Reactions of nucleophilic substitution, nucleophilic addition. The electrophilic addition reaction includes several stages. Hydrocarbons are characterized by nucleophilic addition reactions
Due to the higher electronegativity of the carbon atom, in the sp hybridization state, compared to the carbon atom in the sp 2 hybridization state, alkynes, unlike alkenes, can enter into nucleophilic addition reactions.
Nucleophilic addition reactions (type reactions Ad N ) are called addition reactions in which the attacking particle is a nucleophile.
An example of nucleophilic addition is the addition of alcohols to alkynes in the presence of an alkali ( Favorsky's reaction , 1887):
The reaction mechanism of nucleophilic addition to a triple bond includes the following steps:
1. At the first stage, according to the acid-base reaction, an alcoholate anion or an alkoxide ion is formed, which is a strong base:
2. In the second stage, the alkoxide ion is added to the alkyne. This step is the rate limiting step. Moreover, if the alkyne is unsymmetrical, then the addition proceeds in accordance with the Markovnikov rule, namely: the anion, being a nucleophilic particle, is attached to the least hydrogenated carbon atom:
3. At the third stage, the resulting carbanion splits off a proton from another alcohol molecule, which leads to the formation of an ether and the regeneration of the alcoholate anion:
The resulting vinyl ester can add another molecule of alcohol. This forms a compound called an acetal:
Vinylation.
The formation of vinyl esters from acetylene and alcohols is an example of the so-called vinylation reactions. These reactions include:
1. Addition of hydrogen chloride to acetylene:
2. Attachment of hydrocyanic acid to acetylene in the presence of copper salts:
3. Addition of acetic acid to acetylene in the presence of phosphoric acid:
hydrogenation
Under conditions of heterogeneous catalysis, alkynes add hydrogen similarly to alkenes:
The first stage of hydrogenation is more exothermic (it proceeds with a large release of heat) than the second, which is due to the greater energy reserve in acetylene than in ethylene:
As heterogeneous catalysts, as in the hydrogenation of alkenes, platinum, palladium, and nickel are used. Moreover, the hydrogenation of the alkene proceeds much faster than the hydrogenation of the alkyne. To slow down the process of alkene hydrogenation, so-called "poisoned" catalysts are used. The slowing down of the alkene hydrogenation rate is achieved by adding lead oxide or acetate to palladium. Hydrogenation on palladium with the addition of lead salts leads to the formation cis-olefin. Hydrogenation by the action of metallic sodium in liquid ammonia leads to the formation trance- olefin.
Oxidation.
Alkynes, like alkenes, are oxidized at the site of the triple bond. Oxidation proceeds under harsh conditions with a complete cleavage of the triple bond and the formation of carboxylic acids. Similar to the exhaustive oxidation of olefins. As oxidizing agents, potassium permanganate is used when heated or ozone:
It should be noted that carbon dioxide is one of the oxidation products in the oxidation of terminal alkenes and alkynes. Its release can be observed visually and thus it is possible to distinguish terminal from internal unsaturated compounds. When the latter are oxidized, no carbon dioxide emission will be observed.
Polymerization.
Acetylene hydrocarbons are capable of polymerization in several directions:
1. Cyclotrimerization of acetylenic hydrocarbons using activated carbon ( according to Zelinsky ) or a complex catalyst of nickel dicarbonyl and an organophosphorus compound ( according to Reppe ). In particular, benzene is obtained from acetylene:
In the presence of nickel cyanide, acetylene undergoes cyclotetramerization:
In the presence of copper salts, linear oligomerization of acetylene occurs with the formation of vinylacetylene and divinylacetylene:
In addition, alkynes are capable of polymerization with the formation of conjugated polyenes:
substitution reactions.
Metal plating
Under the action of very strong bases, alkynes having a terminal triple bond are completely ionized and form salts, which are called acetylenides. Acetylene reacts like a stronger acid and displaces the weaker acid from its salt:
Acetylides of heavy metals, in particular copper, silver, mercury, are explosives.
