dickdastardly (Stranger)
11-04-01 05:26
No 232845
      reductive amination  Bookmark   

hello all just one question. I would like to know a relativly simple way to aminate L-PAC. A method for a beginner chemist that anyone could understand without the big chemical names.
 
 
 
 
    pimpmaster
(Newbee)
11-06-01 22:23
No 233872
      Re: reductive amination  Bookmark   

it should not be relatively hard to do a elecrolytic reduction of L-PAC to form ephedrine. if you look up
 Sugino, K.; Ohdo, K.; Elecrolytic Preparation of Ephedrine; Japan Patent 3308 (51') June 26; Chemical Abstracts (1953) 1510 e-f

you would see that this is a great otc synth.
the hardest thing about this procedure is getting L-PAC ,
 
 
 
 
    wirringun
(Stranger)
01-22-03 07:03
No 400360
      whilst on the subject of reductive animation...  Bookmark   



  whilst on the subject of reductive animation
does anybee have step by step method on reductive animation of deoxybenzoin with dimethylamine for a nonchemist swim has only experience with simple meth/methcat production also SWIM has completed codiene 2 morphine with success and is now looking for something more novel, lefetamine sounds like an interesting compound to synth
if there any bees that could help us out even with some refs would bee great.
would you end up with lefetamine if swim used triethylamine
if not would you end up with a lefetamine like analogue
if this sounds stupid please bee be easy on me as im not a chemist swim just like drugs and is willing to give things a go you only live once so swim makes the most of it.
cheers
 
 
 
 
    Rhodium
(Chief Bee)
01-22-03 16:24
No 400432
      Lefetamine  Bookmark   

For Lefetamine, ../rhodium/chemistry /redamin.titanium.html works ok, using deoxybenzoin/dimethylamine hydrochloride. Lefetamine is not that interesting though, and requires quarter gram dosages.
 
 
 
 
    Organikum
(Hive Addict)
01-22-03 19:14
No 400469
      L-PAC reductive alkylation  Bookmark   

Never seen this thread.
back on topic:
The reductive alkylation of L-PAC aka hydroxyphenylacetone aka 1-hydroxy-1-phenyl-2-propanone, the fermentation product of benzaldehyde and bakers yeast to yield ephedrine, is nearly identical to the reductive alkylation of P2P or MDP2P as described in literature here at the HIVE or on Rhodiums page.
The only difference I found in relating patents and articles was that a stochiometric amount of methylamine was used or only a slight overfold of 1.5 to 1 molar MeAm to L-PAC in opposite to P2P procedures where usually a huge overfold of minimum 3 to 1 is MeAm to P2P is applied. It seems the additional hydroxygroup makes the use of so much methylamine obsolete.
I myself couldnīt encounter any differences if 1,2x or 3x methylamine where used. This is only tried with Al/Hg style reactions, if this is valid for other reactions has to be evaluated. I donīt doubt this as references make no difference between the different methods.
The yields can be approximated in a 10% range as the feed of the reaction is the only rougly separated product of the fermentation and have been for me in a estimated 50%-65% range what is more as I expected as being new to this business.

What I did is, that I ran every part of the whole process (including the fermentation) several times without substrate to get used to the setup and howto. Helped me a lot.  A good book on labaratory practice for organic chemistry (like the famous "ORGANIKUM" smile) and the VOGELS III edition from Rhodiums page. Terbium is right.

Some references:
Patent CH156890 withAl/HG and collodial platinum
Patent GB360334 Al/Hg, and Pt in aqueous solution
Patent DE548495 identical
Patent US1956950 nearly the same

The most interesting is that it is claimed to be possible to do the reductive alkylation on the crude substrate gained by a simple etherreal extraction of the fermentation broth. I distilled this extract under diminished pressure so I canīt tell if this is as easy working as said. If yes it would eliminate the need for a strong vacuum source necessary for L-PAC distillation. This could strongly boost the popularity of the biosynth pathway.

