Author Topic: Iodination of benzylic alcohols w/o HI  (Read 11858 times)

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Rhodium

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Iodination of benzylic alcohols w/o HI
« on: February 13, 2004, 02:19:00 PM »
Amberlyst-15 is an acidic ion exchange resin, which is simply filtered off after the reaction and is regenerated by washing it with aqueous bicarbonate, water and finally a dilute acid. 500g costs at most $50 and it can be reused over and over again. This reaction should be really nifty for iodinating (pseudo)ephedrine to iodoephedrine for use together with other methods of reduction than HI/P.

Selective Iodination of Alcohols with NaI/Amberlyst-15 in Acetonitrile
Mahmood Tajbakhsh, Rahman Hosseinzadeh, Zahra Lasemi

Synlett 2004; 01/29/2004 (eFirst)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/iodination.nai-amberlyst15.pdf)
DOI:

10.1055/s-2004-815445



Abstract
A simple and effective procedure for conversion of primary, secondary, allylic and benzylic alcohols into the corresponding iodides is described using NaI/Amberlyst-15 in acetonitrile at room temperature. Selective conversion of benzylic alcohols in the presence of saturated alcohols into the corresponding benzylic iodides is achieved under these conditions.


A number of synthetic methods for transformation of alcohols into iodides has been developed during the past two decades. Some methods involve mild conditions and the use of iodotrimethylsilane, bromotrimethylsilane, chlorotrimethylsilane-sodium iodide, hexamethyldisilazane-iodine, P2I4 in CS2, N,N-diethylaniline-borane-I2, CeCl3·7H2O/NaI system, sodium iodide over KSF-clay under microwave irradiation, and KI/H2SO4 supported on natural kaolinitic clay under microwave irradiation as reagents. However, some of these suffer from drawbacks, which include the use of toxic and/or hazardous materials, reagents that are not commercially available, long reaction times, low yields and tedious work-up procedures. As such mild and efficient methods that can be used to promote the transformation of hydroxyl groups into iodides are of increasing importance to overcome such difficulties.

We report herein an exceedingly mild preparation of iodides from alcohols by the use of a NaI/Amberlyst-15 system in acetonitrile at room temperature.

The results of the iodination reactions are summarized in Table 1. The data indicate that iodination of a variety of allylic or benzylic and saturated primary or secondary alcohols occurs using a NaI/Amberlyst-15 system in acetonitrile at room temperature. The iodination of benzyl alcohol was selected for optimization of the reaction conditions. It was observed that when benzyl alcohol was treated with NaI without Amberlyst-15, no change took place, implying that Amberlyst-15 plays an important role in this reaction.

We have also examined the effect of solvent in this reaction. When benzyl alcohol reacted with NaI/Amberlyst-15 in various solvents such as acetonitrile, ethyl acetate, chloroform, dioxane, dichloromethane and THF, we found that the reaction proceed most rapidly and give optimal yields in acetonitrile.

Benzyl alcohol with NaI/Amberlyst 15 provided benzyl iodide in excellent yield. In the case of primary alcohols the conversion into the corresponding iodides requires longer reaction times. Likewise, secondary alcohols such as cyclohexanol and 5-nonanol were also converted into the corresponding alkyl iodides.

General Procedure for the Conversion of Alcohols to Iodides

To a stirred suspension of alcohol (1 mmol) and NaI (0.150 g, 1 mmol) in MeCN (10 mL) was added Amberlyst-15 (H+-form, 1 g), and the resulting mixture was stirred at r.t. After completion of the reaction (TLC or GC), Et2O (10 mL) was added and washed with aq sat. NaHCO3 solution, followed by NaHSO4. The resultant organic layer was extracted with Et2O (3×10 mL) and the combined extract dried over anhyd Na2SO4. The solvent was removed under reduced pressure to afford iodides in almost pure form. If necessary, products were purified by column chromatography (eluent: hexane-EtOAc).



