Anilides, reactions

In general the para isomer is the main product but about 5 % ortho isomer was detected6 when the solvent was aqueous acetic acid. All the evidence suggests that the rearrangement is intermolecular involving the reversible formation of free chlorine and the anilide, reaction (2), followed by C-chlorination of the anilide, reaction (3)... 

Anilides, (a) To 1 ml. of aniline in a small conical flask add very slowly and carefully about i ml. of acetyl chloride. A vigorous reaction occurs and a solid mass is formed. Add just sufficient water (about 15 ml.) to dissolve the solid completely on boiling. On cooling, crystals of acetanilide separate out filter and determine the m.p. 

Give the isocyanide (carbylamine) reaction, if the anilide is an acylated primary amine. 

Isocyanide reaction. Heat together gently 0 2 g. of the anilide, 3 ml. of ethanolic NaOH solution and i ml. of chloroform hydrolysis of the anilide occurs, and the odour of the isocyanide can be detected after about i minute s heating. [This test clearly differentiates an anilide of type R CONHC Hj from one of type R CO N(CH3)CeH5.]... 

Transition-Metal Catalyzed Cyclizations. o-Halogenated anilines and anilides can serve as indole precursors in a group of reactions which are typically cataly2ed by transition metals. Several catalysts have been developed which convert o-haloanilines or anilides to indoles by reaction with acetylenes. An early procedure involved coupling to a copper acetyUde with o-iodoaniline. A more versatile procedure involves palladium catalysis of the reaction of an o-bromo- or o-trifluoromethylsulfonyloxyanihde with a triaLkylstaimylalkyne. The reaction is conducted in two stages, first with a Pd(0) and then a Pd(II) catalyst (29). 

IsoxazoIe-5-carboxyIic acid anilide, 3,4-diphenyI-synthesis, 6, 86 Isoxazolecarboxylic acids applications, 6, 128 IR spectra, 6, 5 potentiometry, 6, 11 reactions, 6, 52 synthesis, 6,27, 85-86 thermochemistry, 6, 10 IsoxazoIe-3,4-dicarboxyIic acid esters... 

Similar sulfenylation reactions of the 2-subsdtuted cyclic enamines of -keto carboxylic acid anilides are also possible, The trifluoromethanesulfenyl substitution takes place according to ring size Sulfenylation occurs at positions 2 and 5 with five-membered rings, at posibon 6 with six-membered tings, and at position 7 with seven-membered rings [5J (equation 4) (Table 1). Acid hydrolysis of the enamines proceeds readily to form the corresponding keto compounds. 

All the anilides are hydrolysed by strong mmeial acids or alkalis and the acid ladlcal removed (see also Beckmann s reaction, Prep, too, p. 212). 

Enamines of cyclic ketones do not form cycloaddition products, but give the mono- or dicarboxanilides (110,111). Thus the enamine (113) on reaction with 1 equivalent of phenyl isocyanate gave 160. Treatment of 113 with 2 equivalents, or 160 with 1 equivalent, of phenyl isocyanate gave the 2,6-disubstituted product (161). Mild acid hydrolysis of 160 and 161 produced the corresponding cyclohexanone(2-mono- and 2,5-di)carbox-anilides (110). 

The Knorr quinoline synthesis refers to the formation of a-hydroxyquinolines 4 from P-ketoesters 2 and aryl amines 1. The reaction usually requires heating well above 100°C. However, some cases do exist when the cyclization takes place in the presence of a catalytic amount of mineral acid at temperatures as low as -10 °C. The intermediate anilide 3 undergoes cyclization by dehydration with concentrated sulfuric acid. The reaction is conceptually close to the Doebner-Miller and Gould-Jacobs reactions. ... 

A variety of aryl systems have been explored as substrates in the Knorr quinoline synthesis. Most notable examples are included in the work of Knorr himself who has demonstrated the high compatibility of substituted anilines as nucleophilic participants in that reaction. In the case of heteroaromatic substrates however, the ease of cyclization is dependent on the nature and relative position of the substituents on the aromatic ring." For example, 3-aminopyridines do not participate in ring closure after forming the anilide... 

