Chloride ions nucleophilicity

The Lewis bases that react with electrophiles are called nucleophiles ( nucleus seek ers ) They have an unshared electron pair that they can use m covalent bond formation The nucleophile m Step 3 of Figure 4 6 is chloride ion... 

Perhaps the most convincing evidence for nucleophilic attack at an unexpected ring position comes from the direct observation of intermediate Meisenheimer complexes in the NMR spectrum. When 2-chloro-3,6-diphenylpyrazine is treated with KNH2 in liquid ammonia, the intermediate (29) was observed directly (Scheme 8). It was postulated that this initially formed complex rearranges to (30) which gives the observed product by elimination of a chloride ion (73RTC708). 

Chloride ions are comparatively weak nucleophiles and do not react with azoles. In general, there is also no interaction of halide ions with azolium compounds. 

Benzimidazole 3-oxides, e.g. (189), react with phosphorus oxychloride or sulfuryl chloride to form the corresponding 2-chlorobenzimidazoles. The reaction sequence involves first formation of a nucleophilic complex (190), then attack of chloride ions on the complex, followed by rearomatization involving loss of the fV-oxide oxygen (191 -> 192). 

The acid-catalyzed additions of bromide and chloride ion to thiiranes occurs readily, with halide preferentially but not exclusively attacking the most substituted carbon atom of the thiirane. The reaction of 1-substituted thiiranes with acetyl chloride shows a slight preference for halide attack at the less substituted carbon atom (80MI50601). For further discussion of electrophilic catalysis of halide ion attack see Section 5.06.3.3.2. The reaction of halogens with thiiranes involves electrophilic attack on sulfur (Section 5.06.3.3.6) followed by nucleophilic attack of halide ion on carbon. 

Halide ions may attack 5-substituted thiiranium ions at three sites the sulfur atom (Section 5.06.3.4.5), a ring carbon atom or an 5-alkyl carbon atom. In the highly sterically hindered salt (46) attack occurs only on sulfur (Scheme 62) or the S-methyl group (Scheme 89). The demethylation of (46) by bromide and chloride ion is the only example of attack on the carbon atom of the sulfur substituent in any thiiranium salt (78CC630). Iodide and fluoride ion (the latter in the presence of a crown ether) prefer to attack the sulfur atom of (46). cis-l-Methyl-2,3-di-t-butylthiiranium fluorosulfonate, despite being somewhat hindered, nevertheless is attacked at a ring carbon atom by chloride and bromide ions. The trans isomer could not be prepared its behavior to nucleophiles is therefore unknown (74JA3146). 

Although it is conceivable that the nucleophilic chloride ion initiates the attack, much experience supports the classification of (1-4) as an electrophilic reaction. Of course, if is the attacking electrophile, the double bond must be functioning as a nucleophile.] Equation (1-5) shows an AdN reaction. 

Even polyalkoxy-s-triazines are quite prone to nucleophilic substitution. For example, 2,4,6-trimethoxy-s-triazine (320) is rapidly hydrolyzed (20°, dilute aqueous alkali) to the anion of 4,6-dimethoxy-s-triazin-2(l )-one (331). This reaction is undoubtedly an /S jvr-4r2 reaction and not an aliphatic dealkylation. The latter type occurs with anilines at much higher temperatures (150-200°) and with chloride ion in the reaction of non-basified alcohols with cyanuric chloride at reflux temperatures. The reported dealkylation with methoxide has been shown to be hydrolysis by traces of water present. Several analogous dealkylations by alkoxide ion, reported without evidence for the formation of the dialkyl ether, are all associated with the high reactivity of the alkoxy compounds which ai e, in fact, hydrolyzed by usually tolerable traces of water. Brown ... 

Nucleophilic chlorination of 1,5-naphthyridine mono- and di-N-oxides yields 2-chloro- and 2,6-dichloro-naphthyridines via electrophilic catalysis of the reaction of intermediates such as 430 with chloride ion. An interesting example of electrophilic catalysis is the... 

OKO-l,3,7-triazanaphthalene (450) forms acyloxy derivatives in situ with phosphorus oxychloride and pentasulfide which undergo nucleophilic displacement with chloride ion and with a complex sulfide ion, respectively, to form the 4-chloro and 4-thioxo derivatives. The 4-carboxymethylthio compoimd failed to undergo the ring-opening reaction (see below) characteristic of more activated azino- and diazino-pyrimidines, but it did yield about 10% of the 4-0X0 displacement product. 

Today, we refer to the transformations taking place in Walden s cycle as nucleophilic substitution reactions because each step involves the substitution of one nucleophile (chloride ion, Cl-, or hydroxide ion, HO-) by another. Nucleophilic substitution reactions are one of the most common and versatile reaction types in organic chemistry. 

The reaction occurs by a nucleophilic acyl substitution pathway in which the carboxylic acid is first converted into a chlorosulfite intermediate, thereby replacing the -OH of the acid with a much better leaving group. The chloro-sulfitc then reacts with a nucleophilic chloride ion. You might recall from Section 17.6 Hint an analogous chlorosulfite is involved in reaction of an alcohol with SOCb to yield an alkyl chloride. 

Chiral (2 )-(Z)-l-methyl-2-butenylboronate 13 was synthesized by way of a-chloroethylboronate 12,0. This route, in which the dichloromethyl starting material is first alkylated with methyllithi-um and then 12 is treated with (Z)-2-propenyllithium, was developed since a-chloro-2-butenyl-boronates such as 7 and 15 are sensitive to racemization, owing to the presence of nucleophilic chloride ions, during the reactions of (4f ,5/ )-2-(dichloromethyl)-4,5-dimethyl-l,3,2-dioxa-borolane and (Z)- or ( )-2-propenyllithium. The route to 13 may be performed as a one-pol operation with an overall yield of >90%. The diastereomeric purity of 13 was estimated to be >98% based on a subsequent reaction with benzaldehyde. 

Nucleophilic catalysis of diazotizations by chloride ions was also observed in methanol, first by Schmid (1954) and later in a detailed investigation by Schelly (1972), which included work with methanol/CCl4 mixtures. 

Another two-phase system using phase-transfer catalysis for the oxidation of diaryl-iV-arylsulphonyl sulphilimines to sulphoximines has also been described188. In this reaction the oxidizing reagent is sodium hypochlorite and yields are in excess of 90% in most cases (equation 70). This reaction presumably occurs by initial attack by the nucleophilic hypochlorite ion on the sulphur atom followed by chloride ion elimination. 

The tertiary amines 303 and the acid chlorides 304 (X = Cl) initially formed acylammonium salts 305, which underwent a von Braun type degradation by an attack of the nucleophilic chloride ion at the allyl system to give allyl chlorides 306/307 and carboxylic acid amide functions. 

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