I'm not dead, just defeated.

<a href="http://malaria.ourexperiment.org/data/16847.html" rel="nofollow noopener" target="_blank">http://malaria.ourexperiment.org/data/16847.html</a>

A second attempt of TM-DP-1-1 Synthesis of (Z)-2-(4-chlorophenyl)-3-hydroxypent-2-enenitrile - TM-DP-1-1 with longer reflux, also using fresh sodium methoxide. 2-(4-chlorophenyl)-3-oxopentanenitrile 4-chlorophenylacetonitrile (2.02 g, 13.3 mmol, 1 eq), ethyl propanoate (1.44 g, 14.1 mmol, 1 eq), and fresh sodium methoxide (1.07 g, 19.9 mmol, 1.5 eq) were combined in ethanol (25 mL) and heated at reflux for 14 h. The solution was allowed to cool, then quenched with water (150 mL), acidified with HCl (1 M, 10 mL), and extracted with tert-butyl methyl ether (3 x 50 mL). The organic fractions were dried over Na2SO4 and concentrated in vacuo to give a red oil (1.67 g, 8.0 mmol). As well as starting material, TLC (10:90 ethyl acetate: hexane) showed two additional spots at Rf = 0.1 and 0.7. SGS 10-1 (4 is 4-chlorophenylacetonitrile, E is ethyl propanoate which was not seen by UV, R is crude reaction mixture) Performed by: Charles Jameson, Christopher Lai, Milan Leonard, Dylan Siow-Lee, James Wood, Patrick Ngo, Brandon Lee, Austin Zhang.

<a href="http://malaria.ourexperiment.org/daraprim_synthesis" rel="nofollow noopener" target="_blank">http://malaria.ourexperiment.org/daraprim_synthesis</a>

Thanks for looking into it. I've researched this method before and the main problem is large amounts of reagents it uses. To make my target of 200mL of p-chlorotoluene the method implies i'd need around 10L of polar solvent (methanol or acetonitrile). I'm still exhausting my other methods before i attempt this one.

NurdRage

Hi NurdRage, Thank you for your hard work. You can try to chlorinate toluene using Oxone and potassium chloride as a chlorine source in acetonitrile. This is an oxychlorination reaction of aromatic rings wich is said to be highly regioselective in the sens that the p-chlorotoluene is obtained at a yield of 68%, 29% for the ortho-chlorotoluene and only 3% of 2,4-dichlorotoluene. But the residence time is high: 24 hours. HIGHLY EFFICIENT, PARA-SELECTIVE OXYCHLORINATION OF AROMATIC COMPOUNDS USING POTASSIUM CHLORIDE AND OXONE <a href="http://chemistry.mdma.ch/hiveboard/rhodium/pdf/aromatic.chlorinaton.oxone.kcl.pdf" rel="nofollow noopener" target="_blank">http://chemistry.mdma.ch/hiveboard/rhodium/pdf/aromatic.chlorinaton.oxone.kcl.pdf</a> Good luck.

Regardless of what you decide, however, I'm behind what happens. Your gouge has been top rate since day one, and as an IT dude, Im probably not the best judge of such things. :D

Roger Lee

I kinda agree. Science isn't always about things being perfect. Sometimes things just take a while, and other things are just not easy (or possible) without some expensive engineering costing millions of $(US or Can), £, Euros, what have you. I agree with the thought that a compilation along with explanations as to why it might not have worked as expected would go a long way toward forwarding Chemistry education.

Roger Lee

I will be happy to see your crappy method. Video of failure can be interesting.

Keith

No worries! Excellent content always takes time!

ninja_padeiro

Don't worry about it man. Keep making great content!

Post some of the "failures" with a discussion of what happened (if you know why). Any information is good to help understand the chemistry involved

BiggieJohn

No worries! You always make videos that are worth the wait!

Paul Grodt

We still &lt;3 you! Keep being awesome. Quality over quantity, and your goal is worth waiting to get it right!

Jamie F

I appreciate your work, thank you very much for continuing to make these videos. Even if the yeild is poor, it might still be worthwhile to show. Best of luck on your future videos!

Thank you as well. Science isn't always about successes; sometimes it's just figuring out what doesn't work, too. I'd be just as happy to see a video of what you tried that didn't work as expected - please don't feel that 'crappy methods' don't have value to show.

LVE

Thank you for producing all of your great videos -- we wish you the best of luck!

PseudsPie