(Hive Bee)
09-29-02 15:42
No 362086
(Rated as: excellent)
Snoopy went to the library, did some research for his master and came up with a list of refs. for the synthesis of several analgesics.
Anileridine
* J. Am. Chem. Soc. 78, 2342 (1956)
* U.S. Pat. 2,966,490
http://l2.espacenet.com/dips/bnsviewer?C
Bezitramide
* Belg. Pat. 633,495
* U.S. Pat. 3,196,157
http://l2.espacenet.com/dips/bnsviewer?C
Clonitazene
* Experientia 13, 400 (1957)
* U.S. Pat. 2,935,514
http://l2.espacenet.com/dips/bnsviewer?C
Desomorphine
* J. Amer. Chem. Soc. 55, 3863 (1933)
Dextromoramide
* J. Amer. Chem. Soc. 78, 3862 (1956)
* Brit. Pat. 822,055
http://l2.espacenet.com/espacenet/bnsvie
Diampromide
* J. Amer. Chem. Soc. 81, 1518 (1959)
* U.S. Pat. 2,944,081
http://l2.espacenet.com/dips/bnsviewer?C
Diethylthiambutene
* J. Chem. Soc. (pg)885 (1950)
* U.S. Pat. 2,561,899
http://l2.espacenet.com/dips/bnsviewer?C
Dimenoxadol
* Arch. Pharm. 288, 42 (1955)
* Pharm. Chem. J. 8, 189 (1974) (improved method)
Dimepheptanol
* J. Amer. Chem. Soc. 71, 57 (1949)
* J. Org. Chem. 17, 321 (1952)
* U.S. Pat. 2,565,592
http://l2.espacenet.com/dips/bnsviewer?C
* U.S. Pat. 2,668,814
http://l2.espacenet.com/dips/bnsviewer?C
* U.S. Pat. 2,649,445
http://l2.espacenet.com/dips/bnsviewer?C
Dioxaphetyl Butyrate
* J. Amer. Chem. Soc. 71, 57 (1949)
* J. Chem. Soc. (pg)500, (1949)
* U.S. Pat. 2,230,774
http://l2.espacenet.com/dips/bnsviewer?C
Diphenoxylate
* U.S. Pat. 2,898,340
http://l2.espacenet.com/dips/bnsviewer?C
Dipipanone
* J. Chem. Soc. (pg)2158, (1950)
* Brit. Pat. 654,975
http://l2.espacenet.com/espacenet/bnsvie
Snoopy is a good dog.
(PVC-Analog Taste-Tester)
09-29-02 19:15
No 362166
Dipipanone
Med. J. 12, 304-307 (1960) (variations using phenyllithium)
1-Methyl-4-Piperidinols Having Also A Hydrocarbon Substituent In The 4-Position
US2765315
US2498433
Love my country, fear my government.
(Hive Bee)
10-09-02 04:38
No 366439
Here's the link to the bezitramide Belgium patent. Those dudes from Janssen Pharmaceutics are really great.
http://l2.espacenet.com/espacenet/bnsvie
(Hive Bee)
10-09-02 04:48
No 366444
A friend told me they developed fentanyl. Can't confirm that, but I do know they like to play around with fentanyl analogues.
http://www.janssenpharmaceutica.be/index
Durogesic... nice
.WOMAN.ZIP: Great Shareware, but be careful of viruses...
(Hive Bee)
10-09-02 05:22
No 366456
Your friend is right, they invented fentanyl. They developped dextromoramide too.
http://www.janssenpharmaceutica.be/healt
(Hive Bee)
10-10-02 18:37
No 367102
BTW those are good finds.
The question here is about the patents that BWITi included.
In one of the methods orthophosphoric acid is employed to facilitate esterification or cyclization.
If one were using this method with more readilly available alphamethylstyrene, would there be a danger of MPTP formation.
It seems possible.
