ab5000
Harmless
Posts: 5
Registered: 25-8-2011
Member Is Offline
Mood: No Mood
|
|
8-Methoxycaffeine synthesis
Hello, this is my first message. I'm a 15 years old italian boy who likes experimenting with chemistry. I recently started doing some organic
chemistry. I got some pure caffeine and i wondered if i could attach a methoxy group at the 8- position.
All I could find about this is that the first step is chlorination of caffeine to give 8-chlorocaffeine. This is done bubbling chlorine gas in a
caffeine solution in an inert solvent. Then 8-methoxycaffeine is obtained by substituting the chlorine atom with a methoxy group using NaOH in MeOH. I
bubbled Cl2 from bleach/hcl in a DCM solution of caffeine. I got 0.66g of supposedly 8-chlorocaffeine from 0.5g caffeine, so I guess it isn't very
pure... it has a bleach odour. I'm trying to purify it now. Unfortunately i don't have apparatus to check the melting point.
I guess i managed to make 8-chlorocaffeine, but now how do I insert the methoxy group? I can't find enought info on methoxylation with NaOH in MeOH. I
got two references, one about the chlorination and one about the methoxylation which could give me some more informations, but the articles are in
german and i can't understand them.
Reference on 8-chlorocaffeine: Fischer and Reese, Justus Liebig Annalen der Chemie, 221, 336 (1883) (Article name "Ueber Caffeïn, Xanthin und
Guanin")
Reference on 8-methoxycaffeine: Fischer, Berichte der deutschen chemischen Gesellschaft, 17, 1785 (1884) (Article name "Ueber die Harnsäure. II")
I actually have access only to the second one (I have limited access to Wiley which has got the first one but i can't access that article). But anyway
i can't understand them.
Does somebody know how to methoxylate 8-chlorocaffeine? Maybe someone who knows german?
Thanks,
Andrea.
|
|
|
drago57
Harmless
Posts: 16
Registered: 13-8-2011
Member Is Offline
Mood: No Mood
|
|
That chlorination should work well enough. Recrystallise from DCM/hexane according to "Water Science and Technology (1982), 14(6-7), 629-40"
For the 8-MeO:
Ralph C. Huston, Winston F. Allen, J. Am. Chem. Soc., 1934, 56 (6), pp 1356–1358
Add 8-chlorocaffeine to 1.5eq sodium methoxide in enough methanol to solubilise the caffeine whilst hot (~5 mL MeOH per g of caffeine). Reflux for 45
minutes. Filter off NaCl whilst hot. Product should crystallise out upon cooling.
I've had a look at various references. Older ones all seem to refer to that Annalen der Chemie reference for making 8-chlorocaffeine. Newer ones don't
mention it at all since you can buy the stuff now!
To make the methoxy, everyone suggests dissolving Na metal in MeOH then adding the 8-chlorocaffeine. It's a better way of doing it but, if you can't
get hold of Na metal, I should think doing it with NaOH in refluxing MeOH would work if you add some sieves or something to dry the NaOMe solution
before adding the 8-chlorocaffeine.
EDIT:
I would assume refluxing your 8-chlorocaffeine with NaOH in THF or something similar would give you 8-hydroxycaffeine. Methylating that would be
simple enough and get you to 8-MeO. Depends what chemicals you can get hold of.
[Edited on 26-8-2011 by drago57]
|
|
|
MeSynth
Hazard to Others
Posts: 107
Registered: 29-7-2011
Member Is Offline
Mood: http://www.youtube.com/watch?v=5ZltqlVuDIo
|
|
I just read about this and it sounds like this is a bad substance to play around with. It breaks dna strands? Why would you want this compound?
|
|
|
bbartlog
International Hazard
Posts: 1139
Registered: 27-8-2009
Location: Unmoored in time
Member Is Offline
Mood: No Mood
|
|
Orange juice breaks DNA strands. As long as he doesn't snort the stuff I don't see the problem (and I didn't see him saying anything about 'playing
around with it'). Chemistry involves a lot of substances more dangerous than a non-volatile solid like this.
|
|
|
ab5000
Harmless
Posts: 5
Registered: 25-8-2011
Member Is Offline
Mood: No Mood
|
|
First, i don't want to take the stuff. I can't find enought about the toxicity. Looks like it's more potent than caffeine so it would be even more
risky. I just want to make it because i have the reagents needed and it's an interesting but not too complicated synthesis.
