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Iodination of benzylic alcohols w/o HI

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Rhodium:
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:
here's a good old fashioned stoopid question...what the heck do you do with idoephedrine?

Rhodium:
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:
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:
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...

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