Substituted sulphonamides

Benzenesulphonyl chloride reacts with primary and secondary, but not with tertiary, amines to yield substituted sulphonamides (for full discussion, see Section IV,100,3). The substituted sulphonamide formed from a primary amine dissolves in the alkaline medium, whilst that produced from a secondary amine is insoluble in alkali tertiary amines do not react. Upon acidifying the solution produced with a primary amine, the substituted sulphonamide is precipitated. The reactions form the basis of the Hinsberg procedure for the separation of amines see Section IV,100,(viii) for details. Feebly basic amines, such as o-nitroaniline, react slowly in the presence of allcali in such cases it is best to carry out the reaction in pyridine solution see Section IV,100,3. ... 

The sulphonamides are used in the preparation of chloramines which are good disinfectants. Ring substituted sulphonamides are used in the preparation of sulphadrugs. 

Copper sulphate solution. This detects V-substituted sulphonamides. 

Exchange of substituents in substituted sulphonamides may occur by transamination as shown in equation 114463. Helferich and Kleb464 and others465,466 have prepared sultams (cyclic sulphonamides) using a similar methodology, as shown in equation 115. 

One of the most general, and facile, synthetic routes to both unsubstituted and substituted sulphonamides is by the reaction of ammonia466-469 or amines455,465,470-476 with a sulphonyl chloride, as shown in equation 116. Sulphonyl fluorides may also be used as precursors in a similar synthetic procedure477. This method is, however, prone to produce disulphonamides as by-products if the stoichiometry of the reaction is not carefully controlled4, or if the reaction mixture is alkaline478-481. 

Aromatic sulphonyl chlorides have been synthesized from unsubstituted sulphona-mides by reaction with PC15639. On the other hand, AT-alkyl substituted sulphonamides undergo a rather surprising reaction with the same reagent, as shown in equation 160640. Sulphonyl fluorides may be prepared from unsubstituted sulphonamides by reaction of the latter with HF and sodium nitrite641. 

A is a bivalent radical selected from (1), (2), and (3) and R1 and R3 are the same or different and each is a substituent selected from H, Cl, Q- alkyl, methoxy, ethoxy, and sulphonic acid radical or a salt thereof, sulphonamide radical, and Q- alkyl-substituted sulphonamide radical. 

Benzenesulphonyl chloride is a useful reagent to distinguish between the three classes of amines. The method was first described by Hinsberg. When a primary amine is treated with the chloride in the presence of sodium hydroxide, a substituted sulphonamide is formed —... 

Adams and Tjepkema [33] have published the infra-red spectra of sixteen N iV -di-substituted sulphonamides, and noted that a strong band occurs in all cases in the range 1180—1160 cm" which they ascribe to the —SO2 — grouping. Schrieber [23] has pointed out that, in addition, these spectra also have a strong band in the 1360— 1330 cm" region corresponding to the second sulphone band. 

The reaction of trialkylboranes with lead(iv) acetate or phenyliodosoacetate to yield the corresponding alkyl acetate has been described as has the reaction of trialkylboranes or 5-alkyl-9-BBN derivatives with JV-substituted 2-lithioindoles to give, after iodination, 2-alkylindoles. It has also been reported that trialkylboranes react with chloramine-T and its analogues to produce A-substituted sulphonamides [reaction (5)]. ... 

Fuse about 0 5 g of the substance with 2 g of potassium hydroxide in a hard-glass test-tube, or better, in a nickel crucible for 10 minutes. A simple sulphonamide evolves ammonia, while a substituted sulphonamide liberates an amine, the vapour of which may be detected by means of filter-paper moistened with saturated ethanolic 2,4-dinitrochlorobenzene solution a strong yellow colour is a positive test. 

At-Mono-substituted sulphonamides, 3335-3205 3.00-3.12 s m-w N-H str, one band only. Dilute solutions... 

The kinetics of the binding of anions and sulphonamides to carbonic anhydrase have been measured by the stopped-flow technique. The results are consistent with a mechanism involving a pH-dependent equilibrium between two co-ordination forms of the enzyme in which anions selectively combine with the low-pH form of the enzyme whereas sulphonamides combine with the high-pH form. The effect of pH on the anion affinity correlates with the pH dependence of the spectral change associated with the cobalt(n) form of the enzyme. Further evidence on the similarity of the conformations at the active sites of the zinc and cobalt(n) forms of carbonic anhydrase has been provided by spin-labelling. A nitroxide-substituted sulphonamide was used as the spin label and its e.s.r. spectrum was found to be almost identical in the two forms of the enzyme-inhibitor complex. 

---