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

General structural features of amines

As 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 realized 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, if we are talking about reactions in aqueous solutions, then 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 medium strength inorganic acids. In this case, phenylammonium salts are formed:

Reaction 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 amino acid molecules, 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).

Amines

Classification and nomenclature

Amines are organic derivatives of ammonia, in the molecule of which one, two or three hydrogen atoms are replaced by radicals. On this basis, one distinguishes primary (RNH 2) secondary (R 2 NH) and tertiary (R 3 N) amines.

Depending on the nature of the radical, amines can be limiting or aromatic, as well as limiting aromatic (methylamine, aniline and methylaniline, respectively). A branched radical can also be attached to the nitrogen atom (for example, tert butylamine), and polycondensed, which is demonstrated by the example of adamantylamine (aminoadamantane), which has a biological effect and is used in medicine

According to the principles of rational nomenclature, the name of this class of substances consists of the name of the radicals at the nitrogen atom, called amine. In the name of primary amines according to the international nomenclature, the amine nitrogen atom is given the name ami-but, used with its location before the name of the hydrocarbon chain. However, many amines retained their trivial names, for example, aniline".

In addition to the amino group, other substituents may also be present in the molecules of organic substances, as is the case, for example, in the case of sulfanilic acid. The amine nitrogen atom can also be included in the saturated cycle. Saturated heterocyclic amines include a three-membered strain-constructed ethyleneimine, with strong mutagenic activity. The ethyleneimine cycle is part of the molecules of some drugs. The tetrahydropyrrole and piperidine rings present in the molecules of a number of alkaloids (including nicotine and anabasine, see Section 20.4) are built without strain. With their participation, as well as with the help of the morpholine ring, the molecules of many drugs are built.

Heterocyclic aromatic amines are, for example, pyrrole and pyridine. Finally, the amino group can also be linked to a heterocycle, which is illustrated by the example of adenine (6-aminopurine), an indispensable fragment of nucleic acids.

Ammonia derivatives also include organic substances that can be built from ammonium salts or its hydroxide by replacing all four hydrogen atoms with various hydrocarbon radicals, as can be seen in the example of tetramethylammonium hydroxide:

Another example of tetrasubstituted ammonium derivatives - quaternary ammonium bases or their salts - is neuron, a toxic substance formed during the decay of animal tissues.

The quaternary nitrogen atom can be part of heterocycles, for example, the corresponding salt from the pyridine series - N-alkylpyridinium salt. These quaternary salts include some alkaloids. In addition, the quaternary nitrogen atom is part of many medicinal substances and some biomolecules.

The above examples demonstrate the diversity of amino compounds and their great biomedical significance. To this it must be added that the amino group is part of such classes of biomolecules as amino acids and proteins, nucleic acids, and is present in a number of natural derivatives of carbohydrates called amino sugars. The amino group is the most important functional group of alkaloids and numerous drugs for various purposes. Some examples of such substances will be given below.

24.3.2. Amines as organic bases

The presence of a free electron pair of nitrogen gives amines the properties of bases. Therefore, a characteristic feature of amines is the reaction with acids with the formation of the corresponding ammonium salts, as can be seen from the reaction for the primary limiting amine:

Similarly, aniline salt is formed from aniline, pyridinium salt from pyridine, etc. Like ammonia, amines in aqueous solutions create an alkaline environment, according to the equation:

Quantitatively, the basicity of nitrogen-containing bases in an aqueous medium is reflected by the value of the equilibrium constant (TO b ) (more often use the value RK b ) ilip / C a (BH +), characterizing the acidity of the conjugate acid of a given base.

The strongest bases will be compounds containing a nitrogen atom, in which the lone pair of nitrogen is in the lone 5p 3 hybrid orbital (aliphatic amines, ammonia, amino acids), and the weakest ones will be those in which this pair participates in p, p-conjugation ( amides, pyrrole, pyridine).

Electron donor substituents, which include alkyl groups, should increase the basicity of amines, since they increase the electron density at the nitrogen atom. Yes, methylamine (pK b = 3.27) is a stronger base than ammonia (pK b = 4.75), and dimethylamine (pK b = 3.02) is a stronger base than methylamine. However, on going to trimethylamine, contrary to expectation, the basicity drops somewhat. (pK b = 4.10). The reason for this is that as the number of substituents on the nitrogen atom increases, the approach of the proton becomes more and more difficult. Thus, here we are not talking about the electronic, but the spatial effect of the substituents. This effect of substituents is called steric factor.

Aromatic amines are weaker bases than saturated ones due to the electron-withdrawing effect of the aromatic ring. Therefore, the basicity of pyridine is also low. The accumulation of phenyl substituents noticeably suppresses the activity of the electron pair of the nitrogen atom. So, pK, diphenylamine is 13.12, and triphenylamine does not show the properties of the base at all.

The extremely low basicity of pyrrole is due to the fact that in its molecule the electron pair of the nitrogen atom is involved in the formation of a bl-electron aromatic bond. Its binding with a proton requires a significant additional expenditure of energy. As a result of the formation of pyrrole salts, the aromatic bond and, consequently, the stability of the molecule disappear. This explains the fact that pyrrole in an acidic environment is quickly resinified.

It is interesting to note that the strong electron-withdrawing effect exerted by the pyrrole cycle on the nitrogen atom leads to a weakening of the N-H bond, due to which pyrrole is able to exhibit the properties of a weak acid. (pK a = 17,5).

