Types of nucleophiles

The attacking nucleophile can be negatively charged (Nu ) or neutral (Nu). With neutral nucleophiles, acid catalysis is common. 

Nu = H20 (water), ROH (alcohol), NH3 (ammonia), RNH2 or R2NH (primary or secondary amine). 

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Another type of nucleophilic aromatic substitution occurs under quite different reaction conditions from those discussed to this point and proceeds by a different and rather surprising mechanism It is described m the following section... 

Ultraviolet and infrared spectroscopic investigations and also chemical behavior show unambiguously that the compounds which result from the last-rnentioned type of nucleophilic reagent and cotarnine possess the cyclic form. " Examples of these are cotar-nine anil (20a), cotarnine oxime (20b), cotarnine phenylhydra-zone (20c), anhydrocotarnine carbamide (20d), hydrocotarnyl-acetic acid (20e), anhydrocotarnine acetone (20f), and also the compound (21) obtained from two molecules of cotarnine and one molecule of acetone by the elimination of two molecules of water. The cyclic form had ben demonstrated earlier for anhydrocotarnine-nitromethane (20g) and anhydrocotarnine-acetophenone (20h). ... 

The high reactivity of trichloro-s-triazine and tetrachloropyrimi-dine, the ease of replacement of the first chlorine atom from these compounds with several types of nucleophiles (amines, alcohols, etc.) and, finally, the important role of these reactions in dye chemistry have stimulated many investigations dealing with substituents of the general types RZ and R2Z, where Z is an electron-donor atom or group (NH, 0, S, N). 

Addition of carbon nucleophiles to vinylepoxides is of particular importance, since a new carbon-carbon bond is formed. It is of considerable tactical value that conditions allowing for regiocontrolled opening of vinyloxiranes with this type of nucleophiles have been developed. Reactions that proceed through fonnation of a rr-allyl metal intermediate with subsequent external delivery of the nucleophile, or that make use of a soft carbon nucleophile, generally deliver the SN2 product. In contrast, the Sn2 variant is often the major reaction pathway when hard nucleophiles are employed. In some methods a nucleophile can be delivered selectively at either the Sn2 or SN2 positions by changing the reaction conditions. 

The fundamental understanding of the diazonio group in arenediazonium salts, and of its reactivity, electronic structure, and influence on the reactivity of other substituents attached to the arenediazonium system depends mainly on the application of quantitative structure-reactivity relationships to kinetic and equilibrium measurements. These were made with a series of 3- and 4-substituted benzenediazonium salts on the basis of the Hammett equation (Scheme 7-1). We need to discuss the mechanism of addition of a nucleophile to the P-nitrogen atom of an arenediazonium ion, and to answer the question, raised several times in Chapters 5 and 6, why the ratio of (Z)- to ( -additions is so different — from almost 100 1 to 1 100 — depending on the type of nucleophile involved and on the reaction conditions. However, before we do that in Section 7.4, it is necessary to give a short general review of the Hammett equation and to discuss the substituent constants of the diazonio group. 

This argument has been reviewed in many articles in the past and the corresponding problems in reaching the highest substitution level of the P-Cl bonds in the polydichlorophosphazene deeply analysed [38] therefore, it will not be considered in detail here. What is important to stress in the present paper is that the replacement of these chlorine atoms with variable types of nucleophiles provides many different classes of hydrolytically stable phosp-hazene materials, as reported in Fig. 9. 

In contrast to a, -ethylenic ketones or even a, -ethylenic sulfones, a, ) -ethylenic sulfoxides generally are not sufficiently electrophilic to undergo successful nucleophilic j8-addition . a-Carbonyl-a, j8-ethylenic sulfoxides, however, are potent, doubly activated alkenes which undergo rapid and complete -addition of various types of nucleophiles even at — 78 °C. A brief account summarizing this area is available . The stereochemical outcome of such asymmetric conjugate additions to enantiomerically pure 2-sulfmyl 2-cycloalkenones and 2-sulfinyl-2-alkenolides has been rationalized in terms of a metal-chelated intermediate in which a metal ion locks the -carbonyl sulfoxide into a rigid conformation (36 cf. 33). In this fixed conformation, one diastereoface of the cyclic n... 