Patent GB365535 with Ni and with Pd.
Patent US509309 some Ni catalyst alkylations including some with low temperature and /or high pressure.

It is stated that the reaction does not change the chirality of L-PAC. Basic conditions and high temperatures are known to racemise L-PAC fast, not at least therefor the the possibility to use the crude extract would be a charm.


We will see.
Anybody here worked with collodial Pt (hexachloroplatinic acid + gummi arabicum)?
ORG







Post 399486 (not existing)
 
 
 
 
    PolytheneSam
(Master Searcher)
01-23-03 12:36
No 400787
      In case anyone uses the search engine to find...  Bookmark   

In case anyone uses the search engine to find this.  Electrolytic is spelled correctly here.

Sugino, K.; Ohdo, K.; Electrolytic Preparation of Ephedrine; Japan Patent 3308 (51') June 26; Chemical Abstracts (1953) 1510 e-f

tongue

http://www.geocities.com/dritte123/PSPF.html
The hardest thing to explain is the obvious
 
 
 
 
    java
(Hive Bee)
02-03-03 23:25
No 404106
      Re: Patent references for reductive amination  Bookmark   

Org....... Very good references although it would be niece to have the one's in German translated.  You have been working too hard, I noticed that a couple of your patent references are wrong ,.......

DE 549309,  refers to a shoe machinery
US509309 , refers to an oiler

so, check your references and make the appropriate corrections.
 I hope you don't mind I referenced this post to  the continuing  saga at the biosynthesis- transformation thread in the serious chemistry forum.........java
 
 
 
 
    Organikum
(Hive Addict)
02-05-03 19:50
No 404775
      corrections  Bookmark   

Patent DE548459 a typo. You made also one JAVA look at your post!
It is the same as the english one (GB360334) - you have your translation already.
Patent US2509309 forgot the "2" sorry.

No I donīt have been working to hard I just was sloppy and didnīt check the post as usual - my fault. But so I got the feedback that actually somebody reads and cares what I post - this alone is worth the correction smile.

ORG


nothing special
 
 
 
 
    Rhodium
(Chief Bee)
02-05-03 21:08
No 404787
      Preparation of Ephedrine and Salts Thereof
(Rated as: excellent)
 Bookmark   

Patent US2509309
Preparation of Ephedrine and Salts Thereof

It is known to prepare ephedrine by reducing phenylacetylcarbinol in the presence of methylamine or salts thereof. The processes hitherto described give either the racemic mixture or the laevo-rotatory form of the compound.

It has been proposed to produce the laevorotatory form, which is the more active therapeutically, by means of chemical reduction by activated aluminium in a basic medium in the presence of methylamine, or by means of catalytic reduction in a basic medium in the presence of catalysts based on precious metals, such as colloidal platinum or palladium and in the presence of methylamine, or by means of catalytic reduction in a neutral medium by catalysts of the nickel group, in the presence of salts of methylamine.

On the other hand, it is stated in German patent specification No. 588,880 that catalytic hydrogenation of laevo-rotatory keto-alcohols with metals of the nickel group, in the presence of ammonia or of primary amines, gives racemic compounds.

It has now been found, however, that the rule stated in the said German patent specification is not so general as is claimed and that the nature of the final product depends upon the operating conditions. Thus the production of racemic ephedrine by hydrogenation of laevo-rotatory phenylacetylcarbinol, with catalysts of the nickel group in the presence of methylamine, is due to racemization of the starting substance. This racemization is greater in proportion as the temperature is higher and the duration of reaction more prolonged. It has now been found that a process of rapid hydrogenation at low temperature leads to the production of laevo-rotatory ephedrine with excellent yields.

According to the present invention, therefore, a process for the production of laevo-rotatory ephedrine and salts thereof comprises rapidly hydrogenating laevo-rotatory phenylacetylcarbinol at low temperature in the presence of methylamine and a nickel-containing catalyst.

Laevo-rotatory phenylacetylcarbinol can be prepared, for example, by the process described by C. Neuberg and J. Hirsch in Bioch. Z, 115, 282 (1921).

