Nucleophilic addition reactions (reaction-AdN). Nucleophilic addition reactions (AN) to carbonyl compounds
Nucleophilic addition to alkynes is initiated under the influence of a negatively charged particle - nucleophile. In general, bases are the catalyst for such reactions. General scheme of the first stage of the nucleophilic addition reaction:
Typical nucleophilic addition reactions
A typical example of a nucleophilic addition reaction is the Favorsky reaction - the addition of alcohols in the presence of alkalis to form alkenyl esters:
Primary amines under the action of bases add to alkynes to form imines:
By analogy, acetylene reacts with ammonia to form ethylideneimine:
At high temperature in the presence of a catalyst, the imine dehydrogenates and turns into acetonitrile:
In an environment of very strong bases (for example: KOH + DMSO), acetylene reacts with hydrogen sulfide, forming divinyl sulfide:
Radical addition reactions
In the presence of peroxides or other conditions that promote the formation of free radicals, the addition to alkynes proceeds according to a radical mechanism - against the Markovnikov rule (Harash effect):
According to the free radical mechanism*, the reaction of alkynes with thiols can proceed:
* - In the presence of bases, the reaction proceeds according to the nucleophilic mechanism.
Similarly, the addition of carbenes occurs:
Ethynylation reactions
Ethynylation reactions are called reactions of increasing the carbon skeleton of alkynes with the preservation of the triple bond. They can proceed by both electrophilic and nucleophilic mechanisms, depending on the medium and reaction conditions, the nature of the substrate, and the type of catalyst used.
Obtaining acetylenic alcohols
In the presence of strong bases, alkynes with a terminal triple bond are able to add carbonyl compounds to form alcohols (Favorsky reaction):
The most important reaction from this group is the addition of formaldehyde to acetylene with the formation of propargyl alcohol and then butyn-2-diol-1,4 *:
Obtaining acetylenic esters and acids
Acetylene acids or their esters can be obtained by the Zuzhi reaction:
Catalysts: PdCl 2 , CuCl.
Hydrogenation reactions
Heterogeneous hydrogenation
Hydrogenation of alkynes with hydrogen on heterogeneous catalysts, as a rule, leads to the formation cis- connections. Hydrogenation catalysts are Ni, Pd, Pt, as well as oxides or complexes of Ir, Ru, Rh and some other metals.
At the first stage, an alkene is formed, which is almost immediately hydrogenated to an alkane:
To stop the reaction at the stage of alkene production, Lindlar catalysts (Pd/PbO/CaCO 3) or nickel boride are used.
When acetylene is hydrogenated on a nickel-cobalt catalyst, isobutylene can be obtained:
Homogeneous hydrogenation
Homogeneous hydrogenation is carried out with sodium amide in liquid ammonia or lithium aluminum hydride in tetrahydrofuran. During the reaction, trance-alkenes.
Hydroboration
Alkynes easily add diborane against Markovnikov's rule, forming cis-alkenylboranes:
or oxidize H 2 O 2 to an aldehyde or ketone.
1. Reactions of nucleophilic addition. Heterolytic reactions involving carbon-oxygen π-bonds (aldehydes, ketones). Reactions of carbonyl compounds with water, alcohols, thiols, primary amines. The role of acid catalysis. Hydrolysis of acetals and imines. Reactions of aldol addition, splitting. The biological significance of these processes.
For aldehydes and ketones, nucleophilic addition reactions A N are most characteristic.
General description of the mechanism of nucleophilic addition A N
The ease of nucleophilic attack on the carbon atom of the carbonyl group of an aldehyde or ketone depends on the magnitude of the partial
positive charge on the carbon atom, its spatial availability and acid-base properties of the medium.
Taking into account the electronic effects of the groups associated with the carbonyl carbon atom, the value of the partial positive charge δ+ on it in aldehydes and ketones decreases in the following series:
The spatial availability of the carbonyl carbon atom decreases when hydrogen is replaced by bulkier organic radicals, so aldehydes are more reactive than ketones.
The general scheme of reactions for the nucleophilic addition of AN to a carbonyl group involves a nucleophilic attack on the carbonyl carbon followed by the addition of an electrophile to the oxygen atom.
In an acidic environment, the activity of the carbonyl group, as a rule, increases, since due to the protonation of the oxygen atom, a positive charge arises on the carbon atom. Acid catalysis is usually used when the attacking nucleophile has low activity.
