Author Topic: 4-Methylaminorex Synth w/o CNBr  (Read 8165 times)

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PoohBear4Ever

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Re: 4-Methylaminorex Synth w/o CNBr
« Reply #40 on: October 12, 2001, 07:00:00 PM »
Yep, Mr.Smith, I got the same synthesis, but it appears only 4-6g yield from 500ml of urine. 

Wonder if the Professors used to skip this experiment...

PB

goiterjoe

  • Guest
Re: 4-Methylaminorex Synth w/o CNBr
« Reply #41 on: October 12, 2001, 10:26:00 PM »
If I'm not mistaken, all PPA containing products got pulled off of US shelves about a year ago due to FDA claims of "overdoses" - like 14 over a 30 year span.  and considering it was in slim fast, I imagine it got abused pretty heavily.  your best bet would probably be to extract it out of the ephedra pills containing multiple alkaloids.

Sed quis custodiet ipsos custodes?

IudexK2

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Re: 4-Methylaminorex Synth w/o CNBr
« Reply #42 on: October 12, 2001, 10:32:00 PM »
I am not in the US, and besides, there are always international pharmacies!  ;D

Mr_Smith

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Re: 4-Methylaminorex Synth w/o CNBr
« Reply #43 on: October 13, 2001, 09:57:00 PM »
"Yep, Mr.Smith, I got the same synthesis, but it appears only 4-6g yield from 500ml of urine."

Stockpile..... stockpile.....  ::)

"Daddy, what's it going to be like in the year 2000?"
8)

uemura

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Re: 4-Methylaminorex Synth w/o CNBr
« Reply #44 on: October 15, 2001, 10:11:00 PM »
To the Chief Bee. You wanted to know: Uemura: Is that from the 1850's?
Ahh, it's more 1950, some kind of post WW-II chemistry ;D

psychokitty

  • Guest
Re: 4-Methylaminorex Synth w/o CNBr
« Reply #45 on: October 17, 2001, 05:46:00 AM »
Rhodium:

I don't understand why everyone is afraid of cyanogen bromide.  Especially when it can be made in situ from bromine, methanol, and sodium cyanide.  All of these items are OTC except the bromine which can be made EASILY by reacting sodium bromide and OXONE in water.  The bromine forms immediately without the need for external heat.  Since it distills at about 65 deg C or so, it can be distilled at atmospheric pressure directly into the receiving flask (immersed in ice) containing the correct amount of methanol.  As for the exit to the vacuum adapter one could lead a tube--with one of those fish aquarium anti-suck-back valves inbetween--directly into a flask containing aqueous sodium carbonate (bicarbonate causes too much foaming) to aborb any gaseous bromine that might escape.  And voila!  A methanol solution of bromine.

Next, one would dissolve the correct amount of sodium cyanide in methanol and add it via addition funnel dropwise to the ice-cold methanol-bromine solution contained in a flask (attached to a reflux condenser and sitting in an ice bath).  Proceed from then on out as per usual.

SWIM once tried this under crude conditions in a open beaker with a blowing fan as a ventillation source.  As the sodium cyanide hit the methanol-bromine solution, the bromine color faded and then eventually, it disappeared.  Occassionally, there was a faint mist that would form above the methanol solution, but only for a minute.

As for the precursor amino alcohols, they are easily formed from the intermediate nitro alcohols. 

According to one paper that I have, Nitro alcohols are formed by condensation of a benzaldehyde and a nitro alkane in aqueous alcoholic sodium hydroxide solution.  The nitro alcohols are then reduced in a facile reaction using Zn and aqueous sulfuric acid.  Yields are good for one experiment which details the synthesis of phenylpropanolamine.  Don't remember the yields but I believe it is somewhere around 80%. Furthermore, I have a reference (CA) wherein MD-phenylpropanolamine is synthesized via the same route as above in over 75% yield.

The cool thing about all this is that phenylethanolamine could EASILY be synthesized using benzaldehyde and nitromethane and Zn and aqueous H2SO4 as the reducing mixture.  This is the precursor to aminorex itself, and using it in the cyanogen bromide reaction, according to Poos US patent, would provide a high yield of aminorex.

