Hi,

Polymer-supported TEMPO catalysts are also commercially available.[10]

10) Ciriminna, R.; Pagliaro, M. (2010). "Industrial Oxidations with Organocatalyst TEMPO and Its Derivatives". Organic Process Research & Development (210), 14: 245–251.

TEMPO itself, however, is an expensive chemical, and in order to find wider application in industry its 80 100 $/kg spot price should decrease to∼$20/kg. 6 Therefore, industry generally employs nitroxyl derivatives functionalized in the 4 position such as 4-hydroxy-TEMPO or 4-acetamido-TEMPO obtained from the cheap ($3/kg) precursor triacetoneamine, a readily available chemical manufactured in large amounts as a light stabilizer for plastics. Although TEMPO is usually applied in small quantities (0.1 10 mol %), clearly it must be recovered from homogeneous reaction mixtures and thus separated from the product. Costly azeotropic distillation can only be applied to the most volatile nitroxyl compounds such as TEMPO; hence, recovery is preferably carried out by selective absorption onto a hydrophobic resin such as Amberlite or hydrophobized silica gel. 7

One-pot sequential alcohol oxidation and asymmetric a-oxyamination in aqueous media using recyclable resin-supported peptide catalyst

Kengo Akagawa, Takuma Fujiwara, Seiji Sakamoto and Kazuaki Kudo*

Chem. Commun., 2010, 46, 8040–8042

“z Typical procedure (Table 2): To a mixture of alcohol 4 (0.1 mmol),

TEMPO (0.4 mmol), 2,20 -bipyridine (0.03 mmol), and peptide catalyst

1 9c

(150 mg, 0.02 mmol of the terminal prolyl group) in 0.33 mL of THF and 0.67 mL of distilled water, copper(I) chloride (0.03 mmol) was added. The mixture was stirred under oxygen atmosphere at room

temperature for 36 h, then the catalyst was filtered off and washed with chloroform. To the filtrate solution, 10% citric acid aqueous solution was added, and extracted with chloroform. The organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and excess TEMPO was removed by sublimation using a vacuum pump. The residue was dissolved in 1 mL of THF, and sodium borohydride (0.5 mmol) was added. The mixture was stirred for 1 h, then saturated ammonium chloride aqueous solution was added. The resulting solution was extracted with chloroform, and the organic layer was dried over anhydrous magnesium sulfate. After the removal of the solvent under reduced pressure, the crude product was purified using preparative TLC (hexane–ethyl acetate = 2 : 1) to afford oxyaminated product 3. The absolute configurations of the major products were determined according to the literature. 6 In the examination of recycling peptide catalyst 1, the collected catalyst by filtration after the reaction was washed with DMF and dichloro-methane, and dried in vacuo before the next use. Copper(I) chloride and 2,20 -bipyridine were added in each cycle.

The simultaneous use of immobilised reagents for the one-pot conversion of alcohols to carboxylic acids

Kosuke Yasuda and Steven V. Ley *

J. Chem. Soc., Perkin Trans. 1, 2002, 1024-1025

A typical procedure9 for this oxidation involves reacting the primary alcohol at room temperature with a combination of 4-(polystyrylmethyloxy)-2,2,6,6-tetramethylpiperidin-1-yloxy free radical (PS-TEMPO) (10 mol%), 10 resin bound chlorite7 and buffered with immobilised hydrogen phosphate in aqueous

acetonitrile (1 : 3, water–acetonitrile, v/v) containing potassium bromide (0.1 eq.) and 4 mol% sodium hypochlorite. The polymer-supported chlorite reagent was easily obtained from Amberlyst IRA 900 by ion exchange with sodium chlorite solution. 11 The polymer-supported hydrogen phosphate was

prepared using the same procedure except the resin washing procedure omitted the use of tetrahydrofuran and diethyl ether. After the specified reaction times the reaction mixtures were

filtered then evaporated, generally yielding oils. The oils were then redissolved in the minimum quantity of 25% methanol in chloroform and the solution passed through a short pad of silica gel to clean out the salts. After evaporation, the acids were obtained as essentially pure products. In this way several alcohols have been converted to their corresponding acids in good to excellent yield (Table 1).