According to the above mechanism, a number of important reactions of aldehydes and ketones are carried out.
Many reactions characteristic of aldehydes and ketones occur in the body, these reactions are presented in the subsequent sections of the textbook. In this chapter, the most important reactions of aldehydes and ketones will be considered, which are summarized in the diagram.
addition of alcohols. Alcohols, when reacting with aldehydes, easily form hemiacetals. Hemiacetals are usually not isolated because of their instability. With an excess of alcohol in an acidic environment, hemiacetals are converted to acetals.
The use of an acid catalyst in the conversion of hemiacetal to acetal is clear from the reaction mechanism below. The central place in it is occupied by the formation of a carbocation (I), stabilized due to the participation of the lone pair of electrons of the neighboring oxygen atom (+M effect of the C 2 H 5 O group).
The reactions of formation of hemiacetals and acetals are reversible; therefore, acetals and hemiacetals are easily hydrolyzed by excess water in an acidic medium. In an alkaline environment, hemiacetals are stable, since the alkoxidion is a more difficult leaving group than the hydroxide ion.
The formation of acetals is often used as a temporary protection of the aldehyde group.
Water connection. The addition of water to a carbonyl group - hydration - is a reversible reaction. The degree of hydration of an aldehyde or ketone in an aqueous solution depends on the structure of the substrate.
The product of hydration, as a rule, cannot be isolated by distillation in a free form, since it decomposes into its original components. Formaldehyde in an aqueous solution is more than 99.9% hydrated, acetaldehyde is approximately half, and acetone is practically not hydrated.
Formaldehyde (formaldehyde) has the ability to coagulate proteins. Its 40% aqueous solution, called formalin, is used in medicine as a disinfectant and preservative for anatomical preparations.
Trichloroacetic aldehyde (chloral) is fully hydrated. The electron-withdrawing trichloromethyl group stabilizes chloral hydrate to such an extent that this crystalline substance splits off water only during distillation in the presence of dehydrating substances - sulfuric acid, etc.
The pharmacological effect of CC1 3 CH(OH) 2 chloral hydrate is based on the specific effect of the aldehyde group on the body, which determines the disinfectant properties. Halogen atoms enhance its action, and hydration of the carbonyl group reduces the toxicity of the substance as a whole.
Addition of amines and their derivatives. Amines and other nitrogen-containing compounds of the general formula NH2X (X = R, NHR) react with aldehydes and ketones in two stages. First, nucleophilic addition products are formed, which then, due to instability, split off water. In this regard, this process is generally classified as an addition-elimination reaction.
In the case of primary amines, substituted imines are obtained (they are also called Schiff bases).
Imines are intermediate products of many enzymatic processes. Obtaining imines passes through the stage of formation of amino alcohols, which are relatively stable, for example, in the interaction of formaldehyde with α-amino acids.
Imines are intermediates in the production of amines from aldehydes and ketones by reductive amination. This general method consists in the reduction of a mixture of carbonyl compound with ammonia (or amine). The process proceeds according to the addition-cleavage scheme with the formation of an imine, which is then reduced to an amine.
When aldehydes and ketones react with hydrazine derivatives, hydrazones are obtained. This reaction can be used to isolate aldehydes and ketones from mixtures and their chromatographic identification.
Schiff's bases and other similar compounds are easily hydrolyzed by aqueous solutions of mineral acids to form the starting products.
In most cases, the reactions of aldehydes and ketones with nitrogenous bases require acid catalysis, which accelerates the dehydration of the addition product. However, if the acidity of the medium is increased too much, the reaction will slow down as a result of the conversion of the nitrogenous base into the non-reactive conjugate acid XNH3+.
The presence of a CH-acid center in an aldehyde or ketone molecule leads to the fact that the α-hydrogen atoms of these carbonyl compounds have some proton mobility. Under the action of bases, such protons can be split off with the formation of the corresponding carbanions. Carbanions play the role of nucleophiles with respect to the carbonyl substrate. This makes it possible to carry out reactions in which one molecule, as a nucleophile, is added to the carbonyl group of another molecule of a neutral carbonyl compound. Such processes are referred to as condensation reactions.