Under the action of such an active metal as potassium, its potassium salt, pyrrole-potassium, can be prepared.

The acidic properties of the N–H bond of the pyrrole ring explain, in particular, the ability of porphin and its natural derivatives to form salts with metal cations. Two pyrrole rings of the porphyrin molecule coordinate with the cation due to the electron pairs of their nitrogen atoms, and the other two - replacing hydrogen atoms, like the molecule of pyrrole itself during the formation of pyrrole-potassium. These salts are chlorophyll and hemoglobin.

Amines- these are organic compounds in which the hydrogen atom (maybe more than one) is replaced by a hydrocarbon radical. All amines are divided into:

• primary amines;
• secondary amines;
• tertiary amines.

There are also analogues of ammonium salts - quaternary salts of the type [ R 4 N] + Cl - .

Depending on the type of radical amines can be:

• aliphatic amines;
• aromatic (mixed) amines.

Aliphatic limiting amines.

General formula C n H 2 n +3 N.

The structure of amines.

The nitrogen atom is in sp 3 hybridization. On the 4th non-hybrid orbital is a lone pair of electrons, which determines the main properties of amines:

Electron donor substituents increase the electron density on the nitrogen atom and enhance the basic properties of amines, for this reason, secondary amines are stronger bases than primary ones, because 2 radicals at the nitrogen atom create a greater electron density than 1.

In tertiary atoms, the spatial factor plays an important role: since 3 radicals obscure the lone pair of nitrogen, which is difficult to "approach" to other reagents, the basicity of such amines is less than primary or secondary ones.

Isomerism of amines.

Amines are characterized by isomerism of the carbon skeleton, isomerism of the position of the amino group:

What is the name of the amines?

The name usually lists hydrocarbon radicals (in alphabetical order) and adds the ending -amine:

Physical properties of amines.

The first 3 amines are gases, the middle members of the aliphatic series are liquids, and the higher ones are solids. The boiling point of amines is higher than that of the corresponding hydrocarbons, because in the liquid phase, hydrogen bonds are formed in the molecule.

Amines are highly soluble in water; as the hydrocarbon radical grows, the solubility decreases.

Getting amines.

1. Alkylation of ammonia (the main method), which occurs when an alkyl halide is heated with ammonia:

If the alkyl halide is in excess, then the primary amine can enter into an alkylation reaction, turning into a secondary or tertiary amine:

2. Recovery of nitro compounds:

Ammonium sulfide is used Zinin reaction), zinc or iron in an acidic environment, aluminum in an alkaline environment, or hydrogen in the gas phase.

3. Recovery of nitriles. use LiAlH 4:

4. Enzymatic decarboxylation of amino acids:

Chemical properties of amines.

All amines- strong bases, and aliphatic ones are stronger than ammonia.

Aqueous solutions are alkaline in nature.

Every amine has a lone pair of electrons on its nitrogen atom. When an amine enters water, protons from water can form a new covalent polar bond with the nitrogen atom by the donor-acceptor mechanism, giving an alkyl- or arylammonium ion. Water that has lost a proton turns into a hydroxide ion. The medium becomes alkaline. Thus amines are bases. The strength of these bases depends on the nature and number of radicals associated with nitrogen. Aliphatic radicals, such as methyl, ethyl, etc., showing their electron-donor properties, increase the basicity of amines. Aromatic radicals, on the contrary, greatly reduce the basicity due to the delocalization of a pair of electrons along the benzene ring. According to Linus Pauling's resonance theory, it looks like this:

As can be seen, the lone pair of electrons is present on the nitrogen atom only in one of the resonant structures (mesomeric forms). In three other bipolar structures on the nitrogen atom, on the contrary, there is a “+” charge, which naturally prevents protonation. This is the reason for the sharp decrease in basicity. Availability in about- and P- positions of negative charges allows us to suggest that it is easy for electrophilic substitution reactions to proceed exactly to these positions, where the attacking particle is a cation (for example,

) Examples of reactions of this type with aromatic amines will be given below.

Quantitatively, the strength of the bases is characterized by the values ​​of K b or their negative logarithms pK b. The index "b" means that we are talking about the equilibrium constant between the base - base, which is the amine and its conjugate acid, that is, the ammonium ion:

By definition, such a reversible reaction is described by the analytical expression:

Since the concentration of water in dilute aqueous solutions is practically constant and equal to 55.5 mol/l, then it is introduced into the “new” equilibrium constant:

Multiplying the numerator and denominator of the right side of the equation by [Н + ] and taking into account that [Н + ] [OH - ] = K w = 10 -14 we get:

Taking the logarithm of this analytic expression using decimal logarithms,

we come to the equation:

Reversing the signs and introducing the generally accepted notation: - lg = p, we get:

Since the logarithm of a unit for any base is zero, and 14 is pH = pOH, it is obvious that pK b corresponds to the value of the concentration of hydroxyl ions at which half of the ammonium cations will pass with the elimination of a proton into a free amine. The pK b value for bases is the same as the pK a value for acids. Below is a table, the data of which show the influence of the nature of the radicals and their number on the values ​​of the basicity constants of various amines.

