Ester sulfonates

Trifluoromethanesulfonates of alkyl and allylic alcohols can be prepared by reaction with trifluoromethanesulfonic anhydride in halogenated solvents in the presence of pyridine.3 Since 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 appropriate precautions must be taken to ensure structural and stereochemical integrity. Tertiary alkyl sulfonates are neither as easily prepared nor as stable as those from primary and secondary alcohols. Under the standard preparative conditions, tertiary alcohols are likely to be converted to the corresponding alkene. 

Another general method for converting alcohols to halides involves reactions with halides of certain nonmetallic elements. Thionyl chloride, phosphorus trichloride, and phosphorus tribromide are the most common examples of this group of reagents. These reagents are suitable for alcohols that are neither acid sensitive nor prone to structural rearrangement. The reaction of alcohols with thionyl chloride initially results in the formation of a chlorosulfite ester. There are two mechanisms by which the chlorosulfite can be converted to a chloride. In aprotic nucleophilic solvents, such as dioxane, solvent participation can lead to overall retention of configuration.7 

In the absence of solvent participation, chloride attack on the chlorosulfite ester leads to product with inversion of configuration. 

Primary and secondary alcohols are rapidly converted to chlorides by a 1 1 mixture of SOCl2 and benzotriazole in an inert solvent such as CH2C12.8 

This reagent combination also converts carboxylic acids to acyl chlorides (see Section 3.4.1). The mechanistic basis for the special effectiveness of benzotriazole has not yet been determined, but it seems likely that nucleophilic catalysis is involved. Sulfinyl ester intermediates may be involved, because Z-2-butene-l,4-diol gives a cyclic sulfite ester with one equivalent of reagent but the dichloride with two equivalents. 

Selective Bu2SnO-catalysed monosulfonylation of methyl a-D-xylopyranoside gave 70% of the substitution at 0-2, while similar sulfonylation of methyl p-D-xylopyranoside gave 90% of the esters at 0-4. TSAO-T 38 and TSAOm -T 39, which have internal sulfonate ester moieties, are potent, selective HIV-I reverse transcriptase inhibitors. New analogues were made by the conversion of the alcohol (40, = OH) to esters, carbamates and thiocarbamates (R = 

Polymer-bound protected sugar derivatives such as 43, which are soluble in organic solvents, have been synthesized using xanthate transfer technology. The synthesis of thioacetal 44 was achieved under photochemical conditions. 

Adinolfi, G. Barone, L. Guariniello and A. ladonisi, Tetrahedron Lett., 2000,41, 9305. 

Slivkin and V.L. Lopenko Izv. Vyssh. Uchebn. Zaved., Khim. Khim. Tekhnol., 1999,42,112 Chem. Abstr., 2000,132,152 032). 

Nakano, H. Nakajima, T. Terai, K. Okamoto and S. Kitahata, Biosci. Biotechnol. Biochem., 2000,64,1702. 

CHAPTER 3 FUNCTIONAL GROUP INTERCONVERSION BY NUCLEOPHILIC SUBSTITUTION 

The prominent role of alkyl halides in formation of carbon-carbon bonds by nucleophilic substitution was evident in Chapter 1. The most common precursors for alkyl halides are the corresponding alcohols, and a variety of procedures have been developed for this transformation. The choice of an appropriate reagent is usually dictated by the sensitivity of the alcohol and any other functional groups present in the molecule. Unsubstituted primary alcohols can be converted to bromides with hot concentrated hydrobromic acid.4 Alkyl chlorides can be prepared by reaction of primary alcohols with hydrochloric acid-zinc chloride.5 These reactions proceed by an SN2 mechanism, and elimination and rearrangements are not a problem for primary alcohols. Reactions with tertiary alcohols proceed by an SN1 mechanism so these reactions are preparatively useful only when the carbocation intermediate is unlikely to give rise to rearranged product.6 Because of the harsh conditions, these procedures are only applicable to very acid-stable molecules. 

PhCH(Me)NMe2 (chiral) MNH2 (M = U, K), NH3 KN(SiMe3 2, 18-crown-6 Et2NMgBr 

0-25°C. An alternative for preparing mesylates and tosylates is to convert the alcohol to a lithium salt which is then allowed to react with the sulfonyl chloride.  