Condensation is a reaction that leads to the emergence of a new carbon-carbon bond, and from two or more relatively simple molecules a new, more complex molecule is formed.
So, in an alkaline medium, two molecules of acetaldehyde form hydroxyaldehyde with twice the number of carbon atoms.
The reaction product containing hydroxyl and aldehyde groups is called aldol (from the words aldehyde and alcohol), and the reaction itself is called aldol condensation, or aldol addition.
Under the action of a base in a carbonyl compound, a proton is cleaved from the α-position and a carbanion (I) is formed, in which the negative charge is delocalized with the participation of the carbonyl group.
The anion (I) is a strong nucleophile (shown in color in the next step of the mechanism) that attaches to the second (non-ionized) molecule of the carbonyl compound. As a result of this interaction, a new C-C bond arises and an intermediate alkoxide ion (II) is formed. In an aqueous medium, this anion is stabilized by splitting off a proton from a water molecule and turns into the final product, the aldol.
The aldol addition reaction is shown using propanal as an example (the molecule that adds to the C=O group of another molecule is highlighted in color); a similar reaction is shown using acetone as an example.
The condensation product, the aldol, is capable of splitting off water to form an α,β-unsaturated carbonyl compound. This usually happens at elevated temperatures. In this case, the reaction as a whole is called croton condensation.
Condensation reactions can also occur in a mixed version, using different carbonyl compounds, and one of them may not contain a CH-acid center, such as formaldehyde and benzaldehyde in the following reactions:
Aldol condensation is a reversible reaction; the reverse process is called aldol cleavage (or retroaldol reaction). Both reactions occur in many biochemical processes.
2. Nucleosides. Hydrolysis of nucleosides. Nucleotides. The structure of mononucleotides that form nucleic acids. Hydrolysis of nucleotides. Ribonucleic and deoxyribonucleic acids (RNA, DNA). The role of hydrogen bonds in the formation of the secondary structure of DNA.
In the chemistry of nucleic acids, the heterocyclic compounds of the pyrimidine and purine series included in their composition are usually called nucleic bases. Nucleic bases as substituents in the heterocycle may contain: either an oxo group, as in uracil and thymine; or an amino group, as in adenine; or both of these groups simultaneously, as in cytosine and guanine.
Nucleic acids differ in their heterocyclic bases: uracil is included only in RNA, and thymine in DNA:
Nucleic bases form a bond at the expense of one of the nitrogen atoms with the anomeric center of pentose (D-ribose or 2-deoxy-D-ribose). This type of bond is analogous to a normal glycosidic bond and is known as an N-glycosidic bond, and the glycosides themselves are known as N-glycosides. In nucleic acid chemistry they are called nucleosides. The composition of natural nucleosides includes pentoses in the furanose form (the carbon atoms in them are numbered with a number with a stroke). The glycosidic bond is carried out with the N-1 nitrogen atom of the pyrimidine and N-9 purine bases.
Natural nucleosides are always β-anomers. Depending on the nature of the carbohydrate residue, ribonucleosides and deoxyribonucleosides are distinguished. For nucleosides, common names are derived from the trivial name of the corresponding nucleic base with the suffixes -idine for pyrimidine and -osine for purine nucleosides.
An exception is the name "thymidine" (rather than deoxythymidine), which is used for thymine deoxyriboside, which is part of DNA. In the rare cases where thymine occurs in RNA, the corresponding nucleoside is called ribothymidine. The three-letter nucleoside symbols differ from the base symbols by the last letter. Single-letter symbols are used only for residues (radicals) of nucleosides in more complex structures. Nucleosides are resistant to hydrolysis in a weakly alkaline medium, but are hydrolyzed in an acidic one. Purine nucleosides are easily hydrolyzed, while pyrimidine ones are more difficult.
Nucleotides are called nucleoside phosphates. Phosphoric acid usually esterifies the alcohol hydroxyl at C-5" or C-3" in a ribose (ribonucleotide) or deoxyribose (deoxyribonucleotide) residue. The general principle of the structure of nucleotides is shown on the example of adenosine phosphates. To link the three components in the nucleotide molecule, ester and N-glycosidic bonds are used. Nucleotides can be considered, on the one hand, as nucleoside esters (phosphates), and on the other hand, as acids (due to the presence of a phosphoric acid residue).
