Sulphonamides addition

PRILOCAINE SULPHONAMIDES Risk of methaemoglobinaemia a case report of methaemoglobinaemia with topical prilocaine in a patient taking sulphonamides Additive effect Avoid co-administration... 

SULPHANILAMIDE. (Reaction C.) Add 15 g. of the above thoroughly drained sulphonamide to 10 ml. of concentrated hydrochloric acid diluted with 20 ml. water, and boil the mixture gently under reflux for i hour. Then add 30 ml. of water and heat the mixture again to boiling, with the addition of a small quantity of animal charcoal. Filter the boiling solution, and add powdered sodium carbonate in small quantities to the filtrate with stirring until all eflFervescence ceases and the sulphanilamide is precipitated as a white powder. Cool the mixture thoroughly and filter oflF the sulphanilamide at the pump, wash with water and dry. Yield, ca. 10 g. 

Toluene-/ sulplionamide is almost insolubb in cold water, but dissolves readily in sodium hydroxide solution (as the sodium derivative) aid is immediately reprecipitated on the addition of strong acids. To show the formation of the sodium derivative, dissolve about o-2 g. of metallic sodium in about 10 ml, of ethanol, cool the solution, and then add it to a solution of 1 g. of the sulphonamide in 20 ml. of cold edianol. On shaking the mixture, fine white crystals of the sodium derivative, CH,C,HjSO,NHNa, rapidly separate, and may be obtained pure by filtering at the pump, and washing firet with a few ml. of ethanol, and then with ether. 

Method 2. Place a 3 0 g. sample of the mixture of amines in a flask, add 6g. (4-5 ml.) of benzenesulphonyl chloride (or 6 g. of p-toluenesulphonyl chloride) and 100 ml. of a 5 per cent, solution of sodium hydroxide. Stopper the flask and shake vigorously until the odour of the acid chloride has disappeared open the flask occasionally to release the pressure developed by the heat of the reaction. AUow the mixture to cool, and dissolve any insoluble material in 60-75 ml. of ether. If a solid insoluble in both the aqueous and ether layer appears at this point (it is probably the sparingly soluble salt of a primary amine, e.g., a long chain compound of the type CjH5(CH2) NHj), add 25 ml. of water and shake if it does not dissolve, filter it off. Separate the ether and aqueous layers. The ether layer will contain the unchanged tertiary amine and the sulphonamide of the secondary amine. Acidify the alkaline aqueous layer with dilute hydrochloric acid, filter off the sulphonamide of the primary amine, and recrystaUise it from dilute alcohol. Extract the ether layer with sufficient 5 per cent, hydrochloric acid to remove all the tertiary amine present. Evaporate the ether to obtain the sulphonamide of the secondary amine recrystaUise it from alcohol or dilute alcohol. FinaUy, render the hydrochloric acid extract alkaline by the addition of dilute sodium hydroxide solution, and isolate the tertiary amine. 

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). 

Properties of deposits Deposits can be produced that are adherent, coherent and finely crystalline. Addition agents, e.g. organic sulphonamides can improve the deposit structure so that thick coatings can be produced free of nodules and blisters. The production of very smooth thick deposits of copper has been reported Thin deposits tend to reproduce the substrate topography, but some cases of levelling have been reported. The brightness tends to fall with increasing thickness. 

The success of this reaction was ascribed to the solubility of the chlorozinc intermediate, whereas other chloramine-T derivatives (e.g. the sodium salt) are insoluble. An alternative non-nitrene pathway was not eliminated from consideration. On the other hand, no aromatic substitution or addition, characteristic of a free sulphonyl nitrene (see below), took place on treatment of jV,lV-dichloromethanesulphonamides with zinc powder in benzene in the cold or on heating. The only product isolated was that of hydrogen-abstraction, methanesulphonamide 42>, which appears to be more characteristic of the behaviour of a sulphonyl nitrene-metal complex 36,37). Photolysis of iV.iV-dichloromethanesulphonamide, or dichloramine-B, or dichloramine-T in benzene solution led to the formation of some unsubstituted sulphonamide and some chlorobenzene but no product of addition of a nitrene to benzene 19>. 

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... 

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). 

It has been shown that the thermolysis of arenesulphonyl azides with benzene to yield A-arenesuIphonylazepines (44-80%) is aided by the addition of Adogen [30], Sulphonylazepines have also been obtained from the reaction of tetra-n-butylammo-nium salts of sulphonamides with benzene in the presence of xenon difluoride the reaction probably proceeds via the intermediate nitrene [31 ]. 

ESI operating in the negative ion (Nl) mode has been the interface most widely used for the analysis of anionic PFCs. In addition, ESI has also been optimized for the determination of neutral compounds, such as the sulphonamides PFOSA, Et-PFOSA, and t-Bu-PFOS. The use of atmospheric pressure photoionization (APPI) has been explored by Takino and collaborators [88]. The authors found the main advantage of this technology to be the absence of matrix effects, but the limits of detection were considerably higher than those obtained by LC-ESTMS/MS. 

