Reactions of Amines

Note A number of the tests described in this experiment, such as the Hinsberg reaction, may be given as demonstrations by the instructor. 

Introduction. The object of this experiment is to illustrate some of the most important reactions of amines. Like ammonia, amines are basic and form salts. The strength of the base in aqueous solution can be approximately estimated by determining the pH of the solution. The salts of weak amines undergo hydrolysis. 

Primary and secondary amines possess replaceable amino hydrogen atoms. With acid chlorides (RCOCl) or anhydrides, (RCO)jO, they yield crystalline derivatives which are very useful in their separation and identification. Benzoyl derivatives are often preferred to acetyl derivatives because the former are less soluble and have higher melting points further, benzoyl chloride, unlike acetyl chloride, is not ea.sily hydrolyzed in water, and hence the acylation can be carried out in aqueous solutions. Tertiary amines do not react and therefore can be obtained unchanged. 

Benzenesulfonyl chloride is used for the systematic separation of the three classes of amines  

Derivative (1) is soluble in alkali, while derivative (2) is not. The tertiary amine (3) remains unchanged and can be extracted with ether. 

How would you prepare o-methylbenzylamine from a carboxylic acid, using both Hofmann and Curtius rearrangements  

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. 

Silver oxide acts by exchanging iodide ion for hydroxide ion in the quaternary salt, thus providing the base necessary for elimination. The actual elimination step is an E2 reaction (Section 11.8) in which hydroxide ion removes a proton at the same time that the positively charged nitrogen atom leaves. 

Unlike what happens in other E2 reactions, the major product of the Hofmann elimination is the less highly substituted alkene rather than the more highly substituted one, as shown by the reaction of (l-methylbutyl)trimethyl-ammonium hydroxide to give 1-pentene rather than the alternative 2-pentene. The reason for this non-Zaitsev result is probably steric. Because of the large size 

Using a different method for each part, but taking care in each case to select a good method, show how each of the following transformations might be accomplished  

We have encountered a number of important reactions of amines in earlier sections. In Section 20.3 we saw reactions in which primary, secondary, and tertiary amines act as bases. In Section 20.4 we saw their reactions as nucleophiles in alkylation reactions, and in Chapter 17 as nucleophiles in acylation reactions. In Chapter 15 we saw that an amino group on an aromatic ring acts as a powerfnl activating group and as an ortho-para director. 

The feature of amines that underlies all of these reactions and that forms a basis for our understanding of most of the chemistry of amines is the ability of nitrogen to share an electron pair  

In the preceding examples the amine acts as a nucleophile by donating its electron panto an electrophilic reagent. In the following example, resonance contributions involving the nitrogen electron pair make carbon atoms nucleophilic  

The amino group acting as an activating group and as an ortho-para director in electrophilic aromatic substitution 

The Hofmann elimination reaction is not often used today in the laboratory, but analogous biological eliminations occur frequently, although usually with protonated ammonium ions rather than quaternary ammonium salts. In the biosynthesis of nucleic acids, for instance, a substance called 

WORKED EXAMPLE 18.2 Predicting the Product of a Hofmann Elimination 

Thomson N Click Organic Interactive to use a web-based palette to predict products from a variety of reactions involving amines. 

What product would you expect from Hotiviann elimination of the following amine  

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A Pd-cataly2ed reaction of amines with halides is expected, but actually little is known about the reaction. The CDE ring system of lavendamycin (805) has been constructed by the intramolecular reaction of aryl bromide with aniline derivative in 804, but 1.2 equiv, of Pd(Ph3P)4 is required[679]. 

The reaction of amines with the 4-phenylazo derivative (228) results in their rearrangement into triazolines. Depending on the basicity of the amines and the size of the alkoxy group, three different triazolines (229. 230, and 231) are obtained (Scheme 117) (454. 459, 472). In all cases, the first step involves nucleophilic addition of the amine to the carbonyl group followed by ring opening and further ring closure. 

Section 20 14 Amides are normally prepared by the reaction of amines with acyl chlo rides anhydrides or esters... 