Due to the phosphate residue, nucleotides exhibit the properties of a dibasic acid and under physiological conditions at pH ~ 7 are in a fully ionized state.
For nucleotides, two types of names are used (Table 14.1). One includes the name of the nucleoside, indicating the position of the phosphate residue in it, for example, adenosine-3'-phosphate, uridine-5'-phosphate; the other is constructed by adding -ylic acid to the name of a pyrimidine base, such as 5'-uridylic acid, or a purine base, such as 3'-adenylic acid. Using the one-letter code accepted for nucleosides, 5 "-phosphates are written with the addition of the Latin letter "p" before the nucleoside symbol, 3 "-phosphates after the nucleoside symbol. Adenosine-5 "-phosphate is designated pA, adenosine-3"-phosphate - Ap, etc. These abbreviations are used to record the sequence of nucleotide residues in nucleic acids. In relation to free nucleotides in the biochemical literature, their names are widely used as monophosphates with the reflection of this feature in an abbreviated code, for example, AMP (or AMP) for adenosine-5 "-phosphate, etc. (see Table 14.1).
Cyclophosphates include nucleotides in which one molecule of phosphoric acid simultaneously esterifies two hydroxyl groups of the carbohydrate residue. Almost all cells contain two nucleoside cyclophosphates, adenosine-3",5"-cyclophosphate (cAMP) and guanosine-3",5"-cyclophosphate (cGMP). In polynucleotide chains, nucleotide units are linked through a phosphate group. The phosphate group forms two ester bonds: with C-3" of the previous and C-5" of the subsequent nucleotide units. The backbone of the chain is composed of alternating pentose and phosphate residues, and the heterocyclic bases are "pendant" groups attached to the pentose residues. A nucleotide with a free 5"-OH group is called the 5"-terminal, and a nucleotide with a free 3"-OH group is called the 3"-terminal. The principle of building a chain of RNA is the same as that of DNA, with two exceptions: D-ribose serves as the pentose residue in RNA, and not thymine, but uracil is used in the set of heterocyclic bases. The primary structure of nucleic acids is determined by the sequence of nucleotide units linked by covalent bonds into a continuous polynucleotide chain.
An important characteristic of nucleic acids is the nucleotide composition, i.e. set and quantitative ratio of nucleotide components. The nucleotide composition is established, as a rule, by studying the products of hydrolytic cleavage of nucleic acids. Hydrogen bonds are involved in the formation of the secondary and tertiary structure of the protein, and also connect two strands of DNA to each other.
Nucleosides are much more soluble in water than the parent nitrogenous bases. Like all glycosides, nucleosides are resistant to alkalis, but when heated, they easily undergo acid hydrolysis, breaking the glycosidic bond and forming a base and pentose:
BUT - N \u003d O → CH 2 -CH - COOH
5. Get β-hydroxybutyric acid from ethanal. Specify reaction conditions. What biologically important reactions proceeding by the type of aldol condensation are known to you?
CH 3 - COH + OH - → CH 2 - - COH + H 2 O
CH 3 - COH + CH 2 - - COH → CH 3 - CH - CH 2 - COH → (+ H 2 O, -OH -)
(+ H 2 O, -OH -) → CH 3 - CH - CH 2 - COH
CH 3 - CH - CH 2 - COH + 2OH → CH 3 - CH - CH 2 - COOH +
2Ag + 4NH 3 + H 2 O
Interestingly, the aldol reaction is also used quite often in living organisms. For example, it is included in the sequence of stages of glucose biosynthesis - gluconeogenesis, as well as in the reverse process of glycolysis, which leads to the decomposition of glucose. Similar processes in organisms are catalyzed by special enzymes - aldolases.
The ethanol molecule is not a sufficiently active nucleophile for this reaction. To increase the activity of the electrophilic center (carbonyl carbon with δ+) acid catalysis is used. At the first stage of the reaction, aldehyde (1) interacts with hydrogen chloride at the main center (an oxygen atom with a lone electron pair), forming a cation that exists in the form of two resonance structures (2 and 3). In the carbocation (3), the electrophilic center already has a full positive charge (and not a partial one, as in the starting aldehyde). Thus, the activity of the electrophilic center has increased, and it can interact with a weak nucleophile - an alcohol molecule. A new C-O bond is formed due to the lone electron pair of oxygen, so a positive charge appears on it (4). To stabilize this cation, it is necessary to split off a hydrogen proton. It is taken by the anion Cl - . A molecule of the final reaction product, a hemiacetal, is formed.
