Interaction of amino acids with carboxylic acids. Properties and functions of amino acids

According to the nature of the hydrocarbon substituents, amines are divided into

General structural features of amines

Just like in the ammonia molecule, in the molecule of any amine, the nitrogen atom has an unshared electron pair directed to one of the vertices of the distorted tetrahedron:

For this reason, amines, like ammonia, have significantly pronounced basic properties.

So, amines, like ammonia, reversibly react with water, forming weak bases:

The bond of the hydrogen cation with the nitrogen atom in the amine molecule is implemented using the donor-acceptor mechanism due to the lone electron pair of the nitrogen atom. Limit amines are stronger bases compared to ammonia, because. in such amines, hydrocarbon substituents have a positive inductive (+I) effect. In this regard, the electron density on the nitrogen atom increases, which facilitates its interaction with the H + cation.

Aromatic amines, if the amino group is directly connected to the aromatic nucleus, exhibit weaker basic properties compared to ammonia. This is due to the fact that the lone electron pair of the nitrogen atom is shifted towards the aromatic π-system of the benzene ring, as a result of which the electron density on the nitrogen atom decreases. In turn, this leads to a decrease in the basic properties, in particular the ability to interact with water. So, for example, aniline reacts only with strong acids, and practically does not react with water.

Chemical properties of saturated amines

As already mentioned, amines react reversibly with water:

Aqueous solutions of amines have an alkaline reaction of the environment, due to the dissociation of the resulting bases:

Saturated amines react with water better than ammonia due to their stronger basic properties.

The main properties of saturated amines increase in the series.

Secondary limiting amines are stronger bases than primary limiting amines, which in turn are stronger bases than ammonia. As for the basic properties of tertiary amines, when it comes to reactions in aqueous solutions, the basic properties of tertiary amines are much worse than those of secondary amines, and even slightly worse than those of primary ones. This is due to steric hindrances, which significantly affect the rate of amine protonation. In other words, three substituents "block" the nitrogen atom and prevent its interaction with H + cations.

Interaction with acids

Both free saturated amines and their aqueous solutions interact with acids. In this case, salts are formed:

Since the basic properties of saturated amines are more pronounced than those of ammonia, such amines react even with weak acids, such as carbonic:

Amine salts are solids that are highly soluble in water and poorly soluble in non-polar organic solvents. The interaction of amine salts with alkalis leads to the release of free amines, similar to how ammonia is displaced by the action of alkalis on ammonium salts:

2. Primary limiting amines react with nitrous acid to form the corresponding alcohols, nitrogen N 2 and water. For example:

A characteristic feature of this reaction is the formation of gaseous nitrogen, in connection with which it is qualitative for primary amines and is used to distinguish them from secondary and tertiary. It should be noted that most often this reaction is carried out by mixing the amine not with a solution of nitrous acid itself, but with a solution of a salt of nitrous acid (nitrite) and then adding a strong mineral acid to this mixture. When nitrites interact with strong mineral acids, nitrous acid is formed, which then reacts with an amine:

Secondary amines give oily liquids under similar conditions, the so-called N-nitrosamines, but this reaction does not occur in real USE tasks in chemistry. Tertiary amines do not react with nitrous acid.

Complete combustion of any amines leads to the formation of carbon dioxide, water and nitrogen:

Interaction with haloalkanes

It is noteworthy that exactly the same salt is obtained by the action of hydrogen chloride on a more substituted amine. In our case, during the interaction of hydrogen chloride with dimethylamine:

Getting amines:

1) Alkylation of ammonia with haloalkanes:

In the case of a lack of ammonia, instead of an amine, its salt is obtained:

2) Reduction by metals (to hydrogen in the activity series) in an acidic medium:

followed by treatment of the solution with alkali to release the free amine:

3) The reaction of ammonia with alcohols by passing their mixture through heated aluminum oxide. Depending on the proportions of alcohol / amine, primary, secondary or tertiary amines are formed:

Chemical properties of aniline

Aniline - the trivial name of aminobenzene, which has the formula:

As can be seen from the illustration, in the aniline molecule the amino group is directly connected to the aromatic ring. In such amines, as already mentioned, the basic properties are much less pronounced than in ammonia. So, in particular, aniline practically does not react with water and weak acids such as carbonic.