If piperonal (formed by dichromate oxidation of isosafrole in about 55-65% yield) were used in place of benzaldehyde in the above reaction, one would get as the final product the amino alcohol which could then be reacted with cyanogen bromide to form the MD analogue to aminorex.

--PK

Rhodium

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Re: 4-Methylaminorex Synth w/o CNBr
« Reply #46 on: October 17, 2001, 05:48:00 AM »
Psychokitty: Give me all those refs you are talking about - seems highly interesting!

psychokitty

  • Guest
Re: 4-Methylaminorex Synth w/o CNBr
« Reply #47 on: October 17, 2001, 06:41:00 AM »
The only one I have handy right now is the synthesis of piperonal:

Synthesis of heliotropin from isosafrole by the dichromate method. Koh Kimhok and Roh Siante.  Formosan Sci. 5, 36-8 (1951)(in English).--Isosafrole (50g) with a mixt. of 80 g of K2CrO7, 130 g H2SO4, 4 drops of HNO3, and 800 ml of H2O at 50 deg C yields 66.9% heliotropin (piperonal). 

I have other CA reference and one US patent that basically mirror the above reaction.  I'll post those along with all the other references you requested.

BTW, you've got mail.

--PK

foxy2

  • Guest
Re: 4-Methylaminorex Synth w/o CNBr
« Reply #48 on: October 17, 2001, 07:26:00 AM »
Or this way.

High Selectivity in the Oxidation of Mandelic Acid Derivatives and in O-Methylation of Protocatechualdehyde: New Processes for Synthesis of Vanillin, iso-Vanillin, and Heliotropin.     Bjorsvik, Hans-Rene; Liguori, Lucia; Minisci, Francesco.   
Org. Process Res. Dev.  (2000),  4(6),  534-543. 
CODEN: OPRDFK  ISSN: 1083-6160. 

Abstract
New synthetic procedures for vanillin, iso-vanillin, heliotropin, and protocatechualdehyde starting from catechol are described.  The utilization of statistical exptl. design and multivariate modeling and the mechanistic interpretation of the acid and base catalysis in the condensation of catechol derivs. with glyoxylic acid and in the regiocontrolled methylation of protocatechualdehyde and of the Cu(II) salt catalysis in the oxidative decarboxylation of mandelic acid derivs. have allowed the development of new highly selective processes. 

Methylenation of pyrocatechols.    
Bonthrone, W.; Cornforth, John W.      
J. Chem. Soc. C  (1969),   (9),  1202-4.     

Abstract
High yields in the methylenation of pyrocatechols by CH2Cl2 are obtained by using a polar aprotic solvent for reaction and maintaining low concns. of the pyrocatechol dianion. 



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foxy2

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Re: 4-Methylaminorex Synth w/o CNBr
« Reply #49 on: October 17, 2001, 07:29:00 AM »
Check this out!!

United States Patent  4,190,583 
Bauer ,   et al.  February 26, 1980 
--------------------------------------------------------------------------------
Process for the preparation of 3,4-methylenedioxymandelic acid




The course of the reaction according to the invention is surprising, since it is known, from Gazz. Chim. Ital. 96 (4), 465 (1966), that the reaction of glyoxylic acid alkyl esters with alkyl-substituted aromatic compounds in a strongly acid medium indeed leads to mandelic acid derivatives, but with alkoxy-substituted aromatic compounds, such as veratrole, gives only diphenylacetic acid derivatives.

3,4-Methylenedioxymandelic acid is, inter alia, an important starting material for the preparation of the valuable aroma substance piperonal. Piperonal is prepared from 3,4-methylenedioxymandelic acid by oxidative decarboxylation (see Current Sci. (India) 27, 22 (1958)).

