Sulfonylations alcohols

Reduction The stable Ni(0) complex is a useful catalyst for reduction of carbonyl compounds (to alcohols), sulfonyl azides (to sulfonamides), imines and nitro compounds (to amines) with ammonium formate. 

Alcohol Sulfonyl chloride Sulfonate ester Hydrogen chloride... 

The free-radical addition of TFE to pentafluoroethyl iodide yields a mixture of perfluoroalkyl iodides with even-numbered fluorinated carbon chains. This is the process used to commercially manufacture the initial raw material for the fluorotelomer -based family of fluorinated substances (Fig. 3) [2, 17]. Telomeri-zation may also be used to make terminal iso- or methyl branched and/or odd number fluorinated carbon perfluoroalkyl iodides as well [2]. The process of TFE telomerization can be manipulated by controlling the process variables, reactant ratios, catalysts, etc. to obtain the desired mixture of perfluoroalkyl iodides, which can be further purified by distillation. While perfluoroalkyl iodides can be directly hydrolyzed to perfluoroalkyl carboxylate salts [29, 30], the addition of ethylene gives a more versatile synthesis intermediate, fluorotelomer iodides. These primary alkyl iodides can be transformed to alcohols, sulfonyl chlorides, olefins, thiols, (meth)acrylates, and from these into many types of fluorinated surfactants [3] (Fig. 3). The fluorotelomer-based fluorinated surfactants range includes noiuonics, anionics, cationics, amphoterics, and polymeric amphophiles. 

Alkyl sulfonates are derivatives of sulfonic acids m which the proton of the hydroxyl group is replaced by an alkyl group They are prepared by treating an alcohol with the appropriate sulfonyl chloride usually m the presence of pyridine... 

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 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... 

Potassium fluoride [7789-23-3], KF, is the most frequently used of the alkaU metal fluorides, although reactivity of the alkaU fluorides is in the order CsF > RbF > KF > NaF > LiF (6). The preference for KF is based on cost and availabiUty traded off against relative reactivity. In its anhydrous form it can be used to convert alkyl haUdes and sulfonyl haUdes to the fluorides. The versatility makes it suitable for halogen exchange in various functional organic compounds like alcohols, acids and esters (7). For example, 2,2-difluoroethanol [359-13-7] can be made as shown in equation 9 and methyl difluoroacetate [433-53 ] as in equation 10. 

Chlorpropamide. Chlorpropamide (l-[(p-chlorophenyl)sulfonyl]-3-propylurea), mol wt 276.75, is a white, crystalline powder, having a slight odor, mp 127—129°C. It is sold as Diabinese, is soluble in water at pH 6 (2.2 mg/mL), and practically insoluble at pH 7.3, soluble in alcohol, and sparingly soluble in chloroform, ether, and benzene. 

On dehydration, nitro alcohols yield nitro-olefins. The ester of the nitro alcohol is treated with caustic or is refluxed with a reagent, eg, phthaUc anhydride or phosphoms pentoxide. A mil der method involves the use of methane sulfonyl chloride to transform the hydroxyl into a better leaving group. Yields up to 80% after a reaction time of 15 min at 0°C have been reported (5). In aqueous solution, nitro alcohols decompose at pH 7.0 with the formation of formaldehyde. One mole of formaldehyde is released per mole of monohydric nitro alcohol, and two moles of formaldehyde are released by the nitrodiols. However, 2-hydroxymethyl-2-nitro-l,3-propanediol gives only two moles of formaldehyde instead of the expected three moles. The rate of release of formaldehyde increases with the pH or the temperature or both. 

The sulfonyl chloride group is the cure site for CSM and determines the rate and state of cure along with the compound recipe. It is less stable than the Cl groups and therefore often determines the ceiling temperature for processing. The optimum level of sulfonyl chloride to provide a balance of cured properties and processibiUty is about 2 mol % or 1—1.5 wt % sulfur at 35% Cl. It also undergoes normal acid chloride reactions with amines, alcohols, etc, to make useful derivatives (17). 

This sulfonyl urea, prepared from an amino acid and p-tosyl isocyanate in 20-80% yield, is cleaved by alcohols (95% aq. EtOH, n-PrOH, or -BuOH, 100°, 1 h, 95% yield). It is stable to dilute base, to acids (HBr/AcOH or cold CF3CO2H), and to hydrazine. ... 

These acids are less stable, less soluble and less acidic than the corresponding sulfonic acids. The common impurities are the respective sulfonyl chlorides from which they have been prepared, and the thiolsulfonates (neutral) and sulfonic acids into which they decompose. The first two of these can be removed by solvent extraction from an alkaline solution of the acid. On acidification of an alkaline solution, the sulfinic acid crystallises out leaving the sulfonic acid behind. The lower molecular weight members are isolated as their metal (e.g. ferric) salts, but the higher members can be crystallised from water (made slightly acidic), or alcohol. 

