Rate determining carbonyl derivatives

The Pictet-Spengler reaction is an acid-catalyzed intramolecular cyclization of an intermediate imine of 2-arylethylamine, formed by condensation with a carbonyl compound, to give 1,2,3,4-tetrahydroisoquinoline derivatives. This condensation reaction has been studied under acid-catalyzed and superacid-catalyzed conditions, and a linear correlation had been found between the rate of the reaction and the acidity of the reaction medium. Substrates with electron-donating substituents on the aromatic ring cyclize faster than the corresponding unsubstituted compounds, supporting the idea that the cyclization process is involved in the rate-determining step of the reaction. 

Carbonic acid esters (alkoxycarbonyl derivatives) are diesters of general formula R-O-CO-O-R. A single mechanism operates in the HO -catalyzed (and presumably also in the enzyme-catalyzed) hydrolysis of carbonic acid esters, namely a rate-determining addition of the base to the carbonyl C-atom to form an intermediate whose breakdown yields the drug (ROH), C02, and an alcohol (R OH) (Fig. 8.7,a) [153],... 

Eliminations from Os(CO)4RR occur by dinuclear mechanisms only if either R or R is H. A hydride on one metal is necessary to interact with a vacant coordination site on the other in the dinuclear transition state. With Os(CO)4H2, the vacant site is created by dissociation of CO. With Os(CO)4-(H)CH the vacant site is created by a facile rate-determining isomerization which we suggest is to an acetyl hydride. The unique instability of hydridoalkyl carbonyls thus is explained. The synthesis and properties of Os(CO)4(H)C2H and various polynuclear ethyl osmium derivatives show that (3-hydrogens have no significant effect on these elimination mechanisms. Dinuclear hydridoalkyls are excellent starting points for the synthesis of more complex polynuclear alkyls. 

The catalytic effect of metal ions such as Mg2+ and Zn2+ on the reduction of carbonyl compounds has extensively been studied in connection with the involvement of metal ions in the oxidation-reduction reactions of nicotinamide coenzymes [144-149]. Acceleration effects of Mg2+ on hydride transfer from NADH model compounds to carbonyl compounds have been shown to be ascribed to the catalysis on the initial electron transfer process, which is the rate-determining step of the overall hydride transfer reactions [16,87,149]. The Mg2+ ion has also been shown to accelerate electron transfer from cis-dialkylcobalt(III) complexes to p-ben-zoquinone derivatives [150,151]. In this context, a remarkable catalytic effect of Mg2+ was also found on photoinduced electron transfer reactions from various electron donors to flavin analogs in 1984 [152], The Mg2+ (or Zn2+) ion forms complexes with a flavin analog la and 5-deazaflavins 2a-c with a 1 1 stoichiometry in dry MeCN at 298 K [153] ... 

In a reaction related to azide carbonylation, aromatic nitroso compounds also give isocyanates (equation 94). [Rh2Cl2(CO)4] (96), [RhCl(CO)2py], [RhCl(CO)(PPh3)2] (71) and [RhCl(CO)-(P(OPh)3 2] all catalyzed the reaction. Deoxygenation of the nitrosobenzene derivative was the rate determining step.448 Nitrosomethane can be similarly carbonylated.449-451... 

Treatment of 3-hydroxythietanes 21b-g with aqueous sodium hydroxide led to retro-aldol ring cleavage to produce the carbonyl derivatives 23b-g (Table 1) <1997J(P2)425>. It was proven that the rate of the reaction was determined by the nature of the substituent at the 3-position and by the oxidation state of sulfur. 3-Phenylthietane-3-ol 21b underwent retro-aldol reaction to give sulfide ketone 23b. Thietane-l-oxide-3-ol 21c-e or thietane-l,l-dioxide-3-ol 2 If and 21g derivatives underwent retro-aldol reaction to produce carbonyl sulfoxides 23c-e and carbonyl sulfones 23f and 23g (Table 1) <1997J(P2)425>. 

To understand this difference in reactivity of various acid derivatives look at the first step in the nucleophilic substitution mechanism (involving the addition of a nucleophile to the electrophilic carbonyl carbon) which is the rate-determining step. Therefore, the more electrophilic this carbon is, the more reactive it will be. The nature of Y has a significant effect in this respect ... 

Removal of the amine moiety in piperazine derivatives in acidic medium " is thought to occur from the enolic form of the ammonium salt, at least at very low pH values. However,. step b has not been interpreted entirely from the mechanistic point of view, as far as the participation of ammonium/enolate structures is concerned. Several cyclic transition states have been envisaged, some of which involve the presence of a hydroxy group or the enolic form of the P-aminoketone. In particular, the participation of OH groups belonging to other molecules, such as carboxyacids present in the reaction medium, cannot be excluded. " By contrast, a nucleophilic attack by an acid anion on the carbonyl C atom has been claimed to be the rate-determining step for deamination in the reaction between p-aminoketones and triethyl phosphite in dimethylformamide. ... 

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