EXAMPLE 1

46 g (0.5 mol) of glyoxylic acid monohdrate, 61 g (0.5 mol) of 1,2-methylenedioxybenzene and 200 g (1.74 mols) of 85% strength phosphoric acid are brought together at 25.degree. C. and the mixture is stirred for 5 hours. The temperature thereby rises to 38.degree. C. In order to preserve the stirrability of the reaction mixture, 40 ml of water are added. After 5 hours, a further 160 ml of water are added, the mixture is further stirred for 10 minutes and the crystals obtained are filtered off. The crystals are dissolved in 650 ml of water and 100 ml of toluene at 85.degree. C. and the phases are separated. After washing the toluene phase several times with 20% strength sodium hydroxide solution and distilling off the solvent, 7.1 g of 1,2-methylenedioxybenzene are recovered. After cooling the aqueous phase to room temperature, 57.6 g of 3,4-methylenedioxymandelic acid crystallise out, and after concentrating the mother liquor a further 8.3 g of 3,4-methylenedioxymandelic acid crystallise out. The yield of 3,4-methylenedioxymandelic acid is 76.1% of theory, relative to 1,2-methylenedioxybenzene reacted. It can be increased further by working up the strongly acid filtrate of the reaction mixture. However, since the working up is very expensive, it is more advantageous to concentrate the acid filtrate and re-use it.

EXAMPLE 2

200 g of 90% strength sulphuric acid are added dropwise to a mixture of 148 g (1 mol) of 50% strength aqueous glyoxylic acid and 122 g (1 mol) of 1,2-methylenedioxybenzene at 5.degree. C. in the course of 40 minutes, whilst stirring. After stirring the mixture for a further 6 hours, 500 g of ice-water are added and the mixture is stirred for a further 10 minutes. The crystals which have precipitated are filtered off and worked up as in Example 1. 6.1 g of 1,2-methylenedioxybenzene are recovered from the toluene phase. 167.3 g of 3,4-methylenedioxymandelic acid, corresponding to a yield of 85.3% of theory, relative to 1,2-methylenedioxybenzene reacted, are obtained from the aqueous phase.

EXAMPLE 3

A mixture of 92 g (1 mol) of glyoxylic acid monohydrate and 122 g (1 mol) of methylenedioxybenzene is stirred at 80.degree. C. for 4 hours, 700 ml of water and 150 ml of toluene are then added and the phases are separated. After cooling the aqueous phase to room temperature, 44.7 g of 3,4-methylenedioxymandelic acid crystallise out, and after concentrating the aqueous phase a further 17.3 g of 3,4-methylenedioxymandelic acid crystallise out. After extracting the toluene phase by shaking with 100 ml of 20% strength sodium hydroxide solution and distilling off the toluene, 10.5 g of unreacted 1,2-methylenedioxybenzene are obtained. The yield of 3,4-methylenedioxymandelic acid is 34.6% of theory, relative to 1,2-methylenedioxybenzene reacted.

EXAMPLE 4

39 g (0.424 mol) of glyoxylic acid monohydrate are dissolved in 126 g of trifluoroacetic acid, and 51.7 g (0.424 mol) of 1,2-methylenedioxybenzene are added at 20.degree. C. The initially homogeneous mixture is stirred at 20.degree. C. for 3.5 hours. The crystals which have precipitated are then filtered off and worked up as described in Example 1. 10 g of bis-(3,4-methylenedioxyphenyl)-acetic acid are obtained from the toluene phase. 62.2 g of 3,4-methylenedioxymandelic acid are obtained from the aqueous phase. This corresponds to a yield of 75% of theory, relative to 1,2-methylenedioxybenzene employed. The yield can be increased by working up the strongly acid filtrate of the reaction mixture. However, it is more advantageous to concentrate the acid filtrate and re-use it.

If, instead of glyoxylic acid monohydrate, an equivalent amount of 50% strength aqueous glyoxylic acid is employed and the mixture is stirred for 6 hours instead of 3.5 hours, 8.58 g of bis-3,4-methylenedioxyphenylacetic acid are obtained from the toluene phase and 73.4 g of 3,4-methylenedioxymandelic acid, corresponding to a yield of 76.3% of theory, relative to 1,2-methylenedioxybenzene employed, are obtained from the aqueous phase.