The catalysts employed preferably consist predominantly of nickel. It is possible, for example, to employ catalysts consisting of finely divided nickel which are obtained by dissolving in alkali the aluminium constituent of a nickel-aluminium alloy. It is also possible to start with nickel-aluminium alloys containing small quantities of other alloyed metals, such as chromium, molybdenum, cobalt, platinum and the like.

It is preferable to work under pressure in order to accelerate the reaction. A pressure of between 20 and 30 kg. per sq. cm. generally gives a suitable, speed of hydrogenation, while a higher pressure substantially improves the yield.

The reaction temperature must be chosen sufficiently low to prevent as far as possible racemization of the phenylacetylcarbinol. This racemisation is substantial even at 10°C., and it is therefore important to work at a temperature which is not too far in excess of this limit, and preferably at one which is lower, but it is desirable to cool to a temperature substantially below 0°C.

An advantage of the process according to the invention is that it gives high yields such as could previously only be obtained in the presence of catalyst consisting of precious metals. The nickel catalysts employed in the present process are easily obtained on an industrial scale.

The following examples, in which the parts are by weight, are given by way of illustration and are not intended to limit the invention.

Example I

530 parts of a solution of l-phenylacetylcarbinol in di-n-butyl ether, of which the phenylacetylcarbinol content (determined by titration with hydroxylamine hydrochloride -and calculating all the carbonyl compounds present as phenylacetylcarbinol) is 13.2%, that is, 70 parts of phenylacetylcarbinol, were hydrogenated in the presence of 256 parts of ethyl alcohol (95° G. L.), 229 parts of a 17.5% solution of methylamine in ethyl alcohol and 100 parts of Raney nickel, under a pressure of 30 kg. per sq. cm. at 0° C. The hydrogenation lasted 5.5 hours. The product was filtered, the alcohol was distilled off and the residue was diluted with benzene and extracted with dilute hydrochloric acid. 54.2 parts of crude ephedrine hydrochloride were obtained, from which 40.4 parts of pure 1-ephedrine hydrochloride (42.5% of the theoretical yield) were recovered after purification by known means.

Example II

35 parts of a solution of crude active phenylacetylcarbinol in di-n-butyl-ether, containing 10 parts of phenylacetylcarbinol, were hydrogenated in the presence of 4.4 parts of methylamine (employed in 24.45% alcoholic solution), 36 parts of methanol and 15 parts of platinised Raney nickel (containing 1 % platinum), under a pressure of 30 kg. per sq. cm. and at a temperature between 0°C. and 5°C. Duration of the hydrogenation was 2 hours and 25 minutes. After treatment as described in Example I, 9.35 parts of crude l-ephedrine hydrochloride were obtained, from which 6.3 parts of pure 1-ephedrine hydrochloride were recovered, representing a yield 47% of that theoretically possible.

Example III

244 parts of crude active phenylacetylcarbinol (obtained by fermentation and containing 100 g. of phenylacetylcarbinol as shown by titration with hydroxylamine hydrochloride), 41.5 parts of methylamine in solution in 560 parts of alcohol and 50 parts of chromium-activated nickel, prepared by the alkaline treatment of an. alloy of aluminium with 46% of nickel and 2.2% of chromium, were hydrogenated at 0°C. under a pressure of 25-30 kg. per sq. cm. in 7 hours. By treatment of the product of the reaction as hereinbefore described, and recrystallisation, 66.7 parts of pure 1-ephedrine hydrochloride were recovered. Melting point 216°C., [a]25D=-33.8°, yield 50.4% of that theoretically possible.

In addition, 17.4 parts of a mixture of the hydrochlorides of dl-ephedrine and of l-ephedrine, and 15.65 parts of l-pseudoephedrine hydrochloride were recovered.

