Leaving groups sulfonate reactions

Tosylates and mesylates are commonly used sulfonates that you need to know for the MCAT. The sulfonate ions are very weak bases and excellent leaving groups. When tosylates and mesylates are leaving groups, the reaction may proceed via an SN1 or SN2 mechanism. 

The Truce-Smiles rearrangement is general for diaryl sulfones containing an o-methyl group and involves benzylic deprotonation to the anion which subsequently rearranges to the sulfinate. If the sulfinate contains a suitably placed leaving group, further reactions may occur for example, the chlorophenyl sulfone (114) forms the sulfinate (115), but this... 

These data show that a change from a hard leaving group (sulfonate, sulfate) to a softer leaving group (bromide, iodide) favors carbon alkylation. Another possible factor in C 0 ratios may be the ability of sulfonates to form a six-membered cyclic TS for both modes of reaction, whereas halides can form such structures only for C-alkylation. ... 

Once the alcohol has been activated by being converted into a sulfonate ester, the appropriate nucleophile is added, generally under conditions that favor Sn2 reactions. The reactions take place readily at room temperature because the leaving group is so good. For example, a para-toluenesulfonate ion is about 100 times better than a chloride ion as a leaving group. Sulfonate esters react with a wide variety of nucleophiles, so they can be used to synthesize a wide variety of compounds. 

In Figure 11.2, a sulfonate ester is the leaving group, and reaction with a nucleophile breaks the weaker C-0 bond to generate a sulfonate anion (26). This anion is resonance stabilized and quite stable, which means it is relatively unreactive as a nucleophile. The combination of a weak C-0 bond and the stability and poor reactivity of the sulfonate anion makes sulfonate esters good leaving groups. The most common sulfonate esters (see Chapter 20, Section 20.11) are those derived from methanesulfonic acid, benzenesulfonic acid, or 4-methylbenzenesulfonic acid. Formation of sulfonate esters from sulfonic acids or sulfonyl chlorides will be discussed in Section 11.7.3 and in Chapter 20,... 

Predominant formation of the C-benzylated product can be understood by considering the soft carbon nucleophile attacking the benzyl carbon of the oxosulfonium trilluoromethane sulfonate, with diphenyl sulfoxide acting as a soft leaving group. The reaction also proceeds smoothly with various other substituted benzyl alcohols with moderate to good yields. Sodium enolates derived from esters, a-cyano esters, a-aromatic and aliphatic ketones can also be benzylated with consistent high yields. 

Because halides are poorer leaving groups than p toluene sulfonate alkyl p toluene sulfonates can be converted to alkyl halides by 8 2 reactions involving chloride bro mide or iodide as the nucleophile... 

All lation. In alkylation, the dialkyl sulfates react much faster than do the alkyl haHdes, because the monoalkyl sulfate anion (ROSO ) is more effective as a leaving group than a haHde ion. The high rate is most apparent with small primary alkyl groups, eg, methyl and ethyl. Some leaving groups, such as the fluorinated sulfonate anion, eg, the triflate anion, CF SO, react even faster in ester form (4). Against phenoxide anion, the reaction rate is methyl triflate [333-27-7] dimethyl sulfate methyl toluenesulfonate [23373-38-8] (5). Dialkyl sulfates, as compared to alkyl chlorides, lack chloride ions in their products chloride corrodes and requires the use of a gas instead of a Hquid. The lower sulfates are much less expensive than lower bromides or iodides, and they also alkylate quickly. 

The perhydrolysis reaction could theoretically continue to give four moles of peracid per mole of TAED but stops at this stoichiometry because of the substantial increase in the conjugate acid pify of the leaving group going from an amide (p-R = 17) to an amine (pif = 35) (94,95). Nonanoyloxybenzene sulfonate (NOBS) [101482-85-3] is used in detergent products in the United States and Japan. The NOBS perhydrolysis reaction is shown in equation 20 (96). 

The pify of the leaving group and the hydrophobe chain length can dramatically affect the efficiency of the perhydrolysis reaction. Additionally, the stmcture of the acid portion of the precursor can affect the yield and sensitivity of the reaction to pH. The mono-4-hydroxybenzenesulfonic acid ester of a-decylsuccinic acid (13) undergoes extremely efficient perhydrolysis at much lower pHs than other peracid precursors, eg, decanoyloxybenzene sulfonate (14). This may be because of the neighboring group participation of the adjacent carboxylate as shown in Table 2 (115). 

The most common leaving groups are sulfonate esters and halides. For the sake of convenience, the discussion of certain dehalogenation reactions is also included in this section even though they may not involve 8 2 type displacement. Benzylic alcohols are also known to be displaced by hydrides or deuterides, but there is no evidence for the application of these reactions to the steroid field. 

It is often advantageous to proceed to a desired product through two nucleophilic displacements rather than directly when one can exploit a difference in the reactivity of two leaving groups. An example is the conversion of 4-chloro-2,6-dimethoxypyrimidine (109) (not satisfactorily reactive with sulfanilamide anion) by means of trimethylamine into the more reactive trimethylammonio derivative 110. Conversion of chloro-quinohnes and -pyrimi-dines into nitriles is best accomplished by conversion (with sulfite) into the sulfonic acids before reaction with cyanide. 

In addition to protons, other electrofugic leaving groups such as SO3 (i. e., anions of sulfonic acids), Cl, Br, I, C02, and others can also be displaced in azo coupling reactions with aromatic substrates. The mechanism of such substitutions is in principle the same as that of dehydrogenation (see Fischer and Zollinger, 1972). 

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