Nucleophihc substitutions

BenZotrichloride Method. The central carbon atom of the dye is supphed by the trichloromethyl group from iJ-chlorobenzotrichloride. Both symmetrical and unsymmetrical triphenyhnethane dyes suitable for acryhc fibers are prepared by this method. 4-Chlorobenzotrichloride is condensed with excess chlorobenzene in the presence of a Lewis acid such as aluminium chloride to produce the intermediate aluminium chloride complex of 4,4, 4"-trichlorotriphenylmethyl chloride (18). Stepwise nucleophihc substitution of the chlorine atoms of this intermediate is achieved by successive reactions with different arylamines to give both symmetrical (51) and unsymmetrical dyes (52), eg, N-(2-chlorophenyl)-4-[(4-chlorophenyl) [4-[(3-methylphenyl)imino]-2,5-cyclohexadien-l-yhdene]methyl]benzenaminemonohydrochloride [85356-86-1J (19) from. w-toluidine and o-chloroaniline. 

Dehydrofluorination by primary and secondary aliphatic amines occurs at room temperature and is the basis of diamine cross linkmg, which occurs by dehydrofluonnation and subsequent nucleophihc substitution of the double bond The locus of dehydrofluonnation is a VDF unit flanked by two perfluoroolefin units This selectively base-sensitive methylene group also undergoes elimination as the first step in phase-transfer-catalyzed cross-hnking with quaternary ammo mum or phosphomum salts, bisphenols, and morganic oxides and hydroxides as HF acceptors [31, 32]... 

The 0X0 group, will tend to activate nucleophihc substitution when its oxygen atom is protonated (e.g., 201 when Z is H) in acid-catalyzed reactions 223b,298 qj. hydrogen bonding to the solvent. Acceleration... 

When a hydrogen atom is peri to an azine-nitrogen, there is no steric inhibition of resonance activation as there is in 1-nitronaph-thalene (4-methoxy-dechlorination of its 4-chloro derivative seems to be thereby decelerated only 2-fold in rate). Steric hindrance of nucleophihc substitution by the co-planar peri hydrogen is sometimes... 

The macrocyclization of a peptide was carried out by nucleophihc substitution on a fluorobenzene by the sulfide group of the terminal cysteine of a pentapeptide [164]. The peptide 261 was prepared by standard SPPS and was cyclized under microwave irradiation at 50 °C for 10 min in DMF (Scheme 96). The yields of 262, after cleavage with TFA, were remarkably high for a macrocyclic peptide (70%) and also the resulting HPLC purity was very high. 

A mechanism at the Sj 2Ar/Sj l boundary was proposed for the nucleophihc substitution reaction of aryldiazonium ions in water [86],... 

Wakefield and Varvounis have continued their study of abnormal nucleophihc substitution in 3-trichloromethylpyridines <95T(51)12791>. For example, morpholine and 3-... 

Nucleophihc substitution of sodium thiolate on 2-(perfluorohexyl)ethane iodide leads to extensive elimination (10-20%) and formation of (perfluorohexyl)ethylene (3), Equation 2. 

In an extension of this work, the reuse of the polymeric catalyst was addressed and several new PE-poly(alkene) glycol copolymers were prepared [68]. Commercially available oxidized polyethylene (CO2H terminated, both high and low molecular weight) was converted to the acid chloride and reacted with Jeffamine D or Jeffamine EDR, and subsequently converted to the tributylammonium bromide salt with butyl bromide. These new quaternary salts were shown to catalyze the nucleophihc substitution of 1,6-dibromohexane with sodium cyanide or sodium iodide. While none of the polymeric quaternary salts catalyzed the reaction as well as tetrabutylammonium bromide, the temperature-dependent solubility of the polymers allowed removal of the polymer by simple filtration. 

In an extensive review on abiotic catalysis, Huang (2000) noted that the reactivity of hydrolyzable organic contaminants arises from the presence of electron-deficient (electrophilic) sites within the molecules. Figures 14.2 and 14.3 show the patterns of reactivity in two cases of nucleophihc substitution and monomolecular nucleophilic substitution. The Sj 2 mechanism (nucleophilic substitution) involves attack of the electrophilic sites by OH" or H O, generation of a higher coordination nnmber intermediate, subsequent elimination of the leaving group, and the formation of an hydrolysis product (Fig. 14.2). 

