Nucleophilic displacement reactions, acid mechanism

As in benzenoid chemistry, some nucleophilic displacement reactions can be copper catalyzed. Illustrative of these reactions is the displacement of bromide from 3-bromothiophene-2-carboxylic acid and 3-bromothiophene-4-carboxylic acid by active methylene compounds (e.g., AcCH2C02Et) in the presence of copper and sodium ethoxide (Scheme 136). Analogously, 2-methoxythiophene can be prepared in 83% yield by refluxing 2-bromothiophene in methanol containing excess sodium methoxide, along with copper(I) bromide as catalyst. For the analogous preparation of 3-methoxythiophene, addition of a polar cosolvent (e.g., l-methyl-2-pyrrolidone) is beneficial. In the case of halothiophenes, an SrnI mechanism is involved. 

There are expressions of uncertainty concerning the mechanism of the first step of the Strecker amino acid synthesis13-17. The reaction can proceed via the formation of an imine and subsequent nucleophilic attack of cyanide (path ). Alternatively, it has been speculated that the reaction of the aldehyde with hydrogen cyanide furnishes a cyanohydrin (path ), which then is subjected to a nucleophilic displacement of the hydroxy group by the amino function. 

With such a diversity of N-nItrosatlon pathways theoretically possible. It Is comforting to note that only a few combinations of circumstances have been Implicated In environmental nitrosamlne formation thus far. Two of these are so facile and prevalent that, as of 20 years ago, they were the only recognized mechanisms of N-nItrosatlon. They Involve the Interaction of di-or trisubstituted ammonia derivatives with a nitrite Ion, as Illustrated In Figure 1 for the secondary amines, under the catalytic Influence of acid. Note the Important special cases of nucleophilic displacement of water from the nitrous acldlum Ion, H20-N0 , by a second nitrite Ion to yield NoOo (as in the reaction at the top of Figure 1), and by nitrate (bottom of Figure... 

However, if we consider the alternative nucleophilic displacement, it is known that nucleophilic processes are accelerated by ionic liquids, but more pertinent is the fact that the Sn2 displacement of iodide from alkyl iodide (Mel) by Rh(CO)2l2 is slightly accelerated by ionic liquids (7). Unfortunately, ionic liquids would also be expected to accelerate the nucleophilic displacement of iodide from ethyl iodide by propionic acid to form ethyl propionate (Reaction 8). In fact, as an Sn2 Type II displacement (the interaction of two neutral species), the ester formation from propionic acid and ethyl iodide would be expected to be significantly increased compared to the reaction of Rh(CO)2l2 with EtI. Therefore, by operating in iodide containing ionic liquids, we had set up a situation in which we suppressed the normally predominant hydride mechanism, slightly accelerated the alternative nucleophilic mechanism, but dramatically increased the ethyl propionate by-product forming pathway. 

The methylation of arylacetic acid derivatives is chosen as a model reaction for the mechanistic discussion. Experimental evidence of DMC-mediated alkylation of A1CH2X (X = CN, C02Me) with DMC supports the hypothesis that the reaction does not proceed through a 8 2 displacement of the ArCH X nucleophile on DMC (Bai2 mechanism).Rather, the selectivity arises from consecutive... 

A discussion of nucleophilic reactions in carbonyl systems, and in particular in derivatives of carboxylic acids, is included in the present text because of the importance of these reactions and their analogy with well-known processes in solution. While the actual mechanism of these reactions is more adequately described in many cases as an addition-elimination, we shall restrict our comments to systems which formally behave as displacement reactions. 

Nucleophilic Displacement of Halogens at Saturated Carbon Atoms Box 13.1 The Concept of Hard and Soft Lewis Acids and Bases (HSAB) Illustrative Example 13.2 Some More Reactions Involving Methyl Bromide Illustrative Example 13.3 1,2-Dibromoethane in the Hypolimnion of the Lower Mystic Lake, Massachusetts Polyhalogenated Alkanes — Elimination Mechanisms... 

The "oxyanion hole." A third mechanism by which an enzyme can assist in a displacement reaction on a carbonyl group is through protonation of the carbonyl oxygen atom by an acidic group of the enzyme (Eq. 12-21). This will greatly increase the positive charge on the carbon atom making attack by a nucleophile easier and will also stabilize the tetrahedral... 

Mechanisms of reaction. Activation of an amino acid occurs by a direct in-line nucleophilic displacement by a carboxylate oxygen atom of the amino acid on the a phosphorus atom of MgATP to form the aminoacyl adenylate (Eq. 29-1, step a). For yeast phenylalanyl-tRNA synthetases the preferred form of MgATP appears to be the P,y-bidentate (A screw sense) complex (p. 643).250 This is followed by a second nucleophilic displacement, this one on the C = 0 group of the aminoacyl adenylate by the -OH group of the tRNA (Eq. 29-1, step b Fig. 29-9C). A conformational change in the protein may be required to permit dissociation of the product, the aminoacyl-tRNA. In the complex of a class I synthetase with aminoacyl... 

Addition of a nucleophile to the C-6 position of cytosine often results in fascile displacement reactions occurring at the N4 location. With hydroxylamine attack, nucleophilic displacement causes the formation of an N4-hydroxy derivative. A particularly important reaction for bioconjugate chemistry, however, is that of nucleophilic bisulfite addition to the C-6 position. Sulfonation of cytosine can lead to two distinct reaction products. At acid pH wherein the N-3 nitrogen is protonated, bisulfite reaction results in the 6-sulfonate product followed by spontaneous hydrolysis. Raising the pH to alkaline conditions causes effective formation of uracil. If bisulfite addition is done in the presence of a nucleophile, such as a primary amine or hydrazide compound, then transamination at the N4 position can take place instead of hydrolysis (Fig. 38). This is an important mechanism for adding spacer arm functionalities and other small molecules to cytosine-containing oligonucleotides (see Chapter 17, Section 2.1). 

Due to the presence of a strongly electrophilic carbon centre alkyl halides are susceptible to nucleophilic attack, a nucleophile displaces the halogen as a nucleophilic halide ion (Following fig.). The reaction is called nucleophilic substitution and there are two types of mechanism, i.e. the S I and SN2 mechanisms. Carboxylic acids and carboxylic acid derivatives also undergo nucleophilic substitutions, but the mechanisms are totally different. 

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