The interaction of aniline with acids

Aniline reacts with strong and moderately strong inorganic acids. In this case, phenylammonium salts are formed:

Interaction of aniline with halogens

As already mentioned at the very beginning of this chapter, the amino group in aromatic amines is drawn into the aromatic ring, which in turn reduces the electron density on the nitrogen atom, and as a result increases it in the aromatic nucleus. An increase in the electron density in the aromatic nucleus leads to the fact that electrophilic substitution reactions, in particular, reactions with halogens, proceed much more easily, especially in the ortho and para positions relative to the amino group. So, aniline easily interacts with bromine water, forming a white precipitate of 2,4,6-tribromaniline:

This reaction is qualitative for aniline and often allows you to determine it among other organic compounds.

The interaction of aniline with nitrous acid

Aniline reacts with nitrous acid, but due to the specificity and complexity of this reaction, it does not occur in the real exam in chemistry.

Aniline alkylation reactions

With the help of sequential alkylation of aniline at the nitrogen atom with halogen derivatives of hydrocarbons, secondary and tertiary amines can be obtained:

Chemical properties of amino acids

Amino acids call compounds in the molecules of which there are two types of functional groups - amino (-NH 2) and carboxy- (-COOH) groups.

In other words, amino acids can be considered as derivatives of carboxylic acids, in the molecules of which one or more hydrogen atoms are replaced by amino groups.

Thus, the general formula of amino acids can be written as (NH 2) x R(COOH) y, where x and y are most often equal to one or two.

Since amino acids have both an amino group and a carboxyl group, they exhibit chemical properties similar to both amines and carboxylic acids.

Acidic properties of amino acids

Formation of salts with alkalis and alkali metal carbonates

Esterification of amino acids

Amino acids can enter into an esterification reaction with alcohols:

NH 2 CH 2 COOH + CH 3 OH → NH 2 CH 2 COOCH 3 + H 2 O

Basic properties of amino acids

1. Formation of salts upon interaction with acids

NH 2 CH 2 COOH + HCl → + Cl -

2. Interaction with nitrous acid

NH 2 -CH 2 -COOH + HNO 2 → HO-CH 2 -COOH + N 2 + H 2 O

Note: interaction with nitrous acid proceeds in the same way as with primary amines

3. Alkylation

NH 2 CH 2 COOH + CH 3 I → + I -

4. Interaction of amino acids with each other

Amino acids can react with each other to form peptides - compounds containing in their molecules a peptide bond -C (O) -NH-

At the same time, it should be noted that in the case of a reaction between two different amino acids, without observing some specific synthesis conditions, the formation of different dipeptides occurs simultaneously. So, for example, instead of the reaction of glycine with alanine above, leading to glycylanine, a reaction leading to alanylglycine can occur:

In addition, a glycine molecule does not necessarily react with an alanine molecule. Peptization reactions also take place between glycine molecules:

And alanine:

In addition, since the molecules of the resulting peptides, like the original molecules of amino acids, contain amino groups and carboxyl groups, the peptides themselves can react with amino acids and other peptides due to the formation of new peptide bonds.

Individual amino acids are used to produce synthetic polypeptides or so-called polyamide fibers. So, in particular, using the polycondensation of 6-aminohexanoic (ε-aminocaproic) acid, nylon is synthesized in industry:

The nylon resin obtained as a result of this reaction is used for the production of textile fibers and plastics.

Formation of internal salts of amino acids in aqueous solution

In aqueous solutions, amino acids exist mainly in the form of internal salts - bipolar ions (zwitterions).

Amino acids, proteins and peptides are examples of the compounds described below. Many biologically active molecules include several chemically distinct functional groups that can interact with each other and with each other's functional groups.

Amino acids.

Amino acids- organic bifunctional compounds, which include a carboxyl group - UNSD, and the amino group - NH 2 .

share α and β - amino acids:

Mostly found in nature α - acids. Proteins are composed of 19 amino acids and one imino acid ( C 5 H 9NO 2 ):

The simplest amino acid- glycine. The remaining amino acids can be divided into the following main groups:

1) glycine homologues - alanine, valine, leucine, isoleucine.

Getting amino acids.

Chemical properties of amino acids.

Amino acids- these are amphoteric compounds, tk. contain in their composition 2 opposite functional groups - an amino group and a hydroxyl group. Therefore, they react with both acids and alkalis:

Acid-base conversion can be represented as:

Amino acids contain amino and carboxyl groups and exhibit all the properties characteristic of compounds with such functional groups. When writing amino acid reactions, formulas with non-ionized amino and carboxy groups are used.

