Substitution reactions leaving group

Leaving group The group of atoms (coded green in this text) displaced in a substitution reaction. Leaving-group ability The ease with which a group can be displaced in a nucleophilic substitution,... 

In a ligand substitution reaction, two groups must always receive attention. There is a bond to the leaving group to be broken and a bond to the entering group to be formed. The relative importance of these two processes provides a basic dichotomy for the classification of substitutions. If a reaction rate is sensitive to... 

Among the reactive groups in wool the most important are amino, imino, and hydroxyl groups. Reactions occur in a weakly acidic medium (pH 3-5) and include nucleophilic substitution of leaving groups (usually Cl, F, and, rarely, sulfonate or ammonium groups) or addition reactions to polar aliphatic double bonds. 

The formation of halides by the nucleophilic substitution of leaving groups is commonly used in the synthesis of more elaborate structures. The synthesis of inexpensive bulk chemicals like solvents, however, is mostly done by oxidation or addition reactions. Halides are either used as intermediates or are valuable end products. Authors of publications, especially patent literature, often claim one reaction for three or even four halogens. In practice, this rarely holds true and each of the halogens quite often requires different conditions. The usual order of halide nucleophilicity is I" > Br > Cl > F". In dimethyl-formamide the reverse order Cl > Br > I is observed. This order goes along with the order of the basic... 

In a unimolecular substitution reaction, a group departs initially with a pair of electrons leaving an electron deficient carbonium ion intermediate, which is subsequently attacked by an incoming nucleophile. Note that this is a two step reaction, in which the intermediate can, on occasions, be isolated. In contrast, in a bimolecular substitution reaction, the leaving group departs simultaneously as the nucleophile approaches. In this case, the reaction occurs in one step, with only a transition state and no proper intermediate. 

The Nu-L can substitute the leaving group on carbon and can be followed by an elimination reaction. 

This is the most useful method of amide formation (equation 2). An activated carboxylic acid acylates aiiunonia, primary or secondary amines by a formal Sn2 substitution of leaving group X. The reactivity of the acylating reagent depend on the acidity of HX, and dierefore the order of reactivity is RCOHal > (RC0)20 = RCONs > RCChR > RCONH2 > RCOR. Moreover, the reaction rate increases with higher nucleophilicity of the amine as well as base or acid catalysis. 

Nomenclature Physical properties Interesting alkyl halides The polar carbon-halogen bond General features of nucleophilic substitution The leaving group The nucleophile Possible mechanisms for nucleophilic substitution Two mechanisms for nucleophilic substitution The S 2 mechanism Application Useful Snj2 reactions... 

The fragmentation reaction of Eschenmoser, which gives acetylenes from toluene-p-sulphonyl hydrazones of aj -epoxy-ketones (Scheme 1), has been adapted to the synthesis of acetylenes from ketones substituted with leaving groups in the a-position [(7) -> (8)]. ... 

Another example of thiol chck reaction is the rapid and efficient substitution of leaving group bearing substrates by thiols, a soft nucleophile [58]. These reactions proceed better in the presence of mild organic bases such as trialkylamines. The halide salts formed during this displacement reactions can be removed easily as precipitates in a very simple and effective manner. 

Unsymmetrically substituted dipyrromethanes are obtained from n-unsubstitued pyrroles and fl(-(bromomethyl)pyiToIes in hot acetic acid within a few minutes. These reaction conditions are relatively mild and the o-unsubstituted pyrrole may even bear an electron withdrawing carboxylic ester function. It is still sufficiently nucleophilic to substitute bromine or acetoxy groups on an a-pyrrolic methyl group. Hetero atoms in this position are extremely reactive leaving groups since the a-pyrrolylmethenium( = azafulvenium ) cation formed as an intermediate is highly resonance-stabilized. 

TosOH 4-methylbenzenesulfonic acid = p toluenesiilfonic acid, tosic acid X, Y leaving groups. e.g., halogen, RSOj, in substitution and elimination reactions... 

The wM-diacetate 363 can be transformed into either enantiomer of the 4-substituted 2-cyclohexen-l-ol 364 via the enzymatic hydrolysis. By changing the relative reactivity of the allylic leaving groups (acetate and the more reactive carbonate), either enantiomer of 4-substituted cyclohexenyl acetate is accessible by choice. Then the enantioselective synthesis of (7 )- and (S)-5-substituted 1,3-cyclohexadienes 365 and 367 can be achieved. The Pd(II)-cat-alyzed acetoxylactonization of the diene acids affords the lactones 366 and 368 of different stereochemistry[310]. The tropane alkaloid skeletons 370 and 371 have been constructed based on this chemoselective Pd-catalyzed reactions of 6-benzyloxy-l,3-cycloheptadiene (369)[311]. 

An important method for construction of functionalized 3-alkyl substituents involves introduction of a nucleophilic carbon synthon by displacement of an a-substituent. This corresponds to formation of a benzylic bond but the ability of the indole ring to act as an electron donor strongly influences the reaction pattern. Under many conditions displacement takes place by an elimination-addition sequence[l]. Substituents that are normally poor leaving groups, e.g. alkoxy or dialkylamino, exhibit a convenient level of reactivity. Conversely, the 3-(halomethyl)indoles are too reactive to be synthetically useful unless stabilized by a ring EW substituent. 3-(Dimethylaminomethyl)indoles (gramine derivatives) prepared by Mannich reactions or the derived quaternary salts are often the preferred starting material for the nucleophilic substitution reactions. 

Nucleophilic substitution reactions of alkyl halides are related to elimination reactions m that the halogen acts as a leaving group on carbon and is lost as an anion The... 

All these reactions of octadecyl p toluenesulfonate have been reported in the chemical literature and all proceed in synthetically useful yield You should begin by identifying the nucleophile in each of the parts to this problem The nucleophile replaces the p toluenesulfonate leaving group in an Sn2 reaction In part (a) the nucleophile is acetate ion and the product of nucleophilic substitution IS octadecyl acetate... 

Section 8 14 Nucleophilic substitution can occur with leaving groups other than halide Alkyl p toluenesulfonates (tosylates) which are prepared from alcohols by reaction with p toulenesulfonyl chloride are often used... 

The reactions of alcohols with hydrogen halides to give alkyl halides (Chapter 4) are nucleophilic substitution reactions of alkyloxonium ions m which water is the leaving group Primary alcohols react by an 8 2 like displacement of water from the alkyloxonium ion by halide Sec ondary and tertiary alcohols give alkyloxonium ions which form carbo cations m an S l like process Rearrangements are possible with secondary alcohols and substitution takes place with predominant but not complete inversion of configuration... 

Overall the stereospecificity of this method is the same as that observed m per oxy acid oxidation of alkenes Substituents that are cis to each other m the alkene remain CIS m the epoxide This is because formation of the bromohydrm involves anti addition and the ensuing intramolecular nucleophilic substitution reaction takes place with mver Sion of configuration at the carbon that bears the halide leaving group... 

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