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foxy2

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Re: 4-Methylaminorex Synth w/o CNBr
« Reply #50 on: October 17, 2001, 07:33:00 AM »
United States Patent  4,165,341 
Umemura ,   et al.  August 21, 1979 

--------------------------------------------------------------------------------
Process for preparing protocatechualdehyde and its derivatives


Abstract
A process for preparing protocatechualdehyde or a 3-alkoxy-4-hydroxybenzaldehyde which comprises subjecting catechol or a 2-alkoxyphenol to reaction with glyoxylic acid in a basic aqueous medium in the presence of a catalyst containing one or more compounds selected from aluminium oxide, silicon oxide and hydrated aluminium oxide in an amount of not less than 0.01 g per 1 g of the starting catechol or 2-alkoxyphenol at a temperature of 0.degree. to 50.degree. C., and then oxidizing the thus obtained reaction mixture in a basic medium.

EXAMPLE 1

To 45 ml of a 2 N aqueous solution of sodium hydroxide were added 5.50 g of catechol, 14.25 g of a 20 wt % aqueous solution of glyoxylic acid and 2.50 g of aluminium oxide [manufactured by Kishida Chem. Co., Ltd., trade name: Kassei Alumina], and the mixture was subjected to reaction with stirring at 25.degree. C. for 24 hours.

The aluminium oxide was separated from the reaction mixture by filtration and thus a reaction liquid was obtained. The aluminium oxide separated by filtration was washed with 20 ml of a 1 N aqueous solution of sodium hydroxide and the washing was added to the reaction liquid. The reaction liquid was adjusted to pH 6 by the addition of a 12 N hydrochloric acid and then the unaltered catechol was extracted three times with 50 ml portions of diethyl ether. From the extract was recovered 1.61 g of catechol.

After nitrogen gas was blown into the aqueous layer obtained after extraction to remove the dissolved oxygen, 33 g of sodium carbonate was added thereto to adjust the pH value to 10.5. Further, 20 g of a powdery copper (II) oxide was added thereto, and the mixture was placed into an autoclave and subjected to reaction at 98.degree. C. for 50 minutes with stirring while the pressure was allowed to rise. The pH value of the reaction liquid after reaction was 10.0.

After cooling the reaction mixture, the copper oxide was separated by filtration. To the thus obtained reaction liquid was added a 12 N hydrochloric acid to adjust the pH value to 2. Organic substances in the solution were extracted six times with 150 ml portions of diethyl ether.

Protocatechualdehyde in the extract was determined by gas chromatography.

The conversion of catechol was 70.7%, the yield of protocatechualdehyde was 4.51 g and the selectivity (based on the catechol consumed in the first step; this meaning is applied similarly to the following examples) was 92.4%.

COMPARATIVE EXAMPLE 1

An experiment was run in the same manner as in Example 1 except that aluminium oxide was not used.

After the first step, 2.07 g of catechol was recovered. The conversion of catechol was 62.4%, the yield of protocatechualdehyde was 3.06 g and the selectivity was 71.1%.




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foxy2

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Re: 4-Methylaminorex Synth w/o CNBr
« Reply #51 on: October 17, 2001, 07:35:00 AM »
United States Patent  4,183,861 
Maggioni  January 15, 1980 

--------------------------------------------------------------------------------
Process for preparing aromatic methylene-dioxy compounds
EXAMPLE 1: METHYLENEDIOXYBENZENE:

Methylene chloride (100 ml., 1.56 moles), tetrabutylammonium bromide (6.42 g., 0.02 moles) and water (200 ml.) are placed in an autoclave. To this mixture is added a total of 15 g. pyrocatechin (0.1362 moles) and sodium hydroxide (15.9 g., 0.3975 moles) in flake form in successive stages.

The reaction temperature is maintained at 70.degree. C. and the pressure within the autoclave rises to a maximum of 2.4 atmospheres. The reaction is completed within three hours.