We can now understand and predict why some nucleophihc substitution reactions are favoured and others are not. Thus, it is easy to convert methyl bromide into methanol by the use of hydroxide as nucleophile. On the other hand, it is not feasible to convert methanol into methyl bromide merely by using bromide as the nucleophile. 

Frontier molecular orbital calculations have been employed successfully to predict reactions by examining the LUMO for nucleophihc substitution reactions and the HOMO for electrophilic reactions. Although these calculations have become quite routine, they unfortunately have not been applied to 1,2,3-thiadiazoles. 

Id (Scheme 3) . This was prepared via the corresponding phosphite, which can be synthesized by reaction of the alcohol with chlorodiethyl phosphite and triethylamine. The phosphite then undergoes nucleophihc substitution reaction with anhydrous H2O2 forming the hydroperoxide Id (enantiomeric ratio S/R 65/35) and isomeric hydroperoxide le in a 2 1 mixture in 74% overall yield starting from the alcohol. Purification was possible by normal-phase HPLC. So in this case transformation of the phosphite to the hydroperoxide proceeds with partially retained configuration. 

Generally, only a single stepwise or concerted pathway for aliphatic nucleophihc substitution is detected by experiment because of the very different activation barriers for formation of the respective reaction transition states for these reactions. The description of the borderline between stepwise and concerted nucleophilic substitution reactions presented in this chapter has been obtained through a search for those rare substrates that show comparable barriers to these two reactions and through the characterization of the barrier for nucleophile addition to the putative carbocation intermediate of the stepwise reaction in the region of this change in mechanism. 

In the imidazolium salts 63, obtained by nucleophihc substitution of the iodo-derivative 61 by an imidazole 62, the oxazoline is bnked by the carbon atom in the 4-position. Coordination of the bidentate bgand to the Ir(COD) + complex fragment is then achieved by in situ deprotonation (Scheme 43). This modular design allows facile and rapid access to a large ligand library by variation of the substituents in the 2-position of the oxazoline and at the terminal N-atom of the heterocyclic carbene. 

Compound (4) reacts with halides, preferably their alkylanunonium salts, in acetone or DME with exchange of one CO for a halide, giving anionic complexes of the type Co(CO)2(NO)X (X = Cl, Br, I, CN) (equation 29). Owing to the high charge density at the metal, these anions can act as sources for the hyponitrous ion, NO, which is transferred in nucleophihc substitutions at activated (benzyl) halides, giving aldoximes (e.g. PhCH=NOH from PhCH2Y) (equation 30). ... 

A cross-coupling reaction can be partially defined by equation (1), where Nu is a carbon (or heteroatom) nucleophile see Nucleophile), R X is an electrophilic substrate, X is a halogen or other appropriate leaving group, and M is a metal or metalloid. At first glance, it would appear that simple nucleophihc substitution reactions should fall under this definition. However, what makes the cross-coupling chemistry special is its ability to perform transformations that cannot be accomplished with simple substitution chemistry. 

An oxidatively initiated nucleophihc substitution mechanism has been suggested to account for reactions with electron-rich aromatic substrates such as 4-fluoroanisole [57] (Figure 5.28). 

Skrydstrup and collaborators demonstrated a novel method for the introduction of side chains onto glycine residues of small peptides [11]. In this work, a pyridyl sulfide group was introduced into a series of di-, tri-, and tetrapep-tides via a two-step procedure involving an initial radical-induced bromina-tion of glycine residues with N-bromosuccinimide followed by nucleophihc substitution with 2-mercaptopyridine (Scheme 8, Route A). The yields were... 

A second strategy, analogous to nucleophihc substitution, involves intramolecular homolytic substitution at atom A with loss of a new radical L [Sni, Scheme 1, (2)]. hi this process the atom undergoing substitution (A) cannot be carbon, except for a few special situations, and hence the strategy is hmited in scope [8-10]. The central element in the third strategy is an... 

Over the years, the MNK reaction has emerged as a rehable method, especially for the conversion of aromatic hydroxides into aromatic thiols (and oxidised derivatives). It has received less attention in the aUphatic field because of the existence of alternative methods for transforming alcohols into thiols, namely via ahphatic nucleophihc substitution. Nonetheless, in the aliphatic field, it represents a valuable alternative in the presence of other functional groups and has also been shown to be susceptible to catalysis by a munber of compounds. 

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