About Amberlyst-15

(http://www.medibix.com/detail.jsp?view=detail&sku_id=1377501&product_id=462525)

About Ion Exchange Resins

(https://www.sigmaaldrich.com/aldrich/brochure/al_pp_ionx.pdf)


auntyjack

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um
« Reply #1 on: February 13, 2004, 06:14:00 PM »
here's a good old fashioned stoopid question...what the heck do you do with idoephedrine?


Rhodium

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Iodoephedrine is much easier to reduce
« Reply #2 on: February 13, 2004, 06:41:00 PM »
Iodoephedrine is much easier to reduce in high yields than (pseudo)ephedrine, and you can use a variety of different reducing agents to reduce alkyl iodides to hydrocarbons; catalytic hydrogenation (Pd/H2 or Pt/H2), transfer hydrogenation (Pd-C/potassium formate), sodium borohydride, as well as a variety of metals and metal salts (UTFSE for details/alternatives). Most of these reduction methods are much milder and faster than HI reflux, allowing for higher yields and most definitely a purer product.


Lego

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Iodination of alcohols using ZrCl4/NaI
« Reply #3 on: September 15, 2004, 04:57:00 PM »
A simple, efficient, and highly selective method for the iodination of alcohols using ZrCl4/NaI
Habib Firouzabadi, Nasser Iranpoor and Maasoumeh Jafarpour
Tet. Lett., 2004, 45(40), 7451-7454.pdf
DOI:

10.1016/j.tetlet.2004.08.056




Abstract: Iodination of primary, secondary, allylic, and benzylic alcohols giving their corresponding iodides was achieved with ZrCl4/NaI in anhydrous CH3CN with excellent yields and selectivities.

Typical procedure: To a solution of benzyl alcohol (0.108g, 1mmol) and NaI (0.225 g, 1.5mmol) in dry CH3CN (2mL) was added ZrCl4 (0.116g, 0.5mmol) in several portions (it is very important to note that ZrCl4 with a faint pink hue should not be used). The mixture was stirred at rt and the progress of the reaction was monitored by TLC or GC. After 10min, the reaction mixture was diluted with ether (10mL) and water (10mL). The organic layer was separated and washed with an aqueous solution of Na2S2O3 (10%, 10mL), then H2O (10mL). The organic layer was separated and dried over anhydrous Na2SO4. Evaporation of the solvent under reduced pressure at RT gave benzyl iodide (0.103 g, 95%) of a very high purity.


psi0nic

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cyclisation
« Reply #4 on: September 16, 2004, 06:11:00 PM »
Does this iodination result in the phenyl 2 methyl-aziridine as can happen with HI and is this a problem?

Are there more OTC ion exchangers that can be used? zeolite for example.

I recall maybe SWIM once asked the question but at the time this person only found one reference which it slips my mind what it was... i should utfse AHA

Post 505966 (missing)

(amalgum: "Your making it way harder than it need be.", Stimulants)


microwave leuckhart to reduce it? i take it a leukart would do the job too then? formamide and ammonia formate or something like that...

Offline aYoungKing

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Re: Iodination of benzylic alcohols w/o HI
« Reply #5 on: February 19, 2015, 04:59:08 PM »
worth checking into, so bump.

Offline fishinabottle

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Re: Iodination of benzylic alcohols w/o HI
« Reply #6 on: February 19, 2015, 10:59:27 PM »
Quote
Most of these reduction methods are much milder and faster than HI reflux, allowing for higher yields and most definitely a purer product.
This is complete bullshit. Every single point of the sentence. Astonishing ignorance and it speaks for a kind of "chemical racism".


oh my
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Offline aYoungKing

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Re: Iodination of benzylic alcohols w/o HI
« Reply #7 on: February 20, 2015, 03:20:21 AM »
Quote
Most of these reduction methods are much milder and faster than HI reflux, allowing for higher yields and most definitely a purer product.
This is complete bullshit. Every single point of the sentence. Astonishing ignorance and it speaks for a kind of "chemical racism".


oh my
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lets not forget that this the post was written in 2004.