1) reactions on the amino group. The amino group in amino acids exhibits the usual properties of amines: amines are bases, and in reactions they act as nucleophiles.

1. Reaction of amino acids as bases. When an amino acid reacts with acids, ammonium salts are formed:

glycine hydrochloride, glycine hydrochloride salt

2. Action of nitrous acid. Under the action of nitrous acid, hydroxy acids are formed and nitrogen and water are released:

This reaction is used to quantify free amine groups in amino acids as well as in proteins.

3. Formation of N - acyl derivatives, acylation reaction.

Amino acids react with anhydrides and acid halides, forming N - acyl derivatives of amino acids:

Benzyl ether sodium salt N carbobenzoxyglycine - chloroformic glycine

Acylation is one way to protect the amino group. N-acyl derivatives are of great importance in the synthesis of peptides, since N-acyl derivatives are easily hydrolyzed to form a free amino group.

4. Formation of Schiff bases. When a - amino acids interact with aldehydes, substituted imines (Schiff bases) are formed through the stage of formation of carbinolamines:

alanine formaldehyde N-methylol derivative of alanine

5. Alkylation reaction. The amino group in a-amino acid is alkylated to form N-alkyl derivatives:

The reaction with 2,4-dinitrofluorobenzene is of the greatest importance. The resulting dinitrophenyl derivatives (DNP derivatives) are used in determining the amino acid sequence in peptides and proteins. The interaction of a-amino acids with 2,4-dinitrofluorobenzene is an example of a nucleophilic substitution reaction in the benzene ring. Due to the presence of two strong electron-withdrawing groups in the benzene ring, the halogen becomes mobile and enters into a substitution reaction:

2,4 - dinitro -

fluorobenzene N - 2,4 - dinitrophenyl - a - amino acid

(DNFB) DNF - derivatives of a - amino acids

6. Reaction with phenylisothiocyanate. This reaction is widely used in determining the structure of peptides. Phenylisothiocyanate is a derivative of isothiocyanic acid H-N=C=S. The interaction of a - amino acids with phenylisothiocyanate proceeds according to the mechanism of the reaction of nucleophilic addition. In the resulting product, an intramolecular substitution reaction is further carried out, leading to the formation of a cyclic substituted amide: phenylthiohydantoin.

Cyclic compounds are obtained in quantitative yield and are phenyl derivatives of thiohydantoin (FTH - derivatives) - amino acids. FTG - derivatives differ in the structure of the radical R.

In addition to the usual salts, a-amino acids can form intra-complex salts with heavy metal cations under certain conditions. For all a - amino acids, beautifully crystallizing, intensely blue-colored intra-complex (chelate) copper salts are very characteristic):
Alanine ethyl ester

The formation of esters is one of the methods for protecting the carboxyl group in the synthesis of peptides.

3. Formation of acid halides. When a-amino acids with a protected amino group are treated with sulfur oxydichloride (thionyl chloride) or phosphorus oxide-trichloride (phosphorus oxychloride), acid chlorides are formed:

Obtaining acid halides is one of the ways to activate the carboxyl group in peptide synthesis.

4. Obtaining anhydrides a - amino acids. Acid halides have a very high reactivity, which reduces the selectivity of the reaction when they are used. Therefore, a more frequently used method for activating the carboxyl group in peptide synthesis is its transformation into an anhydride group. Anhydrides are less active than acid halides. When an a-amino acid having a protected amino group interacts with ethyl chloroformate (ethyl chloroformate), an anhydride bond is formed:

5. Decarboxylation. a - Amino acids having two electron-withdrawing groups on the same carbon atom are easily decarboxylated. Under laboratory conditions, this is carried out by heating amino acids with barium hydroxide. This reaction occurs in the body with the participation of decarboxylase enzymes with the formation of biogenic amines:

ninhydrin

The ratio of amino acids to heat. When a-amino acids are heated, cyclic amides are formed, called diketopiperazines:

Diketopiperazine

g - and d - Amino acids easily split off water and cyclize to form internal amides, lactams:

g - lactam (butyrolactam)

In cases where the amino and carboxyl groups are separated by five or more carbon atoms, when heated, polycondensation occurs with the formation of polymeric polyamide chains with the elimination of a water molecule.

