Nucleophilic addition-elimination

A number of compounds of the general type H2NZ react with aldehydes and ketones m a manner analogous to that of primary amines The carbonyl group (C=0) IS converted to C=NZ and a molecule of water is formed Table 17 4 presents exam pies of some of these reactions The mechanism by which each proceeds is similar to the nucleophilic addition-elimination mechanism described for the reaction of primary amines with aldehydes and ketones... 

Fluoride ion produced from the nucleophilic addition-elimination reactions of fluoroolefins can cataly7e isomerizations and rearrangements The reaction of per fluoro-3-methyl-l-butene with dimethylamine gives as products 1-/V,/Vdimeth-ylamino-1,1,2,2,4,4,4-heptafluoro-3-trifluoromethylbutane, N,W-dimetliyl-2,2,4,4,4-pentafluoro 3 trifluoromethylbutyramide, and approximately 3% of an unidentified olefin [10] The butylamide results from hydrolysis of the observed tertiary amine, and thus they share a common intermediate, l-Al,A -dimethylamino-l,l 24 44-hexafluoro-3-trifluoromethyl-2-butene, the product from the initial addition-elimination reaction (equation 4) The expected product from simple addition was not found... 

The pentacoordinate molecules of trigonal bipyramidal form, like PF5, are a very nice example for the study of the formal properties of stereoisomerizations. They are characterized by an appreciable nonrigidity and they permit the description of kinetics among a reasonable number of isomers, at least in particular cases (see below). Therefore the physical and chemical properties of these molecules have been thoroughly investigated in relation to stereoisomerization. Recent reviews may be found in the literature on some aspects of this problem. Mislow has described the role of Berry pseudorotation on nucleophilic addition-elimination reactions and Muetterties has reviewed the stereochemical consequences of non-rigidity, especially for five- and six-atom families as far as their nmr spectra are concerned. 

Fig. 1—2 shows a Hammett diagram for 14 different imidazolides of benzoic acids with a wide range of substituents upon which the reactivity is strongly dependent for example, the difference in rate constants between jV-(4-nitrobenzoyl)imidazole and iV-(4-dimethylaminobenzoyl)imidazole under the same reaction conditions amounts to a factor of about 3000. The Hammett reaction constant p = + 1.85 for the series shown in Fig. 1—2 indicates clearly that the hydrolysis is following a nucleophilic addition-elimination reaction path. 

Hydrolysis of diphenyl phosphorochloridate (DPPC) in 2.0 M aqueous sodium carbonate is also believed to be a two-phase process. DPPC is quite insoluble in water and forms an insoluble second phase at the concentration employed (i.e. 0.10 M). It seems highly significant that the hydrophobic silicon-substituted pyridine 1-oxides (4,6,7) are much more effective catalysts than hydrophilic 8 and 9. In fact, 4 is clearly the most effective catalyst we have examined for this reaction (ti/2 < 10 min). Since derivatives of phosphoric acids are known to undergo substitution reactions via nucleophilic addition-elimination sequences 1201 (Equation 5), we believe that the initial step in hydrolysis of DPPC occurs in the organic phase. Moreover, the... 

Other reactions where the cluster core remains intact are based on nucleophilic addition, elimination, and substitution reactions, as well as electrochemical interconversions. Some examples are given in Equations (47) and (48) 2714 3216... 

The reaction pathway is normally nucleophilic addition/elimination, via a so-called tetrahedral intermediate (157), leading to overall substitution. The difference between the reactions of carboxylic... 

It has been suggested that the elusive zwitterionic state [75], or a novel nucleophilic addition/elimination mechanism at the central carbon of the exocyclic bridge [79], or solvent-solute H-bonding interactions [76, 80] might play a role in modulating cis-trans interconversion. Cis-trans isomerization gives rise also to a remarkable intrinsic photochromism of HBI, as it can be easily and reversibly induced upon light absorption [74—76, 79, 80]. 

The use of pyridinium ylids in the synthesis of carbo- and hetero-cycles has been reviewed (157 references)," with a particular focus on nucleophilic addition-eliminations n = 2,3, 6). 

Rappoport and co-workers work has continued in a study of the substitution of ( )-and (Z)-/3-bromo- or chloro-styrenes, (1) and (2), by MeS in DMSO-d 6 (sometimes in admixture with CD3OD) as solvent. Product studies indicated retention stereochemistry rate measurements found only a small Br/Cl element effect, slower reactions of the p-OMe bromo compounds, and retardation by CD3OD. These results are consistent with Tiecco s suggestion in 1983 that even this system, activated by only a single phenyl group, reacts through the nucleophilic addition-elimination multistep route. 

Some important examples of nucleophilic addition-elimination... 