Offline Impossible

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Re: Iodination of benzylic alcohols w/o HI
« Reply #8 on: February 20, 2015, 06:40:47 AM »
Quote
Most of these reduction methods are much milder and faster than HI reflux, allowing for higher yields and most definitely a purer product.
This is complete bullshit. Every single point of the sentence. Astonishing ignorance and it speaks for a kind of "chemical racism".


oh my
/ORG

lets not forget that this the post was written in 2004.

That's not quite as relevant as you might think.  The HI/(P4/H3PO2/H3PO3) is one of the most discussed, and most poorly understood reactions on drug chemistry boards.  Although the exact mechanism  isstill not completely agreed upon by professional researchers  and nothing new has really come of it in the last 10 years to be fair. 

Offline fishinabottle

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Re: Iodination of benzylic alcohols w/o HI
« Reply #9 on: February 20, 2015, 09:30:08 AM »
Prejudice doesn't go away in ten years, actually it never will. Just because the HI reduction was and is widely used by "cooks" and that it is ancient doesn't make it unclean, low yielding or whatever.
For a matter of fact a correctly done HI reduction of ephedrine gives excellent yields which were only beaten by the Birch (done by chemists in the lab, never reached in the field) and quality (selectivity) is excellent too. I can assure that catalytic hydrogenation of an ephedrine ester or haloephedrine provides yields which are not nearly as good and impurityies which are not easily removed and suspected to have nasty sideeffects on consumption.

For "reaction mechanism" hey! Chemistry has no working theory and those "mechanisms" are pure wanking. I have seen so many completely contradictional interpretations of the same reaction that I can tell you nothing is so useless like this. As it does not provide reproduceability for something related. Not at all.

How are reactions and compounds put to the test nowadays? Big companies in pharma run some thousands of robots which run a 50 reactions a time and analyse the results all automated. Who would do this if he would know "reaction mechanisms"?  Industry uses another approach as stuff is usually simpler in structure and that is "we have to much of A and we want B , some hundred bar of pressure and some zeolithe will do" And thats it.

Chemistry has long since outlived itself for the idea at start was: If we do enough reactions and analyse the outcome we will soon be able to see a structure, develop a working theory and then we are able to synth everything we want, we are god then. Lets exchange our results and 20 years max and we have it.
And so they did.
It was about 1880.

Bad luck boys.


/ORG
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Offline aYoungKing

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Re: Iodination of benzylic alcohols w/o HI
« Reply #10 on: February 20, 2015, 01:08:21 PM »
Prejudice doesn't go away in ten years, actually it never will. Just because the HI reduction was and is widely used by "cooks" and that it is ancient doesn't make it unclean, low yielding or whatever.
For a matter of fact a correctly done HI reduction of ephedrine gives excellent yields which were only beaten by the Birch (done by chemists in the lab, never reached in the field) and quality (selectivity) is excellent too. I can assure that catalytic hydrogenation of an ephedrine ester or haloephedrine provides yields which are not nearly as good and impurityies which are not easily removed and suspected to have nasty sideeffects on consumption.

For "reaction mechanism" hey! Chemistry has no working theory and those "mechanisms" are pure wanking. I have seen so many completely contradictional interpretations of the same reaction that I can tell you nothing is so useless like this. As it does not provide reproduceability for something related. Not at all.

How are reactions and compounds put to the test nowadays? Big companies in pharma run some thousands of robots which run a 50 reactions a time and analyse the results all automated. Who would do this if he would know "reaction mechanisms"?  Industry uses another approach as stuff is usually simpler in structure and that is "we have to much of A and we want B , some hundred bar of pressure and some zeolithe will do" And thats it.

Chemistry has long since outlived itself for the idea at start was: If we do enough reactions and analyse the outcome we will soon be able to see a structure, develop a working theory and then we are able to synth everything we want, we are god then. Lets exchange our results and 20 years max and we have it.
And so they did.
It was about 1880.

Bad luck boys.


/ORG

now i'm starting to get a hint of meaning of the "chemical racism" you mentioned above. rhodium being one of the bees, not a proud HI cooker and you can tell from his posts. max yield w/w in an HI reaction will get 92 percent i think, no one ever gets there though. what is the max yield anyone has ever heard of from a chloroephedrine batch? actual yield as ephedrine converted to meth, and not measured by the yield of chloroephedrine to meth.

