07-03-03 22:08
No 444411
Well it may not be novel but I certainly could not find any info on tfse or google that outlined this exact synthesis so if not novel enough I suppose it can be moved.
This is by no means the most efficient way to produce 2CH but aquiring the needed materials is much easier, and there are less opportunities for failure.
In Shulgins 2CI preparation he iodinates this: (N-(2-(2,5-dimethoxyphenyl)ethyl)phthala
As I said if the yeilds are similar to the 2CI yeilds reported from this reaction then this is not the most efficient route to 2CH, but it is VERY easy, and the precursers are not listed, and it does not take a lot of time. The 2CH may cost twice as much in the end but it is still dirt fucking cheap so wtf.
Just wanted to run this one by the pro's and and get some feedback. If this indeed sounds good then it is a wonderfully easy route to 2CH for us semi-newbies.
Any suggestions/warnings/flames/etc are welcome!
enlightenment through chemistry
(Stranger)
07-03-03 22:29
No 444414
Ok swid feels really stupid now. The reason there was no info when he utfse is because he spelled N-(2-(2,5-dimethoxyphenyl)ethyl)phthalim
But if anybody cares to answer the question feel free to anyway- so one would simply skip the iodination and proceed with the hydrazine hydrate to yeild 2CH? (again assuming that the molar ratios are adjusted properly?)
thanks
(Chief Bee)
07-04-03 08:23
No 444501
Yes, if you want to get 2C-H, then that's the way. But if you want to make 2C-B it's much better to brominate the N-phtalimido substituted 2C-H and hydrolyze afterwards. The phtalimido group will protect the nitrogen from reacting with the bromine.
(Stranger)
07-04-03 12:48
No 444539
Ok so since swid finally spelt the shit right he comes upon a post discussing the us of ethanolamine to hydrolyze. Swid is ever hesitant to go charging ahead without a layed out synthesis. Vibrating lights posted this workup in Post 404393 (Vibrating_Lights: "Will the ring of the phlactamide group also...", Chemistry Discourse)
15 gms(.048m) of N-(2-(2,5 Dimethoxyphenyl)ethyl)phthalimide is placed into 50ml MEOH with 1.02gms(.01m)KBr. Then the solution is stirred while .01m of Oxone(aq) is added. The solution is stirred till completeion. 2ml of (aq)Sodiumbisulfite is added then the rxn is basified with 25%NaOH and extracted 3x50ml of DCM. Dcm extracts are washed with Bisulfate again then once with NaHCO2. The Dcm is removed under vaccume to give N-(2-(4
bromo-2,5-Dimethoxyphenyl)ethyl)phthalim
Ok well this is a somewhat experimental workup. If the above indeed sounds good, what amount of ethanolamine would you bees suggest? Does the above sound good to more experienced bee's? Also does anybody that has tried making 2CH or halogenated phenethylamine using this route(with ethanolamine) have any suggestions for a less experienced bee?
Swids friend has few hundred g's of the N-(2-(2,5 Dimethoxyphenyl)ethyl)phthalimide coming next week. There is no turning back now without losing money out the ass. If swid can post a success with this project then ANYBODY who is semi competant will be assured success. Will post results, when results are known.
Many thanks
ApOstLe oF cHaoS
(Hive Addict)
07-04-03 18:32
No 444597
0.01m KBr is not eneough to brominate 0.048m of your precurser. also the mol weight of the brominated product will be much greater.
Eh? ma faut n'exist pas.
(Chief Bee)
07-04-03 19:11
No 444606
The patent listed by PolytheneSam at the top of that thread does indeed give suggested amounts of ethanolamine to use. I have posted the relevant parts of that patent in Post 444604 (Rhodium: "Cleavage of phthalimides to amines w/ Ethanolamine", Chemistry Discourse) - but to get all the details you should read the patent itself (link available in my post)
(Chief Bee)
07-05-03 15:07
No 444763
(Rated as: good read)
Ethanolamine has been used in phthalimide cleavage with yields from 82 to 90% for 2 h at 60°C in:
Cleavage of Phtalimide protection groups to primary amines
J. Med. Chem. 42(9), 1648-1660 (1999) (../rhodium/pdf /phtalimide.r
(Chief Bee)
12-08-03 04:37
No 475416
(Rated as: excellent)
An Exceptionally Mild Phtalimide Deprotection of Amines
J. O. Osby, M. G. Martin & B. Ganem
Tet. Lett. 25(20) 2093-96 (1984) (../rhodium /phtali
Summary
Phthalimides are converted to primary amines in an efficient, two-stage, one-flask operation using NaBH4/2-propanol, then acetic acid.
(Hive Bee)
12-08-03 05:42
No 475425
nice one, Rhodium! ;)
are there good ways to alkylate p-Dimethoxybenzene with N-(2-Bromoethyl)-phthalimide ala Friedel Craft in a relatively good yield?
i couldnt find good procedures using TFSE...
best wishes,
xicori
(Chief Bee)
12-08-03 07:12
No 475441
I have never seen any friedel-crafts reactions involving N-(2-Bromoethyl)-phthalimide - have you?
(Hive Bee)
12-08-03 07:47
No 475450
yes, i think to remember something like that...
wouldn´t it be possible with a very mild lewis acid as catalysator?
Edit:
Here is the post i´ve been searching for:
Post 414539 (ChemisTris: "Abstract", Novel Discourse)
But they use substituted phenoles as substrate. It may be possible with plain 1,4-Dimethoxybenzene too.
(Chief Bee)
12-08-03 11:06
No 475475
Well, take a look at the comments made in Post 414798 (Antoncho: "Some useful additions to the posted above....", Novel Discourse)
As a side note, .... It is obvious that the low yield in the 1st amino alkylation is due to the low reactivity of the starting phenol, not to its sensitivity..... Bad news.....(that is, we can't use fully methylated precursors).
I don't think you would be able to exceed 50% yield even by using 4-Methoxyphenol - but then again, why not alkylate hydroquinone with N-(2-Bromoethyl)-Phtalimide? Methylation followed by removal of the phtalimide group could very well give high yields of 2C-H.