Sulphones reaction with bases

After the elimination, water-soluble sulphinates can be readily recovered, in shcirp contrast to the alternative Wittig reaction which inevitably suffers from difficulty in recycling phosphine oxide. The sulphone methodology was applied for the first time to the synthesis of vitamin A derivatives by Julia and has been developed as the Rhone-Poulenc process [1-3]. The initial design to prepare retinoic acid (1) involves coupling between the C 15-bromide 2 and the C5-sulphone 3, followed by treatment of the resulting carboxy sulphone 4 with base (Scheme 1) [1]. 

Full details are now available of two syntheses of crown ethers first reported in previous years (Scheme 47). In one approach alkenes are treated with yV-bromosuccinimide in the presence of a polyethylene glycol, and the resultant bromohydrins (86, 87) are cyclized by reaction with base (2,136) the other route involves reaction of polyethylene glycols, either unsubstituted or substituted (88, 89), with a sulphonyl chloride in the presence of base, i.e. in situ sulphonation-cyclization (3,159). Improved procedures for the preparation of the substituted polyethylene glycols (88) and (89) from epoxides and lower polyethylene glycols as shown have also been reported. ... 

The kinetics of desulphonation of sulphonic acid derivatives of m-cresol, mesitylene, phenol, p-cresol, and p-nitrodiphenylamine by hydrochloric or sulphuric acids in 90 % acetic acid were investigated by Baddeley et a/.701, who reported (without giving any details) that rates were independent of the concentration of sulphuric acid and nature of the catalysing anion, and only proportional to the hydrogen ion concentration. The former observation can only be accounted for if the increased concentration of sulphonic acid anion is compensated by removal of protons from the medium to form the undissociated acid this result implies, therefore, that reaction takes place on the anion and the mechanism was envisaged as rapid protonation of the anion (at ring carbon) followed by a rate-determining reaction with a base. 

Dialkyl sulphones may be converted to sulphonic acids by reaction with carbon tetrachloride and base at 80 °C209. This reaction proceeds by initial formation of a-chloro sulphones which are then converted to a thiiren intermediate which decomposes to give a sulphonic acid (equation 92). 

Retinol Derivatives. Aryl sulphones have been used in two new syntheses in the vitamin A series. Reaction of /8-cyclocitryl phenyl sulphone (102) with the bromo-compound (103) gives the intermediate sulphone (104), which on base-catalysed elimination affords methyl retinoate (98). Alternatively retinol (99) has been prepared in high yield by condensation of the C15 bromide (105) with the C5 hydroxy-sulphone (106), followed by elimination of sulphinic acid. The syntheses... 

Since the 4,6-acetal grouping and the glycosidic grouping (27) are stable under basic conditions, though unstable in the presence of acid, the remaining two hydroxyl groups may be suitably protected by reactions that are base catalysed. TTius (27) may be converted into the 2,3-di-O-toluene-p-sulphonyl derivative (28) by reaction with toluene-p-sulphonyl chloride in the presence of pyridine (Expt 5.119) this reaction is analogous to the formation of sulphonate esters of alcohols or phenols. 

Mixtures of primary, secondary and tertiary amines can usually be separated by Hinsberg s method. This is based on the fact that reaction with benzene-sulphonyl (or toluene-p-sulphonyl) chloride converts primary amines into alkali-soluble sulphonamides, secondary amines into alkali-insoluble sulphon-amides and leaves tertiary amines unaffected. 

Strong base anion exchange resins are manufactured by chloromethylation of sulphonated polystyrene followed by reaction with a tertiary amine ... 

Sulphonation with sulphuric acid or oleum is initially rapid and exothermic. The rate of reaction is highly dependent on the concentration of the sulphuric acid, so the reaction slows significantly as the sulphonating agent is consumed and further diluted by the water which is a by-product of the reaction. Processes based on sulphuric acid use large excesses, resulting in high levels of waste acid or residual sulphate in the neutralised product. An alternative is to remove the water from the reaction mixture, usually by two-phase distillation, with excess substrate as a carrier. 

A mechanism of action for the r-deficient 2-heteroaryl derivatives was postulated based upon the reaction of 6-(2-pyridyl)methylene penicillanic acid sulphone (28) with sodium methoxide (Scheme 6.14) [46]. Chen and co-workers proposed that after bimolecular interaction between the enzyme and (28), an aromatic acyl-enzyme ester (76) is obtained. This conjugated... 