Foundation name	Base formula	Base type	K b at 25 o C	The value of pK b at 25 ° C
Ammonia			1,75 10 -5	4,75
methylamine		Primary aliphate.	4,60 10 - 4	3,34
ethylamine		Primary aliphate.	6,50 10 - 4	3,19
Butylamine		Primary aliphate.	4,00 10 - 4	3,40
Isobutiamine		Primary aliphate.	2,70 10 - 4	3,57
Deut-butylamine		Primary aliphate.	3,60 10 - 4	3,44
Tret-butylamine		Primary aliphate.	2,80 10 - 4	3,55
benzylamine		Primary aliphate.	2,10 10 -5	4,67
Dimethylamine		Secondary aliphate.	5,40 10 -4	3,27
diethylamine		Secondary aliphate.	1,20 10 - 3	2,91
Trimethylamine		Tertiary aliphate.	6,50 10 -5	4,19
Triethylamine		Tertiary aliphate.	1,00 10 - 3	3,00
Aniline		Primary aroma.	4,30 10 - 10	9,37
P-toluidine		Primary aroma.	1,32 10 -9	8,88
P-nitroaniline		Primary aroma.	1,00 10 - 13	13,0
N,N-dimethylaniline		Tertiary fatty aromatic	1,40 10 -9	8,85
Diphenylamine		Secondary aroma.	6,20 10 -14	13,21
pyridine		Heteroaromatic	1,50 10 - 9	8,82
Quinoline		Heteroaromatic	8,70 10 -10	9,06
Piperidine		Secondary aliphate. and heterocyclic	1,33 10 -3	3,88
Hydrazine			9,30 10 -7	6,03
Hydroxylamine			8,90 10 - 9	8,05
ethanolamine		Prod. perv. alif.	1,80 10 - 5	4,75

The data in the table allow us to draw the following conclusions:

1) Aliphatic amines are much stronger bases than aromatic ones (about 100,000 - 1,000,000 times)

2) Heteroaromatic amines are similar in basicity to aromatic ones.

3) The basicity of aromatic amines is strongly influenced by substituents located in pair- position to the amino group. Electron-donating substituents increase the basicity of the amine, while electron-withdrawing substituents sharply lower it. The basicity ratio of aromatic amines containing methyl and nitro groups at the indicated position is approximately 10,000:1.

4) Secondary aliphatic amines are slightly more basic than primary ones, while tertiary ones have a basicity at the same level.

5) The nature of the radical in primary amines does not significantly affect the basicity of the amine.

6) Saturated heterocyclic amines have basicity at the level of secondary aliphatic amines.

7) Fatty aromatic amines have basicity at the level of aromatic amines.

8) Secondary aromatic amines have about 10,000 times less basicity than primary ones.

9) Electronegative atoms bound in the molecule to the nitrogen atom of the amino group lower its basicity by 10 (nitrogen) and 1000 times (oxygen).

10) An oxygen atom separated from the amino group by two methylene groups lowers its basicity by only 67 times.

It should also be noted that the basicity of acid amides due to the electron-withdrawing effect of the carbonyl group is very low - even lower than that of secondary aromatic amines: for acetamide pK b = 13.52; acetanilide pK b = 13.60 and urea pK b = 13.82

acetamide acetanilide urea

Like grounds primary, secondary and tertiary amines react with acids:

propylamine propylammonium bromide

dimethylamine dimethylammonium sulfate

trimethylamine trimethylammonium perchlorate

With polybasic acids can form not only medium, but and acid salts:

dimethylamine dimethylammonium hydrogen sulfate

methylisobutylamine methylisobutylammonium dihydroorthophosphate

Primary aromatic, as well as secondary and tertiary fatty aromatic amines with dilute aqueous solutions of strong acids also give salt:

Also able to form salt Under the influence concentrated strong acids, but at dilution with water these salts hydrolyzed, giving a weak base, that is starting amine:

Like very weak foundations, do not give salt neither with concentrated hydrochloric nor with sulfuric acids. True, triphenylamine still gives perchlorate with perchloric acid:

.

Primary aliphatic amines react in two stages: in the first, an extremely unstable in water even when cooled diazonium salt, which in the second stage reacts with water to form alcohol:

propylamine propyldiazonium chloride

propanol-1

In the reaction of a primary amine with sodium nitrite and hydrochloric acid, outgassing(bubbles are clearly visible) and fishy smell amine changes to alcohol is a qualitative reaction to a primary aliphatic amine.

If we sum up the two reactions above, we get:

Secondary amines react in a completely different way: under the action of sodium nitrite and hydrochloric acid, N-nitrosamine- very resistant even when heated connection:

methylethylamine N-nitrosomethylethiamin

In the reaction of a secondary aliphatic amine with sodium nitrite and hydrochloric acid, the formation of a yellow oil, poorly soluble in water and with an extremely unpleasant odor is a qualitative reaction to a secondary aliphatic amine.

Nitrosamines - carcinogens: regardless of the place and method of entry into the body of the experimental animal, they cause liver cancer. Widely used in experimental oncology. They act resorptively, that is, through the skin.

Tertiary aliphatic amines react from a mixture of sodium nitrite and hydrochloric acid only with acid:

There are no visible effects in this reaction. The smell subsides.

Primary aromatic amines react with the formation of relatively stable at temperatures from 0 to 5 o C diazonium salts. This reaction was first published in 1858 in a German chemistry journal by Peter Griess and bears his name:

The Griess reaction involves numerous aniline homologues containing alkyl substituents in o-,m- and P-position to the amino group:

It also includes aniline derivatives containing electron-acceptor, electron-donor substituents and substituents of a special group, for example:

With hydrobromic acid, the reaction is faster, but is rarely used and only in the laboratory due to the high cost and scarcity of this acid.