After the reaction is completed, the organic phase is separated and excess methylene chloride is distilled off and recycled. Pure methylenedioxybenzene (13.8 g.; 83% yield) is obtained by distillation.

Tetrabutylammonium bromide remains as a distillation residue and this material can be recovered and reused as a catalyst to produce additional product.

By substituting pyrocatechoic acid (ie., 2,3-dihydroxybenzoic acid) for the pyrocatechin of Example 1, and otherwise following the procedure described therein, the product 1-carboxy-methylenedioxybenzene is obtained.

EXAMPLE 2: METHYLENEDIOXYBENZENE:

By following the procedure described in Example 1, but substituting hexadecyltributyl phosphonium bromide for tetrabutylammonium bromide in an otherwise analogous process, 11.65 g. of methylenedioxybenzene (70% yield) is obtained.

EXAMPLE 3: 1-METHYL-3,4-METHYLENEDIOXYBENZENE:

Methylene chloride (1.56 g., 100 ml.) and tetrabutylammonium bromide (6.42 g., 0.02 moles) are placed in an autoclave, and to this mixture is added a total of 24.8 g. of 4-methylpyrocatechin (0.2 moles) and caustic soda (24 g., 0.6 moles) in flake form, with agitation, at 80.degree. C. The reaction is completed within five hours.

After the reaction is completed, the product is recovered by following the procedure described in Example 1, that is, the organic phase is separated, excess methylene chloride is distilled off and recycled and 1-methyl-3,4-methylenedioxybenzene (19.4 g.; 71.3% yield) is obtained by distillation.

EXAMPLE 4: PIPERONAL:

Methylene chloride (100 ml., 1.56 moles), tetrabutylammonium bromide (6.42 g., 0.02 moles) and water (200 ml.) are placed in an autoclave. A total of 27.6 g. of protocatechic aldehyde (0.2 moles) and caustic soda (24 g., 0.6 moles) in water (20 ml.) are then added to the autoclave in stages at a temperature of 70.degree. C.

The pressure within the autoclave increases to a maximum of 2.4 atmospheres and the reaction is completed within four hours.

The reaction mixture is allowed to cool to ambient temperatures and the organic phase is separated. Excess methylene chloride is recovered from the organic phase by distillation and high purity piperonal (21 g., 70% yield) is isolated. The product is identified by gas chromatography and infra-red spectrum analysis by comparing against a pure sample.

Upon substituting tetramethylarsonium chloride, for the tetrabutylammonium bromide of Example 4, and otherwise following the procedure described therein, an identical piperonal product is obtained.

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foxy2

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Re: 4-Methylaminorex Synth w/o CNBr
« Reply #52 on: October 17, 2001, 07:49:00 AM »
There I think I added a few weapons to the Hive war chest!!!
:)  ;)  8)  

Here are some more.

United States Patent 3838051  OLD methylation reference
United States Patent 3726924 Methyeneation and prep of strong base(trisdimethlyaminomethane)
United States Patent 3436403 Methyleneation Reactions
United States Patent 2496803 Production of Veteraldehyde from Vanillin

Find these here

http://patft.uspto.gov/netahtml/srchnum.htm



You need a TIFF viewer installed in your browser to look at them.
Later
Foxy



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psychokitty

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Re: 4-Methylaminorex Synth w/o CNBr
« Reply #53 on: October 19, 2001, 05:02:00 AM »
Rhodium:

Here are the references you requested.

Synthesis of nitroalcohols

Can. J. Chem. Vol. 39 (1961) pp.1143-1147
Can. J. Chem. Vol. 41 (1963) pp.543-545
In. Eng. Chem., 32, 34 (1940)
Kamlet, US Patent 2,151, 517
Ann., 470, 157 (1929)

Synthesis of 3,4-methylenedioxynorephedrine

CA Vol. 45 9507d

And last but not least, the formation of the amino alcohols and the reduction strategy using Zn and H2SO4 is in the following reference . . .

Shit.  The article does give information as to where it came from . . . just the page numbers (506-509).

Gee.  I guess I'll just have to type up the relevant information myself.

