Secondary amines anhydrides

Acetyl derivatives. Primary and secondary amines are best acetylated with acetic anhydride ... 

Derivatives with 3-nitrophthalic anhydride. 3-Nitrophthalic anhydride reacts with primary and secondary amines to yield nitro-phthalamic acids it does not react with tertiary amines. The phthalamic acid derived from a primary amine undergoes dehydration when heated to 145° to give a neutral A -substituted 3-nitrophthalimide. The phthalamic acid from a secondary amine is stable to heat and is, of course, soluble in alkali. The reagent therefore provides a method for distinguishing and separating a mixture of primary and secondary amines. 

The quinaldine is separated from any unreacted aniline and from the alkyl-anilines by treatment with acetic anhydride, basified with sodium carbonate and steam distilled. Only the primary and secondary amines are acetylated the acetylated amines are now much less volatile so that separation from the steam-volatile quinaldine (a tertiary amine) is facile. 

For this reason, acetic anhydride is generally preferred for the preparation of acetyl derivatives, but acetyl chloride, in view of its greater reactivity, is a better diagnostic reagent for primary and secondary amines. 

Amidation. Reaction of maleic anhydride or its isomeric acids with ammonia [7664-41-7] (qv), primary amines (qv), and secondary amines produces mono- or diamides. The monoamide derivative from the reaction of ammonia and maleic anhydride is called maleamic acid [557-24-4] (8). Another monoamide derivative formed from the reaction of aniline [62-53-3] and maleic anhydride is maleanilic acid [555-59-9] (9). 

Primary and secondary amines can also act as very weak acids ( 10 ). They react with acyl haUdes, anhydrides, and esters with rates depending on... 

Nitrile Intermediates. Most quaternary ammonium compounds are produced from fatty nitriles (qv), which are ia turn made from a natural fat or oil-derived fatty acid and ammonia (qv) (Fig. 2) (see Fats AND FATTY oils) (225). The nitriles are then reduced to the amines. A variety of reduciag agents maybe used (226). Catalytic hydrogenation over a metal catalyst is the method most often used on a commercial scale (227). Formation of secondary and tertiary amine side-products can be hindered by the addition of acetic anhydride (228) or excess ammonia (229). In some cases secondary amines are the desired products. 

Other Rea.ctlons, The anhydride of neopentanoic acid, neopentanoyl anhydride [1538-75-6] can be made by the reaction of neopentanoic acid with acetic anhydride (25). The reaction of neopentanoic acid with acetone using various catalysts, such as titanium dioxide (26) or 2irconium oxide (27), gives 3,3-dimethyl-2-butanone [75-97-8] commonly referred to as pinacolone. Other routes to pinacolone include the reaction of pivaloyl chloride [3282-30-2] with Grignard reagents (28) and the condensation of neopentanoic acid with acetic acid using a rare-earth oxide catalyst (29). Amides of neopentanoic acid can be prepared direcdy from the acid, from the acid chloride, or from esters, using primary or secondary amines. 

Purification as their N-acetyl derivatives is satisfactory for primary, and to a limited extent secondary, amines. The base is refluxed with slightly more than one equivalent of acetic anhydride for half to one hour, cooled and poured into ice-cold water. The insoluble derivative is filtered off, dried, and recrystallised from water, ethanol, aqueous ethanol or benzene (CAUTION toxic ). The derivative can be hydrolysed to the parent amine by refluxing with 70% sulfuric acid for a half to one hour. The solution is cooled, poured onto ice, and made alkaline. The amine is steam distilled or extracted as above. Alkaline hydrolysis is very slow. 

V,7V,7V, 7V -Tetramethylethylenediamine (TMEDA, TEMED) [110-18-9] M 116.2, b 122°, d 1.175, n 1.4153, pK 5.90, pKj 9.14. Partially dried with molecular sieves (Linde type 4A), and distd in vacuum from butyl lithium. This treatment removes all traces of primary and secondary amines and water. [Hay, McCabe and Robb J Chem Soc, Faraday Trans 1 68 1 1972.] Or, dried with KOH pellets. Refluxed for 2h with one-sixth its weight of n-butyric anhydride (to remove primary and secondary amines) and fractionally distd. Refluxed with fresh KOH, and distd under nitrogen. [Cram and Wilson 7 Am C/iem Soc 85 1245 796i.] Also distd from sodium. 

These Br nsted-type plots often seem to be scatter diagrams until the points are collated into groups related by specific structural features. Thus, p-nitrophenyl acetate gives four separate, but parallel, lines for reactions with pyridines, anilines, imidazoles, and oxygen nucleophiles.Figure 7-4 shows such a plot for the reaction of trans-cmmm c anhydride with primary and secondary aliphatic amines to give substituted cinnamamides.All of the primary amines without substituents on the a carbon (R-CHi-NHi) fall on a line of slope 0.62 cyclopentylamine also lies on this line. If this line is characteristic of normal behavior, most of the deviations become qualitatively explicable. The line drawn through the secondary amines (slope 1.98) connects amines with the structure R-CHi-NH-CHi-R. The different steric requirements in the acylation reaction and in the model process... 