Draco57, thanks for the info  That caffeine derivatives article is interesting.
In fact i don't have a condenser to reflux the MeOH (i didn't need it when i was experimenting with inorganic chem, and i just started doing organic
chem). There's a chemistry shop in my town, i'll check the prices here but i guess i can have a RB flask + liebig condenser for 30-40€. Which i
don't have atm... oh well, i'll make condenser myself, i just need to choose a material compatible with methanol.
I'm thinking of electrolysing molten NaOH to get Na and then using it to make sodium methoxide. Otherwise, what drying agents could be used when
refluxing NaOH and MeOH (no molecular sieves)?
EDIT: I looked at the two-step methoxylation (chlorocaffeine + NaOH -> hydroxycaffeine, hydroxycaffeine + methylating agent -> methoxycaffeine).
That would be simpler than making sodium methoxide with sodium (unless i find a good way to dry NaOH/MeOH without molecular sieves). The methylating
agents i can synth are 2,2-dimethoxypropane from acetone and methanol (umh... catalyst?), Dimethyl sulfate from methanol and sulfuric acid and Methyl
iodide from KI and methanol (with h2so4 as catalyst). Dimethyl sulfate is the simplest but it's too toxic so i'm a bit afraid of using it. Which one
would work best?
[Edited on 27-8-2011 by ab5000]
|
|
|
MeSynth
Hazard to Others
Posts: 107
Registered: 29-7-2011
Member Is Offline
Mood: http://www.youtube.com/watch?v=5ZltqlVuDIo
|
|
I may have misunderstood the article I read. DNA strands breaking just sounds plain bad but bart up there said that Orange Juice breaks dna strands...
Why in my delusional state I had the idea of using this to damage plant dna while in the seed producing stage. Perhaps this is how they got the
marijuana plant called lowryder.
|
|
|
drago57
Harmless
Posts: 16
Registered: 13-8-2011
Member Is Offline
Mood: No Mood
|
|
Quote: Originally posted by ab5000  |
Draco57, thanks for the info That caffeine derivatives article is interesting.
In fact i don't have a condenser to reflux the MeOH (i didn't need it when i was experimenting with inorganic chem, and i just started doing organic
chem). There's a chemistry shop in my town, i'll check the prices here but i guess i can have a RB flask + liebig condenser for 30-40€. Which i
don't have atm... oh well, i'll make condenser myself, i just need to choose a material compatible with methanol.
|
If it's not too expensive I'd suggest getting yourself a decent condenser; you're not likely to get very far without one. Half the fun of organic
chemistry is the glassware-porn after all!
| Quote: Originally posted by ab5000 |
I'm thinking of electrolysing molten NaOH to get Na and then using it to make sodium methoxide. Otherwise, what drying agents could be used when
refluxing NaOH and MeOH (no molecular sieves)?
|
Not too sure what to use for drying NaOH/MeOH if you don't have sieves.
You can electrolyse molten NaOH or indeed molten NaCl. Alternatively reduce NaOH with Mg powder al la this video:
http://www.youtube.com/watch?v=908rjHQ5mmc not sure about the quality of the Na you'd get from that though - I suspect it might be more
appropriate for party tricks than synthesis.
You could get the Li from batteries, use that to make LiOMe and react that with your chlorocaffeine.
If you can get hold of NaH or CaH2 and react them with MeOH, you'd avoid having to dry your solutions and they're substantially easier to handle than
Na or Li metals.
| Quote: Originally posted by ab5000 |
EDIT: I looked at the two-step methoxylation (chlorocaffeine + NaOH -> hydroxycaffeine, hydroxycaffeine + methylating agent -> methoxycaffeine).
