Nucleophiles substituents

Nucleophilic substitution by ammonia on a halo acids (Section 19 16) The a halo acids obtained by halogenation of car boxylic acids under conditions of the Hell-Volhard-Zelinsky reaction are reac tive substrates in nucleophilic substitu tion processes A standard method for the preparation of a ammo acids is dis placement of halide from a halo acids by nucleophilic substitution using excess aqueous ammonia... 

When a molecule that is a substrate for nucleophilic substitution also contains a group that can act as a nucleophile, it is often observed that the kinetics and stereochemistiy of nucleophilic substitution are strongly affected. The involvement of nearby nucleophilic substituents in a substitution process is called neighboring-group participation ... 

Kovacs, G., Ujaque, G. and Lledos, A. (2008) The Reaction Mechanism of the Hydroamination of Alkenes Catalyzed by Gold(I)-Phosphine The Role of the Counterion and the N-Nucleophile Substituents in the Proton-Transfer Step. Journal of the American Chemical Society, 130, 853-864. 

The important role of LU MO in the nucleophilic reactions of saturated hydrocarbons bearing nucleophilic substituents (halogens, alkoxy-, acyloxy-, RSO2O-, etc.) in the molecule has been pointed out 122,123). 

Intramolecular addition can occur when nucleophilic substituents are suitably positioned as in Eq. 14 [88]. When the latter electrolysis is conducted in CH2CI2/BU4 NCI, 75% of the chloro-y-lactone are obtained. Electrolysis of ( )-5-phenyl-4-pentenoic acid affords a 4-(phenyl-methoxymethyl) -4-butanolide [89]. 

Conjugation with glucuronic acid or sulphate requires a nucleophilic substituent to be present in the molecule, normally an hydroxyl function. In the case of the glu-... 

Electrophilic selenium reagents are very effective in promoting cyclization of unsaturated molecules containing potentially nucleophilic substituents.72 Unsaturated carboxylic acids, for example, give selenolactones, and this reaction has been termed selenolactonization73 ... 

Substituent Effects and Reactivity. If the SOMO is relatively low in energy, the principal interaction with other molecules will be with the occupied MOs (three-electron, two-orbital type, Figure 3.8). In this case the radical is described as electrophilic. If the SOMO is relatively high in energy, the principal interaction with other molecules may be with the unoccupied MOs (one-electron, two-orbital type, Figure 3.10). In this case the radical is described as nucleophilic. Substituents on the radical center will affect the electrophilicity or nucleophilicity of free radicals, as shown below. 

Substituents that are electrophilic or are metabolized to electrophilic species are particularly problematic because they are capable of reacting covalently (irreversibly) with nucleophilic substituents of cellular macromolecules such as DNA, RNA,... 

The displacement of halogen with a copper(I) acetylide and subsequent or synchronous copper catalyzed addition of a neighboring nucleophilic substituent to the triple bond (equation 2) constitutes a versatile synthesis of heterocycles. This reaction has been utilized both for the synthesis of furo[3,2-c]pyridines (equation 3) and furo[3,2-6]pyridines (equation 4) (68JHC227, 72MI31700>. 

The reactions of Eqs. 14-44 and 14-45 are unusual because the nucleophilic substituent eliminated is on the a-carbon atom rather than the (3. There is nothing in the structures of the substrates that would permit an... 

Phase I monooxygenations are more likely to form reactive intermediates than phase II metabolism because the products are usually potent electrophiles capable of reacting with nucleophilic substituents on macromolecules, unless detoxified by some subsequent reaction. In the following discussion, examples of both detoxication and intoxication reactions are given, although greater emphasis on activation products is provided in Chapter 8. 

Styryl-type geminal dihalides (e.g., 80) containing a nucleophilic substituent in the ortho-position of the aromatic ring are used in the formation of carbenoids, which can undergo an intramolecular nucleophilic addition to give benzo[b]fiirans (e.g., 81) <95JOC5588>. 

The inversion of the configuration at the carbon atom of the epoxide ring where cleaved in the course of the ring opening during polymerisation indicates that the monomer complexed with the metal atom is attacked from the back side by the nucleophilic substituent X [scheme (1)]. If front side nucleophilic attack of this substituent occurred on the coordinated monomer, i.e. via the four-membered transition state as in scheme (2), no inversion but rather the retention of the configuration at the epoxide ring carbon atom where cleaved should be observed however, this is not the case. 

Aluminium-based catalysts with tetraphenylporphinato [32,35,38,81], Schiff s base [37-40] and calix[4]arene ligands [41] are characterised by the appearance of a non-associated, isolated pentacoordinate metal atom forming an active bond Mt X with nucleophilic substituent X. As stated above, epoxide polymerisation with these catalysts involves the rearward attack of the nucleophilic substituent on the coordinating epoxide molecule [scheme (1)]. In order to explain this, a mechanism involving the simultaneous participation of two catalyst molecules in the initiation and propagation reaction has been proposed [40,41,62,82]. According to this mechanism, the rearward attack of the nucleophilic substituent on the coordinating monomer is carried out by the six-coordinate aluminium species. These species can appear as neutral epoxide... 

Hall and co-wokers [305] formulated a general scheme of initiating the polymerization of vinyl monomers [scheme (82a)] and cyclic ethers [scheme (82b)] using alkenes with electrophilic substituents (A is an electrophilic, D a nucleophilic substituent, and X a dissociable group) ... 

Non-tetrahedral structures of organic derivatives of the silicon subgroup elements are often caused by inter- or intra-molecular coordination interaction X M. This takes place in compounds where there is a nucleophilic substituent at the central M atom. An electronegative X atom, which has at least one unshared electron pair (X = N, P, O, S, halogen) and is directly bonded to M, can be such a substituent. Compounds of this kind tend to be involved in inter-molecular coordination. There can be also a heteroatom X as part of the organic substituent at M in this case an intra-molecular coordination usually occurs . Such compounds, which contain five- or six-membered coordination rings, include, for example, draconoides (4) , their analogues (5) , metalloatranes (6) and others. The stability of a coordination bond X —> M increases with the atomic number of M Si < Ge < Sn < Pb. 

Oxidation of primary aromatic amines bearing a nucleophilic substituent at the ortho position can provide a useful route to some heterocyclic compounds. Some examples, shown in Scheme 10, are syntheses of benzofuroxans, benzotriazoles and benzisoxazoles. ... 

The diazotization of aromatic amines witii a nucleophilic substituent at the ortho position is a common mediod of synthesis of benzo-fosed heterocyclic compounds with two or more contiguous nitrogen atoms. Benzotriazoles (9), benzotriazinones (10), and benzothiadiazoles (11) are examples of heterocyclic ring systems that can be prepared in tiiis way. 

The typical reaction of alkyl halides, we have seen (Sec. 14.5), is nucleophilic substitution. Halogen is displaced as halide ion by such bases as OH, OR, NH3, CN ", etc., to yield alcohols, ethers, amines, nitriles, etc. Even Friedel-Crafts alkylation is, from the standpoint of the alkyl halide, nucleophilic substitu tion by the basic aromatic ring. 

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