Amides, tertiary Amine salts

Acid chlorides are very reactive, and they readily react with ammonia, primary amines, or secondary amines to form an amide. Figure 12-26 illustrates the reaction of an acid chloride with ammonia. Replacing one or two of the hydrogen atoms of ammonia with an organic group will result in an N-substituted amide. Tertiary amines react with acid chlorides to form a carboxylic acid and an ammonium salt. 

The CH2 or CH3 groups next to the nitrogen atom in amines are shifted somewhat. The in-phase stretch in secondary and tertiary amines at 2830-2760 cm is lowered in frequency and intensified, and so stands out among other aliphatic bands. This is because the CH bond which is trans to the non-bonding electron pair on the attached nitrogen has a smaller force constant than the other CH bonds (see Table 5.2). This only applies for amines and not for amides or amine salts (see Table 11.1). 

This type of reaction was first applied to the preparation of polyamides, as discussed above, for which it is somewhat more effective in forming high molecular weight polymers, but it has now been used for the synthesis of a wide variety of aromatic polyesters, either by the self-condensation of hydroxyacids or by the co-condensation of dicarboxylic acids and difunctional phenols.A fairly wide variety of phosphorous compounds can be used as reducing or dehydrating agents in these reactions, in addition to phosphines, including phosphites, chlorophosphates, phosphates, polyphosphates and phosphazenes. In most cases, lithium chloride is added and the reaction is run in either pyridine or an amide solvent system. The reaction has also been found to be catalyzed by tertiary amine salts. 

Acetoiicetyliition Reactions. The best known and commercially most important reaction of diketene is the aceto acetylation of nucleophiles to give derivatives of acetoacetic acid (Fig. 2) (1,5,6). A wide variety of substances with acidic hydrogens can be acetoacetylated. This includes alcohols, amines, phenols, thiols, carboxyHc acids, amides, ureas, thioureas, urethanes, and sulfonamides. Where more than one functional group is present, ring closure often follows aceto acetylation, giving access to a variety of heterocycHc compounds. These reactions often require catalysts in the form of tertiary amines, acids, and mercury salts. Acetoacetate esters and acetoacetamides are the most important industrial intermediates prepared from diketene. 

We ve already studied the two most general reactions of amines—alkylation and acylation. As we saw earlier in this chapter, primary, secondary, and tertiary amines can be alkylated by reaction with a primary alkyl halide. Alkylations of primary and secondary amines are difficult to control and often give mixtures of products, but tertiary amines are cleanly alkylated to give quaternary ammonium salts. Primary and secondary (but not tertiary) amines can also be acylated by nucleophilic acyl substitution reaction with an acid chloride or an acid anhydride to yield an amide (Sections 21.4 and 21.5). Note that overacylation of the nitrogen does not occur because the amide product is much less nucleophilic and less reactive than the starting amine. 

Amines are ammonia derivatives in which one or more hydrogen atoms have been replaced by an organic radical. Amines are sometimes called nitrogen bases. Basic chemistries include fatty amines (as primary, secondary, tertiary, and polyamines), amine salts, quaternary ammonium compounds, amine oxides, and amides. 

Benzylic quaternary ammonium salts, when treated with alkali metal amides, undergo a rearrangement called the Sommelet-Hauser rearrangementSince the product is a benzylic tertiary amine, it can be further alkylated and the product again subjected to the rearrangement. This process can be continued around the ring until an ortho position is blocked. ... 

Other nitrogen compounds, among them hydroxylamine, hydrazines, and amides (15-9), also add to alkenes. Even with amines, basic catalysts are sometimes used, so that RNH or R2N is the actual nucleophile. Tertiary amines (except those that are too bulky) add to Michael-type substrates in a reaction that is catalyzed by acids like HCl or HNO3 to give the corresponding quaternary ammonium salts. " ... 

The tertiary amines 303 and the acid chlorides 304 (X = Cl) initially formed acylammonium salts 305, which underwent a von Braun type degradation by an attack of the nucleophilic chloride ion at the allyl system to give allyl chlorides 306/307 and carboxylic acid amide functions. 

In classical organic chemistry, nltrosamlnes were considered only as the reaction products of secondary amines with an acidified solution of a nitrite salt or ester. Today, it is recognized that nitrosamines can be produced from primary, secondary, and tertiary amines, and nltrosamides from secondary amides. Douglass et al. (34) have published a good review of nitrosamine formation. For the purposes of this presentation, it will suffice to say that amine and amide precursors for nitrosation reactions to form N-nitroso compounds are indeed ubiquitous in our food supply, environment, and par-... 