The etiolate intermediate, generated by the addition of higher-order cyanocuprates to enones, has been trapped with several electrophiles. Thus the addition of trimethylsilyl chloride, diethyl or diphenyl phosphorochloridate and iV-phenyltrifluoro methane-sulphonamide affords the corresponding vinyl silyl ethers, vinyl phosphates and vinyltri-flates. " ... 

In experimental typhoid disease in mice treated with colimycin, the addition of pentoxyl prevents immunological disorders and stimulates an immunological reaction [294]. This compound potentiates the action of sulphonamides in mice infected with type II pneumococcus [295]. In combination with streptomycin, pentoxyl is beneficial in the treatment of experimental tuberculosis in guinea-pigs [296]. However, a single pharmacological report, relative to effects on the central nervous system, was unfavourable [297]. 

Dialkylzinc derivatives are inert towards conjugated enones (e.g. 181) in hydrocarbon or ethereal solvents. The discovery that a conjugate addition can be promoted by Cu(I) salts in the presence of suitable ligands L (e.g. sulphonamide 182) opened a new route to zinc enolates (e.g. 183), and hence to the development of three-component protocols, such as the tandem 1,4-addition/aldol addition process outlined in equation 92186. If the addition of the aldehyde is carried out at —78 °C, the single adduct 184 is formed, among four possible diastereomeric products. The presence of sulphonamide is fundamental in terms of reaction kinetics its role is supposed to be in binding both Cu(I) and Zn(II) and forming a mixed metal cluster compound which acts as the true 1,4-addition catalyst. 

The palladium catalysed addition of N-H or O-H bonds onto allenes has successfully been exploited in the preparation of oxazepines, diazepines, oxazocines and diazocines. The nucleophilic attack of the pendant alcohol or sulphonamide function on the allene moiety was followed by the incorporation of the alcohol, used as solvent, to give the desired cyclic products in good yield (5.15. and 5.16.). The bromoallene in these processes is the synthetic equivalent of an allylic dication.15... 

The strong characteristic i.r. absorption of the S02 (or SO) group exhibited by all these compounds is clearly apparent in the spectrum of toluene-p-sulphonamide (Fig. 3.40). In addition, the absorption arising from the presence of the OH, Cl, NH2 or OR groups is usually easily assigned. The confirmation of aromatic substitution patterns by inspection of the p.m.r. spectra is described in the preparative examples below, wherein the fragmentation patterns observable in the m.s. are also discussed. 

Oxidation of toluene-o-sulphonamide to saccharin. In a 600-ml beaker, mounted on an electric hot plate and provided with a mechanical stirrer, place 12 g (0.07 mol) of toluene-o-sulphonamide, 200 ml of water and 3g of pure sodium hydroxide. Stir the mixture and warm to 34-40 °C until nearly all has passed into solution (about 30 minutes). Introduce 19g (0.32 mol) of finely powdered potassium permanganate in small portions at intervals of 10-15 minutes into the well-stirred liquid. At first the permanganate is rapidly reduced, but towards the end of the reaction complete reduction of the permanganate is not attained. The addition occupies 4 hours. Continue the stirring for a further 2-3 hours, and then allow the mixture to stand overnight. Filter off the precipitated manganese dioxide at the pump and decolourise the filtrate by the addition of a little sodium metabisulphite solution. Exactly neutralise the solution with dilute hydrochloric acid (use methyl orange or methyl red as external indicator). Filter off any o-sulphonamidobenzoic acid (and/or toluene-o-sulphonamide) which separates at this point. Treat the filtrate with concentrated hydrochloric acid until the precipitation of the saccharin is complete. Cool, filter at the pump and wash with a little cold water. Recrystallise from hot water. The yield of pure saccharin, m.p. 228 °C, is 7.5 g (58%). 

Chloramine-T (sodium N-chlorotoluene-p-sulphonamide). For this preparation use dichloramine-T which has been prepared as above and thoroughly drained but not necessarily dried. Heat 45 ml of 10 per cent aqueous sodium hydroxide solution in a beaker to a temperature of about 80 °C, add 3.5 g (0.015 mol) of dichloramine-T in small quantities, stirring the mixture gently after each addition until a clear solution is obtained. When the addition is complete, filter the hot solution if turbid, and then allow it to cool spontaneously. Filter the crystals with suction, wash with a little saturated sodium chloride solution and dry upon filter paper or in a desiccator over anhydrous calcium chloride. The resulting chloramine-T weighs 3g (75%) and is almost pure. It may be recrystallised, if desired, from twice its weight of hot water. 

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). 

A solution of (phenylthio)acetaldehyde (6.05 g) in absolute ethanol (180 ml) was added over 10 min to a solution of 4-hydrazino-N-methylbenzenemethanesulphonamide hydrochloride (10 g) in water (180 ml) with cooling. After addition of the aldehyde was complete, the mixture was stirred at 5°C for a period of 14 h. The precipitated solid was filtered off, washed with water (200 ml), hexane (200 ml) and dried in vacuo to give the N-methyl-4-[2-[2-(phenylthio)ethylidene]hydrazino]benzenemethane-sulphonamide (10.95 g), melting point 110°-112°C. 

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