10914-10922 (hydrogenation RCN); J. Org. Chem. 2022, 87, 13480-13493 (oxidative Henry reaction); 6321-6329 (aminonitrile); ACS Catal. 2022, 12, 2522-2531 (⍺-acylation of amines); J. Org. Chem. 2021, 86, 7141-7147 (hydrogenation cinnamates); J. Am. Chem. Soc. 2020, 142, 19058-19064 (⍺-acylation of amines); Tetrahedron Lett. 2020, 61, 151770 (ylides); J. Org. Chem. 2019, 84, 2654-2659 (imines); ACS Omega 2018, 3, 1871-1880 (asym Henry reaction); Chem. Comm. 2018, 54, 1221 (oxidative aminoalkylation); J. Am. Chem. Soc. 2018, 140, 7083-7087 (imines); 598-601; Green Chem. 2017, 19, 4583-4590 (reduction RNO2); J. Org. Chem. 2017, 82, 13121-13140 (aziridines); 680-687 (reduction RCN); J. Org. Chem. 2016, 81, 6343-6356 (asym Michael addn); Org. Lett. 2016, 18, 92-95 (azomethine ylide); J. Org. Chem. 2015, 80, 2272-2280 (asym Henry reaction); Tetrahedron Lett. 2015, 56, 6590-6592 (ylides); 5278-5281 (ylides); Org. Lett. 2014, 16, 1092-1095 (reduction RCN); Chem. Comm. 2014, 50, 8878-8881 (asym reduction nitrostyrenes); J. Org. Chem. 2013, 78, 6503-6509; Tetrahedron Lett. 2013, 54, 5869-5872 (ylides); Org. Lett. 2012, 14, 1516-1519 (Michael addn); J. Org. Chem. 2011, 76, 3399-3408 (asym Henry reaction); Org. Lett. 2010, 12, 3693-3695 (MeNO2); Org. Proc. Res. Dev. 2010, 14, 114-118 (cyanohydrins); J. Org. Chem. 2010, 75, 1313-1316 (asym Henry reaction); Org. Lett. 2008, 10, 1707-1710 (asym Henry reaction); J. Am. Chem. Soc. 2008, 130, 8606-8607 (imines); Synlett 2008, 2075-2077 (imines); J. Org. Chem. 2008, 73, 8520-8528 (Henry reaction); J. Med. Chem. 2006, 49, 4269-4274 (RCN); J. Am. Chem. Soc. 2005, 127, 17622-17623 (asym Henry reaction); Org. Lett. 2003, 5, 3987-3990 (aziridines); J. Org. Chem. 2002, 67, 4875-4881 (asym Henry reaction); J. Am. Chem. Soc. 2001, 123, 7707-7708 (aziridines); Ang. Chem. Int. Ed. 1997, 36, 1317-1319 (aziridines); J. Org. Chem. 1997, 62, 425-427 (Henry reaction); J. Org. Chem. 1997, 62, 3867-3873 (cyanohydrins); Tetrahedron Lett. 1986, 27, 5759-5762 (acyl imidazolide + MeNO2).

[@bankai416]

Thank you now i know what to do with my piperonal :)

[@knivesnico8775]

2:07
Hallo! Is there any more literature that talks about the permeability and bioavailability of drugs in accordance to their charge? I feel like there are a lot of things I don't know about how absorption kinetics work

[@synthesiswithflorenciozara1848]

Hi, I don't know of any specific article on this issue, but in J. Med. Chem. you'll find many articles on specific topics. Oral bioavailability requires at least some solubility in H2O, and no permanent charge (quaternary ammonium salts are not orally available; that's why you can eat animals killed with tubocurarine). You may also check my book on the topic (free copy available online). But if you study chemistry, better focus on chemistry. Quien mucho abarca, poco aprieta.

[@knivesnico8775]

@@synthesiswithflorenciozara1848 but I'm not studying chemistry, I'm a pharmacist! So pharmacokinetics and pharmacodynamics are my main focus.
Thank you as always :)

[@knivesnico8775]

@@synthesiswithflorenciozara1848 well, a pharmaceutical chemist* actually
So I guess you could say we abarcamos mucho by design

[@prakashbishnoi6593]

Nice explanation
Thank you

[@nnnnnnn1209]

Very nice

[@knivesnico8775]

wonderful

[@SuryanIsaac]

Very interesting! Thank you

[@ChemicaLove]

Thanks!

[@synthesiswithflorenciozara1848]

You're welcome. I've already started thinking about the next subject, but haven't decided yet. But this one was great fun.