Acetamide reactions

When hexamethylbenzene was oxidised in acetonitrile containing acetic acid, perchlorate electrolytes favoured the acetamidation reaction, whereas fluoroborate led to relatively higher acetoxylation yields. This fact was interpreted in terms of preferential solvation of fluoroborate by acetic acid. 

However, this simple mechanism shown in Scheme 2 does not adequately account for all aspects of all acetamidation reactions with aromatic hydrocarbons. For example, it has been shown that in the acetamidation of toluene the distribution of five products— the acetamido derivative (III), a dimeric hydrocarbon (IV), benzyl alcohol (V), benzaldehyde (VI), and benzoic acid (VII)— is dependent upon the electrode potential, the concentration of water in the electrolyte, and the supporting electrolyte itself ... 

A similar protocol was used by Siegel and coworkers [25] in the purification of products from reductive aminations, epoxide openings using amines and urea formation and by Chucholowski et al. [26] in the synthesis of thiazole libraries. A library of 48 ethanolamines in an 8 x 6 array prepared by the monoalkylation of amines with epoxides (Figure 11) was disclosed by Shuker et al. [27]. The synthetic protocol involved the in situ silylation of the amine with bis-(trimethylsilyl)acetamide, reaction with excess epoxide followed by SCX ion-exchange chromatography. 

Amides themselves (e,g., acetamide) also often respond to the reaction ... 

By the action of concentrate aqueous ammonia solution upon esters. This process is spoken of as ammonolysls of the ester, by analogy with hydrolysis applied to a similar reaction with water. If the amide is soluble in water, e.g., acetamide, it may be isolated by distillation, for example ... 

The student should carry out the following simple experiments with acetamide or with any other ahphatic amide, e.g., n-caproamide they illustrate some of the general reactions of primary ahphatic amides. 

Dimethylthiazole (III) may be prepared from thloacetamide (I) and monochloroacetone (II). The thloacetamide is conveniently formed in the reaction mixture from acetamide and phosphorus pentasulphide. 

Nitrosomethylurea. Acetamide method. To a solution of 59 g. of acetamide in 88 g. (28 ml.) of bromine (1) in a 4-litre beaker add dropwise, with hand stining, a solution of 40 g. of sodium hydroxide in 160 ml. of water. Heat the resulting yellow reaction mixture on a steam bath until eflfervescence sets in (2), after which continue the heating for 2-3 minutes. CrystaUisation of the product from the yellow or red coloured solution usually commences immediately. Cool in an ice bath for 1-2 hours, collect the product by suction filtration, wash with a little ice-cold water, and dry in the air. The yield of colourless acetylmethylurea, m.p. 178-180°, is 50 g. 

To make methylamine we start with Acetamide. The general, unbalanced reaction process is thus ... 

Urea is conveniently obtained as a constituent of many fertilizers and so it is easily obtained. Sources have indicated that a 501b bag can be purchased for 15 in the US. It is of less than ideal purity from this source, so some washing will be in order (with what ). Glacial Acetic Acid is easily obtained from photographic supply stores in high purity and for cheap as well. This reaction produces Acetamide with such purity that the product does not... 

One of the virtues of the Fischer indole synthesis is that it can frequently be used to prepare indoles having functionalized substituents. This versatility extends beyond the range of very stable substituents such as alkoxy and halogens and includes esters, amides and hydroxy substituents. Table 7.3 gives some examples. These include cases of introduction of 3-acetic acid, 3-acetamide, 3-(2-aminoethyl)- and 3-(2-hydroxyethyl)- side-chains, all of which are of special importance in the preparation of biologically active indole derivatives. Entry 11 is an efficient synthesis of the non-steroidal anti-inflammatory drug indomethacin. A noteworthy feature of the reaction is the... 

Because huge quantities of by-product acetonitrile are generated by ammoxidation of propylene, the nitrile may be a low cost raw material for acetamide production. Copper-cataly2ed hydration gives conversions up to 83% (11), and certain bacteria can effect the same reaction at near room temperature (12). 

Amines undergo an analogous reaction to yield acetamides, the more basic amines having the greater activity ... 

The uses of dimethyl acetamide are very similar to those for dimethylform amide [68-12-2] (see FoRMiC ACId). DMAC is employed most often where higher temperatures are needed for solution of resins or activation of chemical reactions. 

