Ammonium salts, nucleophilic substitution with

E-(P-Alkylvinyl)phenyliodonium salts react with tetra-n-butylammonium halides to yield the correspondingly substituted Z-haloethenes (80-100% for chloro-, bromo- and iodo-derivatives) [41], In contrast, in the corresponding reaction with Z-(2-benzenesulphonyl-ethenyl)phenyliodonium salts, nucleophilic substitution occurs with retention of configuration to yield the Z-2-benzenesulphonyl-l-haloethenes [42], The ammonium fluorides fail to yield the fluoroethenes, but produce the ethynes by simple elimination [41]. Where carboxylic acids have low solubility in organic solvents, their conversion into the acid chlorides is frequently difficult. Phase-transfer catalysis not only allows the conversion to be effected rapidly, it also results in high yields of a wide range of acid chlorides [43]. 

In a nice illustration of the impact of metal coordination upon the reactivity of phospholes, a methodology for the functionalization of these heterocycles in the /3-position has been described (see also Scheme 22) <2001JOM105>. Here, coordination of both the P-lone pair and the cyclic diene system was undertaken. The resulting multimetallic complex 79 was treated with lithium diisopropylamide (LDA) to afford the lithium salt 350 (Scheme 118). This readily undergoes nucleophilic substitution with a variety of electrophiles to afford the corresponding substituted phosphole complexes 351-353. The free phospholes can be isolated following decomplexation with cerium(iv) ammonium nitrate (CAN). 

Two mechanisms of degradation are proposed for organoclays with ammonium surfactants. First is the elimination-type mechanism (Hofmann elimination), which is assumed to be primary degradation pathway if the salt anions are completely removed from the organoclay, and second is nucleophilic substitution with an attack of residual anions. 

In Chapter 16 (page 218) you learnt how bromoethane undergoes nucleophilic substitution with ammonia to form a mixture of amines. In order to prepare ethylamine (while avoiding the formation of secondary and tertiary amines and ammonium salts) we use excess hot ethanolic ammonia ... 

We ve already studied the two most general reactions of amines—alkylation and acylation. As we saw earlier in this chapter, primary, secondary, and tertiary amines can be alkylated by reaction with a primary alkyl halide. Alkylations of primary and secondary amines are difficult to control and often give mixtures of products, but tertiary amines are cleanly alkylated to give quaternary ammonium salts. Primary and secondary (but not tertiary) amines can also be acylated by nucleophilic acyl substitution reaction with an acid chloride or an acid anhydride to yield an amide (Sections 21.4 and 21.5). Note that overacylation of the nitrogen does not occur because the amide product is much less nucleophilic and less reactive than the starting amine. 

The interfacial mechanism provides an acceptable explanation for the effect of the more lipophilic quaternary ammonium salts, such as tetra-n-butylammonium salts, Aliquat 336 and Adogen 464, on the majority of base-initiated nucleophilic substitution reactions which require the initial deprotonation of the substrate. Subsequent to the interfacial deprotonation of the methylene system, for example the soft quaternary ammonium cation preferentially forms a stable ion-pair with the soft carbanion, rather than with the hard hydroxide anion (Scheme 1.8). Strong evidence for the competing interface mechanism comes from the observation that, even in the absence of a catalyst, phenylacetonitrile is alkylated under two-phase conditions using concentrated sodium hydroxide [51],... 

In contrast with the reactions involving sulphide or hydrogen sulphide anions, aryl alkyl thioethers and unsymmetrical dialkyl thioethers (Table 4.3) are obtained conveniently by the analogous nucleophilic substitution reactions between haloalkanes and aryl or alkylthiols under mildly basic conditions in the presence of a quaternary ammonium salt [9-15] or polymer-supported quaternary ammonium salt [16]. Dimethyl carbonate is a very effective agent in the formation of methyl thioethers (4.1.4.B) [17]. 

Nucleophilic substitution on methyl / -nitrobenzenesulfonate in CH2CI2 has been studied with a series of chloride salts with different structures and solvations BU4NCI, PPNCl [bis(triphenylphosphoranylidene)ammonium chloride], KCl complexed by 18-crown-6 or Kryptofix 2,2,2, and for comparison PPNBr. ° Rate constants and activation parameters are in accordance with an S 2 mechanism. The results were treated by the Acree equation. There are two reaction paths the first, involving the chloride ion, has the same rate for all the salts, whereas the second slower path, involving the ion pair, has a rate related to the dissociation constant of the salt. 

You have read (Unit 10, Class Xll) that the carbon - halogen bond In alkyl or benzyl haUdes can be easily cleaved by a nucleophile. Hence, an allqrl or ben l haUde on reaction with an ethanollc solution of ammonia undergoes nucleophilic substitution reaction m which the halogen atom Is replaced by an amino (-NHJ group. This process of cleavage of the C-X bond by ammonia molecule Is known as ammonolysis. The reaction Is carried out In a sealed tube at 373 K. The primary amine thus obtained behaves as a nucleophile and can further react with allqrl halide to form secondary and tertiary amines, and finally quaternary ammonium salt. 