Trifluoromethanesulfonates of alkyl and allylic alcohols can be prepared by reaction with trifluoromethanesulfonic anhydride in halogenated solvents in the presence of pyridine.  

---

Very few 4-aminothiazoles have been synthetized directly. The reaction of a-halonitriles with thioamides generally fails and only extensive decomposition results. However, the benzene sulfonic ester of mandelonit-rile reacts with thiobenzamide to give 2,5-diphenyl-4-aminothiazole (257), Ri = R2 = Ph, in 37% yield (Scheme 132) (417) Similarly, a-cyano-a-acetylthioacetamide condensed with a-chloroacetonitrile give 257, Ri = CH(CN)CH3 and R2 = H (804). 

Alkyl sulfonate esters resemble alkyl halides m their ability to undergo ehmma tion and nucleophilic substitution... 

The sulfonate esters used most frequently are the p toluenesulfonates They are com monly known as tosylates abbreviated as ROTs... 

Sulfonate esters are subject to the same limitations as alkyl halides Competition from elimination needs to be considered when planning a functional group transforma tion that requires an anionic nucleophile because tosylates undergo elimination reactions just as alkyl halides do... 

An advantage that sulfonate esters have over alkyl halides is that their prepara tion from alcohols does not involve any of the bonds to carbon The alcohol oxygen becomes the oxygen that connects the alkyl group to the sulfonyl group Thus the configuration of a sulfonate ester is exactly the same as that of the alcohol from which It was prepared If we wish to study the stereochemistry of nucleophilic substitution m an optically active substrate for example we know that a tosylate ester will have the same configuration and the same optical purity as the alcohol from which it was prepared... 

The mechanisms by which sulfonate esters undergo nucleophilic substitution are the same as those of alkyl halides Inversion of configuration is observed m 8 2 reac tions of alkyl sulfonates and predominant inversion accompanied by racemization m 8 1 processes... 

The hydrolysis of sulfonate esters of 2 octanol is stereospecific and proceeds with complete inversion of configuration Write a structural formula that shows the stereochemistry of the 2 octanol formed by hydrolysis of an opti cally pure sample of (S) (+) 1 methylheptyl p toluenesulfonate identify the prod uct as / or S and deduce its specific rotation... 

The reaction of alcohols with acyl chlorides is analogous to their reaction with p toluenesulfonyl chloride described earlier (Section 8 14 and Table 15 2) In those reactions a p toluene sulfonate ester was formed by displacement of chloride from the sulfonyl group by the oxygen of the alcohol Carboxylic esters arise by displacement of chlonde from a carbonyl group by the alcohol oxygen... 

Photoresist appHcations in the microelectronics industry have also been disclosed (340). Thermally stable ben2yl sulfonate esters based on 2-methyl-3-nitroben2otrifluoride [6656-49-1] can serve as nonionic photoacid generators to promote a cascade of reactions during irradiation of the resist. 

Sulfonate Esters. These are marketed as efficient and easily processible plasticizers with good resistance to extraction. They are typically aryl esters of a to alkanesulfonic acid. 

PyrogaUol has been cited for use in photosensitive compositions. It is used in the form of sulfonate esters of quinonediazides which hydrolyze when exposed to actinic light to Hberate the acid which, in turn, catalyzes further reaction of novolak resins (60). 

Sulfonate Esters. Sucrose sulfonates are valuable intermediates for the synthesis of epoxides and derivatives containing halogens, nitrogen, and sulfur. In addition, the sulfonation reaction has been used to determine the relative reactivity of the hydroxyl groups in sucrose. The general order of reactivity in sucrose toward the esterification reaction is OH-6 OH-6 > OH-1 > HO-2. 

Stabilization and Digestion. Following the initial washing steps, the stabilization of CN occurs. This involves removal of any remaining sulfuric acid since it would catalyze the decomposition of CN. The sulfuric acid present is both physically entrained in the product and chemically bonded to the cellulose chain. CN can contain 0.2—3% esterified H2SO4, depending on the DS of nitration. The sulfonate ester can be easily removed by... 