First of all, there are three ways to go about forming the intermediate nitro alcohol; however, Kamlet's stands out as the best and easiest:

(c) Method of Kamlet (3).  Benzaldehyde (106 g., 1 mole) was vigorously agitated with sodium bisulfite (110 g., 1.06 mole) in 500 ml of water until the formation of the addition compound was complete.  Simultaneously, nitroethane (or nitromethane) (82.5 g., 1.10 mole) was dissolved in a solution made from sodium hydroxide (45 g., 1.125 moles) dissolved in 200 ml of water.  This solution was gradually added, with agitation and at room temperature, to the addition product of benzaldehyde and sodium bisulfite.  After stirring for a half hour, the mixture was allowed to stand overnight.  The lower layer was discarded and the upper layer was dissolved in ether and washed with sodium bisulfite solution.  The ethereal solution was dried over Drierite, and after removal of ether, distilled (bp 120-130 @ 2-4 mm).  The usual conversion is 90-100g. (50-55%) and the yield, based on benzaldehyde which reacts is nearly quantitative.

Preparation of 2-amino-phenyl-1-propanol.  (a) With zinc and sulfuric acid.  Sulfuric acid (375 g of 30% acid) was added with stiring to a mixture of 2-nitro-1-phenyl-1-propanol (54.3 g., 0.3 mole), zinc dust (90 g., 1.37 mole of 80 mesh zinc), and 100 ml of 95% ethanol.  The acid was added at such a rate that the temperature remained at 45 deg C or below.  Usually 10 to 12 hours were required.  Agitation was continued for 1-2 hours after completing the addition of acid, then after extracting the acidic solution with ether to remove non-basic materials, a large excess of sodium hydroxide (as a 50% solution) was added.  The product which was freed was extracted with ether.  Three extractions, with a total of 500 ml of ether, sufficed.  The ether solution was dried, ether was removed, and the product was distilled (b.p. 122 deg C at 4 to 5 mm); 29-32 g resulted (yield 65-70%).  The viscous liquid solidified on standing, and m. 46-50 deg C.

According to the article, "The unmethylated amino alcohol was obtained by reduction of the nitro alcohol either with zinc and sulfuric acid, tin and hydrochloric acid, sodium amalgam and acetic acid . . . Presumably many of the ordinary metal-acid reducing agents can be used provided the temperature is kept sufficiently low to prevent dehydration."

The above quote implies to me that aluminum amalgam might serve handsomely in the above reaction.

Oh, yes--the CA ref is as follows:

"The iso form of 3,4-methylendioxynorephedrine was obtained by the reduction of a condensate of piperonal, EtNO2, and KHCO3 (yield 45%) with Zn dust and 33% H2SO4 in 75% yield."

Since it seems that not a fucking one of you bees has Poos' original patent, here are the details to the in situ formation of cyanogen bromide:

From Example II, Line 10:

"A solution of cyanogen bromide is prepared from 1.58 g (0.036 mole of sodium cyanide and 5.7 g (0.036 mole) of bromine in methanol . . ." Then it's used as is.

Two more syntheses of piperonal are detailed in the following references:

CA 9061 between 8 and 9 (1938)
CA Vol. 51 16572d

That's all for now.

--PK

BTW, Rhodium, are you NOT getting any of my PMs to you?  I have yet to hear one fucking peep from you at all.  And I believe the references that I sent you are indeed valuable.  It would be nice to at least know that you've gotten them safely and securely.

slappy

  • Guest
Re: 4-Methylaminorex Synth w/o CNBr
« Reply #54 on: October 19, 2001, 08:09:00 AM »
P/K: Don't worry, I haven't heard a peep from him either. I don't think anybody is.

Osmium

  • Guest
Re: 4-Methylaminorex Synth w/o CNBr
« Reply #55 on: October 19, 2001, 12:16:00 PM »
You guys won't believe the amount of PMs some of the moderators receive every day.