A variety of protonic and Lewis acids initiate the cationic polymerization of lactams [Bertalan et al., 1988a,b Kubisa, 1996 Kubisa and Penczek, 1999 Puffr and Sebenda, 1986 Sebenda, 1988]. The reaction follows the mechanism of acid-catalyzed nucleophilic substitution reactions of amides. More specibcally, polymerization follows an activated monomer mechanism. Initiation occurs by nucleophilic attack of monomer on protonated (activated) monomer (XXIV) to form an ammonium salt (XXV) that subsequently undergoes proton exchange with monomer to yield XXVI and protonated monomer. The conversion of XXIV to XXV involves several steps—attachment of nitrogen to C+, proton transfer from... 

Quaternary ammonium salts are known to form ion pairs with nucleophilic anions and to transfer these reagents in organic media. Dou et al.142 have shown that they may also take part in a substitution reaction where the anion is the nucleophile and a tertiary amine is the leaving group. 

The reaction of furans with ammonia and its derivatives is of considerable synthetic utility (B-73MI31 too). Substituted furan-2-carbaldehydes and 2-acylfurans on heating with ammonia and ammonium salts, often under pressure, yield 3-hydroxypyridines. The mechanism of this reaction is thought to involve nucleophilic attack of ammonia at the 2-position. Ring opening affords an amino aldehyde or ketone and thence, by reclosure, the 3-hydroxy-pyridine (Scheme 29). A wide range of substitutents is tolerated. Primary amines with furan-2-carbaldehydes yield A-substituted pyrroles, the closure of the intermediate... 

Aldol reactions using a quaternary chinchona alkaloid-based ammonium salt as orga-nocatalyst Several quaternary ammonium salts derived from cinchona alkaloids have proven to be excellent organocatalysts for asymmetric nucleophilic substitutions, Michael reactions and other syntheses. As described in more detail in, e.g., Chapters 3 and 4, those salts act as chiral phase-transfer catalysts. It is, therefore, not surprising that catalysts of type 31 have been also applied in the asymmetric aldol reaction [65, 66], The aldol reactions were performed with the aromatic enolate 30a and benzaldehyde in the presence of ammonium fluoride salts derived from cinchonidine and cinchonine, respectively, as a phase-transfer catalyst (10 mol%). For example, in the presence of the cinchonine-derived catalyst 31 the desired product (S)-32a was formed in 65% yield (Scheme 6.16). The enantioselectivity, however, was low (39% ee) [65],... 

Norephedrine 9 is alkylated with dibromide 26 to give pyrrolidine derivative 10.2 The hydroxy group of 9 is not alkylated under the conditions applied because of its lower basicity and nucleophilicity. First, the amino group of 9 is monoalkylated and the resulting ammonium salt 27 is deprotonated with NaHC03 as base. This yields secondary amine 28, which then undergoes intramolecular nucleophilic attack to furnish the desired A-pyrrolidinyl norephedrine 10 after deprotonation. Intermolecular nucleophilic substitution was not observed under these conditions. 

The reaction of primary or secondary alcohols with thionyl chloride is a general method for preparing the corresponding chloro compounds. In the first step a chlorosulfne ROSOC) is formed from which S02 is eliminated in a relatively slow step. This decomposition is facilitated by a tertiary amine, e.g. pyridine. The ammonium salt RO-SON+.Cl— formed from the chlorosulftte is subsequently attacked on carbon (in R) by CF. Since nucleophilic substitutions on propargylic carbon proceed more easily than on carbon in saturated compounds, it may be expected that the conversion of propargylic chlorosulfites into the chlorides will take place under relatively mild conditions. 

Since the phosphate anion is resonance stabilised, nucleophilic substitution of the bromine atom of the coumarin derivative can occur by either of the two free oxygen atoms. Thus two diastereomers will be produced, which may be distinguished between merely by considering the configuration at the phosphorus atom. In a publication it was shown that using the tetrabutyl-ammonium salt of cyclic AMP (cAMP) in acetonitrile the diastereoisomeric ratio was 85 15 in favour of the compound with an S-configured phosphorus atom [10]. 

Ligands 179 and 180 were synthesized by the nucleophilic substitution of the sodium glycolate of TV-methyldiethanol amine on either 2,6-dichloropyridine or 2,6-6 (chloromethyl)pyridine. However, 183 and 184 were synthesized by the qua-temization of 181 or 182 with l,2-6is(P-ethoxy)ethane in acetonitrile. In both instances the resulting diquatemary ammonium salts were demethylated by L-Selec-tride in refluxing tetrahydrofuran to afford the desired pyridino coronand. Com-piexation studies have not been performed on any of these coronands and the physical properties of these compounds do not indicate any unusual characteristics m). 

Add chlorides also react with ammonia and 1° and 2° amines to form 1°, 2°, and 3° amides, respectively. Two equivalents of NH3 or amine are used. One equivalent acts as a nucleophile to replace Cl and form the substitution product, while the second equivalent reacts as a base with the HCI by-product to form an ammonium salt. 

Although this process seems straightforward, polyalkylation of the nitrogen nucleophile limits its usefulness. Any amine formed by nucleophilic substitution still has a nonbonded electron pair, making it a nucleophile as well. It will react with remaining alkyl halide to form a more substituted amine. Because of this, a mixture of 1°, 2°, and 3° amines often results. Only the final quaternary ammonium salt, with four alkyl groups on N, cannot react further, and so the reaction stops. 

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