In the production of salt, diazonium is immediately used for the following stages of synthesis, but in the laboratory they are often isolated by an exchange reaction with a saturated solution of sodium tetrafluoroborate:

Diazonium salts are most often used to obtain numerous azo dyes by azo coupling with phenols (naphthols) and aromatic tertiary amines, for example:

The resulting azo dye is a pH indicator: in an acidic environment, due to the formation of a hydrogen bond, it has a flat structure in which the electron-donating effect of the hydroxyl group is weakened - this form is colored yellow. In the alkaline group, a proton breaks off from the hydroxyl group, a “phenolate ion” appears, which is the strongest ED substituent, and the color changes to red-orange:

The role of soda in the course of the azo coupling reaction is the binding of the resulting hydrochloric (or other strong) acid into an acid salt - sodium bicarbonate:

A mixture of sodium carbonate and bicarbonate is a buffer solution that creates a slightly alkaline environment.

With tertiary aromatic amines, azo coupling must take place in a slightly acidic medium, which is ensured by the addition of salts that hydrolyze at the anion, for example, sodium acetate. In a strongly acidic medium, the amine gives an ammonium salt, the cation of which naturally does not react with the diazonium cation.

Sodium acetate instantly reacts with the resulting hydrochloric acid. The result is a buffer solution consisting of weak acetic acid and excess sodium acetate. It provides a slightly acidic environment:

Secondary aromatic amines react with sodium nitrite and hydrochloric acid with education N-nitrosamines. For example, N-methylaniline gives N-nitroso-N-methylaniline - a yellow oil with an extremely unpleasant odor that solidifies at 13 ° C:

Aromatic N-nitrosoamines, like aliphatic ones, are carcinogens. They also cause liver cancer, and are also used in experimental oncology.

Aromatic N-nitrosoamines under the action of dry chloro- or hydrogen bromides or under the action of concentrated sulfuric acid undergo a rearrangement first published in 1886 in a German chemical journal by O. Fischer and E. Hepp. Under these conditions, the nitroso group is selectively transferred to P-position:

The resulting rearrangement of 4-nitroso-N-methylaniline has completely different physical properties and biological activity. It is a green solid with a melting point of 113°C. It fluoresces in solutions in organic solvents. It is not a carcinogen, however, it causes dermatitis.

Tertiary aromatic amines react with sodium nitrite and hydrochloric acid, Giving C-nitroso compounds. The nitroso group is selectively directed to P-position:

C-nitroso compounds are easily reduced by hydrogen on Raney nickel. In this case, unsymmetrical dialkyldiamines are obtained, for example:

Salts of aliphatic and aromatic amines can be easily converted back into amines by the action of alkalis, for example:

propylammonium perchlorate propylamine

methylpropylammonium hydrogen sulfate methylpropylamine

Quaternary ammonium bases, Conversely, they can be translated into quaternary ammonium salts action acids:

Dimethylethylisopropylammonium hydroxide Dimethylethylisopropylammonium chloride

As you can see, this is a common reaction of neutralizing an alkali with an acid - salt and water are obtained.

On page 19 of this manual, it was suggested that the reactions of electrophilic substitution in aromatic amines can easily occur in ortho- and pair- positions of the benzene nucleus. Indeed, aniline is easily brominated into all these positions at once:

N,N-dialkylanilines are sulfonated, nitrated, and diazotized in ortho- and pair-provisions:

With sodium acetate, a strong complex acid is converted into a weak one - acetic:

Application of amines

The simplest primary amine methylamine used in the synthesis of insecticides, fungicides, vulcanization accelerators, surface-active substances (surfactants), drugs, dyes, rocket fuels, solvents. For example, N-methyl-2-pyrrolidone, a popular solvent for varnishes and some dyes, is obtained by reacting methylamine with γ-butyrolactone (4-hydroxybutanoic acid cyclic ester):

γ-butyrolatone N-methyl-2-pyrrolidone

The simplest secondary amine dimethylamine used in the synthesis of insecticides, herbicides, vulcanization accelerators, surface-active substances (surfactants), many drugs, dyes and important solvents such as dimethylforiamid (DMF), dimethylacetamide (DMAA) and hexamethylphosphotriamide (HMPTA) or hexametapol. DMF is produced in industry, for example, by reacting dimethylamine with formic acid methyl ester:

methyl formate dimethylamine DMF methanol

DMAA is produced industrially by reacting dimethylamine with acetic anhydride:

acetic anhydride DMAA

The industrial synthesis of hexametapol consists in the interaction of dimethylamine with phosphorus oxychloride:

phosphorus trichloride HMPTA

The simplest tertiary amine trimethylamine used in the synthesis of quaternary ammonium bases, flotation agents, retardants, feed additives. For example, the last step in the synthesis of carbacholine, a drug used in the treatment of glaucoma and postoperative atony of the intestine or bladder, is the interaction of trimethylamine with a carbamoyl derivative of ethylene chlorohydrin:

carbacholin

Cationic surfactants are obtained similarly:

trimethylalkylammonium chloride

ethylamine used in the production of dyes, surfactants, herbicides. For example, simazine, a herbicide for protecting corn and vegetables from weeds, is obtained by the interaction of ethylamine with the calculated amount of cyanuric chloride in an alkaline medium:

cyanuric chloride simazine

diethylamine used in the production of dyes, pesticides, rubber vulcanization accelerators, corrosion inhibitors, medicines, insect repellents. For example, a well-known mosquito repellent - DEET is obtained by the reaction:

acid chloride m-toluic acid N,N-diethyl- m-toluamide

Isopropylamine, butylamine, isobutylamine, second-butiamine and tert- butylamines used in similar industries.