Halopyridines and other re-deficient nitrogen heterocycles are excellent reactants for nucleophilic aromatic substitution.112 Substitution reactions also occur readily for other heterocyclic systems, such as 2-haloquinolines and 1-haloisoquinolines, in which a potential leaving group is adjacent to a pyridine-type nitrogen. 4-Halopyridines and related heterocyclic compounds can also undergo substitution by nucleophilic addition-elimination but are somewhat less reactive. 

Common reactions of the ylide include (i) [2,3]-sigmatropic rearrangement of allylic, propargylic, and allenic ylides (ii) [l,2]-shift (Stevens rearrangement) (iii) 1,3-dipolar cycloaddition of the ylide generated from carbonyl compounds or imines with dipolarophiles, usually G=G or C=C bonds and (iv) nucleophilic addition/elimination, leading to the formation of epoxides or cyclopropanes (Figure 2). 

If the attacking nucleophile has a pair of nonhonding electrons available in the addition product, water is eliminated in the presence of anhydrous acid from the addition product. This is known as nucleophilic addition-elimination reaction. 

Even simple fluoroalkenes display exploitable electrophilic character. Bailey described an asymmetric synthesis of protected difluoroglycines initiated by nucleophilic addition/elimination at the difluorocentre of chlorotrifluoro-... 

The 7r-electron excessive character of pyrrole and indole renders both systems extremely susceptible to electrophilic attack and the fused benzene rings of carbazole also undergo electrophilic substitution more readily than does an unsubstituted benzene ring. In contrast, the 2/7-isoindole system only survives intact during electrophilic substitution reactions under the mildest of conditions and the system is more susceptible to [ 4 + 2] cycloaddition reactions than is pyrrole. 1,1-Disubstituted IH-isoindoles generally undergo nucleophilic addition-elimination reactions across the 2,3-bond or yield products derived from an initial electrophilic attack at the 2-position. 

A nucleophilic mechanism can be applied in reductions with complex hydrides of highly fluori-nated aliphatic and alicyclic fluoroalkenes with electron-deficient C = C bonds the hydride anion adds as a strong nucleophilic agent to the more electrophilic carbon atom the intermediate anion can then lose a fluoride ion either from the original C = C bond, or from the allylic position finishing an SN2 displacement of the fluorine. Thus, the reductions of vinylic C-F bonds with hydrides proceed by a nucleophilic addition-elimination mechanism. Displacement of fluorine in highly fluorinated aromatic compounds proceeds by the same mechanism ... 

Vinylic fluorine in lithium 2,3,3-trifluoroprop-2-enoate is substituted with hydride ion by a nucleophilic addition-elimination mechanism using lithium aluminum hydride at low temperatures.113... 

A fairly general procedure, which has also been used on the industrial scale, involves heating the alkali metal sulphonate with either sodium or potassium hydroxide in the presence of a small amount of water to aid the fusion process. The reaction mechanism may be formulated as a bimolecular nucleophilic addition-elimination sequence. 

Although the two competing intermediates, the hypothetical ketyl-aryl radical pair (4) and the oxaspirooctadienyllithium (3), are not the rate-determining transition states, they should lie at almost the same energetic level. The rearrangement is in accord with the intramolecular nucleophilic addition/elimination mechanism rather than with homolytic cleavage/recombination. 

In spite of its unusual structural outcome, the N-fusion reaction is a very general process. It was observed in a number of other N-confused macrocycles. For instance, an N-fused intermediate forms in the synthesis of trans doubly N-confused porphyrin 96 [238], N-fusion was also induced by the reaction with PhBCl2, in which case the reaction was promoted by the small radius of the coordinating boron(III) center [251], The resulting boron complexes were also aromatic, even though in some cases further chemical modification of the macrocycle took place (as in 110). The fusion process, which appears to be a nucleophilic addition-elimination, is reversible, and N-fused macrocycles can often be reopened when treated with nucleophiles such as alkoxides [248, 249],... 

Nucleophilic Addition-Elimination (Nucleophilic Acvl Substitution)... 

Know the meaning of Fischer esterification, nucleophilic addition-elimination (nucleophilic acyl substitution), tetrahedral intermediate, saponification, ammonolysis, acyl transfer. 

In contrast, the addition of amines results in nucleophilic addition/elimination at the opposite a-position, resulting in substitution of the a-oxygen substituent, a reaction consistent with the Fischer carbene character embedded into this architecture (Equation 2) <2004JOM2000>. This regioselectivity difference almost certainly arises from the reversible nature of addition reactions using such weakly nucleophilic reagents. 

The next phase of the synthesis was installation of the dimethylamino-oxazoline ring system. This was constructed from the oxazolidinone precursor 19. Oxazolidinone formation occurred when 25 was reacted with thionyl chloride. The more nucleophilic carbonyl of 19 was then O-alkylated with the Meerwein reagent to give an iminium ion that readily participated in a nucleophilic addition/elimination reaction with dime-thylamine to give 26. The final step of the synthesis was O-deacetylation of 26 with sodium methoxide to provide (—)-allosamizoline hydrochloride in 98% yield after acidification. 

---