Chemistry
Electrophile and Nucleophile
Electrophiles are electron-deficient species that seek to accept a pair of electrons, typically through a reaction with a nucleophile. Nucleophiles, on the other hand, are electron-rich species that donate a pair of electrons to form a new chemical bond with an electrophile. In chemical reactions, electrophiles and nucleophiles play crucial roles in determining the direction and outcome of the reaction.
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eBook - ePub- Graham Patrick(Author)
- 2004(Publication Date)
- Taylor & Francis(Publisher)
SECTION E — NUCLEOPHILES AND ELECTROPHILES
E1 Definition
Key Notes
Nucleophiles Nucleophiles are electron-rich molecules and react with electrophiles. Nucleophilic center The nucleophilic center of a nucleophile is the specific atom or region of the molecule which is electron rich. Electrophiles Electrophiles are electron-deficient molecules and can react with nucleophiles. Electrophilic center The electrophilic center of an electrophile is the specific atom or region of the molecule which is electron deficient. Related topics (E2) Charged species (E4) Organic structures (E3) Neutral inorganic species Nucleophiles
Most organic reactions involve the reaction between a molecule which is rich in electrons and a molecule which is deficient in electrons. The reaction involves the formation of a new bond where the electrons are provided by the electron-rich molecule. Electron-rich molecules are called nucleophiles (meaning nucleus-loving). The easiest nucleophiles to identify are negatively charged ions with lone pairs of electrons (e.g. the hydroxide ion), but neutral molecules can also act as nucleophiles if they contain electron-rich functional groups (e.g. an amine).Nucleophilic center
Nucleophiles have a specific atom or region of the molecule which is electron rich. This is called the nucleophilic center. The nucleophilic center of an ion is the atom bearing a lone pair of electrons and the negative charge. The nucleophilic center of a neutral molecule is usually an atom with a lone pair of electrons (e.g. nitrogen or oxygen), or a multiple bond (e.g. alkene, alkyne, aromatic ring).Electrophiles
Electron-deficient molecules are called electrophiles
eBook - ePub- J Fisher, J.R.P. Arnold, Julie Fisher, John Arnold(Authors)
- 2020(Publication Date)
- Taylor & Francis(Publisher)
A molecule or region thereof is electron rich if it has a negative charge, if it has lone pairs of electrons associated with it, or if it involves one or more pi bonds. Some examples of nucleophilic species are provided in Figure 1. As nucleophiles, by definition, are electron rich when they react they do so with species that are electron deficient; that is electrophiles (see below). In establishing which sites in a molecule are electron rich or electron deficient, considerable progress is made towards predicting the outcome of chemical reactions. When considering the strengths of various nucleophiles, it is informative to take account of the stability of the positively charged species that would arise following nucleophilic attack. Consider the simple example of protonation of hydrogen fluoride (HF), ammonia (NH 3), and water (Figure 2). As fluorine is the most electronegative element (Section A1) possessing three lone pairs of electrons in HF, it would be expected to be the most nucleophilic. In fact in this series it is the least, and this is because fluorine will not tolerate the positive charge that would reside on it. In contrast nitrogen is the least electronegative, but ammonia is the most nucleophilic as it will accept a positive charge; this is indicated by the frequency with which ammonium ions appear in chemistry and biology. Figure 1 Common nucleophilic centers. R, alkyl; R′, alkyl or H; ↑, nucleophilic center. Figure 2 Protonation of HF, NH 3, and H 2 O. ⇌, equilibrium. Electrophile The term electrophile (electron-loving) is applied to atoms or regions of molecules that are electron deficient. Electrophiles are, therefore, the exact opposite of nucleophiles, and are the atoms or parts of molecules with which nucleophiles react. Consequently the trend in electrophilic strength is the exact opposite to that of nucleophilic strength. Thus, HF will readily act as an electrophile, taking on negative charge as its hydrogen is abstracted by a base
eBook - ePub- Subrata Pal(Author)
- 2019(Publication Date)
- Academic Press(Publisher)