Figure 7-4. Br nsted-type plot for reaction of aliphatic amines with cinnamic anhydride at 25°C in acetonitrile "" the pK values are for the conjugate acids in water. Open circles primary amines closed circles secondary amines.

Solvents influence the hydrogenation of oximes in much the same way as they do hydrogenation of nitriles. Acidic solvents prevent the formation of secondary amines through salt formation with the initially formed primary amine. A variety of acids have been used for this purpose (66 ), but acids cannot always be used interchangeably (43). Primary amines can be trapped also as amides by use of an anhydride solvent (2,/5,57). Ammonia prevents secondary amine formation through competition of ammonia with the primary amine in reaction with the intermediate imine. Unless the ammonia is anhydrous hydrolysis reactions may also occur. 

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. 

For best results the commercial triethylamine (Matheson, b.p. 89-90°) should be purified to remove primary and secondary amines and water, either by distillation from acetic anhydride and then from barium oxide, or by reaction with phenyliso-cyanate.5 2 3 4... 

The reaction partner of maleic acid anhydride can be changed. Instead of a hydroxyl group a primary or secondary amine can be used. Either monoamides or diamides can be obtained. Simple sulfation as mentioned above closes the reaction series. The variety of sulfosuccinamates (monoamides) and sulfosuccinamides (diamides) is smaller than that of sulfosuccinates. An important use lies in the field of technical applications (Fig. 2). 

By contrast with tertiary amines used in catalytic quantities, primary and secondary amines or acid anhydrides may be used to bring about the cure of epoxy resins by reaction in stoichiometric proportions. A typical amine curing agent used at this level is diaminodiphenylmethane (DDM), which reacts with an individual epoxy-group in the way shown in Reaction 4.17. 

Even though formic anhydride is not a stable compound (see p. 714), amines can be formylated with the mixed anhydride of acetic and formic acids (HCOO-COMe) °°° or with a mixture of formic acid and acetic anhydride. Acetamides are not formed with these reagents. Secondary amines can be acylated in the presence of a primary amine by conversion to their salts and addition of 18-crown-6. ° The crown ether complexes the primary ammonium salt, preventing its acylation, while the secondary ammonium salts, which do not fit easily into the cavity, are free to be acylated. 

When the -OH of a carboxylic acid is replaced by an -NH2, the compound produced is an amide. Amides are neutral to mildly basic compounds. They can be made from acids, acid chlorides, acid anhydrides, and esters by reaction with ammonia or primary and secondary amines. The amide linkage is found in polyamide resins such as nylon. 

Derivatives of Methylene Violet 6 possessing long aliphatic chains are obtained by oxidative coupling of 3-acetoxyphenothiazine with a secondary amine in the presence of an oxidant such as iodine. The oxidative coupling of phenothiazine with amine is well known but in this case the reaction does not stop there but proceeds further at reflux temperatures to the phenothiazinone 74.9 Reduction of the latter dye and treatment with acetic anhydride yields the ballasted phenothiazine 6. Reaction of 75 with the dye chloroformate 70 yields the ballasted leuco dye developer 76. 

Glacial acetic acid, pure or mixed with other solvents, is one of the most attractive solvents for the titration of amines. Commercial acetic acid containing not more than 1% of water (Karl Fischer titration check) can be used in normal practice for the highest accuracy, however, the water content must be lowered to about 0.01% by addition of acetic anhydride and standing for 24 h not more than the stoichiometric amount of acetic anhydride should be used in order to avoid possible reactions with active hydrogen-containing analyte components such as primary or secondary amines or alcohols. A similar procedure is followed in the preparation of perchloric acid titrant from the commercial... 

After cooling and dilution with methyl-Cellosolve (2-methoxyethanol), acetic anhydride is slowly added (in order to convert the secondary amine to amide) and the solution is cooled to room temperature. Finally, the resulting tertiary amine, representing the original unsaturate, is titrated with 0.5 N perchloric acid in methyl-Cellosolve, either visually (with thymol blue + xylene cyanol... 

Summary New lyophilic cationic silicone surfactants have been synthesized by direct quatemization of halogenated siloxanyl precursors or by transformation of these precursors into tertiary amines with a subsequent quatemization step. After transformation of the precursors into secondary amines, reaction with maleic anhydride and neutralization, new anionic products were obtained. 

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]. 

The secondary amine group of the thiadiazole 103 was acylated when heated in the presence of acetic anhydride and ethyl orthoformate to afford the amide 104 in 88% yield (Equation 30) <2002CHE852>. 

Primary and secondary amines are acylated by acid chlorides and anhydrides, in particular also by the chloride of benzene sulphonic add (p. 192). The preparation of acetanilide has already been described (pp. 125, 128). The acetyl- and benzoyl-derivatives of all the simpler primary amines of the benzene and naphthalene series are known, so that these derivatives can always serve for purposes of identification. 

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