By the same mechanism, the further transformation of hemiacetal into acetal occurs:
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These reactions are reversible; in an acidic medium, hemiacetals and acetals are hydrolyzed to the corresponding aldehydes and alcohols. That is why the catalyst in the reactions of their formation is gaseous hydrogen chloride, and not its aqueous solution.
The acetal formation reaction is often used in organic synthesis to protect the aldehyde group from oxidation. After the oxidation reaction, the protection is "removed", i. carry out acid hydrolysis.
Ketones practically do not react with alcohols.
Addition of hydrocyanic acid HCN. This reaction is characteristic of both aldehydes and ketones. Consider it on the example of acetone.
The reaction proceeds in the presence of alkali as a catalyst.
Hydrocyanic acid is a weak acid, with a low degree of dissociation, i.e. poor source of nucleophilic particles (cyanide anions CN -). To activate the nucleophile and use the catalyst:
Further, the reaction proceeds according to the general mechanism of nucleophilic addition:
The nucleophile attacks the electrophilic center of the acetone molecule, the C=O π-bond breaks heterolytically, both of its electrons go to the oxygen atom, so a negative charge (1) appears there, a new C-C bond is formed due to the electrons of the nucleophile. Anion (1) adds a hydrogen proton from a water molecule, forming oxynitrile (2) and a hydroxide anion, which proves that alkali was the catalyst for this reaction.
Cyanhydrins are capable of hydrolysis with the formation of the corresponding oxo compounds and hydrocyanic acid. Some cyanhydrides occur naturally (synthesized by plants). Eating them (pits of plums, cherries, bitter almonds) can lead to poisoning.
Water connection. This reaction is reversible. Its equilibrium is controlled by steric and electronic factors.
Hydrates of most aldehydes and especially ketones are unstable and exist only in solutions. Hydrate of trichloroacetic aldehyde (chloral) is very stable, which is associated with the electron-withdrawing effect of chlorine atoms:
The reduction of ketones leads to the production of secondary alcohols, for example:
Interaction with ammonia and amines. Amines and their derivatives of the X-NH 2 type react with aldehydes and ketones in two stages. First, a nucleophilic addition reaction occurs, the products of which are unstable and split off a water molecule. Therefore, such reactions are characterized as attachment-cleavage.
Consider the reaction mechanism using the example of the interaction of acetaldehyde with ammonia.
Imines are also called Schiff bases.
Imines are intermediates in many enzymatic processes, such as biosynthesis
α-amino acids in the body.
Schiff's bases are easily hydrolyzed by aqueous solutions of mineral acids with the formation of initial products. In the body, hydrolysis of imines occurs in the process of oxidative deamination of α-amino acids.
In addition to ammonia, primary amines (R-NH 2), hydroxylamine (NH 2 -OH), hydrazine (NH 2 -NH 2), phenylhydrazine (C 6 H 5 -NH-NH 2 ), semicarbazide (NH 2 -NH-CO-NH 2):
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All these derivatives are crystalline compounds with clear melting points, so their preparation can be used to identify aldehydes and ketones. And since these derivatives, like imines, are capable of hydrolysis with the formation of starting compounds, these reactions can also be used to isolate oxo compounds from mixtures with other compounds.
Through the stage of formation of aldimine during the interaction of pyridoxal phosphate (see p. 195) and α-amino acids, the reaction of transamination of protein α-amino acids (the main pathway for the biosynthesis of α-amino acids) proceeds.
Aldol condensation reaction characteristic only for aldehydes, in the structure of which there is an α-CH-acid center. The reaction is catalyzed by alkalis.
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Condensation is a reaction that leads to the complication of the carbon skeleton and the emergence of a new carbon-carbon bond, while two or more relatively simple molecules form a new, more complex molecule.
This reaction starts at the CH-acid center of the aldehyde:
The resulting CH-acid anion is stabilized by p,π-conjugation. It is a nucleophile with respect to another aldehyde molecule, and then the reaction proceeds according to the general mechanism of nucleophilic addition:
As a result of the reaction, a compound is formed, which is ald egyd and alcohol (alcog ol) is an aldol.
