Amine nucleophiles mechanism

Equations (30) and (33) when combined with the results recorded in Table 1 reduce to one of two simplified mechanisms, depending upon the basicity of the amine nucleophile. Mechanism (37) can be used to describe condensation reactions in which the amine is a relatively weak base. This mechanism accounts for the general acid... 

We can explain the observed pH dependence of imine formation by looking at the individual steps in the mechanism. As indicated in Figure 19.8, an acid catalyst is required in step 3 to protonate the intermediate carbinolamine, thereby converting the —OH into a better leaving group. Thus, reaction will be slow if not enough acid is present (that is, at high pH). On the other hand, if too much acid is present (low pH), the basic amine nucleophile is completely protonated, so the initial nucleophilic addition step can t occur. 

The reaction of 2-bromo-5-nitrothiazole with weakly basic secondary aliphatic amines gave the expected 2-amino products. The isomeric 5-bromo-2-nitrothiazole with such amines gave mixtures of the expected 5-amino products along with 2-aminated 5-nitrothiazole rearrangement products. A mechanism was proposed which involves the slow thermal isomerisation of the 5-bromo-2-nitrothiazole to the much more reactive 2-bromo isomer which competes, in the case of relatively weak amine nucleophiles, with direct but slow displacement of the 5-bromo group to form the normal displacement product <96JHC1191>. 

The proposed catalytic cycle of the ruthenium-catalyzed intermolecular Alder-ene reaction is shown in Scheme 21 (cycle A) and proceeds via ruthenacyclopentane 100. Support for this mechanism is derived from the observation that the intermediate can be trapped intramolecularly by an alcohol or amine nucleophile to form the corresponding five-or six-membered heterocycle (Scheme 21, cycle B and Equation (66)).74,75 Four- and seven-membered rings cannot be formed via this methodology, presumably because the competing /3-hydride elimination is faster than interception of the transition state for these substrates, 101 and 102, only the formal Alder-ene product is observed (Equations (67) and (68)). 

A polar nucleophilic mechanism has also been advanced (86) (Fig. 4.34C). The mechanism is characterized by a nucleophilic attack of the amine on the 4a position of FAD to form the amine adduct followed by base-catalyzed elimination to the imine and FADH2. 

In other systems, similar kinetic laws were observed when studying the effect of added pyridine, although differentiation with the dimer nucleophile mechanism is made in the interpretation of the experimental results (see below). Rationalizations of the involved phenomena are based on the strong hydrogen-bond interactions between the nucleophile and the pyridine, and on the catalytic effect of a third amine molecule in the decomposition of the zwitterionic intermediate in non-polar solvents. 

Mechanism. The neutral amine nucleophile attacks the carbonyl carbon to form a dipolar tetrahedral intermediate. The intramolecular proton transfer from nitrogen and oxygen yields a neutral carbinolamine tetrahedral intermediate. The hydroxyl group is protonated, and the dehydration of the protonated carbinolamine produces an iminium ion and water. Loss of proton to water yields the imine and regenerates the acid catalyst. 

The polymerization of an NCA may be initiated by any moderately strong base or by nucleophiles. Weak nucleophiles, such as water, alcohols, or primary amines, generally initiate polymerization by the normal (nucleophilic) mechanism or by the carbamate mechanism. Tertiary amines and strong bases, such as methoxide, initiate polymerization by the active monomer mechanism. Secondary or primary amines may initiate polymerization by any one or all of these mechanisms. More than one mechanism may be active at any one time and frequently a polymerization may begin by the active monomer mechanism and then, at a later stage, propagate by the normal mechanism. 16 ... 

There has been a review of relationships between activation parameters and mechanisms for biomolecular reactions in solution, including both nucleophilic substitutions and additions.5 Several studies have been reported involving substitutions by amine nucleophiles where both electronic and steric effects may be important. Kinetic studies of the reactions of 2,4-dinitrophenyl 2,4,6-trinitrophenyl ether (1) with ring-substituted... 

In the context of mechanistic studies, the electrochemical behavior and reactions with nucleophiles of 4-chloro-2,6-diphenylpyrylium and 4-chloro(bromo)flavylium have been studied <1999CHE653>. The proposed mechanism for nucleophilic substitution in halogen-substituted pyrylium and flavylium salts passes through formation of a charge-transfer complex that is converted into an ion-radical pair by simple electron transfer. Heterocyclic cleavage of the C-halogen bond occurs at the stage of the radical or the adduct from the reaction of the pyrylium salt and the nucleophile. In this study, an amine nucleophile was used however, the data are likely relevant for other types of nucleophiles as well (Scheme 5). 

Undecylenic acid has also been shown to react with the surface preferentially at the alkene end, leaving the terminal carboxylic acid group free for further reaction [53], This result was somewhat unexpected as the Si-H sites are considered to be somewhat acidic and the oxophilic nature of silicon should thermodynamically favor reaction with the hydroxyl group of the acid. The preferential reactivity with the alkenyl end is consistent with a free radical, rather than a nucleophilic mechanism. The acid function can be activated with N-hydroxy succinimide (NHS) to facilitate coupling with amine tagged molecules. Schematically,... 

The Menschutkin reaction of benzyl tosylates [21]-OTs with dimethyl-anilines or pyridines in acetonitrile generally proceed by a second-order bimolecular Sn2 mechanism for most ring-substituted compounds the plot of obs vs. [Nu] passes through the origin within experimental uncertainty (Yoh et al., 1989). However, for the reactions of strong ED derivatives under the same conditions, it was found that there was a significant intercept (i.e. a first-order component) in the kobs vs. [Nu] plots represented by (39) the intercept is a constant of the benzyl substrate independent of the amine nucleophiles, indicating a concurrent reaction zeroth-order in amine (Kim et al., 1995, 1998). 

Search for new mechanism based investigations for deducing the mechanism of the enzyme catalyzed activity continues to be active area of research. Mariano and coworkers have used activated flavins such as 5-ethylflavinium perchlorate, whose ground state reduction potentials are high enough to promote oxidative dealkylation of amines, as enzyme models [209]. Studies on the inactivation of the model enzymes by cyclopropylamines and a-silylamines suggest a polar mechanistic model. Silverman attributes this result to the drastically altered nature of the flavin used in these studies, which could favor a nucleophilic mechanism [16]. 

The pattern of base catalysis of reactions with amine nucleophiles provides additional evidence. These reactions are catalyzed by bases only when a relatively poor leaving group (e.g., OR) is present (not Cl or Br) and only when relatively bulky amines are nucleophiles. Bases could not catalyze step 1, but if amines are nucleophiles, bases can catalyze step 2. Base catalysis is found precisely in those cases where the amine moiety cleaves easily but X does not, so that k i is large and step 2 is rate determining. This is evidence for the S Ar mechanism because it implies two steps. Furthermore, in cases where bases are catalysts, they catalyze only at... 

The second step involves an elimination of the tertiary amine (ElcB mechanism) and a coniac. addition of the enolate anion of diethyl malonate to the resulting enone. This device prevent v reactive enone from combining with itself by releasing it only in the presence of an excess c -.ii nucleophile. 

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