Amino acids (AA) - organic molecules that consist of a basic amino group (-NH 2), an acidic carboxyl group (-COOH), and an organic R radical (or side chain) that is unique to each AA

Amino acid structure

Functions of amino acids in the body

Examples of biological properties of AA. Although there are more than 200 different AAs found in nature, only about one tenth of them are incorporated into proteins, others have other biological functions:

• They are the building blocks of proteins and peptides
• Precursors of many biologically important molecules derived from AA. For example, tyrosine is a precursor of the hormone thyroxin and the skin pigment melanin, tyrosine is also a precursor of the compound DOPA (dioxy-phenylalanine). It is a neurotransmitter for the transmission of impulses in the nervous system. Tryptophan is a precursor of vitamin B3 - nicotinic acid
• Sources of sulfur - sulfur-containing AK.
• AA are involved in many metabolic pathways, such as gluconeogenesis - the synthesis of glucose in the body, the synthesis of fatty acids, etc.

Depending on the position of the amino group relative to the carboxyl group, AA can be alpha, α-, beta, β- and gamma, γ.

The alpha amino group is attached to the carbon adjacent to the carboxyl group:

The beta-amino group is located on the 2nd carbon from the carboxyl group

Gamma - amino group on the 3rd carbon from the carboxyl group

Only alpha-AA is included in the composition of proteins

General properties of alpha-AA proteins

1 - Optical activity - a property of amino acids

All AAs, with the exception of glycine, exhibit optical activity, since contain at least one asymmetric carbon atom (chiral atom).

What is an asymmetric carbon atom? This is a carbon atom that has four different chemical substituents attached to it. Why does glycine not exhibit optical activity? Its radical has only three different substituents, i.e. alpha carbon is not asymmetric.

What does optical activity mean? This means that AA in solution can be present in two isomers. Dextrorotatory isomer (+), which has the ability to rotate the plane of polarized light to the right. Left-handed isomer (-), which has the ability to rotate the plane of polarization of light to the left. Both isomers can rotate the plane of polarization of light by the same amount, but in the opposite direction.

2 - Acid-base properties

As a result of their ability to ionize, the following equilibrium of this reaction can be written:

R-COOH<------->R-C00-+H+

R- NH 2<--------->R-NH3+

Since these reactions are reversible, this means that they can act as acids (forward reaction) or as bases (reverse reaction), which explains the amphoteric properties of amino acids.

Zwitter ion - AK property

All neutral amino acids at a physiological pH value (about 7.4) are present as zwitterions - a non-protonated carboxyl group and a protonated amino group (Fig. 2). In solutions more basic than the amino acid isoelectric point (IEP), the amino group -NH3 + in AA donates a proton. In a solution more acidic than IET AA, the carboxyl group -COO - in AA accepts a proton. Thus, AA sometimes behaves like an acid, at other times like a base, depending on the pH of the solution.

Polarity as a general property of amino acids

At physiological pH, AAs are present as zwitter ions. The positive charge is carried by the alpha-amino group, and the negative charge is carboxylic. Thus, two opposite charges are created at both ends of the AA molecule, the molecule has polar properties.

The presence of an isoelectric point (IEP) is a property of amino acids

The pH value at which the net electrical charge of an amino acid is zero and therefore cannot move in an electric field is called IEP.

The ability to absorb in ultraviolet light is a property of aromatic amino acids

Phenylalanine, histidine, tyrosine and tryptophan absorb at 280 nm. On fig. the values ​​of the molar extinction coefficient (ε) of these AAs are shown. In the visible part of the spectrum, amino acids do not absorb, therefore, they are colorless.

AA can be present in two variants of isomers: L-isomer and D- isomers that are mirror images and differ in the arrangement of chemical groups around the α-carbon atom.

All amino acids in proteins are in the L-configuration, L-amino acids.

Physical properties of the amino acid

Amino acids are mostly water soluble due to their polarity and the presence of charged groups. They are soluble in polar and insoluble in non-polar solvents.

AAs have a high melting point, reflecting the presence of strong bonds that support their crystal lattice.

General properties of AK is common to all AK and in many cases are determined by the alpha-amino group and alpha-carboxyl group. AAs also have specific properties that are dictated by their unique side chain.

