Water as a leaving group

To make the ether a second molecule of alcohol must be added but we must not now be tempted to attack the positively charged oxygen atom with the nucleophilic OH group. The second molecule could attack a proton, but that would just make the same molecules. Instead it must attack at carhon expelling a molecule of water as a leaving group... 

Do not give the OH another proton, as that pathway will not quickly lead to the ketone. Students who attempt to protonate the OH group invariably continue by losing water as a leaving group to form a vinylic carbocation. That pathway is too high in energy and simply does not lead to the product. 

A halide ion functions as a nucleophile and attacks the oxonium ion, ejecting water as a leaving group... 

Note that in the S l reaction, which is often carried out under acidic conditions, neutral water can act as a leaving group. This occurs, for example, when an alkyl halide is prepared from a tertiary alcohol by reaction with HBr or HC1 (Section 10.6). The alcohol is first protonated and then spontaneously loses H2O to generate a carbocation, which reacts with halide ion to give the alkyl halide (Figure 11.13). Knowing that an SN1 reaction is involved in the conversion of alcohols to alkyl halides explains why the reaction works well only for tertiary alcohols. Tertiary alcohols react fastest because they give the most stable carbocation intermediates. 

A molecule of water departs as a leaving group as a chromium-oxygen double bond forms. 

The first step of the reaction path involves the addition of H2O2 to the Fe " resting state to form an iron-oxo derivative known as Compound I, which is formally two oxidation equivalents above the Fe state (Fig. 2). The well studied Compound I contains a Fe" = 0 structure and a n cation radical. In the second step. Compound I is reduced to Compound II with a Fe =0 structure. The reduction of the n cation radical by a phenol or enol is accompanied by an electron transfer to Compound I and a proton transfer to a distal basic group (B), probably His 42 (Fig. 3, step 1). The native state is regenerated on one-electron reduction of Compound II by a phenol or an enol. In this process, electron and proton transfers occur to the ferryl group with simultaneous reduction of Fe" to Fe (Fig. 3, steps 2-3) and formation of water as the leaving group (Fig. 3, step 4). 

Chlorosulphonic acid (CSA), HS03C1, has also been used as an effective sulphonating agent. The effectiveness of chloride as a leaving group and the absence of water as a byproduct mean that chlorosulphonation can be run at stoichiometry close to 1 1 and with efficient conversion of the organic substrate. The reaction temperature can be controlled by addition rate of the CSA and some very good product colours can be achieved. The by-product of chlorosulphation is HC1, or NaCl after neutralisation. The salt level in the surfactant is typically < 0.5% and this would need to be accounted for in formulation since it could affect the viscosity. 

Water then acts as a leaving group in the second step to generate the nitronium ion electrophile, N02 -... 

The mechanism for this reaction is presented in Figure 17.3. The electrophile, N02+ (nitronium ion) is generated from the nitric acid by protonation of an OH group. Water then acts as a leaving group to generate the electrophile. The rest of the mechanism is identical to that outlined in Figure 17.1. 

To proceed onward to the imine, the oxygen must be protonated so that water can act as a leaving group. 

The products of bromination in water are called bromohydrins. They can be treated with base, which deprotonates the alcohol. A rapid intramolecular Sjyj2 reaction follows bromide is expelled as a leaving group and an epoxide is formed. This can be a useful alternative synthesis of epoxides avoiding peroxy-acids. 

---