Another question if so would using the method employing only propionic acid, 1,3,5 hexahydro trimethyl triazine, and the olefin be advised instead.
And lastly does anyone understand the fundemental mechanism in this cyclization and esterification reaction going on in the above processes, or know where I can get information on that reaction mechanism.
It looks very tantilizing, although possibly dangerous.
(Hive Bee)
10-11-02 04:22
No 367277
US patent 2,765,315 seems to be the only safe way to make prodine, since a file on Rhodium's site says that it is unlikely that MPTP is formed as a side product.
../rhodium/pdf /prodine.pdf
(Hive Bee)
10-11-02 06:12
No 367291
Then those are the same methods I was speaking of and on the plus side very convenient processes.
but in the stricter sense I think they were actually saying that the dehydration product which in that case is 1,3-dimethyl-4-phenyltetrahydropiperidin
I could be wrong so I'll double check that.
Nope, you were right.
But parkinson's disease at age 30 is not a goal of mine so it is important to know for sure.
In the real world I live in alpha-ethylstyrene isn't commercially available so the methyl homlouge would be used, as it is more common in industry.
I see that they use the anhydride to bind water, this sounds important because, if water were present the ester could hydrolyse, and the resultant alcohol may be prone to dehydration.
(Hive Bee)
10-11-02 06:34
No 367295
Yes, you're right ... I was a little bit confused. The dehydratation product in the prodine synthesis would of course be 1,3-dimethyl-4-phenyl-1,2,3,6-tetrahydro
If I were you, I 'd stick to the described prodine synthesis. Alpha-ethyl styrene can be prepared by a Wittig reaction between a methyl halide and propiophenone.
(Hive Bee)
10-11-02 06:43
No 367296
That's just the little research tool I needed don't you just love named reactions.
Makes searching for the info a lot easier.
Thanks for that tip.
I don't know about you but a syringe full of smack has become one of my favorate past times as of lately, due to injuries and what not analgesics are a great companion.
One question it appears triphenylphosphine is crucial to this reaction, or in the wittig horner variation, triethylphosphite, these don't sound very otc, hit another brick wall.
But there may be a way around this?
Would it be possible to prepare this from ethanol and PCL3?
Or would a straight up exchange occur and give phosphorus acid and chloroethane?
Hmmm...
(Hive Bee)
10-11-02 08:53
No 367333
Triphenylphosphine is a very common lab reagent. I think PCl3 would be more suspicious to acquire, since that compound can be used for the synthesis of organophosphorus compounds (read: nerve gasses). It would certainly be overkill to try make it yourself (I mean the triphenylphosphine, not the sarin
).Check out the post of Rhodium and the other posts of this thread: Post 363416 (Rhodium: "Wittig gets my vote", Chemistry Discourse).
If you really want to do something exotic, you can use the Tebbe reagens.
(Hive Bee)
10-11-02 10:18
No 367355
A goldmine and yes that tebbe reagent looks pretty exotic.
The horner variation using triethyl phosphite is easier to do.
It gives a diethylphosphonate ethyl ester on reaction with alkyl chloride.
This reacts with ketones in the presence of bases to afford alkenes and a diethyl phosphonic acid.
(Chief Bee)
05-08-03 16:54
No 432214
(Rated as: excellent)
Wittig Synthesis of alpha-Ethylstyrene
-Ethylstyrene (2-phenyl-1-butene) was prepared by the Wittig reaction from ethyl phenyl ketone (propiophenone) and methyltriphenylphosphorane according to the following general procedure: To a solution of diisopropylamine (7.7 g, 76 mmol) in 100 mL of anhydrous tetrahydrofuran cooled at -30°C was added n-butyllithium (51 mL, 1.5 M in hexane, 76 mmol) dropwise under nitrogen. After 15 min, methyltriphenylphosphonium iodide (30.7 g, 76 mmol) was added under stirring.