To synthesize new surfactants, having incorporated both structural elements, the known siloxanyl modified halogenated esters and ethers of dicyclopentadiene [5] were treated with different amines according to the reaction scheme. Triethylamine yielded quaternary ammonium salts directly. Alternatively, after reaction with diethylamine or morpholine, the isolated siloxanyl-modified tertiary amines were also converted to quaternary species. To obtain anionic surfactants, the halogenated precursors were initially reacted with n-propylamine. In subsequent reaction steps the secondary amines formed were converted with maleic anhydride into amides, and the remaining acid functions neutralized. Course and rate of each single reaction strongly depended on the structure of the initial ester or ether compound and the amine applied. The basicity of the latter played a less important role [6]. 

There has been a study of the mechanism of the activation of carboxylic acids to peptide formation by chloro-s -triazines in combination with tertiary amines. The first step, exemplified in Scheme 2 by the reaction of 2-chloro-4,6-disubstituted-l,3,5-triazines (18) with A -methylmorpholine, is formation of a quaternary triazinylammonium salt (20). Here there is NMR evidence for the formation at —50°C of the intermediate (19), showing that the substitution involves the two-step SnAt mechanism rather than a synchronous pathway. The subsequent reaction of (20) with a carboxylic acid yields the 2-acyloxy derivative (21), which carries an excellent leaving group for the amide-forming step. ... 

The lower members of the homologous series of 1. Alcohols 2. Aldehydes 3. Ketones 4. Acids 5. Esters 6. Phenols 7. Anhydrides 8. Amines 9. Nitriles 10. Polyhydroxy phenols 1. Polybasic acids and hydro-oxy acids. 2. Glycols, poly-hydric alcohols, polyhydroxy aldehydes and ketones (sugars) 3. Some amides, ammo acids, di-and polyamino compounds, amino alcohols 4. Sulphonic acids 5. Sulphinic acids 6. Salts 1. Acids 2. Phenols 3. Imides 4. Some primary and secondary nitro compounds oximes 5. Mercaptans and thiophenols 6. Sulphonic acids, sulphinic acids, sulphuric acids, and sul-phonamides 7. Some diketones and (3-keto esters 1. Primary amines 2. Secondary aliphatic and aryl-alkyl amines 3. Aliphatic and some aryl-alkyl tertiary amines 4. Hydrazines 1. Unsaturated hydrocarbons 2. Some poly-alkylated aromatic hydrocarbons 3. Alcohols 4. Aldehydes 5. Ketones 6. Esters 7. Anhydrides 8. Ethers and acetals 9. Lactones 10. Acyl halides 1. Saturated aliphatic hydrocarbons Cyclic paraffin hydrocarbons 3. Aromatic hydrocarbons 4. Halogen derivatives of 1, 2 and 3 5. Diaryl ethers 1. Nitro compounds (tertiary) 2. Amides and derivatives of aldehydes and ketones 3. Nitriles 4. Negatively substituted amines 5. Nitroso, azo, hy-drazo, and other intermediate reduction products of nitro com-pounds 6. Sulphones, sul-phonamides of secondary amines, sulphides, sulphates and other Sulphur compounds... 

In a detailed study on phosphonate diester and phosphonamidate synthesis, Hirschmann, Smith, and co-workers reported that pyrophosphonate anhydrides may be produced as side products during conversion of phosphonate monoesters into phosphonochloridates. 72 They recommended adding the phosphonate monoester to a solution of the chlorinating agent (thionyl chloride or oxalyl chloride) to minimize formation of the less reactive anhydrides. They also found that addition of tertiary amines (e.g., TEA) to the phosphonochloridates, prior to addition of the alcohol or amine component, results in formation of a phospho-nyltrialkylammonium salt that is more reactive than the corresponding phosphonochloridate and leads to better yields of the phosphonate esters and amides. 

The rate is slower in basic aprotic amide solvents, and faster in acidic solvents such as / -cresol. In general, the imidization reaction has been shown to be catalyzed by acid (14,32,33). Thermal imidization of poly(amic acid)s is catalyzed by tertiary amines (34). High temperature solution polymerization in -cresol is often performed in the presence of high boiling tertiary amines such as quinoline as catalyst. Dialkylaminopyridines and other tertiary amines are effective catalysts in neutral solvents such as dichlorobenzene (35). Alkali metal and zinc salts of carboxylic acids (36) and salts of certain organophosphorus compounds (37) are also very efficient catalysts in one-step polycondensation of polyimides. 

Our experience with tributylamine shows that its cathodic potential limit may be as low as 0 V Li/Li+. The cathodic limiting reaction may be the reduction of the cation (for alkaline metals and TAA salts). We have evidence that tributylamine reacts with lithium to form amides (RjNLi, 0 < x < 2, ldeposition potentials of the alkaline metals are reached, trialkylamine solvents will react with the deposits. The anodic limit of most of the trialkylamines, as well as of secondary amines, is in the 3.5-4 V range versus Li/Li+. The reaction is probably the formation of tetraalkyl ammonium cations, protons, and nitrogen. Hence, the electrochemical limit of amines may range between 2-4 V (higher for the tertiary amines). 

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