1,6-hexanediamine widely used for the synthesis of nylon by the reaction of polycondensation with 1,4-butanedicarboxylic (adipic) acid:

Among drugs, many contain amino groups of various types. So, for example, out of 1308 drugs listed in the M.D. Mashkovsky, at least 70 are primary amines, at least 52 are secondary and at least 108 are tertiary. In addition, there are 41 quaternary ammonium salts and more than 70 amides of carboxylic acids, 26 amides of arylsulfonic acids and 12 amides of orthophosphoric acid derivatives among the drugs. There are also cyclic amides - lactams. There are 5 of them. Derivatives of natural amino acids - 14 items. The following are examples of medicinal products containing the listed functional groups:

Anestezin- ethyl ether P-aminobenzoic acid. It is a primary aromatic amine and an ester at the same time.

It has a local anesthetic effect. It is used to anesthetize wound and ulcerative surfaces, with vomiting of pregnant women, sea and air sickness.

Baclofen– 4-amino-3-( P-chloro)phenylbutanoic acid. It is a primary aliphatic amine, an ester and a halogen derivative of the benzene series at the same time.

Reduces muscle tension, has an analgesic effect. Used for multiple sclerosis.

Salbutamol – 2-tert-butylamino-1-(4"-hydroxy-3"-hydroxymethyl)phenylethanol. It is a secondary aliphatic amine, secondary and primary alcohols and phenol at the same time.

It has a bronchodilatory effect and prevents premature contractions in pregnant women. It is used in bronchial asthma and in obstetric practice.

Ortofen- sodium salt of 2-(2",6"-dichloro)phenylaminophenylacetic acid. It is a secondary aromatic amine, a salt of a carboxylic acid and a halogen derivative of the benzene series at the same time.

It has anti-inflammatory, analgesic and antipyretic effects. It is used for acute rheumatism, rheumatoid arthritis, Bechterew's disease, arthrosis, spondyloarthrosis.

Isoverin- N-isoamyl-1,5-pentanediamine dihydrochloride. It is a diammonium salt of primary and secondary amines simultaneously.

Lowers blood pressure, increases tone and enhances contractions of the muscles of the uterus. It is used as a labor accelerator and to stimulate uterine contractions in the postpartum period.

methylene blue- N,N,N',N'-tetramethylthionine chloride. It is both a tertiary fatty aromatic amine and an ammonium salt of the same amine. In addition, it contains a heteroaromatic ring with a "pyridine" nitrogen atom.

Applied externally as an antiseptic for burns, pyoderma and folliculitis. For cystitis and urethritis, the cavities are washed with a 0.02% blue solution.

Pentamine– 3-methyl-1,5-bis-(N,N-dimethyl-N-ethyl)ammonium-3-azapentane dibromide. It is both a tertiary aliphatic amine and a doubly quaternary ammonium salt of the same amines.

It has ganglioblocking activity. It is used for hypertensive crises, spasms of peripheral vessels, spasms of the intestines and biliary tract, renal colic, for the relief of acute attacks of bronchial asthma, with edema of the lungs and brain.

Nicotinamide– 3-pyridinecarboxylic acid amide. It is an amide of a carboxylic acid and a derivative of the nitrogen-containing heteroaromatic cycle - pyridine.

It has anti-pellagric properties, improves carbohydrate metabolism, has a positive effect on mild forms of diabetes, diseases of the liver, heart, peptic ulcer of the stomach and duodenum. It is used for gastritis with low acidity, acute and chronic hepatitis, cirrhosis, spasms of the vessels of the extremities, kidneys and brain.

Sulfadimezin – 2-(P- aminobenzenesulfamido)-4,6-dimethylpyrimidine. Representative of a large group of sulfa drugs. It is simultaneously a sulfanilamide, a primary aromatic amine and a derivative of the nitrogen-containing heteroaromatic cycle - pyrimidine.

Like all drugs in this group, sulfadimezin is an active antimicrobial agent. It is used for pneumococcal, streptococcal, meningococcal infections, sepsis, gonorrhea, as well as infections caused by Escherichia coli and other microbes.

Fopurine - 6-diethyleneamidophosphamido-2-dimethylamino-7-methylpurine. It is simultaneously three times a phosphamide, a tertiary aromatic amine and a derivative of a nitrogen-containing heteroaromatic bicycle - purine

Hemodez- 6% aqueous-salt solution of low molecular weight polyvinylpyrrolidone. The elementary unit of the polymer contains a lactam ring.

Binds toxins circulating in the blood and quickly removes them through the renal barrier. Used for dysentery, dyspepsia, salmonellosis, burn disease in the phase of intoxication.

Histidine– L-β-imidazolylalanine or L-α-amino-β-(4-imidazolyl)propionic acid. It is an α-amino acid and a derivative of the nitrogen-containing heteroaromatic cycle - imidazole

Histidine is an essential amino acid; found in various organs, is part of carnosine, a nitrogenous extractive substance of muscles. In the body, it undergoes decarboxylation with the formation of histamine, one of the chemical factors (mediators) involved in the regulation of vital functions.

Angiotensinamide– L-asparaginyl-L-arginyl-L-valyl-L-tyrosinyl-L-valyl-L-histidinyl acetate – L-prolyl-L-phenylalanine. It is an acetic salt of an octapeptide consisting of natural α-amino acids.

