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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.

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

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

hi, I would focus on organic chemistry. Subjects like medicinal chemistry or industrial chemistry are too superficial, and one ends up knowing a bit of everything, but nothing really well. Once you've mastered organic synthesis you can learn pharmacology, toxicology, etc when the need for it appears at your job. When working as a medicinal chemist, the most important qualification is to be able to prepare any compound, to know how to isolate and purify compounds (including water soluble compounds), and to have a good feel for their stability and reactivity (high reactivity = toxicity (usually)).

@@synthesiswithflorenciozara1848 thanks for your answer! It‘s great to be able to talk someone experienced in this field. May i ask how you learned pharmacology etc. on the job? Did you attend a postdoc program or did you learn things „on the fly“ when needed ? Also would you say that computational chemistry/theoretical chemistry is a necessary skill to be able to design molecules or is it more useful to invest more time into pure organic chemistry? Thank you !

@@maxfrost2360 when I started at Novo Nordisk they sent the 'new' chemists on a one-week course on medicinal chemistry (at Drew University, New Jersey), but that was too fast/too superficial. I read some medicinal chemistry books in my spare time, but these were also too general. Anyway, this gave me some basics (patents, toxicology, pharmacokinetics). But one learns most during the specific projects. For instance, I worked many years on CNS-drugs. I had to design and prepare compounds that were orally available, metabolically stable, and which cross the blood-brain barrier. And are selective and potent ligands at the target receptor. Very difficult.......So, here the best is to check the structures of similar drugs, and to read case stories of the development of similar drugs. Concerning computational chemistry: nooooo, forget that. There are some free online tools to quickly calculate the logP and polar surface area of compounds (critical for CNS drugs; e.g. molinspiration.com), that's all you need. Way more important are case stories. A book I liked was 'Drug Discovery, a history' (Walter Sneader); Sneader also wrote many useful case stories of drug development in various journals. One important lesson: the best starting point for a new drug is an old drug.

oxazoles are pretty low on my to-do-list, because they are not very useful (and often unstable). Top priority have: piperidines, phenols, then maybe some videos on aromaticity, cycloadditions, development of research projects. We'll see; thanks for the suggestion.

@@synthesiswithflorenciozara1848 would indols be something that interests you? I think cycloadditions can come in quite handy here

You're welcome, glad you liked it. Any suggestions and ideas for new videos will be greatly appreciated.

Yes supère channel, discovered like a week ago. Le

☝️

thanks, yes, I've started doing that, but only with the newer videos. You'll find them under the 'community' tab of my channel. Maybe in the future I'll do an update of older videos, with pdf.

@@synthesiswithflorenciozara1848 that would be awesome, these are great revision resources too

Hallo, ja, ich habe das selber abgestellt, weil ich weder Zeit noch Toleranz für Quatsch, Beleidigungen, usw habe. Auf meinem channel gibts eine email Adresse, und jeder kann mir gerne Fragen, Kommentare oder Anregungen schicken.

@@synthesiswithflorenciozara1848 alles kla gut zu wissen dan würde ich nur immer die email in der Video Beschreibung hinzufügen damit Leute nicht verwirrt seine bei fragen

Your're welcome, and thanks for your kind words. I am not yet getting much feedback, but still believe that a repository of reactions including their practical limitations from the view of an industrial chemist can be of some value. Thanks.

Oh absolutely, this is very interesting for beginners but also those who would like to broaden their knowledge. I must say that your comments on waste mgmt are very important and many a synthesis has been documented here but that topic is just glassed over.

hi, no, I have no practical experience with this reaction, but there are some references in my last three videos about phenethylamines. In one procedure benzoic acid anhydride is heated with NaCN, and the benzoyl cyanide is just distilled off. This will probably not work with PhCOCl, otherwise they wouldn't have used the anhydride.

Hi Nico, yes, of course, go ahead.

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

Thanks for the reference. Yes, elimination is a good strategy. I am always amazed that almost no substitution occurs. Thank you.

Thanks, glad you liked it. Any suggestions of improvements or further subjects to discuss will be greatly appreciated. Thank you.

Thanks, you're welcome. I really appreciate any feedback and suggestions for new videos. Thank you.

Thanks, glad you liked it. Currently I havn't access to any reaction database, but the homepages of the largest journals make searching relatively easy, using keywords and 'cited by'. Organic Synthesis is also a good source, as well as Espacenet (patents) and Google. For the next videos I am not sure yet, but almost certainly some important class of target compounds. Do you have suggestions? I really appreciate any feedback. Thank you.

@@synthesiswithflorenciozara1848The pyridine videos were really cool. It would be nice to see a video about other heterocycle. To be honest, There are not many good channels on chemistry in English, which is very strange

ok, yes, I was considering imidazoles, thiophenes, pyrazoles, and some other heterocycles. I've worked myself a lot with these. To make it more relevant I'll have to dig deeply into their history, uses, etc, but that's fun. We'll see, haven't decided yet. If you have more ideas, just let me know, thanks.

​@@synthesiswithflorenciozara1848 Regarding the heterocycles, there has been an update to the Comprehensive Heterocyclic Chemistry Encyclopedia. My institution can't afford the 15k, but maybe you have access? Endless content really. How about a named reactions series? Or I'm sure many aspiring scientists would benefit from you sharing your perspective and experience navigating the job market. What skills you think are most valuable, advice for your past self, ect. I really enjoy your channel, great stuff!