In cases where a large excess of acid is undesirable, chlorosulfonic acid is employed. An excess of chlorosulfonic acid leads to the introduction of a chlorosulfonyl group which is a useful synthon for the preparation of sulfonamides and sulfonate esters. 

Cl Disperse Blue 87 (107) and related dyestuffs are also prepared from l-oxo-3-imino-4,7-diamino-5,6-phthaloyhsoiQdoline [13418-50-3] (111) by alkylation with corresponding alkyl haUdes (122), sulfonic esters (123), or alkyl amines (124), ie, X of RX = halogen, -toluenesulfonyloxy, or NH2. 

Ethers. In the presence of anhydrous agents such as ferric chloride (88), hydrogen bromide, and acid chlorides, ethers react to form esters (see Ethers). Esters can also be prepared from ethers by an oxidative process (89). With mixed sulfonic—carboxyhc anhydrides, ethers are converted to a mixture of the corresponding carboxylate and sulfonate esters (90) ... 

The sulfonate ester of o-hydroxyacetophenone oximes, when treated with pyridine, are similarly converted into a benzoxazole, but cyclize to a 1,2-benzisoxazole when treated with aqueous KOH <73JCS(P1)2220, 71T711). 

An aiyl methane- or toluenesulfonate ester is stable to reduction with lithium aluminum hydride, to the acidic conditions used for nitration of an aromatic ring (HNO3/HOAC), and to the high temperatures (200-250°) of an Ullman reaction. Aiyl sulfonate esters, formed by reaction of a phenol with a sulfonyl chloride in pyridine or aqueous sodium hydroxide, are cleaved by warming in aqueous sodium hydroxide. ... 

The utility of methanesulfinyl chloride lies in its great chemical reactivity. Through its ready hydrolysis, it serves as a convenient source of methanesulfinic acid. It reacts at low temperature with aromatic amines to form sulfinamides, and with alcohols to form sulfinate esters. When it is hydrolyzed in the presence of an equimolar quantity of sulfenyl chloride, a thiol-sulfonate ester is produced. 

Sulfonate esters are especially useful substrates in nucleophilic substitution reactions used in synthesis. They have a high level of reactivity, and, unlike alkyl halides, they can be prepared from alcohols by reactions that do not directly involve bonds to the carbon atom imdeigoing substitution. The latter aspect is particularly important in cases in which the stereochemical and structural integrity of the reactant must be maintained. Sulfonate esters are usually prepared by reaction of an alcohol with a sulfonyl halide in the presence of pyridine ... 

Tertiary alcohols are more difficult to convert to sulfonate esters, and because of their high reactivity they are often difficult to isolate. ... 

A series of 0-labeIed sulfonate esters was prepared, and the extent of scrambling... 

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. 

Only one of these methods, namely the reaction of halides with lithium aluminum deuteride, is a true displacement reaction, following the same course as the previously discussed displacement of sulfonate esters (section Vl-A). Thus, lithium aluminum deuteride treatment of 7a- and 7jS-bromo-3 -benzoyloxy-5a-cholestanes (195) and (196) gives the corresponding deuterium labeled cholestanols (197) and (198) respectively." ... 

Ester eliminations are normally one of two types, base catalyzed or pyrolytic. The usual choice for base catalyzed j5-elimination is a sulfonate ester, generally the tosylate or mesylate. The traditional conditions for elimination are treatment with refluxing collidine or other pyridine base, and rearrangement may occur. Alternative conditions include treatment with variously prepared aluminas, amide-metal halide-carbonate combinations, and recently, the use of DMSO either alone or in the presence of potassium -butoxide. 

The most satisfactory method of dehydrating 12a-alcohols appears to be through the sulfonate esters Engel and coworkers have shown (ref. 236 and ref. cited therein) that treatment of such sulfonates with alumina gives A -compounds. The reaction appears to be subject to steric acceleration in that bulky IToc-substituents and cw-fused A-rings aid elimination, and that yields increase with increasing size of the sulfonate employed. 

Reaction of Halides and Sulfonate Esters with Meta ... 

Olefin formation by elimination from sulfonate esters, 331... 

---