Codiene--> Morphine : Boron Trihalides

Guest · Sat Feb 05, 2005 6:21 pm

Boron Triahlides can yield up to 95% Morphine when codeine is solvated with chloroform.

Boron Tribromide is documented in Literature to yiled 98% Morphine, but a lessor known "little sister" Boron Trichloride,(which can be seasily produced from graphite, borax & Hcl Gas) produces also the desired effect.

Patent No.

Ref Text:

( Just a little taste of what is to come)
Once reference(s) are verified, this post will become active, and then graded.

fan of zwitterion · Sun Feb 06, 2005 2:24 pm

Succesfull demethylation has been accomplished through treating codeine with a 3 molar excess of Bcl3, in a suitable sovent[chloroform]

Chloroform Synth

http://frigo.ath.cx/chemistry/chloroform.html

A yield of 95% is usual.

Boron Trichloride is an etching gas, who manufacture is relativly simple, with numerous proceedures, and basic precursors.

Borax+Graphite+Cl(g)@450c--> produces relativly clean Bcl3

Boric Oxide +Nacl--->Bcl3@1000c--->again produces good Bcl3

These patents are availabe in the Patent Search Engine Area.

fan of zwit

java · Consumer

Tricyclic delta-opioid modulators
The invention is directed to delta opioid receptor modulators. More specifically, the invention relates to tricyclic ?-opioid modulators. Pharmaceutical and veterinary compositions and methods of treating mild to severe pain and various diseases using compounds of the invention are also described.

Agent: Philip S. Johnson Johnson & Johnson - New Brunswick, NJ, US
Inventors: John R. Carson, Ellen Codd, Christine M. Razler, Andrea Works, Mark McDonnell, James J. McNally
Class: 514297000 (USPTO), A61K031/473 (Intl Class)

..................read more here fresh patents

DrugPhreak · Working Bee

This is the only demethylation SWIDP hasn't tried. Also, has anyone tried HI on compounds similar to Hydrocodone? I can't remember their structure at the present time, but I have come across demethylations via very short HI reflux in the literature so I guess it doesn't rupture the carbon-nitrogen skeleton of these compounds, but wouldn't it affect their keto group? SWIDP has a decent amount of Hydro, but they are getting bored with it.

chrigu · Thu Apr 21, 2005 11:22 pm

I have a question. What are the possible dangers in trying to convert codeine to morphine or hydro- or oxycodone.
Like:

1. What are the dangers of the chemicals themselfes
2. How dangerous might the final product become, if so.mething is done wrong.

I read alot about that, but some say this and others that ...

Lets say I would like to make Hydrocodone from Codein ...

Would be cool to have a discussion about that because for home chemists like me without any chemical eductaion its kind of frightning and i could probably easily make bad mistakes.

Thanks

brain · Linguist Extraordinaire

when you pure it on TLC -its simple, can take in muscles or blod

Better pure opium, or smoke opium-its safer Smile

Guest · Wed May 18, 2005 5:59 am

Alot if not all the chemicals used in everyday synthesis are hazardous,

Especially BBr3, BCl3, chloroform,

A fumehood is generally recommended, but it is also wise to get the msds for each chemical, as you encounter it,

For example for Boron trichloride, type "boron trichloride msds" in google, to find out it's risks and safety precautions,

Syn

Aleister · Thu May 19, 2005 6:13 pm

this might not be the right place for this, but does anyone know a silmilar method for hydrocodone --> to hydromorphone? this would be very useful as hydrocodone is actually more easily available in some parts and the increase in potency and general euphoria is more dramatic than codiene to morphine. as always any help is appreciated Smile

Guest · Mon May 30, 2005 4:10 pm

Aleister,

If you go to our rhodium section, and have a look at the rhodium section,
There are numerous methods under opiates.

Here:
https://www.synthetikal.com/Rhodiums_pdfs/chemistry/index.html

syn

teragon · Mon Sep 19, 2005 9:23 am

A Rapid, High-Yield Conversion of Codeine to Morphine

Kenner C. Rice

Medicinal Chemistry Section, Laboratory of Chemistry, National Institute of Arthritis, Metabolic and Digestive Diseases,
National Institutes of Health, Bethesda, Maryland 20014. Received May 3, 1976

Brief treatment of codeine (1) in chloroform with boron tribromide has consistently given morphine (2) in 90-91% yield after a simple isolation procedure. The yield and simplicity of operation in this method are vastly superior to those previously reported for this transformation. Essentially all the codeine (1) produced today is prepared by the 0-methylation of morphine (2), the major alkaloid of the opium poppy, Papaver somniferum. Because of the possible shortage of licit opium1 and the diversion of morphine (2) to the illicit production of heroin (3), thebaine (4) which is elaborated (to the exclusion of morphine) by Papaver bracteatum is under serious consideration~,~ as a source of the widely used codeine (1).

Thus, a practical procedure for the conversion of 1 (for which a commercially feasible total synthesis may eventually be developed) to the oft-prescribed 2 would be highly desirable.

Pyridine hydrochloride at elevated temperature has been used by Rapoport4 for 0-demethylation of a I4C-labeled 1, by Gates5 in his total synthesis of (-)-2, and by Goto6 in the preparation of (+)-2. Practical difficulties were encountered in isolation and purification and yields were low (15-34%). More recently, Takeda et al. have utilized lithium diphenylphosphide to convert B/C trans-codeine(5)7 and B/C trans-isocodeine (6)8 to the corresponding morphines (7 and 8 ) in 61% yield (in the case of 8 ), but this procedure appears to lack practicability for large-scale preparation. In this paper, a solution to the long-standing problem of simple, efficient conversion of 1 to 2 is reported.