After anilide 30 (1.12 g, 4.46 mmol) is hydrolized in 6 M HCl at 100 °C (by TLC analysis), toluene (5 mL) is added and then aldehyde 5 (0.74 mL, 8.92 mmol) is added dropwise at the same temperature. The reaction was stirred for 2 h and then cooled to room, temperature. The aqueous layer is removed and neutralized with aqueous NaOH to afford 31 as a crystalline solid. The crude product is purified by silica gel chromatography (hexanesiethyl acetate, 5 1) to give 31 (802 mg, 70%) as colorless crystals, mp 103 °C. 

The first representatives of this group of compounds, 1,5-benzotelluroazepinones 57, have been prepared in 17% yield by the reaction between 2-iodopropyolanilides and NaHTe (98H631). The reaction proceeds, most probably, as nucleophilic substitution of the iodine, resulting in telluroles 58 and the subsequent nucleophilic addition of a hydrotelluride group to the triple bond. An alternative mechanism involving initial addition of NaTeH to the triple bond followed by the nucleophilic substitution of the iodine atom was mled out because the anilides PhNHCOC=CR do not react with NaTeH under the conditions at which the heterocycles 57 were obtained. Neither of the adducts PhNHCOCH=C(R)TeH or [PhNHCOCH=C(R)Te]2 was isolated. 

A synthesis of 4-methylquinolines 277 by the modified Fiiedlander reaction from ort/io-lithiated anilides 276 and 4-methoxybut-3-en-2-one (—20°C, THF, pentane, 2 h) in 14-17% yields (in the cyclization stage) has been described (91JOC7288). 

The pH is adjusted to 5.5 and the water phase separated and extracted with additional ether in order to remove the surplus dimethyl anilin. After addition of an excess of ammonia to the solution, the reaction product, N-methylpipecolic acid 2,6-dimethyl anilide, is recovered by extraction with isoamyl alcohol. The isoamyl alcohol solution is evaporated to dryness, the product dissolved in dilute hydrochloric acid, treated with charcoal and reprecipitated with NaOH. N-methylpipecolic acid 2,6-dimethyl anilide is obtained in crystalline form. 

A mixture of 9.05 g (0.05 mol) of bcnzaldchydc anilide and 7.87 g (0.07 mol) of potassium /-butoxidc in 200 mL of DMb is cooled to —40 C under N2. This mixture is stirred and maintained at this temperature while a solution of 10.47 g (0.07 mol) of 2-chloro-Ar,/V-diethylacetamide in 125 mL of l)MF. is added over a 2-hr period. The reaction is allowed to warm to r.t. over a 30-min period and concentrated to a small volume in vacuo at 35 C. The residue is diluted with H20 and Et,0. After removal of the Ei20 layer, the aqueous fraction is extracted with another two portions of Er2(), and the combined extracts are dried over MgS04. Filtration and evaporation gives 16.32 g of crude material. This material is chromatographed on deactivated alumina with initial elution with pet. ether followed by benzene. Two pure fractions are obtained which, after reciystalli/.aiiou from ben/ene/pet. ether, are identified as the (ranj-isomer 3a yield 1.03 g (7%) mp 90-92eC. and the cts-isomer 3b yield 8.53 g (58%) mp 80.5-82.5cC. 

Heptadecanoic acid, 43,39 Heptane, 1,1,1-trifluoro, 41, 104 Heptanoic acid, 3-methyl-, 41, 60 Heptanoic add, reaction with sulfur tetrafluoride, 41,104 1-Hepten4-ol, 4,6-dimethyl-, 41,30 Hexachloroacetone, reaction with aniline to form ,M,a-trichloroacet-anilide, 40,103... 

Dialkylphosphonoacetic acid esters react with p-aminobenzoic acid to anilides. The potassium salt of the diamyl ester is said to be surface-active [126]. Phosphorus organic carbonic acid amides can also be obtained by the following reaction [127] see Eq. (76). 

C. Reactions of Phosphoric and Phosphinic Acid Derivatives.—The optically active phosphinate ester (90) has been shown to react with benzyl Grignard reagents or lithium anilide with inversion of configuration. Oxidation of... 

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 . ... 

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