Sodium anilide

Substituted amination has sometimes been effected, as in the conversion of pyridine by sodium anilide into a small yield of 2-anilinopyridine3 i, and the related preparation of 2-alkylaminopyridines . The reaction with sodium N-methylanilide and lithium dibutylamide failed ... 

Reflux Distillation Unit. The apparatus shown in Fig. 38 is a specially designed distillation-unit that can be used for boiling liquids under reflux, followed by distillation. The unit consists of a vertical water-condenser A, the top of which is fused to the side-arm condenser B. The flask C is attached by a cork to A. This apparatus is particularly suitable for the hydrolysis of esters (p. 99) and anilides (p. 109), on a small scale. For example an ester is heated under reflux with sodium hydroxide solution while water is passed through the vertical condenser water is then run out of the vertical condenser and passed through the inclined condenser. The rate of heating is increased and any volatile product will then distil over. 

Hydrolysis to p-Nitroaniline. For this purpose use 70 sulphuric acid, the usual reagent employed for the hydrolysis of anilides (p. 108). Add 5 g. of the recrystallised />-nitro-acetanilide to 30 ml. of 70%sulphuric acid, and boil the mixture gently under a reflux water-condenser for 20 minutes. Then pour the clear hot solution into about 150 ml. of cold water, and finally add an excess of sodium hydroxide solution until precipitation of the yellow p-nitroaniline is complete. Coo the mixture in ice-water if necessary, and then filter at the pump, wash well... 

The above simple experiments illustrate the more important properties of aliphatic acid chlorides. For characterisation, the general procedure is to hydrolyse the acid chloride by warming with dilute alkali solution, neutralise the resulting solution with dilute hydrochloric acid (phenol-phthalein), and evaporate to dryness on a water bath. The mixture of the sodium salt of the acid and sodium chloride thus obtained may be employed for the preparation of solid esters as detailed under Aliphatic Acids, Section 111,85. The anilide or p-toluidide may be prepared directly from the acid chloride (see (iii) above and Section III,85,i). 

Salicyl-u-toluide has been prepared only by the action of phosphorus oxychloride upon a mixture of salicylic acid and o-toluidine. The useful methods of preparation of salicylanilide are by the interaction of salicylic acid and aniline in the presence of phosphorus trichloride, by heating phenyl salicylate and aniline, and from o-hydroxybenzamide and bromobenzene in the presence of small amounts of sodium acetate and metallic copper. A number of these and other anilides have been described. ... 

It is intriguing to note that this reaction scheme for the reduction of a sulphone to a sulphide leads to the same reaction stoichiometry as proposed originally by Bordwell in 1951. Which of the three reaction pathways predominates will depend on the relative activation barriers for each process in any given molecule. All are known. Process (1) is preferred in somewhat strained cyclic sulphones (equations 22 and 24), process (2) occurs in the strained naphtho[l, 8-hc]thiete 1,1-dioxide, 2, cleavage of which leads to a reasonably stabilized aryl carbanion (equation 29) and process (3) occurs in unstrained sulphones, as outlined in equations (26) to (28). Examples of other nucleophiles attacking strained sulphones are in fact known. For instance, the very strained sulphone, 2, is cleaved by hydride from LAH, by methyllithium in ether at 20°, by sodium hydroxide in refluxing aqueous dioxane, and by lithium anilide in ether/THF at room temperature. In each case, the product resulted from a nucleophilic attack at the sulphonyl sulphur atom. Other examples of this process include the attack of hydroxide ion on highly strained thiirene S, S-dioxides , and an attack on norbornadienyl sulphone by methyllithium in ice-cold THF . ... 

Add 4-0 g. (4 0 ml.) of pure aniline dropwise to a cold solution of ethyl magnesium bromide (or iodide) prepared from 1 - 0 g. of magnesium, 5 0 g. (3-5 ml.) of ethyl bromide (or the equivalent quantity of ethyl iodide), and 30 ml. of pure, sodium-dried ether. When the vigorous evolution of ethane has ceased, introduce 0-02 mol of the ester in 10 ml. of anhydrous ether, and warm the mixture on a water bath for 10 minutes cool. Add dilute hydrochloric acid to dissolve the magnesium compounds and excess of aniline. Separate the ethereal layer, dry it with anhydrous magnesium sulphate and evaporate the ether. Recrystallise the residual anilide, which is obtained in almost quantitative yield, from dilute alcohol or other suitable solvent. 

For the high-performance liquid chromatography (HPLC) determination of napro-anilide and its metabolite, 200 mL of 2% sodium sulfate in 0.1M potassium hydroxide solution are added to the concentrate derived from Section 2.2.2. The solution is shaken twice with 100 mL each of dichloromethane or ethyl acetate-n-hexane (1 1, v/v) for 10 min. The combined organic layer is concentrated. " ... 

Kuroda and Suzuki used reaction of 267a with 2-bromoaniline leading to anilide 312 as the first step of their sequence in the preparation of 1H-imidazo[4,5-c]quinolin-4(5//)-ones (Scheme 77) (91TL6915). Reaction of 267a with amines usually does not require any catalyst and/or base, but in this case use of sodium hydride was reported. The anilide 312 was sequentially alkylated, first with methyl iodide in ethanol with potassium hydroxide at room temperature and then with different alkyl iodides in acetone at reflux to provide intermediate 313. This compound was then cyclized via palladium catalyzed reaction leading to product 314. This reaction provides a new entry to l//-imidazo[4,5-c]quinolin-4(5//)-ones that are of current interest as antiasthmatic agents. 

The synthesis involves nitrosating the corresponding substituted acetoacetic anilide with sodium nitrite in acetic acid and subsequently, by adding hydroxyl-amine to the same reaction vessel, converting the compound to the oxime. Finally, complexation is achieved by means of a Ni(II) salt. 

B. 7-Fluoroisatin (3). A 250-mL, three-necked, round-bottomed flask fitted with a condenser and a thermometer is charged with 100 mL of coned sulfuric acid. After heating to 70°C, 30.0 g (0.165 mol) of anilide 2 (Note 9) is added over a period of 1 hr. The resulting deep red solution is heated to 90°C (Note 10) for 60 min (Note 11) and then is cooled to room temperature (20°C) over an ice bath (Note 12). The mixture is then added rapidly to a vigorously stirred mixture of 1.0 L of ice water and 200 mL of ethyl acetate (Note 13). The organic phase is separated and the almost black aqueous phase is extracted twice with 200 mL of ethyl acetate (Note 14). The combined red organic phases are dried with sodium sulfate. The solvent is removed under reduced pressure and the crude product is dried at low pressure, whereupon 12.9 to 15.7 g (47-57%) of an orange powder, mp 186-190°C, is obtained (Note 15). The crude product is sufficiently pure for the next step. Further purification is possible by recrystallization from acetone/water. 

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