The method consists of addition of a chloroform solution of 1 to excess boron tribromide in chloroform with brief stirring, followed by quenching the reaction mixture with ice-ammonium hydroxide and simply filtering the 2 hydrate which results. The slightly off-white 2 hydrate which was obtained reproducibly9 in this manner (8748% yield) was chromatographically homogeneous on TLC and identical with an authentic sample. Work-up of the filtrate, as described below, afforded additional material (2-3%, total yield 90-91 %).

Although boron tribromide has been used to cleave methyl ethers of phenolslO previously, this high-yielding 0-demethylation of 1 seems remarkable in view of the labile nature4," of the oxide bridge and allylic alcohol functions, present in 1 and 2, toward strongly acidic reaction conditions.

Experimental Section
The NMR (Me₂ SO-d₆ ), ir (KBr), and mass spectra (70 eV) were determined using a Varian HR-220, Perkin-Elmer 257, or Hitachi Perkin-Elmer RMU6E spectrometer, respectively. Melting points were determined in open capillary tubes and are corrected. The composition of the reaction mixtures from various runs was monitored by TLC on silica gel 60 GF plates (Analtech, Inc.,Newark, Del.) which were developed with either CHCl₃ -MeOH (85:15) or CHCl₃ -MeOH-NH40H (80:18:2).

0-Demethylation of Codeine (1) to Morphine (2).
A solution of 2.99 g (10 mmol) of anhydrous l in 25 ml of CHCl₃ was added during 2 min to a well-stirred solution of 15 g (59.9 mmol) of BBr₃ in 175 ml of CHCl₃ maintained in the range 23-26"C. A 10-ml portion of CHCl₃ , which was used to rinse the addition funnel, was added to the reaction mixture and stirring was continued for 15 min at 23-26 "C. The reaction mixture which consisted of a suspension of white solid (in CHCl₃ ) was then poured into a well-stirred mixture of 80 g of ice and 20 ml of concentrated (28-30% NH₃ ) NH₄ OH. The two-phase system was kept at -5 to 0 "C for 0.5 h (continuous stirring) and filtered. The resulting crystalline material was washed thoroughly with small portions of cold CHCl₃ and H₂ 0 and dried to give 2.67 g (88.1%) of slightly off-white 2*H₂ 0, mp 252.5-254 "C dec (lit3 mp 254-256"C), which was homogeneous on TLC and identical (NMR, ir, MS, and TLC) with an authentic sample. The aqueous phase from the filtrate above was saturated with NaCl and extracted with 4 X 50 ml of CHCl₃ -EtOH (3:1). The combined extracts were evaporated and the residue (151 mg) was dissolved in 2 ml of H₂ O containing 1 drop of 37% HCl. After addition of 0.5 ml of CHCl₃ , the pH of the aqueous phase was adjusted to 9.0 (Hydrion paper) with concentrated NH₄ OH while stirring. The crystalline material which soon separated was filtered, washed with cold H₂ O and CHCl₃ , and then dried to give 86 mg (total yield 2.76 g, 91%) of 2*H₂ 0, mp 251-253 "C dec. Additional 2*H20 could be obtained by further extraction of the aqueous phase and (presumably) by chromatography of the foam (317 mg) which resulted from evaporation of the CHCl₃ phase from the original filtrate. This foam was shown by TLC (CHCl₃ -MeOH, 85:15) to contain 1, 2, and three unidentified by-products.

References and Notes
(1) Proceedings, AMA Symposium on Supplies of Opium for Medical Use, March 3-4, 1975.

(2) United Nations Secretariat, Division of Narcotic Drugs,
Scientific Research on Papaver bracteatum, No. 1, Report
of the Working Group on Papaver bracteatum, Geneva, Dec
12-14, 1972, Document No. ST/SOA/SER.J/l.

(3) J. W. Fairbairn, Planta Med., 29, 26 (1976).

(4) H. Rapoport, C. H. Lovell, and B. M. Tolbert, J. Am. Chem.
SOC., 73, 5900 (1951).
M. Gates and G. Tschudi, J. Am. Chem. SOC., 78, 1380
(1956).
K. Goto and 1. Yamamato, Proc. Jpn. Acad., 30,769 (1954)
[Chem. Abstr., 50, 1052h (1956)l.
M. Takeda and K. Kugita, Japanese Patent 29 153 [Chern.
Abstr., 75,141 030v (1971)l.

The entry "O-demethylation" indexed in Chem. Abstr., 8th Collect. Index, under 7,8- didehydro-4,5~-epoxy-3-methoxy-17-methy~orp~nan-6~-01 (B/C cis-codeine, natural codeine) actually refers to B/C trans-codeine and not to natural codeine.

H. Inoue, M. Takeda, and H. Kugita, Chem. Pharm. Bull.,
18, 1569 (1970) [Chem. Abstr., 73, 99071r (197011.

Using the procedure described here, the total isolated yields
of 2*H20 for three identical runs were 90-91%.
J. F. W. McOmie, M. L. Watts, and D. E. West, Tetrahedron,
24, 2289 (1968).

Significantly longer reaction times than reported here gave
increased amounts of two by-products and lower yields of
2.H20. Less satisfactory results were obtained with other
solvents or with boron trichloride. Reagent grade CHCl₃ (J. T. Baker) containing 0.75% EtOH was used throughout in this work.

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Taken from here: http://pubs.acs.org/cgi-bin/archive.cgi/jmcmar/1977/20/i01/pdf/jm00211a036.pdf

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