Although replacement reactions of the pentameric system are also known, these have not been as well studied (14). The following account gives a description of some of the different types of nucleophilic substitution reactions that have been well studied. The sequential replacement of chloride substituents by fluoride has been studied, and is discussed elsewhere (14, 23). 

The chemistry of chlorocyclophosphazenes continues to be of great interest. Many of the mechanistic features involving the aminolysis reactions are now understood. However, rigorous kinetic studies on reactions of chlorocyclophosphazenes with other types of nucleophiles are quite rare. The most promising utility of the chlorocyclophosphazenes is their reactive periphery combined with a robust framework. It... 

The asymmetric addition of different types of nucleophiles at the C-l position of 3,4-dihydroisoquinolines were highlighted in a number of publications. Schreiber et al. described an enantioselective addition of terminal alkynes 136 to 3,4-dihydroisoquinolinium bromide 137 in the presence of triethylamine, catalytic copper bromide, and QUINAP <06OL143>. The resulting 1-substituted tetrahydroquinolines 138 were isolated in high yield and high enantiomeric excess in most cases. 

Other types of nucleophiles can also react with the electrophically activated triple bond. An O-acyl group has been shown to be an excellent participating group. Interestingly, this process, which is reminiscent of the well-known palladium(ll)-mediated 1,3-migration of allylic acetates327 represents a highly efficient means for the formation of... 

Some derivatives of the [l,2,4]triazolo[4,3-3]pyridazine ring system 33 were subjected to a special type of nucleophilic substitution called vicarious nucleophilic substitution (VSN) <2006TL4259>. In the course of this transformation a formal substitution of az aromatic hydrogen atom - occurring via an addition-elimination mechanism - takes place. 

Secondary amines react with aldehydes and ketones via addition reactions, but instead of forming imines, produce compounds known as enamines. Initially, there is the same type of nucleophilic attack of the amine onto the carbonyl system, followed by acid-catalysed dehydration but, since the amine is secondary, the product of dehydration is an iminium... 

Thiols undergo the same types of nucleophilic reaction with carboxylic acid derivatives as do alcohols. However, reactivity tends to be increased for two reasons. First, sulfur, because of its larger size, is a better nucleophile than oxygen (see... 

Types of Nucleophilic Substitution Reactions. A reaction described as SnI, short for substitution, nucleophilic (un-imolecular), comprises two steps ... 

With each of the C, P and S centers, compounds with several oxidation states are possible, thus multiplying the types of nucleophilic reactions extant. Importantly, the types of compounds cover a variety of classes each with its characteristic behaviors and reactivities, each defining a specific area in chemistry. Since the C, P and S reactive centers are incorporated in the majority of molecules in living systems it follows that the chemistry to be considered in this chapter is closely tied with the chemistry of life, i.e. bioorganic reaction mechanisms. It is known in fact that many organophosphorus and organosulfur compounds are toxic toward mammalian organisms which renders their destruction under mild conditions of critical importance. 

Trifluoroacetyl triflate is probably the most powerful trifluoro-acetylating agent known, as evidenced by its reactivity toward several types of nucleophiles under mild conditions. A sterically hindered base, 2,6-di-... 

The regioselectivity of nucleophilic addition is a function of the type of nucleophile employed and in many instances can be controlled to give Michael addition to the /3 carbon. 

Dichloropropionic acid is a cheap reagent that can be linked to insoluble polymers either as an ester or an amide (1, Fig. 2). Although both chlorine atoms of this substrate were expected to show a slightly different reactivity toward nucleophiles, all attempts to displace these two leaving groups by two different nucleophiles failed. Regardless of the reaction conditions and the type of nucleophile used, both chlorine atoms were displaced by the first nucleophile. 

We could imagine two types of nucleophilic attack upon a ligand. The first involves the formation of a new bond to the incoming nucleophile and the associated loss of some other leaving group. This corresponds to nucleophilic displacement. The second type of reaction does not involve the loss of any other species and corresponds to an addition reaction. There are a number of ways in which the polarisation of the ligand can enhance a... 

The second major type of nucleophilic substitution mechanism is the S 1 mechanism. This mechanism proceeds via two steps. The first step (the slow step) involves the breakdown of the alkyl halide into an alkyl carbocation and a leaving group anion. The second step (the fast step) involves the formation of a bond between the nucleophile and the alkyl carbocation. 

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