Offline Impossible

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Re: Iodination of benzylic alcohols w/o HI
« Reply #11 on: February 20, 2015, 02:48:48 PM »
Long post

Don't get me wrong, I agree with you.  The HI/Phos reaction was one of the first procedures I performed, and one of the ones I've studied the most.  If anything I'd prefer as much discussion on (any) reaction as possible.


now i'm starting to get a hint of meaning of the "chemical racism" you mentioned above. rhodium being one of the bees, not a proud HI cooker and you can tell from his posts. max yield w/w in an HI reaction will get 92 percent i think, no one ever gets there though. what is the max yield anyone has ever heard of from a chloroephedrine batch? actual yield as ephedrine converted to meth, and not measured by the yield of chloroephedrine to meth.

Highest yield reported in literature was around 90% using supported palladium or platinum catalysts.  The multitude of reported yields on the hive/wetdreams etc. can't really be considered reliable information for the most part, but the general consensus for HI yields was "decent."

Many people tried out the catalytic hydrogenation procedures with dissappointing results.  It turns out the catalyst preparation has a huge impact on it's performance and the reports were mostly self prepared.   
« Last Edit: February 20, 2015, 02:58:57 PM by Impossible »

Offline fishinabottle

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Re: Iodination of benzylic alcohols w/o HI
« Reply #12 on: February 27, 2015, 07:57:21 AM »
no no no....
It is 92g of meth from 100g of ephedrine is the most one could get as that would be 100% yield.
Not 92% thats wrong.

HI reduction proceeds best in batches between 100g and 500g ephedrine, more or less then this diminishes yields (not extremly but noticeable). From 1kg ephedrine 800g meth (both as HCl salt) can be expected, and 800g with 920g as 100% says 87% yield, up to 90% more has been reported but I doubt the validity of the claims as product was not recrystallized or even dried and crystal-water + HCl adds up to 10% weight or more what explains reports of 104g meth from 100g ephedrine.
The 87% are recrystallized shards bonedry.
One does not get this on the first shot, or with much luck only.

Don't want to comment on Rhodium except that he is completely overrated, when searching for information, valid information in the archives I go for other names first and read Rhodiums posts only for completeness. Be warned he and Barium loved to include "typos" on amounts or other things confusing into their posts, if taken verbatim and not recalculated you can get royally fucked.

The majority of bees were meth cooks, those into MDMA only represented only a marginal faction.

/ORG
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Offline Vesp

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Re: Iodination of benzylic alcohols w/o HI
« Reply #13 on: February 27, 2015, 08:18:46 AM »
Would be cool to create a new archive like rhodiums. Fix errors, etc.
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Offline aYoungKing

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Re: Iodination of benzylic alcohols w/o HI
« Reply #14 on: February 27, 2015, 03:11:38 PM »
no no no....
It is 92g of meth from 100g of ephedrine is the most one could get as that would be 100% yield.
Not 92% thats wrong.

HI reduction proceeds best in batches between 100g and 500g ephedrine, more or less then this diminishes yields (not extremly but noticeable). From 1kg ephedrine 800g meth (both as HCl salt) can be expected, and 800g with 920g as 100% says 87% yield, up to 90% more has been reported but I doubt the validity of the claims as product was not recrystallized or even dried and crystal-water + HCl adds up to 10% weight or more what explains reports of 104g meth from 100g ephedrine.
The 87% are recrystallized shards bonedry.
One does not get this on the first shot, or with much luck only.

Don't want to comment on Rhodium except that he is completely overrated, when searching for information, valid information in the archives I go for other names first and read Rhodiums posts only for completeness. Be warned he and Barium loved to include "typos" on amounts or other things confusing into their posts, if taken verbatim and not recalculated you can get royally fucked.

The majority of bees were meth cooks, those into MDMA only represented only a marginal faction.

/ORG

of course, yield by mole will be different that yield by weight.