The chemical properties of a-amino acids are determined, in the most general case, by the presence of carboxyl and amino groups on the same carbon atom. The specificity of the side functional groups of amino acids determines the differences in their reactivity and the individuality of each amino acid. The properties of side functional groups come to the fore in the molecules of polypeptides and proteins, i.e. after the amine and carboxyl groups did their job, they formed a polyamide chain.

So, the chemical properties of the amino acid fragment itself are divided into reactions of amines, reactions of carboxylic acids and properties due to their mutual influence.

The carboxyl group manifests itself in reactions with alkalis - forming carboxylates, with alcohols - forming esters, with ammonia and amines - forming acid amides, a-amino acids are quite easily decarboxylated when heated and under the action of enzymes (Scheme 4.2.1).

This reaction is of great physiological importance, since its implementation in vivo leads to the formation of the corresponding biogenic amines that perform a number of specific functions in living organisms. When histidine is decarboxylated, histamine is formed, which has a hormonal effect. In the human body, it is in a bound form, released during inflammatory and allergic reactions, anaphylactic shock, causes capillary expansion, contraction of smooth muscles, and sharply increases the secretion of hydrochloric acid in the stomach.

Also, by the decarboxylation reaction, together with the hydroxylation reaction of the aromatic ring, another biogenic amine, serotonin, is formed from tryptophan. It is found in humans in intestinal cells in platelets, in the poisons of coelenterates, mollusks, arthropods and amphibians, and is found in plants (bananas, coffee, sea buckthorn). Serotonin performs mediator functions in the central and peripheral nervous systems, affects the tone of blood vessels, increases the resistance of capillaries, and increases the number of platelets in the blood (Scheme 4.2.2).

The amino group of amino acids manifests itself in reactions with acids, forming ammonium salts, acylated

Scheme 4.2.1

Scheme 4.2.2

and alkylates upon interaction with acid halides and haloalkyls, with aldehydes it forms Schiff bases, and with nitrous acid, like conventional primary amines, it forms the corresponding hydroxy derivatives, in this case hydroxy acids (Scheme 4.2.3).

Scheme 4.2.3

The simultaneous participation of the amino group and the carboxyl function in chemical reactions is quite diverse. a-Amino acids form complexes with ions of many divalent metals - these complexes are built with the participation of two amino acid molecules per metal ion, while the metal forms two types of bonds with ligands: the carboxyl group gives an ionic bond with the metal, and the amino group participates in its unshared electron pair, coordinated to the free orbitals of the metal (donor-acceptor bond), giving the so-called chelate complexes (Scheme 4.2.4, the metals are arranged in a row according to the stability of the complexes).

Since both acidic and basic functions are present in the amino acid molecule, the interaction between them is inevitable - it leads to the formation of an internal salt (zwitterion). Since it is a salt of a weak acid and a weak base, it will easily hydrolyze in an aqueous solution, i.e. the system is balanced. In the crystalline state, amino acids have a purely zwitterionic structure, hence the high levels of these substances (Scheme 4.2.5).

Scheme 4.2.4

Scheme 4.2.5

The ninhydrin reaction is of great importance for the detection of amino acids in their qualitative and quantitative analysis. Most amino acids react with ninhydrin, releasing the corresponding aldehyde, while the solution turns into an intense blue-violet color (nm), orange solutions (nm) give only proline and hydroxyproline. The reaction scheme is rather complicated and its intermediate steps are not entirely clear; the colored reaction product is called "Ruemann's violet" (Scheme 4.2.6).

Diketopiperazines are formed by heating free amino acids, and preferably by heating their esters.

Scheme 4.2.6

The reaction product can be determined by its structure - as a pyrazine heterocycle derivative, by the reaction scheme - as a cyclic double amide, since it is formed by the interaction of amino groups with carboxyl functions according to the nucleophilic substitution scheme (Scheme 4.2.7).

The formation of polyamides of a-amino acids is a variation of the above-described reaction for the formation of dikepiperazines, and the one

Scheme 4.2.7

Scheme 4.2.8

variety, for the sake of which Nature probably created this class of compounds. The essence of the reaction is the nucleophilic attack of the amino group of one α-amino acid on the carboxyl group of the second α-amino acid, while the amine group of the second amino acid sequentially attacks the carboxyl group of the third amino acid, etc. (diagram 4.2.8).

The result of the reaction is a polyamide or (called in relation to the chemistry of proteins and protein-like compounds) a polypeptide. Accordingly, the -CO-NH- fragment is called a peptide unit or a peptide bond.