The hydrolysis of the 4-hydroxy-CPA derivatives (74 b-d) and subsequent ring reclosure of the corresponding (75) are qualitatively related to the same steps for 4-hydroxy-CPA (74 a) itself. However, (74,-a) and (74 d) undergo general acid-catalyzed ring opening, whereas for (74 b) and (74 c) the reaction is specifically base-catalyzed. A difference in behaviour is also to be noticed in their reactions with sodium 2-nercaptoethane sulphonate here, (74,-a) and (74 d) react readily whereas (74 b) and (74 c) fail... 

The formation of the amine (496) when 3)5-toluene-p-sulphonates are treated with 2-dimethylaminoethanol involves both inversion at C-3 and demethyla-tion. The reaction of androstane-16,17-ketols and 17 -acetoxy-16a,Ha-epoxide with morpholine to give a-morpholino-ketones has been thoroughly investigated and rationalised. H/5-Aminoandrosta-3,5-diene, prepared by reduction of the H-oxime, possesses some antimicrobial activity which is not enhanced by substitution of the amino-groups with 2-chloroethyl, 2-hydroxy-ethyl, or 3-aminopropyl groups similar 2-chloroethyl substituted H)5-amines have been cyclised by treatment with base to give H -aziridines. All four... 

A test for sulphonic acids is based on conversion to the sulphonyl chloride and then reaction with hydroxylamine. The reaction product can be converted with a drop of acetaldehyde to a hydroxamic acid which is detected in the classical way through the brown-violet colour with a drop of a Fe3+ reagent264. 

There have been many different approaches to their synthesis. Sulphonic acid salts (2), halides (3), esters (4) and amides (5) may be thought of as derivatives that are formed by reaction of the parent acid with bases, halogens, alcohols and amines respectively, although there are many other routes that have been taken to these compounds. 

Some functional groups that are sensitive to reaction with strong bases, like alkoxides, undergo reaction under these reaction conditions380,381. Thus 2-chloroethanesulphonyl chloride reacts with alkoxides to give the unsaturated sulphonate ester, as indicated in equation 84. Such side-reactions may be averted by reaction of the sulphonyl chloride, or fluoride, with the trimethylsilyl derivative of the alcohol382, as indicated by equation 85. The derivative may be formed under mild conditions from the alcohol. 

Earlier, it was shown that sulphenes, formed by reaction of sulphonyl halides with a base, reacted with alcohols to give sulphonate esters. These same reactive intermediates have also been used for the formation of sultones, by reaction with carbonyl-containing compounds424-428, as shown in equation 98. If the carbonyl compound contains an a-... 

If the sulphonation step is prolonged all the anthraquinones are almost exclusively converted into 2,6- and 2,7 anthraquinone disulphonic acids. After dilution of this reaction mixture to 40% sulphuric acid, saturating the solution with salts can precipitate the compounds. After fusion with base a mixture of 1,2,6- en 1,2,7-trihydroxy anthraquinones is obtained that leads to a more yellowish red on fabrics that have been impregnated with aluminium mordant [20],... 

Pyridine is a tertiary amine its aqueous solution shows an alkaline reaction and precipitates the hydroxides of metals, some of which are soluble in an excess of the amine. Salts of pyridine like those of other amines form characteristic double salts with metallic halides. The ferrocyanide of pyridine and the addition-product of pyridine and mercuric chloride are difficultly soluble in water these compounds are used in the purification of the base. Pyridine is a very stable compound it can be heated with nitric acid or chromic acid without undergoing change but at 330° it is converted by a mixture of nitric acid and fuming sulphuric acid into nitropyridine, a colorless compound that melts at 41° and boils at 216°. At a high temperature pyridine is converted into a sulphonic acid by sulphuric acid. Chlorine and bromine form addition-products, e.g., C5H5N.CI2, at the ordinary temperature when these are heated to above 200°, substitution-products are formed. The hydroxyl derivative of pyridine is made by fusing the sulphonic acid with sodium hydroxide it resembles phenol in chemical properties. The three possible carboxyl derivatives of pyridine are known. The a-acid is called picolinic acid, the jS-acid nicotinic acid (664), and the 7-acid isonicotinic acid. 

Mannich reaction of propiophenone with formaldehyde and dimehtylamine yields the corresponding amino ketone, which on treatment with benzylmagnesium bromide gives rise to the corresponding amino alcohol. Esterification of this alcohol with propionic anhydride forms the levopropoxyphene base, which on reaction with an equimolar quantity of 2-naphthalene sulphonic aeid gives the official compoimd. 

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