Amine from acid chlorides

Further examples of the synthesis of amines from acid chlorides, aziridines, aldehydes,and amides, a new synthesis of a-aminoamidines, and a total synthesis of the naturally occurring polyamine thermospermine have been reported. ... 

Schotten-Baumann alkaline conditions from primary and secondary amines using acid chlorides ben2amides from ben2oyl chloride distinguish 1 ° and 2°... 

Condensa.tlon, This term covers all processes, not previously iacluded ia other process definitions, where water or hydrogen chloride is eliminated ia a reaction involving the combination of two or more molecules. The important condensation reactions are nitrogen and sulfur heterocycle formation, amide formation from acid chlorides, formation of substituted diphenyl amines, and misceUaneous cyclizations. 

This reaction is simple and qualitative36 37 the diamine can be both an aromatic and an aliphatic diamine. With this method, even star-shaped PAs have been synthesized.37 Solution polymerization from acid chlorides and aliphatic diamines is more difficult due to the strong basicity of the aliphatic amine groups. Acid binders which have been used with aliphatic diamines are the tertiary amines with high kb values these include dimethylbenzylamine and diisopropylethylamine.4 38... 

Synthesis of amides from amines and acid chlorides Glass DCM 77 EOF... 

Amides prepared from carboxylic acids and primary amines using azolides obtained from acid chloride/imidazolea) or ketene/imidazole systems.b)... 

Amines also react with esters by a method similar to the reaction of an acid chloride with an cimine (which was described in the previous section, From acid chlorides ). Figure 12-28 illustrates the formation of benzamide by this type of reaction, using ammonia and methyl benzoate. Again, the mechanism is similar to the reaction of an acid chloride with an amine (Figure 12-26). 

Oxazolines.1 Hydroxy amides, prepared from p-hydroxy amines and acid chlorides, are converted into 2-oxazolines with the Mitsunobu reagent at 0 — 25° (equation I). 

Amides generally are formed from acid chlorides, acid azides, acid anhydrides, and esters. It is not practical to prepare them directly from an amine and a carboxylic acid without strong heating or unless the reaction is coupled to a second reaction that activates the acid (see Exercise 15-25). Notice that esters of phenols are more reactive toward amines than esters of alcohols because phenols are stronger acids than alcohols. 

In the presence of a base, acid chlorides react readily with aziridines to give acylated aziridines (2,22,160—163). In the absence of a base, however, ring opening takes place and 2-chloroethylamides are obtained (2,164). Under suitable conditions acylated trialkylammonium salts of ethylenediamine can be prepared from acid chlorides, ethyleneimine, and tertiary amines (71). Acylated aziridines can be rearranged to 2-oxazolines by the action of heat, nucleophiles, or acids. The rearrangement of thioacylaziridines proceeds analogously (7,8,165—171). 

Amines are at the same low oxidation level as alcohols and consequently are easily prepared by reduction. Amides and nitriles are reduced efficiently by LAH to amines. Nitriles give only primary amines while amides give 1°, 2°, or 3° amines depending on the number of carbon substituents on the amide nitrogen. The advantage of this method is that amides are easy to prepare from acid chlorides and amines while nitriles are available by displacement reactions. 

A simple example of using combinatorial chemistry to prepare a library of small molecules is the synthesis of secondary amides (9.46) from primary amines (9.44) and acid chlorides (9.45) (Scheme 9.4). Amides of type 9.46 have two points of variation the R-group of the amine and the R -group from the acid chloride. A third point of variation may be introduced by V- a I k y I ation with an alkyl halide (9.47) to form a tertiary amide (9.48). With just 15 building blocks—five amines, five acid chlorides, and five alkyl halides—125 (53) different tertiary amides may be prepared. 

Amides can be prepared from acid chloride by nucleophilic substitution. When ammonia is treated with acid chlorides it gives a primary amide. Acid chloride on treatment with a primary amine gives a secondary amide, and on treatment with a secondary amine gives a tertiary amide. Tertiary amines cannot be used on this reaction because they do not form a stable product. 

As these mechanisms show, the formation of amides from acid chlorides and amines is accompanied by production of one equivalent of HCI, which needs to be neutralized by a second equivalent of amine. An alternative method for making amides is to carry out the reaction in the presence of another base, such as lMaOH. which then does the job of neutralizing the HCI. The trouble is, OH" also attacks acy chlorides to... 

More information can be gained on the mechanism of the reaction if two separate experiments can be carried out with the mechanistic probe inserted at two different sites on the reagents. If we are studying a reaction between a nucleophile and an electrophile, it may be possible to make Hammett plots from the variation of substituents on both reagents. The acylation of amines with acid chlorides is an example. 

The product is a N,jV-disubstituted amine, which can be formed by reduction of an amide. The amide results from treatment of an acid chloride with the appropriate amine. The acid chloride is the product of the reaction of SOCI2 with a carboxylic acid that is formed by carboxylation of the Grignard reagent synthesized from the starting material. 

When we made acid anhydrides from acid chlorides plus car-boxylate salts, we used an anionic nucleophile RCO2 but, when we made amides from acid chlorides plus amines, we used a neutral nucleophile NH3, and not NH2. For proper comparisons, we should include in our table ROH (pXaH = -5 in other words, -5 is the pXa of ROH2) and NH3 (pXgH = 9 in other words, 9 is the pKaofNHj). 

Extraction of Zn and Hg from acidic chloride solutions Extraction of U, V, W, and Mo from acidic sulfate solutions Extraction of Re from acidic nitrate solution Quaternary amines Extraction or Mo from earbonale solution... 

Ketenes are usually prepared in situ by elimination from acid chlorides with a tertiary amine. Thus (6) gives dimethyl ketene. If no other reagent is present, dimer (5) is formed. If a nucleophile is present, product (3) is formed, whilst thermal 2 + 2 cycloadditions take place with alkenes to give cyclobutanones (7). ... 

---