Alkyl tosylates reactions

The hydroxy groups of sugars can be further alkylated, tosylated (reaction with p-toluenesulfonyl chloride (79), or tritylated. In the latter case only primary hydroxy groups react (80). 

Alcohols react with p-toluenesulfonyl chloride (tosyJ chloride, p-TosCl) in pyridine solution to yield alkyl tosylates, ROTos (Section 11.1). Only the 0-H bond of the alcohol is broken in this reaction the C—O bond remains intact, so no change of configuration occurs if the oxygen is attached to a chirality center. The resultant alkyl tosylates behave much like alkyl halides, undergoing both SN1 and Sjsj2 substitution reactions. 

Table 10B Relative rates of reaction of some alkyl tosylates with ethanol at 25 °C...

Consistent with this mechanism is the fact that the reaction takes place with inversion of configuration at the reaction centre (Johnson and Nidy, 1975). For alkyl tosylates similar results have been reported (San Fillippo et al., 1975). The formation of alcohols under these conditions has been ascribed to secondary reactions (Chern et al., 1978 Johnson et al., 1978). Under certain conditions alcohols are even the only isolated products (Corey et al., 1975). 

Alkyl tosylates and mesylates are cleaved on the action of KOj in DMSO and give rise to the corresponding alcohols. This reaction also proceeds with inversion of configuration at carbon atoms (Morkovnik and Okhlobystin 1979). Such process may be of importance in prostaglandin chemistry. 

Although there are many claims in patents to the preparation of alkylguanidines by reaction of guanidine with alkyl halides, this method, which was first studied by Schenck [ 16 5 ], has only rarely been found satisfactory. Primary and secondary alcohols in 80-85 per cent sulphuric acid react with guanidines to give the mono-and di-alkyl derivatives [166]. A process for direct alkylation of guanidine by an alkyl tosylate has been developed [95, 138, 167]. 

Trifluoromethanesulfonates of alkyl and allylic alcohols can be prepared by reaction with trifluoromethanesulfonic anhydride in halogenated solvents in the presence of pyridine.3 Because the preparation of sulfonate esters does not disturb the C—O bond, problems of rearrangement or racemization do not arise in the ester formation step. However, sensitive sulfonate esters, such as allylic systems, may be subject to reversible ionization reactions, so that appropriate precautions must be taken to ensure structural and stereochemical integrity. Tertiary alkyl tosylates are not as easily prepared nor as stable as those from primary and secondary alcohols. Under the standard conditions, tertiary alcohols are likely to be converted to the corresponding alkene. 

Alcohols react with sulphonyl chlorides to yield sulphonate esters via Sn2 reaetions. Tosylate esters (alkyl tosylates) are formed from alcohols from the reaetion with p-toluenesulphonyl ehloride (TsCl). The reaction is most commonly carried out in the presenee of a base, e.g. pyridine or triethyla-mine (Et3N). 

Similarly, alkyl tosylate reacts with other nucleophiles, e.g. H, X , HO , R 0 , R , NH2 or NH3, CN, Ns" and R C02 following the Sn2 reaction mechanism, and produces a number of other functional groups as follows. 

The ionization of alkyl tosylates to give carbocations is an endothermic reaction. Knowing that 3° carbocations are more stable than 2° carbocations, we would conclude that the activation barrier for ionization of the 3° tosylate is lower than that of the 2° tosylate, and thus the 3° tosylate should ionize faster (Figure 5.13). 

To a mixture of alkyl tosylate (0.83 mmol), Nal (1.33 mmol) and AIBN (cat.) in 1,2-dimethoxyethane (5 ml) was added Bu3SnH (0.83 mmol), and the mixture was refluxed for 1 h. After the reaction, the solvent was removed, and the residue was chromatographed on silica gel to give the reduction product [33]. 

But why are these alkyl iodides made They are needed for reactions with other nucleophiles in which iodide is again displaced. As well as being one of the best nucleophiles for saturated carbon, iodide ion is one of the best leaving groups from saturated carbon (see p. 430). Yields are often higher if the alkyl iodide is prepared than if the eventual nucleophile is reacted directly with the alkyl tosylate or chloride. 

Solvent efficacy. 1-Acetyl-4-methylpiperazine proved to be a reasonably good solvent for reactions requiring a polar aprotic medium, such as the conversion of alkyl tosylates into the corresponding halides with lithium halides.750... 

Substrates susceptible to Sn 1 attack and those bearing leaving groups other than halides have also been employed in the Michaelis-Arbuzov reaction, for example, dialkyl sulfates, alkyl mesylates, alkyl tosylates, quaternary ammonium species, activated acetates as have other electrophiles, for example, alkyl fluoroborates, lactones, lactams, aziridines, sulfones, iminium cations, and orf/io-quinonoids.6,13-15,18... 

The tosylate group can be displaced from alkyl tosylates by dialkyl-cuprates 256, 297, 301), presumably by attack at carbon by the d electrons of copper. A transient copper(III) intermediate may be formed [Eq. (87)], as suggested for similar reactions with alkyl halides. An analogous reaction was reported between a copper(I) carboxylate and an alkyl tosylate 185). (Carboxyethyl)methylcopper, C2H5O2CCH2CU, failed to react with butyl tosylate in THF 181). However, copper compounds of the type RCu are generally less reactive than the cuprates. 

Primary and secondary alkyl halides and tosylates react cleanly with R3SnM (equation 11) however, with tertiary alkyl halides, some elimination reaction can also result. The mechanisms of the R3 SnM/alkyl halide or tosylate reactions can be (i) Sn2 type (with inversion of configuration) (ii) an electron transfer (or radical pair) mechanism (with possible predominant inversion of configuration) or (iii) an initial halogen-metal exchange, followed by substitution (with overall retention of configuration) (equation 12). Temperature, solvent, halide, and method of preparation of RsSnM (and consequent presence of additional species, snch as RM or M) affect the mechanism. 

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