Diastereomeric Amides Derived from Malonic Acid: the Role of Chiral Auxiliaries and of the Nature of Co-Acids in the Mixed Kolbe Electrolyses

Abstract

Experimentos visando o acoplamento diastereosseletivo de mono-amidas do ácido metilmalônico, sintetizadas a partir de aminas quirais comerciais [S-(+)-1-ciclo-hexiletilamina e (R)-(+)-1-feniletilamina] foram realizados, utilizando-se oxidação anódica de Kolbe [cela não dividida, Pt (ânodo e cátodo), MeOH, neutralização de 5% a 10% com solução metanólica de KOH (1 M), 200 a 250 mA/cm 2 ], usando diferentes co-ácidos (ácidos hexanóico, trimetilsililacético, dietilfosfonoacético e ftaloilglicina).Amidas de cadeia longa ou sililadas (dímeros mistos de Kolbe) foram obtidas com bom rendimento (56 a 63%) e baixa diastereosseletividade, na presença de excesso de co-ácidos, em conjunto com produtos derivados de caminhos alternativos, principalmente produtos de desproporcionamento e derivados metoxilados.O acoplamento radicalar mostrou-se altamente sensível à natureza dos radicais envolvidos, sendo mais efetivo entre radicais de reatividade oposta. Radicais eletrofílicos acoplam entre si em muito pequena extensão.Acoplamentos diastereosseletivos, na presença dos auxiliares quirais acíclicos, não foram expressivos.Eletrólise de Kolbe realizada com a ftaloilglicina forneceu dímeros simétricos, N-metoximetilhidroxilactama e N-metoxiftalimida. Na presença de ácido hexanóico, além dos produtos já citados, foram obtidas uma imida alquilada e a hidroxilactama correspondente. New long chain and silylated amides (mixed Kolbe dimer) were obtained in good yields (56 to 63%) and low diastereoselectivity, in the presence of a large excess of co-acids, together with disproportionation and non-Kolbe (nK) products, mainly methoxy derivatives.Coupling was more effective with radicals with opposite reactivity. Electrophilic radicals couple between themselves to a lesser extent.Diastereoselective induction was not high. Studies performed with phthaloylglycine, under Kolbe conditions, in the absence and presence of hexanoic acid as a co-acid led to the symmetrical dimer, a N-methoxymethyl-hydroxylactam and a N-methoxyphthalimide. In the presence of hexanoic acid, the latter products were obtained together with alkylated imide and the corresponding hydroxylactam.

(Non-)Kolbe electrolysis in biomass valorization – a discussion of potential applications

“…The formed esters showed promising octane ratings (71-99) for application in gasoline. Furthermore, the calculated cetane numbers of the obtained alkanes (45-60) are comparable or even superior to benchmark biodiesel fuels (45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55). In conclusion, the different bio-derivable mono-and diacids can be reassembled to a desired composition like single bricks.…”

“…29,46 For cross-coupled Kolbe dimers, the use of acids with antagonistic reactivities (nucleophilic vs. electrophilic) appears to be essential. 47 Additionally, ultrasonic mixing proved to be advantageous which is assumed to enhance the adsorption of organic acids on the electrode surface also increasing mass transport. 48 Nevertheless, studies elucidating the rate determining step in Kolbe electrolysis are not available.…”

Crystallographic and Kinetic Studies of Human Mitochondrial Acetoacetyl-CoA Thiolase: The Importance of Potassium and Chloride Ions for Its Structure and Function,

“…The remaining solution was acidified with HCl and extracted with ether, after which the ether layer was dried with MgSO 4 . Freshly distilled thionyl chloride was added slowly into the ether solution of 2-methylacetoacetic acid and refluxed for 2 h. Excess SOCl 2 and ether were eliminated by evaporation to dryness (26). The prepared 2-methylacetoacetoyl chloride was used to acylate CoA (trilithium salt) at pH 8.5.…”

Sustainable electrochemical decarboxylative acetoxylation of aminoacids in batch and continuous flow

“…This compound is formed by cathodic reduction of the carbonyl group and can be favored when proton reduction has a high overpotential. 24 Mixtures of AcOH with MeCN, which had been shown as suitable solvents in previous studies, 21a provided significantly reduced selectivity (entries 2-4). In the presence of MeCN, the carbocation was partially trapped by the nitrile, resulting in the formation of the corresponding amide via an electrochemical Ritter-type reaction.…”