Aldol condensation also occurs in biological systems. For example, the biosynthesis of citric acid, neuraminic acid proceeds by the mechanism of aldol condensation.
Those aldehydes that do not have hydrogen atoms at the α-carbon atom, i.e. do not show CH-acid properties, in the presence of alkalis they react differently. They are characterized Cannizzaro reaction. Another name for this reaction is disproportionation, or oxidoreduction reaction: one aldehyde molecule is oxidized while the other is reduced.
The Cannizzaro reaction is typical, for example, for benzaldehyde:
In the case of formaldehyde, the Cannizzaro reaction proceeds in an aqueous solution without a catalyst:
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Formic acid accumulates in aqueous solutions of formaldehyde, so these solutions are acidic.
Due to the CH-acid center, halogenation reactions, for example, the so-called iodoform reaction:
This reaction is given by all oxo compounds in the structure of which there is a group
Those. acetaldehyde and all methyl ketones (acetone, methyl ethyl ketone, methyl propyl ketone, etc.). The resulting iodoform has a characteristic "pharmacy" odor, and at sufficient concentration it precipitates as a yellowish precipitate.
The iodoform reaction is used as a qualitative reaction to distinguish acetaldehyde from all other aldehydes. In medical practice, the iodoform reaction is used to detect acetone in the urine of diabetic patients.
Oxidation reactions of aldehydes. Aldehydes oxidize very easily. Even such weak oxidizing agents as an ammonia solution of silver hydroxide (Tollens' reagent) and copper (II) hydroxide oxidize aldehydes to the corresponding carboxylic acids. Both of these reactions are used as qualitative ones for the detection of the aldehyde group.
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For aldehydes and ketones, nucleophilic addition reactions are most characteristic A N .
General description of the nucleophilic addition mechanismA N
The ease of nucleophilic attack on the carbon atom of the carbonyl group of an aldehyde or ketone depends on the magnitude of the partial
positive charge on the carbon atom, its spatial availability and acid-base properties of the medium.
Taking into account the electronic effects of the groups associated with the carbonyl carbon atom, the value of the partial positive charge δ+ on it in aldehydes and ketones decreases in the following series:
The spatial availability of the carbonyl carbon atom decreases when hydrogen is replaced by bulkier organic radicals, so aldehydes are more reactive than ketones.
General scheme of nucleophilic addition reactions A N to the carbonyl group involves a nucleophilic attack on the carbonyl carbon followed by the addition of an electrophile to the oxygen atom.
In an acidic environment, the activity of the carbonyl group, as a rule, increases, since due to the protonation of the oxygen atom, a positive charge arises on the carbon atom. Acid catalysis is usually used when the attacking nucleophile has low activity.
According to the above mechanism, a number of important reactions of aldehydes and ketones are carried out.
Many reactions characteristic of aldehydes and ketones occur in the body, these reactions are presented in the subsequent sections of the textbook. This chapter will discuss the most important reactions of aldehydes and ketones, which are summarized in Scheme 5.2.
addition of alcohols. Alcohols, when interacting with aldehydes, easily form hemiacetals. Hemiacetals are not usually isolated due to their instability. With an excess of alcohol in an acidic environment, hemiacetals turn into acetals.
The use of an acid catalyst in the conversion of hemiacetal to acetal is clear from the reaction mechanism below. The central place in it is occupied by the formation of a carbocation (I), stabilized due to the participation of the lone pair of electrons of the neighboring oxygen atom (+M effect of the C 2 H 5 O group).
The reactions of formation of hemiacetals and acetals are reversible; therefore, acetals and hemiacetals are easily hydrolyzed by excess water in an acidic medium. In an alkaline environment, hemiacetals are stable, since the alkoxidion is a more difficult leaving group than the hydroxide ion.
The formation of acetals is often used as a temporary protection of the aldehyde group.
Water connection. Adding water to a carbonyl group - hydration- reversible reaction. The degree of hydration of an aldehyde or ketone in an aqueous solution depends on the structure of the substrate.
The product of hydration, as a rule, cannot be isolated by distillation in a free form, since it decomposes into its original components. Formaldehyde in an aqueous solution is hydrated by more than 99.9%, acetaldehyde is approximately half, and acetone is practically not hydrated.