That would be simpler than making sodium methoxide with sodium (unless i find a good way to dry NaOH/MeOH without molecular sieves). The methylating
agents i can synth are 2,2-dimethoxypropane from acetone and methanol (umh... catalyst?), Dimethyl sulfate from methanol and sulfuric acid and Methyl
iodide from KI and methanol (with h2so4 as catalyst). Dimethyl sulfate is the simplest but it's too toxic so i'm a bit afraid of using it. Which one
would work best?
[Edited on 27-8-2011 by ab5000] |
Little bit of acid to catalyse the 2,2-dimethoxypropane synthesis.
Specifically which of those would work best for this reaction? Don't know, never tried it! If in doubt, MeI is always a good, solid, reliable place to
start.
[Edited on 28-8-2011 by drago57]
|
|
|
ThatchemistKid
Hazard to Others
Posts: 132
Registered: 2-6-2010
Member Is Offline
|
|
I am not sure the lithium methoxide would worth the same the lithium alkoxides are generally less nucleophilic I believe.
|
|
|
Nicodem
Super Moderator
Posts: 4230
Registered: 28-12-2004
Member Is Offline
Mood: No Mood
|
|
I'm confident you can use just NaOH dissolved in methanol. It is a simple nucleophilic aromatic substitution, so a little water in your sodium
methoxide solution should not hurt. Besides the prevalent methoxide, you can expect the presence of some hydroxide in methanolic NaOH and this would
compete to give some 1,3,7-trimethyluric acid (the prevalent tautomer of 8-hydroxycaffeine), but this would only form as an impurity that should be
removable by recrystallization. I don't think 8-methoxycaffeine could be effectively made by 1,3,7-trimethyluric acid methylation, because any
alkylation would likely give the N-methyl product as the major one.
Check also the two halogenation references cited in this thread.
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
|
|
|
ab5000
Harmless
Posts: 5
Registered: 25-8-2011
Member Is Offline
Mood: No Mood
|
|
Well, since i can't access sodium and molecular sieves, i'll give it a try tomorrow with NaOH + MeOH. Thanks Nicodem.
About the sodium production: can't NaOH be reduced with Li instead of Mg?
|
|
|
Nicodem
Super Moderator
Posts: 4230
Registered: 28-12-2004
Member Is Offline
Mood: No Mood
|
|
You would better recrystallize your putative 8-chlorocaffeine and measure the mp. You should not just believe you have pure enough and the right
product without any analysis whatsoever. The results of the subsequent reaction could be misinterpreted if you don't approach scientifically.
You don't need any special apparatus to take the mp. You take one small test tube into which a thermometer barely fits, fill the bottom with enough
sample to compress it with the thermometer bulb, immerse this in an oil bath and slowly heat up (meaning slower than 1 K/min). You take the
temperature of the beginning and the end of the phase transition (the mp interval). This method is not accurate, but will do for your needs.
A better way is to get yourself a glass tube of approximately 1 mm diameter. You cut it in about 5 cm long pieces and melt one end to form a tiny test
tube. This is filled with the sample and used in a home made Thiele apparatus (meaning an oil bath equipped with a thermometer and a stirrer - just
improvise). Filling the tube with the sample is done by taking in the sample on the open end and dropping it trough half a meter long tube to fall on
the closed end. The sample self compress at the closed end by the speed acquired. These are old and obvious techniques, but I'm unsure if they are
still being thought to younger generations, so I reiterate them.
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
|
|
|
gutter_ca
Hazard to Others
Posts: 173
Registered: 7-6-2010
Location: California
Member Is Offline
Mood: Bored at work!
|
|
| Quote: Originally posted by MeSynth | | I may have misunderstood the article I read. DNA strands breaking just sounds plain bad but bart up there said that Orange Juice breaks dna strands...
Why in my delusional state I had the idea of using this to damage plant dna while in the seed producing stage. Perhaps this is how they got the
marijuana plant called lowryder. |
Nope.
Lowryder is C. Ruderalis, Siberian ganja. Flowers under any light conditions due to environment.
|
|
|
![[*]](images/xpblue/default_icon.gif){kind=icon}
