Ammonia amides from

Amides. TVeat the acid chloride cautiously with about 20 parts of concentrated ammonia solution (sp. gr. 0 - 88) and warm for a few moments. If no solid separates on cooling, evaporate to dryness on a water bath. Recrystallise the crude amide from water or dilute alcohol. 

Alternatively, dissolve or suspend the acid chloride in 5-10 ml. of dry ether or dry benzene, and pass in dry ammonia gas. If no solid separates, evaporate the solvent. Recrystallise the amide from water or dilute alcohol. 

This procedure, which is based on the work of Ishii and co-workers, affords a mild and general method for converting a wide variety of esters to primary, secondary, and tertiary amides (Table 1). While the preparation of the tertiary amide, N,N-dimethylcyclohexanecarboxamide, described here is carried out in benzene, aluminum amides derived from ammonia and a variety of primary amines have been prepared by reaction with trimethylaluminum in dichloromethane and utilized for aminolysis in this solvent. Although 1 equivalent of the dimethylaluminum amides from amines was generally sufficient for high conversion within 5-48 hours, best results were obtained when 2 equivalents of the aluminum reagent from ammonia was used. Diethyl-aluminum amides can also effect aminolysis, but with considerably slower rates. 

Like thallium(I) amide from which it is derived by treatment with potassium amide in liquid ammonia, the ammoniated salt (x = 2 or less) explodes violently on heating, friction, or contact with dilute acids or water. 

Figure 6.20. Annotated spectrum used in Example 3. The 17 Th mass difference corresponds to ammonia loss from the amide amino acids side-chains. Such peaks being non-sequence-specific themselves, can be very useful during sequencing.

The apparatus is assembled as shown in Fig. 5. Ammonia gas from a commercial cylinder (Note 1) enters the system at K. R is a mercury trap which would serve as a safety valve if the system should become blocked by solidification of the amide owing to an accidental drop in temperature. J is a U-tube containing just enough mercury to seal the bend, and it serves to estimate the rate of ammonia Sow. I is a Kjeldahl trap which prevents any mercury from being thrown into the fusion pot A, which (Note 2) is conveniently supported on a tripod set on bricks to raise it to a convenient height above the burner M. Through the cover of the fusion pot passes an outlet tube B, a thermometer well T, and the combined inlet tube CDE. The... 

As mentioned earlier, the synthesis of primary amides is rather challenging due to technical difficulty in handling gaseous ammonia. Thus, the use of ammonia substitutes such as HMDS and formamide has been studied (see Schemes 21 and 22). With the use of microwave irradiation, however, it has been shown that it is possible to generate both CO and ammonia at the same time for the synthesis of primary amides from aryl bromides. This protocol is very useful for laboratory organic syntheses, especially combinatorial syntheses. As Scheme 29 illustrates, the Pd-catalyzed aminocarbonylation of aryl bromides 200 with formamide (33.5 equiv.) in the presence of KOBu (1.5 equiv.) and imidazole (1 equiv.) with microwave irradiation for 400 s (6.7 min) gave the corresponding benzamides... 

Phenylacetylene has been prepared by treatment of /3-bromo-styrene with potassium hydroxide and with sodium amide in liquid ammonia, and from styrene dibromide by treatment with sodium amide in liquid ammonia. ... 

The final piece of the puzzle is the placement of the mole of ammonia released from the original peptide on acid hydrolysis. The ammonia comes from a primary amide function ... 

The increase in amide-like ammonia formation can be explained by the mechanisms given in Reactions 20-27. From these it would be expected that the yield of amide-like nitrogen would be doubled by the presence of oxygen since in the absence of oxygen (Reactions 20-23) two a-carbon free radicals are needed to form one amide group. In the presence of O2, every a-carbon free radical which combines with O2 is transformed into an amide group (Reactions 20 and 24-27). It is also possible that in the presence of O2, amide-like ammonia arises from reactions in the side chains. One such possibility for PGA is discussed in the next section. 

The requisite intermediate, 10-(3-chloropropyl)-2-acetylphenothiazineis prepared as follows To a suspension of sodium amide (from 3 grams of sodium) in 300 ml of liquid ammonia is added 30 grams of 2-acetylphenothiazine. After stirring for one hour, there is added 19 grams of 1-bromo-3-chloropropane. The ammonia is allowed to evaporate and the residue is diluted with 200 ml of water. The mixture is extracted with ether and the ether solution is dried over anhydrous sodium sulfate, filtered and concentrated. 

This reaction represents the best general method for amide preparation. Cold, concentrated aqueous ammonia is used as in the preparation of iso-butyramide (83%),or the reaction may be carried out by passing dry ammonia into a solution of the acyl halide in anhydrous ether as in the formation of cyclopropanecarboxamide (91%). Separation of the amide from ammonium chloride is usually accomplished by extraction of the amide by organic solvents. Aqueous sodium hydroxide is employed to take up the hydrogen chloride when amine hydrochlorides are used in place of the free amines as in the preparation of N-methylisobutyramide (75%). When phosphorus trichloride is added to a mixture of an amine and a carboxylic acid, phosphazo compounds, RN=PNHR, rather than acyl halides, are believed to be intermediates. These compounds have been shown to react with carboxylic acids to give amides. ... 

Figure 10.3 Possible mechanisms of photochemical ammonia formation from amides/peptides. The ketone is listed as a possible photosensitizer (Wang etal, 2000).

Liquid ammonia (b.p. -33°C) is a solvent which is not encountered frequendy, but which does have several important general uses, in particular dissolving metal reductions ("Birch" type reductions) and most reactions involving lithium amide or sodium amide as bases. Ammonia gas from a cylinder is condensed directly into the flask (Fig. 14.5). 

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