Reaction of amines with acyl chlorides (Section... 

In addition to being more basic than arylammes alkylammes are also more nucleophilic All the reactions m Table 22 4 take place faster with alkylammes than with arylammes The sections that follow introduce some additional reactions of amines In all cases our understanding of how these reactions take place starts with a consideration of the role of the unshared electron pair of nitrogen... 

The reaction of amines with alkyl halides was seen earlier (Section 22 7) as a complicat ing factor in the preparation of amines by alkylation of ammonia... 

Reactions of Amines Discussed in This Chapter (Continued)... 

A simpler nonphosgene process for the manufacture of isocyanates consists of the reaction of amines with carbon dioxide in the presence of an aprotic organic solvent and a nitrogeneous base. The corresponding ammonium carbamate is treated with a dehydrating agent. This concept has been apphed to the synthesis of aromatic and aUphatic isocyanates. The process rehes on the facile formation of amine—carbon dioxide salts using acid haUdes such as phosphoryl chloride [10025-87-3] and thionyl chloride [7719-09-7] (30). 

An excess of phosgene is used during the initial reaction of amine and phosgene to retard the formation of substituted ureas. Ureas are undesirable because they serve as a source for secondary product formation which adversely affects isocyanate stabiUty and performance. By-products, such as biurets (23) and triurets (24), are formed via the reaction of the labile hydrogens of the urea with excess isocyanate. Isocyanurates (25, R = phenyl, toluyl) may subsequendy be formed from the urea oligomers via ring closure. 

Other approaches have explored the reaction of amines with dimethyl carbonate or its precursors (28). A reaction scheme for the production of polymeric MDI is as follows ... 

Chemical Properties The formation of salts with acids is the most characteristic reaction of amines. Since the amines are soluble in organic solvents and the salts are usually not soluble, acidic products can be conveniendy separated by the reaction with an amine, the unshared electron pair on the amine nitrogen acting as proton acceptor. Amines are good nucleophiles reactions of amines at the nitrogen atom have as a first step the formation of a bond with the unshared electron pair of nitrogen, eg, reactions with acid anhydrides, haUdes, and esters, with carbon dioxide or carbon disulfide, and with isocyanic or isothiocyanic acid derivatives. 

The primary reactions of amines and hydrogen sulfide and carbon dioxide are those of a base with acids ... 

Symmetrically substituted bora2iaes are generally prepared by reaction of amines and boranes (94). 

The Michael addition reaction of amines and thiols with bismaleimides or functionalized monomaleimides is a versatile tool ia the synthesis of chain-extended maleimide-terroinated prepolymers. These prepolymers generally are soluble ia organic solvents from which they can be processed to prepreg and molded to high quaUty, void-free laminates. 

Reaction of amines with acyl chlorides (Section 20.4) Amines are converted to amides on reaction with acyl chlorides. Other acylating agents, such as carboxylic acid anhydrides and esters, may also be used but are less reactive. 

An alternative approach to thionitrosoarenes involves the reaction of amines with SCla. This method has also been adapted to the production of selenonitrosoarenes ArN=Se by using the selenium(If) synthon PhSOaSeCl as the Se source (Scheme 10.2). It is likely that SeCla, generated in situ in THF, could also be used in this process. The Diels-Alder cycloaddition of ArN=Se species with dimethylbutadiene gives 1,2-selenazine derivatives in low yields. 

The reaction is known to be complex, proceeding through a tetrahedral intermediate called a carbinolamine. Generalizing to the reactions of amines with carbonyls, the two-step reaction sequence is... 

A more convenient high-yield synthesis of Bi2Hi2 is by the direct reaction of amine-boranes with BiqHu in the absence of solvents ... 

Many of the reactions of amines are familiar from past chapters. Thus, amines react with alkyl halides in S 2 reactions and with acid chlorides in nucleophilic acyl substitution reactions. Amines also undergo E2 elimination to yield alkenes if they are first qualernized by treatment with iodomethane and then heated with silver oxide, a process called the Hofmann elimination. 

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