Rhodium

  • Guest
Re: 4-Methylaminorex Synth w/o CNBr
« Reply #56 on: October 19, 2001, 04:40:00 PM »
I got 10 PM's in the last 12 hours, and I have 50-60 unanswered ones in my in-box. I got your message PK, I have just not had the time to answer it yet. The references looked good, and than you immensely for this addition you just posted. Now we can all make substituted phenylpropanolamines to use with this reaction.

psychokitty

  • Guest
Re: 4-Methylaminorex Synth w/o CNBr
« Reply #57 on: October 20, 2001, 11:05:00 PM »
Rhodium:

Thanks for taking a load off my shoulders.  For awhile there, I was thinking I was the victim of some conspiracy.

Something I realized when I was away from the computer:

The first two Canadian Journal references are GOLD!!!  I hadn't really looked at them in over two years and didn't really know just how valuable they are.  Well, was I wrong not to include the relevant experimental details in this thread. 

In both papers are given the details to synthesizing a number of substituted nitroalcohols, the 3,4-MD derivative included, in very good yield using a RIDICULOUSLY simple synthesis.  I'll post all the detailed information at a later date, but for now, here is what I remember:

A quantity of a benzaldehyde is dissolved in 95% EtOH along with an excess of nitromethane (or nitroethane).  To this mixture is added a dilute solution of sodium hydroxide which may be at reduced temperature, but I don't think so.  The mixture is stirred (for most benzaldehydes) about sixty seconds--that's right, ABOUT SIXTY SECONDS--and then the mixture is quenched with 5% acetic acid and left to stand.  The formed nitro alcohol is isolated and then recrystallized if necessary.

I'll be back soon with the reference.

--PK

psychokitty

  • Guest
Re: 4-Methylaminorex Synth w/o CNBr
« Reply #58 on: October 20, 2001, 11:31:00 PM »
Doooooooooooooooode!!!!  This is so fucking easy!!!

Taken from Canadian Journal of Chemistry Vol. 39, 1961 pp1143-47:

Experimental:
 
"General Procedure

(i) Nitroalcohols.--Aqueous sodium hydroxide (10%; 1.05 mole)was added with vigorous stirring to a mixture of the aldehyde (1.0 mole) and nitromethane (2-3 mole) dissolved in 95% ethanol at ca. 5 deg C.; the reaction mixture was vigorously stirred for a short time (under 3 minutes), accurately timed on a stop watch.  Aqueous acetic acid (2%) was added to arrest the reaction and decompose the sodium derivative of the nitroalcohol; the crude product precipitated out as a yellow or colorless solid or oil.  After being allowed to stand at 4 deg C for 4-5 hours, the crude product was filtered and purified by repeated crystallization from a suitable solvent.

They used many substituted benzaldehydes in this reaction but no 3,4-dimethoxy or methoxy derivatives.  However, 3,4-methylenedioxy-a-nitromethylbenzylalcohol is listed as one of their examples:

 1.) 10 g. of piperonal (piperonaldehyde)
 2.) 11 ml of nitromethane
 3.) 135 ml of 95% ethanol
 4.) 20 ml of 10% sodium hydroxide
 5.) 160 ml of 2% acetic acid
 6.) Reaction time was 60 seconds
 7.) Yield of purified product was 9.3 grams
 8.) Product was obtained as fine colorless needles from    benzene
 9.) mp was 98 deg C
10.) Literature mp was 91, 95-96, 91, and 94 all taken from different sources.

Note: All benzaldehydes that had a phenolic group on the benzene ring failed to react to form the expected nitroalcohols.

Also, using mineral acids in place of acetic acid to free up the sodium derivatives of the nitroalcohols led to some dehydration of the alcohol group to form the nitroalkenes. With a few modifications, this could end up as a good way to substituted nitroalkenes.

--PK


Rhodium

  • Guest
Re: 4-Methylaminorex Synth w/o CNBr
« Reply #59 on: October 20, 2001, 11:42:00 PM »
This good way to nitroalkenes has already been published on my page:

https://www.thevespiary.org/rhodium/Rhodium/chemistry/mdp2np.html