References Cited

The following references are of record in the file of this patent:

United States Patents

Patent US1951302
Patent US1956950

Foreign Patents

Patent GB360334
Patent GB365535
Patent GB365540
 
 
 
 
    murder_1_2_3
(Stranger)
02-11-03 17:22
No 406698
      abuse potential of lefetamine  Bookmark   

according to this post Post 168705 (SPHYBRID: "Re: Non-fentanyl analgesic phenethylamine derivitive..", Serious Chemistry):, lefetamine was a drug of abuse in the 1950's.  From what I understand, the 50's were a great time to be doing drugs (benzedrine OTC).  If it were possible to take benzoin from a soapmaking supply store, reduce the alcohol using a birch of HI, and reductively aminate using dimethylamine (made from anhydrous ammonia and a methyl halide).  Then even if it only had the abuse potential of darvon, it would be worth it considering the cost.
   
 
 
 
 
    ylid
(Stranger)
04-08-03 18:05
No 424761
      More reductive amination refs
(Rated as: good read)
 Bookmark   

Here are a couple more references for reductive aminations:

Freudenberg, Schoeffel, Braun. J.Amer.Chem.Soc. (1932) 54:234.
  6g of l-phenylacetylcarbinol, 2g of palladium black and 30ml of a 25% alcoholic solution of methylamine were hydrogenated at pressures of 1 and of 20 atmospheres. In the first case 450ml of hydrogen was absorbed, which is 30% of the theoretical. The yield of ephedrine is rather independent of the pressure. After evaporation of the alcohol and methylamine under reduced pressure a syrupy mass was obtained which was taken up in 2ml of warm alcohol and 10ml of a dry ethereal solution of hydrochloric acid added. A dark brown oil separated which began to crystallize after washing twice with 10ml of absolute ether. The crystalline mass was then washed with 2ml of dry chloroform, the white crystals filtered, dissolved in 2ml of absolute alcohol and recrystallized by careful addition of absolute ether. The chloroform filtrate was made alkaline, extracted with ether for 72h,the ether extract acidified with dry hydrochloric acid, and the brown oil separating out was treated as above, yielding a second somewhat impure crystallization product which may contain a stereoisomer.

1. methylamine, ether, 0°C
2. Zn(BH4)2, -76°C, 1h
Jackson, Jacobs, Jayatilake, Matthews, Watson. Aust.J.Chem. (1990) 43:2045-2062.


...and some reductive aminations leading to the amphetamine (in German):

Patent DE587586  Pd, NH3, ethanol
Patent DE599433  Ni, NH4Cl, aqueous methanol
Patent DE588880  Ni, NH3, methanol

Who do you believe, me or your own eyes?
 
 
 
 
    Organikum
(Hive Addict)
05-11-03 22:25
No 432677
      The nickel catalysed reductions Rhodium  Bookmark   

presented via the patent are definitivly the last to use for us. Why? Because basic conditions let L-PAC razemise very fast and even decompose. Thats why the reductions with Ni are made under pressure (speed counts) with highly active Ni catalysts and at low temperatures. If you donīt have grip on industrial catalyst and equipment, donīt try to do this with Ni! The AL/Hg reductive alkylation is much preferable and more trustworthy/yielding in special if crude extract is used. Pt/black would be the first choice, but I believe itīs not worth the more effort and risks involved.

btw, anyone knows how to prepare a colloidal platimum suspension with gummi arabicum for example?

!
 
 
 
 
    Pimpo
(Stranger)
05-13-03 19:46
No 432967
      colloidal Pt
(Rated as: good read)
 Bookmark   

Translation of an excerpt from A. Gutbier et G. Hofmeier, J. f. prakt. Chemie [2] 71, 1905, p. 359:

Add to a diluted solution of PtCl2 (1:1000) about the same volume of gummi arabicum sol. (1:100) that has been heated to 95°C 3 hours before. Reduction is effected by adding a few drops of hydrazine hydrate sol. (1:2000). A rather stable, deep-brown to black sol is produced. Some of the water can be boiled of, the Pd can be completely dried in vacuo over conc. H2SO4. The dried solid product can completely be dissolved in warm water.

Hope it helps!wink