Sulphonamides alkylation

Hexamethylphosphoramide has found important uses as a solvent in various organic reactions, such as carboxylic ester formation, hydrolysis of sulphonamides, alkylation of ketones, decyanation of nitriles, the Beckmann rearrangement and so on. HMPA may be used to make cyclodiphospha-zanes (7.250). 

The acidic properties of sulphonamides and their mono-substitution derivatives are particularly well illustrated in the alkyl ubstitution compounds, which by reason of these properties can be prepared by two distinct methods. Thus mono- and di-ethylamine, when subjected to the Schotten-Baumann reaction using benzenesulphonyl chloride, gi e benzenesulphonethylamide, and bcnzenesulphondiethylamide respectively. These compounds can also... 

The mixed aliphatic - aromatic ethers are somewhat more reactive in addition to cleavage by strong hydriodio acid and also by constant b.p. hydrobromio acid in acetic acid solution into phenols and alkyl halides, they may be bromi-nated, nitrated and converted into sulphonamides (Section IV,106,2). 

Pioneering work on the desulphonylation of jS-ketosulphones was carried out by Corey and Chaykovsky - . This reaction was part of a sequence which could be used in the synthesis of ketones, as shown in equation (53). The main thrust of this work was in the use of sulphoxides, but Corey did stress the merits of both sulphones and sulphonamides for different applications of this type of reaction. The method soon found application by Stetter and Hesse for the synthesis of 3-methyl-2,4-dioxa-adamantane , and by House and Larson in an ingenious synthesis of intermediates directed towards the gibberellin skeleton, and also for more standard applications . Other applications of the method have also been madealthough it does suffer from certain limitations in that further alkylation of an a-alkyl- -ketosulphone is a very sluggish, inefficient process. Kurth and O Brien have proposed an alternative, one-pot sequence of reactions (equation 54), carried out at — 78 to — 50°, with yields better than 50%. The major difference between the two routes is that the one-pot process uses the desulphonylation step to generate the enolate anion, whereas in the Corey-House procedure, the desulphonylation with aluminium amalgam is a separate, non-productive step. 

Evidence for the formation of alkyl and aryl radicals in some cases following loss of SO2 (Scheme 1) has been obtained. Thus, a small amount of M-pentane was formed in the decomposition of M-pentanesulphonyl azide in mineral oil ). Thermolysis of diphenyl sulphone-2-sulphonyl azide (8) in dodecane at 150 °C gave diphenyl sulphone 9 (27%) and diphenyl sulphone-2-sulphonamide 10 (9%) which arise by hydrogen abstraction by the aryl radical and sulphonyl nitrene, respectively. When this thermolysis was carried out in Freon E-4 at 150 °C, the products were diphenylene sulphone 77 (1.3%) (Pshorr-type cyclization product of the aryl radical) and 10 (1.5%) together with tars 16h Ferro-... 

R = H, halo, hydroxy, alkyl, alkoxy X = H, sulpho, carboxyl, sulphonamide Y = alkylene, cycloalkylene linkages... 

An efficient synthesis of A-alkylated-4-substituted isothiazolidine-dioxides (sultams) 251 has been developed utilizing epoxides 248 <06TL4245>. Addition of a secondary sulphonamide 247 to epoxide 248 in hot 1,4-dioxane affords the amino alcohol 249, which is... 

These unexacting requirements make the simplest unsulphonated azo structures, often monoazo types, quite acceptable [80]. Typical of the least polar members of this class are Cl Solvent Yellow 2 (4-68), Cl Solvent Orange 1 (4.69) and Cl Solvent Red 17 (4.70). Simple azo structures carrying sulphonamide, sulphone or carboxylate ester groups are used where a somewhat more polar, less soluble dye is needed. Simple disazo compounds (4-amino-azobenzene— 2-naphthol, for example) are used as red solvent dyes. Probably the only structural feature worthy of note in this class is the occasional adoption of structures carrying long alkyl chains to enhance solubility, as in the case of the disazo dye Cl Solvent Yellow 107 (4.71). 

Orthophosphoric and benzylphosphonic acids have been selectively alkylated with triethyl phosphite in a new synthesis of mono-, di-, and triethyl phosphates and of mono- and di-methyl phosphonates.62 A-Methylol carboxamides and sulphonamides react with trialkyl phosphites to give the phosphonate derivatives (78) and (80), respectively.63 However, the mechanism appears to be quite different in each case while the carboamides react by a transesterification-rearrange-ment pathway, the sulphonamides undergo elimination-addition via the imine (79). 