The nucleophile-electrophile interaction can be explained based on what is known as the frontier molecular orbital (FMO) theory. Instead of looking at the total electron density in the reactant species, the FMO theory focuses on the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) as they are most likely to be involved in chemical reactivity. Electrons are most easily removed from the HOMO which, therefore, can donate electrons to form a bond (as a nucleophile). At the same time, it is energetically most facile to fill the LUMO with additional electrons. An electrophile is represented by its LUMO. The nucleophile-electrophile interaction can be seen essentially as a HOMO-LUMO interaction.Let us consider a nucleophilic reactionC 2H 5O −+H 3C - I →C 2H 5O -+C H3I −(4.33)where the ethoxide ion (nucleophile) displaces (substitutes) the iodide ion (leaving group) from the methyl carbon. The general form of the reaction can be written as in Fig. 4.16 . Such a mechanism in which the donation of an electron pair by a nucleophile to an atom displaces a leaving group from the same atom in one step (without any reactive intermediate) is called an SN 2 reaction. (S, N, and 2, respectively, symbolize substitution, nucleophilic, and bimolecular).⁎⁎⁎⁎⁎⁎⁎⁎⁎⁎⁎⁎⁎⁎⁎⁎⁎⁎Fig. 4.16 General scheme of SN 2 reaction. LG, leaving group.While discussing the underlying principles of structures and processes in this chapter, we have kept the illustrations limited to very simple and small molecules. As we move ahead, we shall find in chapters to follow that the biological system consists of small molecules as well as large molecules or macromolecules with a varying degree of complexity in their structures and the processes they are involved in. Nevertheless, the fundamental physicochemical principles we have learnt so far can be applied to the biological system as well, albeit with more sophisticated approaches.
eBook - ePubBiochemistry
An Organic Chemistry Approach
- Michael B. Smith(Author)
- 2020(Publication Date)
- CRC Press(Publisher)
3 Nucleophiles and ElectrophilesAliphatic substitution reactions are early examples of organic chemical reactions in a typical undergraduate organic chemistry course. Such reactions involve the reaction of nucleophilic species with an electrophilic species, and for the most part they follow first-order or second-order kinetics. There are nucleophiles that are prevalent in biochemical reactions, including alcohols, amines, and thiols. Substitution reactions in a typical organic chemistry course involve reactions at carbon that is connected to a heteroatom moiety such as a halogen leaving group. In biochemistry the leaving group is often a phosphonate ester or another biocompatible group. Another type of nucleophilic reaction involves carbonyl compounds, including acyl addition of ketone and aldehyde moieties and acyl substitution reactions of carboxylic acid derivatives.This chapter will briefly review the SN 2 and SN 1 reactions and then describe nucleophiles that are common in biochemical applications and the substitution reactions that are common for these nucleophiles. Nucleophilic reactions require electrophilic species. Electrophiles or electrophilic substrates are common in biochemistry, including phosphonate derivatives, carbonyl compounds and imine compounds. Any discussion of typical nucleophilic reactions also requires an understanding of such electrophilic substrates. The fundamentals of both acyl addition and of acyl substitution reactions will be presented for carbonyl electrophilic centers and the reactions of these electrophilic centers with nucleophiles.3.1 Nucleophiles and Bimolecular Substitution (the SN 2 Reaction)The SN 2 reaction is one of the seminal reactions in a typical undergraduate organic chemistry course. The reaction of 1-bromo-3-methylbutane with sodium iodide (NaI) using acetone as a solvent gave 1-iodo-3-methylbutane, in 66% yield.1 In terms of the structural changes, the iodide ion substitutes for the bromine, producing bromide ion (Br– ). Iodide reacted as a nucleophile in the reaction at Cδ+ of the alkyl bromide, breaking the C—Br bond and transferring the electrons in that bond to bromine. In molecules that contain the C—Br bond, or indeed a C—C bond, where X is a heteroatom-containing group, the carbon will have a δ+ dipole. In other words, the carbon atom is electrophilic, and the substrate that reacts with the nucleophile is called an electrophile. The reaction of a nucleophile with an aliphatic electrophile is formally called nucleophilic aliphatic substitution , illustrated in Figure 3.1 . The displaced atom or group (e.g., chloride), departs (leaves) to become an independent ion. Displacement of chlorine leads to the chloride ion (Cl– ), but the bromide ion, iodide ion, or a sulfonate anion also correlates to X, which is referred to as a leaving group . In many biochemical reactions, the leaving group is a phosphate, —O–PO2