Formaldehyde (formaldehyde) has the ability to coagulate proteins. Its 40% aqueous solution, called formalin, used in medicine as a disinfectant and preservative of anatomical preparations.
Trichloroacetic aldehyde (chloral) is fully hydrated. The electron-withdrawing trichloromethyl group stabilizes chloral hydrate to such an extent that this crystalline substance splits off water only during distillation in the presence of dehydrating substances - sulfuric acid, etc.
The pharmacological effect of CC13CH(OH)2 chloral hydrate is based on the specific action of the aldehyde group on the body, which determines the disinfectant properties. Halogen atoms enhance its action, and hydration of the carbonyl group reduces the toxicity of the substance as a whole.
Addition of amines and their derivatives. Amines and other nitrogen-containing compounds of the general formula NH2X (X = R, NHR) react with aldehydes and ketones in two stages. First, nucleophilic addition products are formed, which then, due to instability, split off water. In this regard, this process is generally classified as a reaction attachment-detachment.
In the case of primary amines, substituted imines(also called Schiff bases).
Imines are intermediates in many enzymatic processes. The preparation of imines proceeds through the formation of amino alcohols, which are relatively stable, for example, in the reaction of formaldehyde with α-amino acids (see 12.1.4).
Imines are intermediates in the production of amines from aldehydes and ketones by reductive amination. This general method consists in the reduction of a mixture of carbonyl compound with ammonia (or amine). The process proceeds according to the addition-cleavage scheme with the formation of an imine, which is then reduced to an amine.
When aldehydes and ketones react with hydrazine derivatives, hydrazones. This reaction can be used to isolate aldehydes and ketones from mixtures and their chromatographic identification.
Schiff's bases and other similar compounds are easily hydrolyzed by aqueous solutions of mineral acids to form the starting products.
In most cases, the reactions of aldehydes and ketones with nitrogenous bases require acid catalysis, which accelerates the dehydration of the addition product. However, if the acidity of the medium is increased too much, the reaction will slow down as a result of the conversion of the nitrogenous base into the non-reactive conjugate acid XNH3+.
polymerization reactions. These reactions are characteristic mainly of aldehydes. When heated with mineral acids, aldehyde polymers decompose into the starting products.
The formation of polymers can be viewed as the result of a nucleophilic attack by an oxygen atom of one aldehyde molecule on the carbonyl carbon atom of another molecule. So, when formalin is standing, a polymer of formaldehyde, paraform, precipitates in the form of a white precipitate.
Let's think about what can happen to this molecule in an aqueous solution. First, let's give this molecule the right name. The longest chain consists of three atoms, the root of the name is "prop". So three atoms in the longest chain means prop. All bonds are single, so it's propane. Signed: propane. Of the three carbon atoms of the main chain, the second is connected to the methyl group and, in addition, to the bromine atom. It means "2-bromine". I'll write down: "2-bromo-2-methyl." Although no, it won't. Sloppy came out, I need more space. So, this substance will be called as follows. Let's write it down: 2-bromo-2-methylpropane. How does this substance react with water? In this case, water is a nucleophile. There are these electron pairs here. In addition, the oxygen atom has a high electronegativity. The nucleophilic properties are not as strong as the hydroxide anion that was in the Sn2 reactions, but they are still there. It is a weak nucleophile. Water is a weak nucleophile. It is drawn to the positively charged nuclei of atoms, because the oxygen atom has a partial negative charge due to its electronegativity. And here is a partial positive charge. Even if this is not a full charge, but only a partial one, it still means a desire to give up an electron. It is a weak nucleophile. Weak nucleophile. There will be a few more videos about this type of reactions and I will explain when reactions of this type take place, and when reactions of the Sn2 type take place. But let's go back to our example. The molecule contains a bromine atom. It has a high electronegativity and becomes stable by gaining a negative charge. The presence of a charge degrades stability. But it will have 8 valence electrons. Slowly and gradually, the bromine atom pulls the electron density away from the carbon. It pulls electrons towards itself due to its electronegativity. Look at its valence electrons. One of them forms a bond with a carbon atom. And here is the second electron of this bond. Plus 6 more valence electrons. 1, 2, 3, 4, 5, 6, 7. 