MPD-1 fibers may be obtained by the polymeriza tion of isophthaloyl chloride and y -phenylenediamine in dimethyl acetamide with 5% lithium chloride. The reactants must be very carefully dried since the presence of water would upset the stoichiometry and lead to low molecular weight products. Temperatures in the range of 0 to —40° C are desirable to avoid such side reactions as transamidation by the amide solvent and acylation of y -phenylenediamine by the amide solvent. Both reactions would lead to an imbalance in the stoichiometry and result in forming low molecular weight polymer. Fibers are dry spun direcdy from solution. 

Peroxide-Ketazine Process. Elf Atochem in France operates a process patented by Produits Chimiques Ugine Kuhhnaim (PCUK). Hydrogen peroxide (qv), rather than chlorine or hypochlorite, is used to oxidize ammonia. The reaction is carried out in the presence of methyl ethyl ketone (MEK) at atmospheric pressure and 50°C. The ratio of H202 MEK NH2 used is 1 2 4. Hydrogen peroxide is activated by acetamide and disodium hydrogen phosphate (117). Eigure 6 is a simplified flow sheet of this process. The overall reaction results in the formation of methyl ethyl ketazine [5921-54-0] (39) and water ... 

The mechanism of this reaction involves an activation of the ammonia and hydrogen peroxide because these compounds do not themselves react (118—121). It appears that acetamide functions as an oxygen transfer agent, possibly as the iminoperacetic acid (41) which then oxidizes the transient Schiff base formed between MEK and ammonia (40) to give the oxaziridine (42), with regeneration of acetamide ... 

The methyl ethyl ketazine forms an immiscible upper organic layer easily removed by decantation. The lower, aqueous phase, containing acetamide and sodium phosphate, is concentrated to remove water formed in the reaction and is then recycled to the reactor after a purge of water-soluble impurities. Organic by-products are separated from the ketazine layer by distillation. The purified ketazine is then hydrolyzed under pressure (0.2—1.5 MPa (2—15 atm)) to give aqueous hydrazine and methyl ethyl ketone overhead, which is recycled (122). The aqueous hydrazine is concentrated in a final distillation column. 

The aramids are formed in the low temperature reaction, -10 to 60°C, of equimolar amounts of the diacid chloride and the diamine in an amide solvent, typically dimethyl acetamide (DMAc) or A/-meth5i-2-pyrrohdinone (NMP) and usually with a small amount of an alkaU or alkaline-earth hydroxide and a metal salt, such as LiOH [1310-65-2] LiCl, Ca(OH)2 [1305-62-0] or CaCl2 added to increase the solubiUty of the polymer and neutralize the hydrochloric acid generated in the reaction. 

The two-step poly(amic acid) process is the most commonly practiced procedure. In this process, a dianhydride and a diamine react at ambient temperature in a dipolar aprotic solvent such as /V,/V-dimethy1 acetamide [127-19-5] (DMAc) or /V-methy1pyrro1idinone [872-50-4] (NMP) to form apoly(amic acid), which is then cycHzed into the polyimide product. The reaction of pyromeUitic dianhydride [26265-89-4] (PMDA) and 4,4 -oxydiani1ine [101-80-4] (ODA) proceeds rapidly at room temperature to form a viscous solution of poly(amic acid) (5), which is an ortho-carboxylated aromatic polyamide. 

Nucleophilic Substitution Route. Commercial synthesis of poly(arylethersulfone)s is accompHshed almost exclusively via the nucleophilic substitution polycondensation route. This synthesis route, discovered at Union Carbide in the early 1960s (3,4), involves reaction of the bisphenol of choice with 4,4 -dichlorodiphenylsulfone in a dipolar aprotic solvent in the presence of an alkaUbase. Examples of dipolar aprotic solvents include A/-methyl-2-pyrrohdinone (NMP), dimethyl acetamide (DMAc), sulfolane, and dimethyl sulfoxide (DMSO). Examples of suitable bases are sodium hydroxide, potassium hydroxide, and potassium carbonate. In the case of polysulfone (PSE) synthesis, the reaction is a two-step process in which the dialkah metal salt of bisphenol A (1) is first formed in situ from bisphenol A [80-05-7] by reaction with the base (eg, two molar equivalents of NaOH),... 

Similar disproportionation reactions are catalyzed by organic catalysts, eg, adiponittile, pyridine, and dimethyl acetamide. Methods for the redistribution of methyUiydridosilane mixtures from the direct process have been developed to enhance the yield of dimethylchlorosilane (158). 

---