In shock conditions, it is used for rapid and severe vasoconstriction of internal organs, skin, and kidneys. Angiotensinamide also has the ability to reduce the smooth muscles of the uterus, intestines, urinary and gallbladder. It stimulates the release of adrenaline from the adrenal glands and the production of aldosterone.

Amines. Definition
Classification of amines according to the number of hydrogen atoms in ammonia, replaced by radicals
Classification of amines according to the nature of the radicals associated with the nitrogen atom
Isomerism and nomenclature of aliphatic amines
Methods for obtaining amines
Obtaining amines from other nitrogen-containing compounds
From nitro compounds
From nitroso compounds
From oximes
From hydrazones
From amides of carboxylic acids
From nitriles of carboxylic acids: 7
Obtaining amines from compounds of other classes
From aldehydes and ketones by the Leuckart-Wallach reaction
Preparation of primary aliphatic amines by alkylation of ammonia
Obtaining secondary aliphatic amines by alkylation of primary
Obtaining tertiary aliphatic amines by alkylation of secondary
Preparation of quaternary ammonium salts from tertiary amines
Preparation of quaternary ammonium bases from quaternary ammonium salts
Thermolysis of quaternary ammonium bases
Alkylation of primary aromatic amines to symmetrical ones
tertiary amines
Four-step synthesis of secondary fatty-aromatic amines
Obtaining pure primary amines according to Gabriel
Obtaining amines from alcohols
Obtaining aromatic amines
Recovery of aromatic nitro compounds according to N.N. Zinina
Recovery of aromatic nitro compounds according to Béchamp
Catalytic reduction of aromatic nitro compounds with hydrogen
Physical properties of aliphatic amines
Aggregate state of aliphatic amines
The dependence of the boiling points of aliphatic amines on the structure
Solubility of aliphatic amines in water and organic solvents
Physical properties of aromatic amines
Aggregate state and solubility of aromatic amines
Chemical properties of amines
Relationship of the electronic structure of amines with basicity
Basicity constants and pK b values ​​for aliphatic, aromatic and heterocyclic amines and some related compounds
Reactions of amines with acids
Reaction of amines with sodium nitrite and hydrochloric acid
Conversion of primary aliphatic amines to alcohols via diazo compounds
Conversion of secondary aliphatic amines to N-nitroso compounds
Carcinogenicity of aliphatic N-nitrosamines
Interaction of tertiary aliphatic amines with sodium nitrite
and hydrochloric acid
Conversion of primary aromatic amines to diazonium salts
Isolation of diazonium salts from solutions in the form of tetrafluoroborates
Azo coupling reaction with phenols (naphthols)
Azo dyes as pH indicators
Azo coupling reaction with tertiary aromatic amines
Conversion of secondary fatty aromatic amines to N-nitrosamines
Carcinogenicity of fatty-aromatic N-nitrosamines
Fischer-Hepp rearrangement
Conversion of tertiary aromatic amines to C-nitroso compounds
Catalytic reduction of aromatic C-nitroso compounds with hydrogen
The interaction of salts of aliphatic and aromatic amines with alkalis
Interaction of quaternary ammonium bases with acids
Electrophilic substitution reactions in aromatic amines
Application of amines
The use of methyl and dimethylamines
Preparation of popular organic solvents: DMF, DMAA and HMPTA
The use of trimethyl- and ethylamines
The use of diethylamine
The use of diamines to obtain polyamide polymers
Drugs - amines and amine derivatives
Anestezin
Baclofen
Salbutamol
Ortofen
Isoverin
methylene blue
Pentamine
Nicotinamide
Sulfadimezin
Fopurine
Hemodez
Histidine
Angiotensinamide
Content

Amines - these are derivatives of ammonia (NH 3), in the molecule of which one, two or three hydrogen atoms are replaced by hydrocarbon radicals.

According to the number of hydrocarbon radicals that replace hydrogen atoms in the NH 3 molecule, all amines can be divided into three types:

The group - NH 2 is called an amino group. There are also amines that contain two, three or more amino groups.

Nomenclature

The word "amine" is added to the name of organic residues associated with nitrogen, while the groups are mentioned in alphabetical order: CH3NC3H - methylpropylamine, CH3N(C6H5)2 - methyldiphenylamine. For higher amines, the name is compiled, taking the hydrocarbon as a basis, adding the prefix "amino", "diamino", "triamino", indicating the numerical index of the carbon atom. Trivial names are used for some amines: C6H5NH2 - aniline (systematic name - phenylamine).

For amines, chain isomerism, functional group position isomerism, isomerism between types of amines is possible

Physical Properties

Lower limiting primary amines - gaseous substances, have the smell of ammonia, dissolve well in water. Amines with a higher relative molecular weight are liquids or solids, their solubility in water decreases with increasing molecular weight.

Chemical properties

Amines are chemically similar to ammonia.

1. Interaction with water - the formation of substituted ammonium hydroxides. Ammonia solution in water has weak alkaline (basic) properties. The reason for the basic properties of ammonia is the presence of a lone electron pair at the nitrogen atom, which is involved in the formation of a donor-acceptor bond with a hydrogen ion. For the same reason, amines are also weak bases. Amines are organic bases.

2. Interaction with acids - the formation of salts (neutralization reactions). As a base, ammonia forms ammonium salts with acids. Similarly, when amines react with acids, substituted ammonium salts are formed. Alkalis, as stronger bases, displace ammonia and amines from their salts.

