James M. Bobbitt

Organic nitrosonium salts as oxidants in organic chemistry

Les sels de nitrosonium obtenus par oxydation de nitroxyles peuvent etre utilises pour oxyder les alcools en aldehydes ou cetones, les amines primaires en aldehydes, ou dans certains cas (RCH 2 NH 2 ) en nitriles, les cetones en α-dicetones, et les phenols en quinones

Synthesis of 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate and 4-acetamido-(2,2,6,6-tetramethyl-piperidin-1-yl)oxyl and their use in oxidative reactions

We describe the synthesis of the lesser-known stoichiometric oxidation reagent 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (1, Bobbitts salt), as well as of 4-acetamido-(2,2,6,6-tetramethyl-piperidin-1-yl)oxyl (2, AcNH-TEMPO). Several representative oxidation reactions are also presented to demonstrate the salts oxidative capabilities. Bobbitts salt has a range of applications, from the oxidation of various alcohols to their corresponding carbonyl derivatives to the oxidative cleavage of benzyl ethers, whereas 2 has been shown to serve as a catalytic or stoichiometric oxidant. The oxyl radical can be obtained in 85% yield over two steps on a 1-mole scale from commercially available 4-amino-2,2,6,6-tetramethylpiperidine (5), and is far more cost-effective to prepare in-house than purchase commercially. An additional step converts the oxyl radical into the oxoammonium salt (1, Bobbitts salt) in 88% yield, with an overall yield of 75%. The synthesis of the salt takes ∼5 d to complete. Oxoammonium salts are metal-free, nontoxic and environmentally friendly oxidants. Preparation of 1 is also inherently ′green′, as water can be used as the solvent and the use of environmentally unfriendly materials is minimal. Moreover, after it has been used, the spent oxidant can be recovered and used to regenerate 1, thereby making the process recyclable.

Oxidative cleavage of benzylic and related ethers, using an oxoammonium salt.

Benzylic ethers and related ArCH(2)OR substrates are oxidatively cleaved by 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (1) in wet CH(3)CN at room temperature to give the corresponding aromatic aldehyde and alcohol in high yield. Primary or secondary alcohol products are further oxidized by 1 to give carboxylic acids and ketones, respectively. The oxidation likely involves a formal hydride abstraction from the benzylic carbon as evidenced by slow reaction of substrates bearing electron-withdrawing substituents.

4-AcNH-TEMPO-CATALYZED OXIDATION OF ALDOSES TO ALDARIC ACIDS USING CHLORINE OR BROMINE AS TERMINAL OXIDANTS

The 4-AcNH-TEMPO-catalyzed oxidation of d-glucose to d-glucaric acid using elemental chlorine or bromine as the terminal oxidant is reported. The pH and temperature of the reactions were closely controlled to be between 0–5°C and pH 11.5, respectively. Spectroscopically (1H NMR) determined yields of glucarate were greater than 90%; yields of crystalline monopotassium d-glucarate (or disodium d-glucarate), isolated and purified by precipitation, were between 70 and 85%. Oxidations of mannose to mannaric acid and galactose to mucic acid were also demonstrated.

Enantioselective electrocatalytic oxidation of racemic sec-alcohols using a chiral 1-azaspiro[5.5]undecane-N-oxyl radical

Nitroxyl radical (6S,7R,10R)-4-acetylamino-2,2,7-trimethyl-10-isopropyl-1-azaspiro[5.5]-undecane-N-oxyl reveals a reversible redox peak in cyclic voltammetry at + 0.62 V vs. Ag/AgCl. A preparative electrocatalytic oxidation of racemic sec-alcohols on the nitroxyl radical yielded mixtures of 51.4 – 63.9 % ketones and 36.1 – 48.6 % alcohols by 10 h of electrolysis. The current efficiency and turnover number of the reactions were 85.6 – 87.9 % and 20.6 – 25.6, respectively. The enantiopurity of the remaining (R)-isomers was 50 – 70 % and the S values as a selective factor was 4.1 – 4.6.

Enantioselective, electrocatalytic oxidative coupling of naphthol, naphthyl ether and phenanthrol on a TEMPO-modified graphite felt electrode in the presence of (–)-sparteine (TEMPO = 2,2,6,6-tetramethylpiperidin-1-yloxyl)

Constant potential electrolysis of 2-naphthol, 2-methoxynaphthalene and 10-hydroxyphenanthrene at 0.6 V vs. Ag/AgCl on a TEMPO-modified graphite felt electrode in the presence of (–)-sparteine in acetonitrile yields, enantioselectively, (S)-binaphthyl type dimers in >92% isolated yield and with >88% current efficiency with enantiomeric excesses of 98, 91 and 97% respectively for each dimer, respectively.

Selective oxoammonium salt oxidations of alcohols to aldehydes and aldehydes to carboxylic acids.

The oxidation of alcohols to aldehydes using stoichiometric 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (1) in CH(2)Cl(2) at room temperature is a highly selective process favoring reaction at the carbinol center best able to accommodate a positive charge. The oxidation of aldehydes to carboxylic acids by 1 in wet acetonitrile is also selective; the rate of the process correlates with the concentration of aldehyde hydrate. A convenient and high yield method for oxidation of alcohols directly to carboxylic acids has been developed.

Facile nitroxide-mediated oxidations of d-glucose to d-glucaric acid

The oxidation of D-(+)-glucose to D-glucaric acid using the TEMPO-like nitroxide oxidation catalyst, 4-acetamido-2,2,6,6-tetramethyl-1-piperidinyloxy (4-acetamido-TEMPO) was carried out using several oxidizing agents and co-catalyst. The pH and temperature of the reactions were closely monitored to decrease degradations during the oxidation, and several isolation methods were explored.

Organic nitrosonium salts. II, Stability studies and oxidations of some indole derivatives

The electrochemical preparation,studies of the stability of certain nitrosonium salts and their reaction with some indole derivatives are reported

Facile Oxidation of Primary Amines to Nitriles Using an Oxoammonium Salt

The oxidation of primary amines using a stoichiometric quantity of 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (1) in CH2Cl2-pyridine solvent at room temperature or at gentle reflux affords nitriles in good yield under mild conditions. The mechanism of the oxidation, which has been investigated computationally, involves a hydride transfer from the amine to the oxygen atom of 1 as the rate-limiting step.