The cold bath was removed, and the mixture was allowed to react 2 h at room temperature. The ketone (76 mmol) was added dropwise, and the mixture was allowed to react for a period of time ranging from 1 to 10 h depending on the structure of the ketone (follow the reaction on TLC).
After filtration and solvent evaporation, light petroleum was added and most of the crystallized triphenylphosphine oxide was removed by filtration. Chromatography of the resulting solution on silica gel (light petroleum as the eluent) and successive distillation gave
-ethylstyrene more than 99.9% pure by GLC analysis. -Ethylstyrene (2-phenyl-1-butene): 68%; bp15 64-64.5°C; 1H NMR
7.50-7.15 (m, 5 H), 5.28 (m, 1 H), 5.07 (m, 1 H), 2.52 (b q, J = 7.7 Hz, 2 H), 1.10 (t, J = 7.7 Hz, 3 H); MS m/z 132 (M+, 67), 117 (100), 103 (9), 91 (33), 77 (16).
Reference:
J. Org. Chem., Vol. 56(15), 4772-4778 (1991) (../rhodium/pdf /alpha-ethyls
(Hive Addict)
05-09-03 10:35
No 432345
but the horner adaptation would be easier because you have choices of different more commonly available bases, the reaction is more forgiving, and the by-products are water soluble so you can avoid having to use chromatography to isolate the end product instead you can get the product by solvent extraction.
I looked into the availability of propiophenone and it's only documented use is a pharmacuetical intermediate, this makes aqusition of this stuff very hard, do you have any suggestions?
(Chief Bee)
05-09-03 11:19
No 432352
Propiophenone is a common chemical in organic synthesis, it's available everywhere except OTC.
(Stranger)
05-15-03 09:46
No 433363
They don't seem to be much fun, but anyway...
"Struktur – Wirkungsbeziehungen an Bicyclo[3.3.1]nonan-9-on-1,5-diestern und anderen k-selektiven Opioiden"
http://webdoc.gwdg.de/ebook/w/2002/pub/b
(Moderator)
05-15-03 12:30
No 433387
Not much fun? Post 433158 (ChemisTris: "Salvinorin A (journal article)", General Discourse)
(Stranger)
05-16-03 13:18
No 433601
I didn't know about that!
I wonder why the German paper states k-agonists to be of limited therapeutic use, because they cause sedation, dysphoria and diuresis (page 8). No mention of hallucinations or psychosis or something. Kind of confusing.
(PVC-Analog Taste-Tester)
05-17-03 21:33
No 433833
If you're bent on producing a prodine-like compound, then I advise you to take a close look at that Wittig synthesis of alpha-ethylstyrene that Rhodium posted, because it's hard to find someone that'll track down and sell a-ethylstyrene. Maybe other prodine-analogue precursors are easier to get, but I can only speak of the above precursor.. Which precursor would be the easiest to obtain? Availability of prodine-analogue precursors? Peace!
Love my country, fear my government.
(Hive Bee)
10-22-03 15:26
No 466183
(Rated as: good read)
Buprenorphine
Patent US3433791
Patent DE1620206
Pentazocine
Patent BE611000
JMC (1964) vol 7 p 123
Pethidine
Patent US2167351
Patent DE679281
Methadone
Patent DE865314
Patent DE870700
Patent DE890506
Justus Liebigs Ann. Chem. (1948) vol 561 p 52 - Post 483448 (Rhodium: "Bockmühl's Original Methadone Synthesis", Methods Discourse)
racemate resolution:
Patent US2644010
Patent US2983757
The Narcs
(Hive Bee)
10-23-03 15:38
No 466410
(Rated as: good read)
dextromethorphan
Patent US2676177
Helv Acta (1951) vol 34 p 2211
dextromoramide
Patent BE544757
Patent DE1117126
nor-methadone
Patent DE865314
Patent DE870700
Justus Liebigs Ann Chem (1948) vol 561 p 52 - Post 483448 (Rhodium: "Bockmühl's Original Methadone Synthesis", Methods Discourse)