7 valence electrons. Imagine that bromine pulls an electron from a carbon atom. Let me show you for clarity. This electron will be here. He will be attracted to this place. Again, this is a slow process, but it is possible. And, since the process is slow, an equilibrium occurs. In the course of this intramolecular reaction, an equilibrium occurs. What will happen here? A carbon atom, a methyl group behind it, a methyl group in front, and also another group on top. And the bromine is split off. I'll draw it here. The connection is broken. Here are his original valence electrons: 1, 2, 3, 4, 5, 6, 7. Another electron belonged to the carbon atom, but bromine took it with him. As a result, naturally, a negative charge arose. Carbon, having lost an electron, receives a positive charge. Now let's add an oxygen atom here. Although, no, not oxygen, let's add a water molecule. Here is a water molecule. I'll draw a water molecule. Although it is a weak nucleophile, carbon really needs an electron. It is a tertiary carbocation that is fairly stable. Otherwise, nothing would have happened. If this atom were primary or would not be associated with others at all, the transformation into a carbocation would be extremely difficult. However, it is tertiary and stable, except that the charge spoils everything. He needs an electron. And he will borrow this electron from a water molecule. Water will give up one electron, for example, this one, sharing with a carbon atom. The nucleophile is attracted to the positively charged carbon nucleus. And what's next? At this stage, the reaction is greatly accelerated. On the left is a fairly stable situation, and therefore the balance. But now the reaction is accelerating and the arrow goes in one direction. Like this. It turns out something like that. Here is the original carbon atom with substituents. There's a methyl group behind him and another in front of him. Water comes into play. Here is an oxygen and two hydrogens. The oxygen atom has its own electrons, which I will show in different colors. Here are the electrons. One of the electrons of this pair is donated to carbon. Now he is here. There is a connection. The electron pair formed a bond. Water had a neutral charge, but by giving up one of its electrons, it acquires a positive charge, while turning into a cation. The charge is positive. And at that moment, another water molecule or even bromine can take one of the hydrogen atoms. In this case, the electron will return to oxygen. I'd rather draw it. For example, there is another water molecule. A lot of them. Here is another water molecule. I'll picture it here. This molecule is reacting. Everything happens at the same time. Oxygen donates one of its electrons to a hydrogen atom. At the same time, an electron from hydrogen returns to its former owner. So oxygen returns an electron. What will be the result? We draw the original molecule again. Let's draw the original molecule. A methyl group at the back, a methyl group at the front, and another one at the top. And, of course, do not forget about oxygen with one hydrogen atom, because the bond with the second is broken. And here is the bromide anion and its 8 valence electrons. And the hydronium ion. This oxygen atom donated an electron to hydrogen, forming a bond with this atom. The valence electrons of this oxygen atom will look like this. These two: one, two. Another electron is involved in bonding with carbon. I'll show you in a different color. This electron ends up right here. Another one is also in the link, this one. I'll explain now. As part of a bond with a hydrogen atom. It's a bond to a hydrogen atom, but it's not a hydrogen bond. I hope you understand. One of the valence electrons is now in the bond. Here is another valence electron. This electron is bonded to a hydrogen atom. Now he is here. And another one came back from the hydrogen atom, here it is. It has 6 valence electrons again. Let's recalculate: 1, 2, 3, 4, 5, 6. This is how 2-bromo-2-methylpropane interacts with a weak nucleophile. I'll talk more about different nucleophiles. What happened as a result? The longest chain is 3 atoms. The root of the name will still be "prop". We have not yet talked about the hydroxyl group, but its very presence means that we have alcohol in front of us. The suffix "anol" is used in the names of alcohols. Now we will write down this name - propanol. Propanol. It is necessary to indicate at which atom the hydroxyl group is located. It's propanol-2. Good. Propanol-2. Do not forget also about the presence of a methyl group. This is 2-methylpropanol-2. The mechanism of this reaction is called Sn1. I think you understand why Sn1 and not Sn2. I'll write it down. Sn1 reaction. S stands for "replacement". I will sign again. n stands for "nucleophilic", as we already know. Nucleophilic. The reaction involved a weak nucleophile, namely water. The number 1 means the slowest. That is, the limiting stage of this mechanism occurs with the participation of only one of the reagents. In the very first rate-limiting step, bromine takes an electron from carbon. Water is not involved in this. The rate of the Sn2 reaction is determined by both reagents, but here only one. That is why it is called Sn1. See you! Subtitles by the Amara.org community
