Intramolecular nucleophilic substitution reaction

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... 

An a ,/3-epoxycarboxylic ester (also called glycidic ester) 3 is formed upon reaction of a a-halo ester 2 with an aldehyde or ketone 1 in the presence of a base such as sodium ethoxide or sodium amide. Mechanistically it is a Knoevenagel-type reaction of the aldehyde or ketone 1 with the deprotonated a-halo ester to the a-halo alkoxide 4, followed by an intramolecular nucleophilic substitution reaction to give the epoxide 3 ... 

An a-halosulfone 1 reacts with a base by deprotonation at the a -position to give a carbanionic species 3. An intramolecular nucleophilic substitution reaction, with the halogen substituent taking the part of the leaving group, then leads to formation of an intermediate episulfone 4 and the halide anion. This mechanism is supported by the fact that the episulfone 4 could be isolated. Subsequent extrusion of sulfur dioxide from 4 yields the alkene 2 ... 

When the allene moiety of 2,3-allenylamines was substituted with Br, an intramolecular nucleophilic substitution reaction led to a chiral 2,3-ds-ethynylaziridine 323. The diastereoselectivity depends on the absolute configuration of the allene moiety, i.e. typically for a matched-mismatched pair the S,aR-isomer afforded the product with much higher stereoselectivity [155, 156],... 

Under acidic conditions, amino-substituted imidazoles and triazoles 135 (X = CH, N) underwent intramolecular nucleophilic substitution reaction to give 136 in yields depending on the C(2 ) substituent orientation <1999CAR190, 1999MI441>. Thiouridine derivative 73 (R = Me) (Scheme 12) cyclized similarly to 72 on treatment with hexamethyldisilazane(HMDS)-ammonium sulfate <1992NN603>. 

Intramolecular nucleophilic substitution reactions of phenol ether derivatives induced by activated iodine(III) reagents such as PIFA-TMSOTf and PIFA-BF3 Et20 [Eq. (7) - (11)] have been applied to total or formal synthesis of various types of bioactive natural products. 

The carbonyl group at G-4 of the 3-aryl-4-benzoylazetidin-2-one is reduced with sodium borohydride to the corresponding hydroxyl group <2003T5259>. Treatment of azetidin-2-one 372 with sodium hydride gave a fused tricyclic azetidin-2-one 373 (Equation 140) as a result of an intramolecular nucleophilic substitution reaction of the alkoxide with an aromatic group at the C-3 position. 

Epoxides are important intermediates in many industrial processes. For example, the reaction of the simplest epoxide, ethylene oxide, with water is employed to produce ethylene glycol, which is used in antifreeze and to prepare polymers such as Dacron. One method for the preparation of ethylene oxide employs an intramolecular nucleophilic substitution reaction of ethylene chlorohydrin ... 

The ortho/para alkylation ratio of the intramolecular nucleophilic substitution reaction of sodio-4-(3-hydroxyphenyl)butyl tosylate, according to Eq. (5-137), was shown to be solvent-dependent [381]. In general, an increase in the ortho/para alkylation ratio resulted when the polarity of the solvent was decreased. The orientation of the reaction was explained in terms of the nature of the association between the metal and phenolate ions in different solvents [381]. 

The a./y alkylation ratio of the intramolecular nucleophilic substitution reaction of an a,y9-unsaturated cyclohexenone tosylate can also be controlled by the right choice of solvent. The desired y-alkylation - the final step of the total synthesis of the sesquiterpene yS-vetivone - is favoured by NaOH in CH3SOCH3/H2O, in contrast to (CH3)3C0K/(CH3)3C0H, which promotes a-alkylation [670],... 

Intramolecular nucleophilic substitution reactions of chlorine " " or bromine with alco-holates lead to tetrahydropyrans. The alcoholate can be formed in situ by deprotccting an alcohol.Activated aromatic chlorides give in nucleophilic aromatic substitution reactions a six-membered heterocyclc, e.g, reaction of 1 to give 2. ... 

The formation of the sultone (160) probably involves addition of the complex across the alkene double bond, a 1,2-hydride shift and an intramolecular nucleophilic substitution reaction. The sultone (161) is formed by addition of sulfur trioxide to give the unstable p-sultone which rearranges to the more stable y-isomer (161). Another useful route to sultones is by metallation of alkanesulfonate esters for example, butane-1,3-dimethylsulfonate (162), prepared from butanel,3-diol, yields the 8-sultone, namely 6-methyl-l,2-oxathiin-2,2-dioxide (163) (Scheme 67). 

V. Yaylayan, J. R. J. Pare, R. Laing, and P. Sporns, Intramolecular nucleophilic substitution reactions of Lysine and tr5T)tophan Amadori products. In "The Maillard reaction in food processing, human nutrition and physiology", P. A. Finot, H. U. Aeschbacher, R. F. Hurrell, and R. Liardon, (eds.), Birkhaiiser-Verlag, Basel, pp. 115-120 (1990). 

Finally, as mentioned above, intramolecular nucleophilic substitution reactions present the most developed approaches to 1,2-oxaphasphocyclanes. However, for this purpose electrophilic substitution can be used as well, which is illustrated by catalytic cleavage of tungsten complex 106 to afford substituted benzo[d]-2-oxo-1,2-oxaphosphinane 107 (Scheme 62) [138],... 

The formazan (278) undergoes an intramolecular nucleophilic substitution reaction... 

A base-catalyzed intramolecular nucleophilic substitution reaction on isoquinoline Reissert compounds (222) is the basis of a benzo[a]quinolizidine synthesis developed by Popp et al. (Scheme 42) <72JHC541>. 

This is an example of an intramolecular nucleophilic substitution reaction. A cyclic intermediate is formed that undergoes attack by an externed nucleophile, typically H2O, to form products. These reactions typically involve 3-, 5-, or 6-membered ring intermediates. 

Intramolecular nucleophilic substitution reactions also are thought to compete with hydrolysis (i.e., 8 2 reaction with H2O) in the hydrolysis of several or-ganophosphorus esters. For example, the C-S cleavage of thiometen (R = H) and disulfoton (R = CH3) can occur by intramolecular nucleophilic substitution by the sulfur atom of the electron-withdrawing group, which results in the formation of the cyclic sulfonium ion which subsequently reacts with water to give 2-(ethylthio)ethanol (Wanner et al., 1989). 

Both linear and angular annulated 2-methylfurobenzopyranones can be prepared by this route <94BCJ1972>. Benzofuran-3-ones (3-hydroxybenzofurans) are available by an intramolecular nucleophilic substitution reaction (Scheme 45), (Auwers-Pohl reaction). 

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