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 ... 

The chloride of triflic acid (trifluoromethanesulfonyl chloride) is an effective sulfonylating agent Like triflic anhydride, it usually reacts with alcohols and other nucleophiles with the formation of the corresponding derivatives of tnflic acid [69] However, in some reactions, it acts as a chlorinating reagent [98] The reactions of tnfluoromethanesulfonyl chloride with 1,3-dicarbonyl compounds or some carboxylic esters in the presence of a base result m the formation of chlonnated products in high yields (equation 49)... 

Aliphatic sulfonyl chlorides that have a-hydrogen substituents, react with simple tertiary amines, such as trimethylamine, to generate sulfenes or perhaps their amine adducts 446). These species are suggested by the incorporation of one (but not more) deuterium atoms on reaction of sulfonyl chlorides with deuterated alcohols and triethylamine (447-450). A 2 1 adduct of sulfene and trimethylamine with proposed sulfonyl-sulfene structure could be isolated (451). 

The neopentyl alcohol, prepared from the sulfonyl chloride (Pyr, 95% yield), is cleaved nucleophilically under rather severe conditions (Mc4N CP, DMF, 160°, 16 h, 100% yield). ... 

Epoxidation of the simplest allylic alcohol, allyl alcohol 7, is achieved in 88-92% ee with yields of 50-60% using diisopropyl tartrate as ligand. In situ derivatization of the product glycidol 8 via esterification, sulfonylation, or ring opening with nucleophile is an attractive alternative to isolating glycidol. 

Another point for structural diversification is the sulfonamide group. Imai had already shown that a wide variety of groups could be introduced at this position to optimize the reaction. Since a wide variety of sulfonyl chlorides are commercially available, a number of different types of groups could be examined (Scheme 3.34). Testing of a variety of aryl and alkyl groups on the 1,2-cyclohexanediamine backbone demonstrates that the simple methanesulfonamide 122 is clearly superior or equal to many other analogs in the cyclopropanation of cinnamyl alcohol (Table 3.11). Another concern which was directly addressed by this survey was the question of catalyst solubility. 

The suspension is dissolved by the addition of 20 ml of 1 N caustic soda. The alkaline solution is extracted with ether, acidified with dilute hydrochloric acid and filtered. The precipitate is washed with water and recrystallized from alcohol/water to yield 1-(p-toluene-sulfonyl)-3-(2-endo-hydroxy-3-endo-bornyl)-urea having a melting point of 193° to 195°C. 

Into a solution of 15.9 grams of 3-amino-2-phenyl-pvrazole in 60 cc of anhydrous pyridine, 29 grams of p-carbethoxyamino-benzene sulfonyl chloride are introduced within about 25 minutes. When the reaction subsides, heating is carried out for a further hour to 90° to 95°C internal temperature. The reaction solution is then poured into 300 cc of 2 N hydrochloric acid. The precipitate is filtered with suction and recrystallized from dilute alcohol. The 3-(p-carbethoxyaminobenzene sulfonamido)-2-phenyl-pvrazole is obtained thus in white crystals of MP 175° to 176°C. 

The most important group of derivatives for the amino function (Fig. 7-4) is the carbamate group, which can be formed by reactions with acids, acid chlorides or acid anhydrides. A series of chlorides as 2-chloroisovalerylchloride [1], chrysanthe-moylchloride [2] and especially chloride compounds of terpene derivatives (cam-phanic acid chloride [3], camphor-10-sulfonyl chloride [4]) are used. The a-methoxy-a-trifluoromethylphenylacetic acid or the corresponding acid chloride introduced by Mosher in the 1970s are very useful reagents for the derivatization of amines and alcohols [5]. 

Removal of the carbonate ring from 7 (Scheme 1) and further functional group manipulations lead to allylic alcohol 8 which can be dissected, as shown, via a retro-Shapiro reaction to give vinyl-lithium 9 and aldehyde 10 as precursors. Vinyllithium 9 can be derived from sulfonyl hydrazone 11, which in turn can be traced back to unsaturated compounds 13 and 14 via a retro-Diels-Alder reaction. In keeping with the Diels-Alder theme, the cyclohexene aldehyde 10 can be traced to compounds 16 and 17 via sequential retrosynthetic manipulations which defined compounds 12 and 15 as possible key intermediates. In both Diels-Alder reactions, the regiochemical outcome is important, and special considerations had to be taken into account for the desired outcome to. prevail. These and other regio- and stereochemical issues will be discussed in more detail in the following section. 

The cyclization of aryl 3-chloropropyl sulfones by potassium t-butoxide in t-butyl alcohol at 30 °C (equation 20) has a p value of 2.32 for substituents in Ar202. This is considered by Bird and Stirling to indicate the formation of an intermediate carbanion which is essentially in equilibrium with the reactants. A recent review by Stirling203 deals with structure-reactivity aspects of many sulfonyl promoted reactions of this type. 

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