Guys, please check this out:
From N-acetylanthranilic Acid [5]
This method is similar to Klosa's first synthesis of methaqualone, the difference being that this one uses POCl3 instead of PCl5, and uses ready made N-acetylanthranilic acid. By performing the reaction in toluene, the yield is very good. In spite of this, the method is best left alone, as the POCl3 will release lots of HCl gas during decomposition.
o-Toluidine (10 grams) is mixed with a solution of N-acetylanthranilic acid (20 grams) in toluene (30 grams) in a vessel equipped with a stirrer and means of cooling. A solution of phosphorus oxychloride (10 grams) in toluene (30 grams) is added dropwise with stirring and then the temperature is raised to the boiling point for two hours with further stirring. After cooling, the precipitate so formed is filtered off, dried and dissolved in boiling dilute HCl. On cooling and making alkaline with NaOH, a viscous oil separates which crystallises after a few hours. The crystals are collected the next day and purified by recrystallisation from alcohol to yield about 80% of the theoretical quantity of methaqualone freebase (m.p. 114-115°C). The salts my be obtained by the addition of the appropriate acids to the base formed above.
I have a major problem with that quoted synth which I can't clarify because I have no library access. This synth is calling for the use of two moles of acetylanthranilic acid per mole of ortho-toluidine---WHY???
The stoichiometry of the reaction is a simple 1:1 mole ratio, why do they call for the use of two moles of anthranilic acid ester? It doesn't make sense to me, especially considering I have seen synths using this exact coupling procedure with other substituted anilines and anthranillic acid derivatives- only a 1:1 mole ratio was quoted. Does anyone have any idea on what the deal is here? Personally, I think its an error.
n-acetyl anthranilic mol 179
o-toluidine 107
(20/179) / (10/107) = 1.195 molar excess anthranilic?
No Blondie, you are right.
o-toluidine, C7H9N, MM = 107.155 g/mol
n-acetyl anthranilic acid, C9H9NO3, MM = 179,175 g/mol
So they use 0.0933 mol o-toluidine and 0.1116 mol n-acetyl anthranilic acid. That 's a 19.6 mol % excess of n-acetyl anthranilic acid.
why do they call for the use of two moles of anthranilic acid ester?
I am confused, isn't it the acetyl amide of anthranilic acid?
I looked up the molecular weight of N-acetylanthranilic acid in a VERY old CRC and it said it was 119g/mol. I should have calculated the MW myself before posting this and wasting everyones time. Anyway, thanks for pointing that out blondie-- and Cyrax, yes you are correct; the anthranillic acid derivative is indeed the amide and not the ester. Boy, do I feel like a dumbass :-[ :-[ :-[ .
The funny thing is I wasn't even fucked up when I posted that ::)
Do you people look up molecular weights of such small organics? I usually picture the molecule in my head, count the atoms and add the atomic weights together on my trusty calculator, it's usually faster. I look up chemical data in the Merck Index paper version faster than I do it using the CD version though.
Look at these intellectually crippled youngins. Back when this old cranky chemist went to school there was no such thing as compooters and calculators had the size of a typewriter! Everyone was guesstimating shit with slide rules, and most people had stuff like the more important values of sin X remembered!
That's why I calculate molar weights in my head after picturing the molecule. If the molecule isn't too familiar I write down the structure, count the atoms and add the weights. Ít's faster that way than having to search for that shitty calculator thing.
I'm not fat just horizontally disproportionate.
With my ADD, I don't have place for a molecular structure as well as an addition scrapboard in my short term memory. If I start doing the calculation in my head, it is like the molecular structure is "overwritten" by the numerical data - if I go back to concentrate on the structure so that it doesn't fade, the numbers I have in my head gets all jumbled up instead.
I usually have an easier time finding my big calculator than a tiny working pencil though, as you would understand if you saw what my place looked like. Analog data storage is so last century anyway ;)
Ritter, don't worry. I feel like a dumbass too. Check out post
Post 365504 (https://www.thevespiary.org/talk/index.php?topic=12875.msg36550400#msg36550400)
(Cyrax: "Good work", Tryptamine Chemistry). I completely fucked up. And ... it weren't the drugs ...
Indeed Osmium, the young intellectually crippled ... :) (but I guess sometimes, we all can have a bad day).
glad to be able to help out - just send that unused mole of anthranilic that youve now got this way and we'll call it square. ;D :)
7g Anthranilic Acid, 5ml o-Toluidine and 4 ml glacial acetic acid was mixed in a round-bottomed flask. To this mixture was slowly added 40-50 grams of polyphosphoric acid, and the mixture was heated during 20-30 minutes to 140-160°C. After this, the mixture was heated to 180°C for 10 minutes, then cooled and poured in 150-200ml water, and neutralized with 20% Na2CO3 solution. Methanol was added until a lasting turbidity became present in the solution, and after one hour, the free base Methaqualone precipitated, mp 111-113°C, and was once more recrystallized in this fashion, mp 113-115°C. Yield 55%.
Well, you have a yield stated, that usually means someone performed the synthesis and calculated the yield. Where did you find it?
https://www.thevespiary.org/rhodium/Rhodium/chemistry/quaalude.html (https://www.thevespiary.org/rhodium/Rhodium/chemistry/quaalude.html)
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That method is taken from an article by the professional german chemist J. Klosa, from the journal J. Prakt. Chem. 20, 283-4 (1963) - so you can be sure that the works much better than half of the stuff posted here...