Bill

If you were using the acetamido nitroxide, you would be able to crystallize it from the reaction crude with dry ether, where it is insoluble. I tend to pass the ether over a small pad of silica afterwards to remove the last trace.

Washing with saturated solution of Na2S2O3 removes TEMPO that becomes light yellow.If the organic phase still remains to be orange after 2washings, the solution is shaken in a separating funnel containg 50ml of saturated Na2S2O3 solution and 15 ml of 0.5N HCl until it becomes light yellow( in fact this step is invariably necessary).

As its 100% removal is a must, the best thing will be to test its absence by ESR so that the final product is ESR INACTIVE. Any ESR activity will show the presence of traces of TEMPO (2, 2,6, 6-Tetramethylpiperidinyloxy free radical) whose presence will show ESR peaks.

Dear Ping He

I , being 71, suggest that that the young scholars should not use such harsh words to differ with another person however divergent may be his/ her view point.

I, now, very humbly, reiterate my OLD VIEW POINT which is very well supported by the following references:

Organic Synthesis

Vol. 83,

p.18-23(2006) .

Coll vol.11,

p.71-81(2009).

I will appreciate if you carefully read NOTE-8 reproduced from the above reference in toto:

Washing with saturated aqueous sodium thiosulfate REMOVES( PLS. NOTE)

TEMPO from the organic phase that becomes light yellow. If the organic

phase should be still orange after the two washings, the solution is shaken in

the separatory funnel with 50 mL of saturated aqueous sodium thiosulfate

and 15 mL of 0.5 N HCl until it becomes light yellow (the checkers found

this extra thiosulfate-HCl wash to be necessary). TEMPO must be removed

carefully at this stage, because it cannot be removed in the chromatographic

purification.

Regards.

Hi,

The thiosulfate reduces TEMPO to the N-OH form. You can also reduce it to the NH form, with R2S orther reagents. In any case, speck softly and add a correct answer.

Bill

(sorry about that... I'm not a scholar I'm just an undergrad studying chemistry) I tried exactly the same thing but didn't work out in the end =.=

2 equivalence of sodium thiosulfate, 2 equivalence of HCl, the solution was still red... I ended up discarded everything and restarted from benzoin to benzil

Hi,

I wonder if you may not have used thiosulfate, but some other S reagent? Maybe try it again?

Bill

 Dear Prof. William Frost Berkowitz & Manohar Sehgal

Hi,

First of all I appreciate your wonderful convincing technique of TEMPO separation along with valuable reference it’s your greatness you guys contributing significantly and guiding the new scientist/researcher in this field.

I am in area of Organis radicals and Polymer Chemistry, need your guideline.

My Question is I want synthesize the successful formation of biopolymer e.g. PEG-co-PAA, but all time esterformation peak in NMR missing or not well defined, I tried it multiple time, can you guide me please? Following article I followed for final product synthesis process.

Synthesis of PAA-PEG2000. PAA (14 mg, 8 μmol) was dissolved in 8 mL of a 100 mM potassium phosphate buffer (KPO4) at pH 6.0. EDC (192 mg, 1 mmol) and NHS (24 mg, 200 μmol) were dissolved in 2 mL of KPO4 and added to the above solution. The formation of activated NHS ester groups is indicated by a slight clouding of the reaction mixture. After 20 min of stirring at room temperature, 200 mg (100 μmol) of PEG2000 in 8 mL of KPO4 was

added and the reaction mixture was adjusted to pH 8.2 by titration with 1 M NaOH. At this pH, the NHS ester functionalities will react with amino groups to form stable amide bonds. The reaction was allowed to proceed for 4 h at room temperature, after which the reaction mixture was dialyzed for 24 h against deionized water. Andrea Seehuber et al. ,Langmuir (2012), 28, 8700−8710, ; Doi.org/10.1021/la2050652  

Thank you.

Warmest Regards,

Dr Alam