3. Combustion of amines. Amines are combustible substances. The combustion products of amines, as well as other nitrogen-containing organic compounds, are carbon dioxide, water and free nitrogen.

Alkylation is the introduction of an alkyl substituent into the molecule of an organic compound. Typical alkylating agents are alkyl halides, alkenes, epoxy compounds, alcohols, less often aldehydes, ketones, ethers, sulfides, diazoalkanes. Alkylation catalysts are mineral acids, Lewis acids and zeolites.

Acylation. When heated with carboxylic acids, their anhydrides, acid chlorides or esters, primary and secondary amines are acylated to form N-substituted amides, compounds with a -C(O)N moiety<:

The reaction with anhydrides proceeds under mild conditions. Acid chlorides react even more easily, the reaction is carried out in the presence of a base to bind the HCl formed.

Primary and secondary amines interact with nitrous acid in different ways. With the help of nitrous acid, primary, secondary and tertiary amines are distinguished from each other. Primary alcohols are formed from primary amines:

C2H5NH2 + HNO2 → C2H5OH + N2 +H2O

This releases gas (nitrogen). This is a sign that there is primary amine in the flask.

Secondary amines form with nitrous acid yellow, sparingly soluble nitrosamines - compounds containing the >N-N=O fragment:

(C2H5)2NH + HNO2 → (C2H5)2N-N=O + H2O

Secondary amines are hard to miss, the characteristic smell of nitrosodimethylamine spreads throughout the laboratory.

Tertiary amines simply dissolve in nitrous acid at ordinary temperatures. When heated, a reaction with the elimination of alkyl radicals is possible.

How to get

1. Interaction of alcohols with ammonia during heating in the presence of Al 2 0 3 as a catalyst.

2. Interaction of alkyl halides (haloalkanes) with ammonia. The resulting primary amine can react with excess alkyl halide and ammonia to form a secondary amine. Tertiary amines can be prepared similarly

Amino acids. Classification, isomerism, nomenclature, obtaining. Physical and chemical properties. Amphoteric properties, bipolar structure, isoelectric point. Polypeptides. Individual representatives: glycine, alanine, cysteine, cystine, a-aminocaproic acid, lysine, glutamic acid.

Amino acids- these are derivatives of hydrocarbons containing amino groups (-NH 2) and carboxyl groups -COOH.

General formula: (NH 2) f R(COOH) n where m and n most often equal to 1 or 2. Thus, amino acids are compounds with mixed functions.

Classification

isomerism

The isomerism of amino acids, as well as hydroxy acids, depends on the isomerism of the carbon chain and on the position of the amino group in relation to the carboxyl (a-, β - and γ - amino acids, etc.). In addition, all natural amino acids, except aminoacetic, contain asymmetric carbon atoms, so they have optical isomers (antipodes). There are D- and L-series of amino acids. It should be noted that all amino acids that make up proteins belong to the L-series.

Nomenclature

Amino acids usually have trivial names (for example, aminoacetic acid is called differently glycocol or iicin, and aminopropionic acid alanine etc.). The name of an amino acid according to the systematic nomenclature consists of the name of the corresponding carboxylic acid, of which it is a derivative, with the addition of the word amino- as a prefix. The position of the amino group in the chain is indicated by numbers.

How to get

1. Interaction of α-halocarboxylic acids with an excess of ammonia. In the course of these reactions, the halogen atom in halocarboxylic acids (for their preparation, see § 10.4) is replaced by an amino group. The hydrogen chloride released at the same time is bound by an excess of ammonia into ammonium chloride.

2. Hydrolysis of proteins. Complex mixtures of amino acids are usually formed during the hydrolysis of proteins, however, using special methods, individual pure amino acids can be isolated from these mixtures.

Physical Properties

Amino acids are colorless crystalline substances, readily soluble in water, melting point 230-300°C. Many α-amino acids have a sweet taste.

Chemical properties

1. Interaction with bases and acids:

a) as an acid (carboxyl group is involved).

b) as a base (amino group is involved).

2. Interaction within the molecule - the formation of internal salts:

a) monoaminomonocarboxylic acids (neutral acids). Aqueous solutions of monoaminomonocarboxylic acids are neutral (pH = 7);

b) monoaminodicarboxylic acids (acidic amino acids). Aqueous solutions of monoaminodicarboxylic acids have pH< 7 (кислая среда), так как в результате образования внутренних солей этих кислот в растворе появляется избыток ионов водорода Н + ;

c) diaminomonocarboxylic acids (basic amino acids). Aqueous solutions of diaminomonocarboxylic acids have pH > 7 (alkaline), because as a result of the formation of internal salts of these acids, an excess of OH - hydroxide ions appears in the solution.

3. The interaction of amino acids with each other - the formation of peptides.

4. Interact with alcohols to form esters.

The isoelectric point of amino acids that do not contain additional NH2 or COOH groups is the arithmetic mean between the two pK values: respectively for alanine .

The isoelectric point of a number of other amino acids containing additional acidic or basic groups (aspartic and glutamic acids, lysine, arginine, tyrosine, etc.) also depends on the acidity or basicity of the radicals of these amino acids. For lysine, for example, pI should be calculated from half the sum of pK" values ​​for α- and ε-NH2 groups. Thus, in the pH range from 4.0 to 9.0, almost all amino acids exist predominantly in the form of zwitterions with a protonated amino group and a dissociated carboxyl group.

Polypeptides contain more than ten amino acid residues.