@@ChemicaLoveThank you. Yes, heterocycles are definitely an interesting subject, and it's on my to-do-list. I'll also add your suggestions. You're right, students may certainly also be interested in the jobs available for chemists, and in what to look for. I've plenty of experience there. Right now I've started with a new, short series on phenethylamines, which are important in medicinal chemistry. Isn't it surprising that people are still writing books? Today you can find almost any original research directly, with google, and for free. And it's getting better by the day. So, no bright future there for publishers and authors of textbooks and for Chemical Abstracts...

there is a video in my channel about the hydrogenation of ketones to alcohols with some examples: ruclips.net/video/4fA0Jje8vIA/видео.html In industry copper-based catalysts at high temperature are often used (you may search espacenet for examples). If ethylbenzene is your target, then PtO2 + AcOH + H2 may work. In US4996374 they use Pd/C to prepare the alcohol.

thank you! more are on the way (in 3 months or so), probably about alkenes.

Hi, probably not from cyclopentanone. There is a good synthesis from isobutyronitrile (J.Org.Chem. 2011, 76, 5198). Alternatively, maybe there is a way to cyclize and rearrange 2,6-heptanedione (pinacol, then Wagner-Meerwein), or rearrange the mixed pinacol product from acetone and cyclobutanone (if you can make it). The isobutyronitrile route looks good and can probably be optimized a lot (e.g., Michael addn to acrolein, reduction, etc). Cheers.

Well, diazonium salts would indeed be formed upon nitrosation from primary, unprotected amino groups. Secondary amines yield N-nitroso amines (at 7.02 min above), and amides/sulfonamides/ureas/carbamates sometimes are nitrosated, sometimes not, depending on the conditions.

oh, danke Paul. Besonders spannend fand ich die Azid-Chemie, Nitrierungen, Reduktionen und die unkatalysierten Substitutionen. Muss mal sehen welche Stoffklasse jetzt dran ist, vielleicht Phenole. Hoffe es geht dir gut. Grüsse.

Hello, here you are. It's on page 89 of this patent: worldwide.espacenet.com/patent/search/family/044799332/publication/WO2011130595A2?q=wo2011130595

You're welcome, and thanks for subscribing.

Glad you like them. Just stay tuned, more are coming.....

Thanks, glad you liked it. Well, this is only for real hard-core chemists, you know, those who really want to know how things work. In a month or so I'll upload 6 or 7 videos about the synthesis of pyridines. So, keep an eye on this channel. And thanks for subscribing and good luck with fighting the russians. This war is really a tragedy, so many talented chemists and musicians, both in russia and ukraine, not being able to work.

yes, thanks, hope you're fine, too. Are you still studying chemistry? I've now started with a series of videos about heterocyclic chemistry. I had a lot to do with these in the past. Cheers.

​@@synthesiswithflorenciozara1848 Yes! I'm still studying pharmacy, but my work in investigation was unfortunately dead on arrival, I'm trying to get my professors to link me up with investigators again so I may actually do some research, but as of now, I just study that which I'm required to in order to get my degree...

@@synthesiswithflorenciozara1848 I will be sure to study some of those videos, heterocycles are truly fascinating

Glad you enjoyed it. Industrial organic synthesis, safety, and side reactions are definitely not discussed thoroughly enough in most textbooks or presentations, so, I'll keep posting videos highlighting such issues. Just stay tuned.....

@@synthesiswithflorenciozara1848 I certainly will! I really appreciate your work!

Hi, you can reduce chlorobenzonitriles to benzonitrile by catalytic hydrogenation or with a combination of some hydrogenation catalyst (Ni, Pd, Pt) and reducing agents (Mg in MeOH, formic acid, maybe aluminum isopropoxide). When you generate Raney Nickel from Al-Ni and H2O/NaOH a lot of hydrogen evolves, which can also bring about the hydrogenation. With sodium methoxide (NaOMe) alone, it will probably not work but only yield 2-methoxy or 2-hydroxybenzonitrile (or the amide or acid).

@@synthesiswithflorenciozara1848 thank you my friend, fortunetly i have some nickiel to try first with it, also way with magnesium doesn’t look too hard, so just for my curiosity I’ll try. And what about temp for rxn with nickel? If I good remember ~60-70* should be enough?

@@poprostuprosty4177 Aryl chlorides are often difficult to reduce, so, heat as much as you can. If you work in your kitchen you may also use sugar as reducing agent. But I would just buy benzonitrile, its much easier. Under too harsh conditions the cyano group may also be reduced or hydrolyzed. Here's a link to a procedure: pubs.acs.org/doi/abs/10.1021/om010949%2B?journalCode=orgnd7&quickLinkVolume=21&quickLinkPage=1554&selectedTab=citation&volume=21

@@synthesiswithflorenciozara1848 hey mate. Sorry for a spam in comments but that’s only way to communicate with ye. I forgot ask you before what is a ratio of: raney/benzonitrile

@@poprostuprosty4177 if you have the Raney Ni-Al alloy, you can use an excess (2-5 equiv) so that enough H2 is generated. If you use another reducing agent, catalytic amounts of nickel should be enough (1-10%).

Hi, hydrogen peroxide adds (reversibly) to the ketone to yield R2C(OH)OOH. This intermediate has similar reactivity as an alkyl hydroperoxide (R-O-O-H), and is more reactive than H2O2.

Congratulations! Of my former jobs, the one I most enjoyed was medicinal chemistry research at a pharmaceutical company. I hope you can also find something as fun. All the best, and happy easter holidays, too.

@@synthesiswithflorenciozara1848 :)

I never had any problems with MCPBA or tBuOOH or even with isolated ozonides, but, yes, new unknown peroxides should not be made in large quantities. My worst explosions (or next-lab-explosions) were NaOH+CHCl3, 2-bromo-3-methylthiophene, substituted acetylenes, and H2O2 in an autoclave, and many implosions of evacuated glassware. So, safety glasses and keeping the hood shut down and its glass panel in front of your face is really critical for survival...

Oh Its an alkyl being added, not the alcoholic part being turned into the radical, like I originally thought