The alkylating agent (0.11 mol) is added with stirring to the sulphonamide (0.05 mol), powdered KOH (7.0 g), K2C03 (7.0 g), and TBA-HS04 (1.7 g, 5 mmol) in PhH (60 ml) at room temperature. The mixture is stirred at ca. 50°C for 3-4 h and then cooled to room temperature and filtered. The solid residue is washed with PhH (3 x 20 ml) and the combined PhH solutions are washed with H20 until neutral, dried (MgS04), and evaporated to yield the alkylated sulphonamide. 

Duolite A-IOID [CL form] is washed with an aqueous solution of the sodium salt of the sulphonamide, obtained by the dissolution of the sulphonamide in aqueous NaOH (0.5 M, 100 ml). The resin is washed repeatedly with H,0, EtOH and MeCOMe and dried over P205 for 12 h. The resin (5 g) is then shaken with the alkylating agent (5 mmol) in EtOH (20 ml) at room temperature. The mixture is filtered and the filtrate evaporated to yield the A-monoalkylated product. 

Table 5.25). Diazacycloalkanes are also obtained from the reaction of a,(o-dibromoalkanes with the bis(tosylamino)alkanes, whereas intermolecular reaction of l-bromo-10-tosylaminodecane yields both 1 1 and 2 2 cyclic products (55% and 8%) under the basic conditions (Scheme 5.13). The reaction of p-tolucncsulphonamide with H-bromododecane yields the di-A-alkylated sulphonamide (84%) [50],... 

Amides. Amides are stable compounds. The lower-melting members (such as acetamide) can be readily purified by fractional distillation. Most amides are solids which have low solubilities in water. They can be recrystallised from large quantities of water, ethanol, ethanol/ether, aqueous ethanol, chloroform/toluene, chloroform or acetic acid. The likely impurities are the parent acids or the alkyl esters from which they have been made. The former can be removed by thorough washing with aqueous ammonia followed by recrystallisation, whereas elimination of the latter is by trituration or recrystallisation from an organic solvent. Amides can be freed from solvent or water by drying below their melting points. These purifications can also be used for sulphonamides and acid hydrazides. 

However, these bifunctionalisation methods are comparatively laborious and applicable only in special cases, since the monofunctionalisation step is limited to substrates possessing an additional coupling site in protected form for the second functional unit. A more versatile method of local bifunctionalisation, which has no need of a deprotection step and also utilises commercially available dendrimer scaffolds, consists in the functionalisation of POPAM dendrimers bearing amine terminal groups with sulphonyl chlorides and subsequent substitution of the sulphonamide proton with other sulphonyl chlorides [63] or with alkyl- or (dendritic) benzyl bromides [64] (see Fig. 3.13). 

Subsequent substitution of the sulphonamide proton with other sulphonyl chlorides or with alkyl- or (dendritic) benzyl bromides. 

The stilbene carbon unit has also been peripherally bound to POPAM cores. Although it does not strictly belong to the hydrocarbon dendrimers, the formula of a G2 dendrimer of this type (Fig. 4.21) is depicted here as an example. It was obtained by alkylation of the corresponding eightfold mono-sulphonamide with 4-(bromomethyl)stilbene. Its fluorescence, E/Z isomerisation, photoisomerisation (see Section 5.2.2), and excimer formation were compared with those of non-dendritic stilbenes. The quantum yields of photoisomerisation (0.30) and fluorescence of the E isomer (0.014) of the dendrimer proved to be substantially lower [38]. 

The central ring systems found to yield antiviral compounds have included fluorene (fluorenone), dibenzofuran, dibenzothiophene, fluoranthene, anthraquinone, acenaphthene, xanthene, thioxanthene, phenothiazine, carbazole, phenanthrene and others. The side chains were represented by basic ethers, basic ketones, basic esters plus carboxamides, sulphonamides, alkanols, methylene and others attached to the various ring systems. The amine function was usually substituted to the tertiary amine with various alkyl substituents although a few ring types (e.g., pyrrole or piperidino) were synthesized. 

Methyl-, benzyl- and toluene-sulphonamide react with aromatic diazonium compounds to give isolable triazenes which decompose in the presence of alkali with the formation of the corresponding aromatic azide and the alkyl- or aryl-sulphinic acid salt . This sequence (equation 123), known as the Dutt-Wormall reaction, is mechanisti-... 

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