Sulfonic anhydrides, hydrolysis

A heterocyclic ring may be used in place of one of the benzene rings without loss of biologic activity. The first step in the synthesis of such an agent starts by Friedel-Crafts-like acylation rather than displacement. Thus, reaction of sulfenyl chloride, 222, with 2-aminothiazole (223) in the presence of acetic anhydride affords the sulfide, 224. The amine is then protected as the amide (225). Oxidation with hydrogen peroxide leads to the corresponding sulfone (226) hydrolysis followed by reduction of the nitro group then affords thiazosulfone (227). ... 

Christensen (1966, 1967) found that aromatic sulfonic anhydrides undergo rapid, uncatalyzed hydrolysis in either acetone or aqueous dioxan (t1/2= 17 s at 25°C for Ar =p-tolyl in 65% dioxan). Added strong acids (or added salts like NaCl or LiCl) have no effect on the rate at concentrations up to 0.01 M. The solvent isotope effect associated with this spontaneous hydro-... 

The LAB-sulfonic acid has to be then aged and residual traces of anhydrides have to be hydrolyzed standard condition for this step of the LAS production is to operate at a temperature range 45-50°C to allow the complete conversion of LAB into LAS over 45 to 60 min, whereas the amount of HjO added for anhydride hydrolysis accounts for 0.5% with respect to the mass of the acid. 

Free oil in LAS consists not only of unsulfonated alkylbenzene but also of sulfones. Anhydrides are also formed in the sulfonation reaction but are completely eliminated from the commercial product by a hydrolysis step during LAS production (54) ... 

In further modifications of these norprogestins, reaction of norethindrone with acetic anhydride in the presence of p-toluene-sulfonic acid, followed by hydrolysis of the first-formed enol acetate, affords norethindrone acetate (41). This in turn affords, on reaction with excess cyclopentanol in the presence of phosphorus pentoxide, the 3-cyclopentyl enol ether (42) the progestational component of Riglovic . Reduction of norethindrone affords the 3,17-diol. The 33-hydroxy compound is the desired product since reactions at 3 do not show nearly the stereoselectivity of those at 17 by virtue of the relative lack of stereo-directing proximate substituents, the formation of the desired isomer is engendered by use of a bulky reducing agent, lithium aluminum-tri-t-butoxide. Acetylation of the 33,173-diol iffords ethynodiol diacetate, one of the most potent oral proves tins (44). ... 

Synthetic polymers and natural polymers suitable for drilling muds are listed in Tables 1-7 and 1-8, respectively. Polyacrylamides are eventually hydrolyzed in the course of time and temperature. This leads to a lack of tolerance toward electrolyte contamination and to a rapid degradation inducing a loss of their properties. Modifications of polyacrylamide structures have been proposed to postpone their thermal stability to higher temperatures. Monomers such as AMPS or sulfonated styrene/maleic anhydride can be used to prevent acrylamide comonomer from hydrolysis [92]. 

Although anhydride formation is more favorable thermodynamically for a sulfinic acid than for most types of acids, it is still true that in media containing any significant amount of-water the equilibrium in (132) for acyclic sulfinyl sulfones lies far to the left, and when placed in such media sulfinyl sulfones are hydrolyzed completely to the corresponding sulfinic acid. Let us now discuss what is known about the mechanism of this hydrolysis reaction. 

That an a-disulfone may properly be considered to be a mixed anhydride of a sulfinic and a sulfonic acid is shown by the fact that a-disulfones undergo relatively easy spontaneous hydrolysis (188) to give one molecule each of a sulfinic and a sulfonic acid (Kice and Kasperek, 1969). 

Unlike sulfinyl sulfones (the anhydrides of sulfinic acids), whose heat of hydrolysis is much less than that for most anhydrides, the heat of hydrolysis of an cr-disulfone (see Table 5, p. 114) is comparable to that for typical anhydrides (Kice et al., 1977). 

Other examples of the solvolysis of sulfonates to give oxolanes have been reported. Thus, when 2,3-0-benzylidene-tri-0-(methylsulfonyl)-D-arabinitol, in a mixture of 9 M acetic acid and 10 M hydrochloric acid is heated for 30 minutes at 100°, it gives 2,5-anhydro-l,4-di-0-(methylsulfonyl)-D-arabinitol.88 Additional instances of the formation of internal anhydrides (not always well characterized) by acid hydrolysis of various sulfonic esters of alditols have been given by the same authors.88... 

The reduced basicity of phenothiazine nitrogen requires that even acylation proceed via the anion. The amide (34-2) from the methyl thioether (34-1) can be prepared, for example, by sequential reaction with sodium amide and acetic anhydride. Oxidation of that intermediate with peracid proceeds preferentially on the more electron-rich alkyl thioether to give the sulfone this affords the phenothiazine (34-3) on hydrolysis of the amide. Complex side chains are most conveniently incorporated in a stepwise fashion. The first step in the present sequence involves reaction of (34-3) as its anion with l-bromo-3-chloropropane to give (34-4). The use of that halide with alkylate piperidine-4-carboxamide (34-5) affords the antipsychotic agent metopimazine (34-6) [35]. 

A one-pot synthesis of alkyl perfluoroalkyl ketones has been developed. Phosphoranes, generated in situ, are acylated with a perfluoroacyl anhydride, and the resulting phosphonium salts are hydrolyzed with alkali [48] (equation 48) Hydrolysis of a carbon-sulfur bond in 2-chloro-2,4,4-trifluoro-1,3-dithietane-S-trioxide, which can be obtained from 2,2,4,4-tetrachloro-l,3-dithietane by fluor-ination with antimony trifluonde followed by selective oxidauons, opens the ring to produce 2-chloro-l,l,2-trifluorodimethyl sulfone [49] (equation 49)... 

Mixed anhydride 6b is a sulfonylating rather than a phos-phorylating agent. Thus, hydrolysis with 0 gives acid 6c and propylsulfonic acid in which the - -°0 isotope is incorporated only in the sulfonic acid (Eq. 2). Compound 6b reacts with either alcohols (methanol, ethanol, sec-butanol) or L-cysteine to yield acid 6c and with triethylamine to give the anion of 6c. probably via propylsulfene (4) (Eq. 2). 

The digestion and hydrolysis temperatures are controlled between 110 and 125°F. During hydrolysis, approximately 2 parts of water per 100 parts of reaction product are added to convert acid anhydrides to sulfonic acid. Both the oleum and S03 sulfonation processes are quite exothermic and almost instantaneous. In order to prevent decomposition and maintain optimum product color, an efficient reactor heat removal system is necessary. 

The mixture of the (R)-HMPC and the (S)-acetate 4 from the enzymatic hydrolysis was esterified with methanesulfonyl choride and triethylamine to afford a mixture of the corresponding (R)-sulfonate 5a and the (S)-acetate 4. The (S)-acetate 4 was unaffected by the sulfonation conditions. The resultant mixture of two esters, 4 and 5a, was hydrolyzed in the presence of a small amount of calcium carbonate. The (R)-sulfonate 5a was converted into the (S)-HMPC 6 as a result of inversion of configuration. On the other hand, the (S)-acetate 4, was hydrolyzed with retention of configuration. Consequently, all of the racemic acetate J3, was converted with maximum efficiency to the desired (S)-HMPC 6, by the sequence enzymatic hydrolysis and sulfonation followed by inversion of the chiral center in (R)-HMPC without separation of the (S)-acetate Similar transformations could also be carried out via nitrate ester intermediate 5b obtained from the reaction of the (R)-HMPC with nitric acid and acetic anhydride. 

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