Leaving groups, reactivity in nucleophilic

Indeed, the order of leaving-group reactivity in nucleophilic aromatic substitution is the... 

Indeed, the order of leaving-group reactivity in nucleophilic aromatic substitution is the opposite of that seen in aliphatic substitution. Fluoride is the most reactive leaving group in nucleophilic aromatic substitution, iodide the least reactive. 

The order of alkyl halide reactivity in nucleophilic substitutions is the same as their order m eliminations Iodine has the weakest bond to carbon and iodide is the best leaving group Alkyl iodides are several times more reactive than alkyl bromides and from 50 to 100 times more reactive than alkyl chlorides Fluorine has the strongest bond to car bon and fluonde is the poorest leaving group Alkyl fluorides are rarely used as sub states m nucleophilic substitution because they are several thousand times less reactive than alkyl chlorides... 

The objective in selecting the reaction conditions for a preparative nucleophilic substitution is to enhance the mutual reactivity of the leaving group and nucleophile so that the desired substitution occurs at a convenient rate and with minimal competition from other possible reactions. The generalized order of leaving-group reactivity RSOj" I- > BF > CF pertains for most Sw2 processes. (See Section 4.2.3 of Part A for more complete data.) Mesylates, tosylates, iodides, and bromides are all widely used in synthesis. Chlorides usually react rather slowly, except in especially reactive systems, such as allyl and benzyl. 

There does not have to be a leaving group if the nucleophile reacts with a double bond however, in general, alkenes are not very reactive toward nucleophiles. An exception is if the double bond is polarized by conjugation with a carbonyl group. The reaction of... 

We will defer consideration of the particular pattern of nucleophile reactivity observed until Section 9. There we will compare it with what is found for the same group of nucleophiles reacting with (a) an aryl rr-disulfone ArS02S02Ar, a substitution that involves the same leaving group as in (139) but which takes place at a sulfonyl ( S02) rather than a sulfinyl ( S=0) sulfur, and (b) an aryl thiolsulfonate, ArSSOzAr, a substitution where ArSO is displaced from a sulfenyl ( S) sulfur. 

Tricoordinate phosphorus >P-X compounds containing a suitable leaving group are indispensable in the synthesis of biophosphates and their structural analogues. In contrast to phosphoryl >P(0)-X and thiophosphoryl >P(S)-X, compounds they are spectacularly more reactive in nucleophilic displacements at the phosphorus centre. Westheimer has compared reactions of P compounds with nucleophiles to enzymatic reactions regarding their reactivity [1]. The essential feature of P compounds is their free electron pair with all the structural, stereochemical and mechanistic consequences that follow. P compounds have the structure of a trigonal pyra-... 

Even more reactive towards acetylcholinesterase are the organophosphorus derivatives developed as chemical warfare nerve agents, e.g. sarin. Such compounds react readily with the enzyme and form very stable addition intermediates. It is unusual to see fluoride as a leaving group, as in sarin, but its presence provides a huge inductive effect, thus accelerating the initial nucleophilic addition step (see also Section 13.7). 

In fact, most of the data that have accumulated since 1935 are qualitatively in accord with their predictions,19 but the predictions should not be used indis-criminately without considering the effect the solvent may have on nucleophile and leaving-group reactivity (see pp. 190-194). 

Leaving groups at C5 of 2-substituted 1,2,3-triazoles are predicted to be the most reactive in nucleophilic aromatic substitution reactions following an AE mechanism (see Section 1.4.2). Accordingly, chlorine at C5 of 360 could be replaced by strong nucleophiles like methanethiolate or methoxide to give 377 or 378. The unactivated 2-phenyl-4-chloro-l,2,3-triazole 380 (R=Ph) was inert toward these nucleophiles (1981JCS(P1)503) (Scheme 115). 

Acidic reaction conditions can also lead to protonation of some leaving groups, thereby increasing their reactivity in nucleophilic substitutions. Such groups include, for instance, alcohols, ethers, amines, amides, or alkyl fluorides. 

Hydrolysis of letraa I koxy silane (TMOS or TEOS) is generally performed in the presence of a catalyst which can be an acid, a base or a nucleophile. This is also the case for the hydrolysis of R/Si(OMe)350. In the case of TMOS and TEOS, the acid catalysis is due to the reversible protonation of the alkoxy group which converts it to a better leaving group. However, the nucleophilic attack of the oxygen atom of water is still a key step (equation 17). In the case of basic catalysis, nucleophilic attack of the OH- anion at the silicon centre leads to a penta-coordinated intermediate, followed by the elimination of the RO group (equation 18). For nucleophilic catalysis (promoted by F, HMPA, imidazole, 7V,7V-dimethylaminopyridine as well as OH ) the formation of a penta-coordinated species (equation 19) increases the reactivity of the silicon atom towards the nucleophilic attack of water that leads to an hexa-coordinated intermediate, which finally leads to the product of hydrolysis or condensation. 

In the first step the electrons of the o bond are pulled away by the positive charge and the very stable leaving group, N2- In the second step lone pair electrons are pulled into the very reactive cation by the nonbonding empty orbital on carbon. Fven very weak nucleophiles such as water will react with such cations as a real example shows. 

Other types of leaving groups and of nucleophilic reagents also show greater reactivity at the 4-position 2,4-dichloropyrimidine with alcoholic potassium thiocyanate ° (to 304) and with chemical monodehalogenation (zinc and ammonia or ammonium chlor-ide), 2,4-(lH,3/f)-pyrimidinedithione with ammonia or amines to give 305, 2,4-(l/f,3 f)-pyrimidinedione thiona-tion o 8 o with phosphorus pentasulfide (of. 126 and 127), pyrimidine with phenyl lithium, and 2,4,6-trichloropyrimidine with several sulfanilamide anions. In the latter reaction, the absence of a... 

Epoxides have a leaving group located in a strained three-membered ring, making them reactive to strong nucleophiles and acids HZ that contain a nucleophilic atom Z (9.15). 

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