Glycine (aminoacetic acid, aminoethanoic acid) is the simplest aliphatic amino acid, the only amino acid that does not have optical isomers. Empirical formula C2H5NO2

Alanine (aminopropanoic acid) is an aliphatic amino acid. α-alanine is part of many proteins, β-alanine is part of a number of biologically active compounds. Chemical formula NH2 -CH -CH3 -COOH. Alanine is easily converted into glucose in the liver and vice versa. This process is called the glucose-alanine cycle and is one of the main pathways of gluconeogenesis in the liver.

Cysteine ​​(α-amino-β-thiopropionic acid; 2-amino-3-sulfanylpropanoic acid) is an aliphatic sulfur-containing amino acid. Optically active, exists in the form of L- and D-isomers. L-cysteine ​​is a component of proteins and peptides and plays an important role in the formation of skin tissues. It is important for detoxification processes. The empirical formula is C3H7NO2S.

Cystine (chem.) (3,3 "-dithio-bis-2-aminopropionic acid, dicysteine) is an aliphatic sulfur-containing amino acid, colorless crystals, soluble in water.

Cystine is a non-coding amino acid that is a product of the oxidative dimerization of cysteine, during which two cysteine ​​thiol groups form a cystine disulfide bond. Cystine contains two amino groups and two carboxyl groups and is a dibasic diamino acid. Empirical formula C6H12N2O4S2

In the body, they are found mainly in the composition of proteins.

Aminocaproic acid (6-aminohexanoic acid or ε-aminocaproic acid) is a hemostatic drug that inhibits the conversion of profibrinolysin to fibrinolysin. Gross-

formula C6H13NO2.

Lysine (2,6-diaminohexanoic acid) is an aliphatic amino acid with pronounced base properties; essential amino acid. Chemical formula: C6H14N2O2

Lysine is part of proteins. Lysine is an essential amino acid that is part of almost any protein, it is necessary for growth, tissue repair, production of antibodies, hormones, enzymes, albumins.

Glutamic acid (2-aminopentanedioic acid) is an aliphatic amino acid. In living organisms, glutamic acid in the form of glutamate anion is present in proteins, a number of low molecular weight substances and in free form. Glutamic acid plays an important role in nitrogen metabolism. Chemical formula C5H9N1O4

Glutamic acid is also a neurotransmitter amino acid, one of the important members of the excitatory amino acid class. The binding of glutamate to specific receptors of neurons leads to the excitation of the latter.

Simple and complex proteins. peptide bond. The concept of the primary, secondary, tertiary and quaternary structure of the protein molecule. Types of bonds that determine the spatial structure of the protein molecule (hydrogen, disulfide, ionic, hydrophobic interactions). Physical and chemical properties of proteins (precipitation, denaturation, color reactions). isoelectric point. The value of proteins.

Squirrels - these are natural high-molecular compounds (biopolymers), the structural basis of which is polypeptide chains built from α-amino acid residues.

Simple proteins (proteins) are high-molecular organic substances consisting of alpha-amino acids connected in a chain by a peptide bond.

Complex proteins (proteids) are two-component proteins that, in addition to peptide chains (a simple protein), contain a component of a non-amino acid nature - a prosthetic group.

Peptide bond - a type of amide bond that occurs during the formation of proteins and peptides as a result of the interaction of the α-amino group (-NH2) of one amino acid with the α-carboxyl group (-COOH) of another amino acid.

The primary structure is the sequence of amino acids in a polypeptide chain. Important features of the primary structure are conservative motifs - combinations of amino acids that play a key role in protein functions. Conservative motifs are preserved during the evolution of species; they often make it possible to predict the function of an unknown protein.

Secondary structure - local ordering of a fragment of a polypeptide chain, stabilized by hydrogen bonds.

Tertiary structure - the spatial structure of the polypeptide chain (a set of spatial coordinates of the atoms that make up the protein). Structurally, it consists of secondary structure elements stabilized by various types of interactions, in which hydrophobic interactions play an important role. In the stabilization of the tertiary structure take part:

covalent bonds (between two cysteine ​​residues - disulfide bridges);

ionic bonds between oppositely charged side groups of amino acid residues;

hydrogen bonds;

hydrophilic-hydrophobic interactions. When interacting with surrounding water molecules, the protein molecule “tends” to curl up so that the non-polar side groups of amino acids are isolated from the aqueous solution; polar hydrophilic side groups appear on the surface of the molecule.

Quaternary structure (or subunit, domain) - the mutual arrangement of several polypeptide chains as part of a single protein complex. Protein molecules that make up a protein with a quaternary structure are formed separately on ribosomes and only after the end of synthesis form a common supramolecular structure. A protein with a quaternary structure can contain both identical and different polypeptide chains. The same types of interactions take part in the stabilization of the quaternary structure as in the stabilization of the tertiary one. Supramolecular protein complexes can consist of dozens of molecules.

Physical Properties

The properties of proteins are as diverse as the functions they perform. Some proteins dissolve in water, forming, as a rule, colloidal solutions (for example, egg white); others dissolve in dilute salt solutions; others are insoluble (for example, proteins of integumentary tissues).

Chemical properties

In the radicals of amino acid residues, proteins contain various functional groups that are capable of entering into many reactions. Proteins enter into oxidation-reduction reactions, esterification, alkylation, nitration, they can form salts with both acids and bases (proteins are amphoteric).

For example, albumin - egg white - at a temperature of 60-70 ° is precipitated from a solution (coagulates), losing the ability to dissolve in water.