The alkynide anions (or ions) that make up the acetylenides are strong nucleophiles. This property has found application in organic synthesis for the preparation of acetylene homologues using haloalkyls.
We have the HX reagent, which decomposes
A nucleophilic particle attacks, forming an anion.
Then there is a rapid attachment to the anion of a positively charged particle H + , a reaction product is formed.
Electron-withdrawing substituents, pulling the electron density onto themselves, increase the carbon atom and the rate of the reaction. Therefore, chloroacetic aldehyde is more active than acetic.
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In ketones, unlike aldehydes, two radicals are associated with the ketone group, which reduce the activity of the molecule. Therefore, ketones are less active than aldehydes. Aryls are even stronger electron donors, so aromatic aldehydes and ketones are less active than aliphatic ones. Carbonyl compounds can be arranged in order of decreasing activity:
The reactivity of the carbonyl group is also affected by the size of the radical, since a large size of R makes it difficult for the reagent to access the carbon atom:
Based on the mechanism, we give examples of nucleophilic addition reactions:
addition of hydrogen. Primary alcohols are obtained from aldehydes, and secondary alcohols are obtained from ketones:
Addition of hydrogen cyanide (HCN). This produces cyanohydrins (hydroxynitriles):
The addition of sodium hydrosulfite (NaHSO 3), in this case, hydrosulfite compounds are obtained:
These substances easily decompose when heated with dilute acids, releasing pure aldehydes and ketones.
Addition of organomagnesium compounds (MOS) (Grignard reagent):
Conclusion: from formic aldehyde and any MOS are obtained primary alcohols, from other aldehydes and any MOS - secondary alcohols, and from ketones and any MOS - tertiary alcohols. In order to obtain, for example, butanol-1 - the primary alcohol CH 3 - CH 2 - CH 2 - CH 2 OH, it is necessary to take formic aldehyde and CH 3 - CH 2 - CH 2 - MgJ.
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. Nucleophilic properties are not as strong as those of the hydroxide anion, which 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. Here'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. Fine. 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
Nucleophilic addition reactions - addition reactions in which the attack at the initial stage is carried out by a nucleophile - a particle that is negatively charged or has a free electron pair.
In the final step, the resulting carbanion undergoes electrophilic attack.
Despite the commonality of the mechanism, addition reactions are distinguished by carbon-carbon and carbon-heteroatom bonds.
Nucleophilic addition reactions are more common for triple bonds than for double bonds.
Nucleophilic addition reactions at carbon-carbon bonds
Multiple bond nucleophilic addition is usually a two-step Ad N 2 process - a bimolecular nucleophilic addition reaction:
Nucleophilic addition at the C=C bond is quite rare, and, as a rule, if the compound contains electron-withdrawing substituents. The Michael reaction is of the greatest importance in this class:
Attachment at the triple bond is similar to attachment at the C=C bond:
Nucleophilic addition reactions at a carbon-heteroatom bond Nucleophilic addition at a multiple carbon-heteroatom bond has an Ad N 2 mechanism
As a rule, the rate-limiting stage of the process is a nucleophilic attack, electrophilic addition occurs quickly.
Sometimes the addition products enter into an elimination reaction, thereby collectively giving a substitution reaction:
Nucleophilic addition at the C=O bond is very common, which is of great practical, industrial and laboratory importance.
Acylation of unsaturated ketones
This method involves treating the substrate with an aldehyde and cyanide ion in a polar aprotic solvent such as DMF or Me 2 SO. This method is applicable to a,b-unsaturated ketones, esters and nitriles.
Condensation of esters with ketones
When esters are condensed with ketones, the yield of α-diketone is low, about 40%, this is due to the side reaction of ester self-condensation.
Hydrolysis of nitro compounds (Nef reaction)
The Nef reaction is a reaction of acid hydrolysis of nitro compounds with the formation of carbonyl compounds. Discovered in 1892 by the Russian chemist M.I. Konovalov and J. Nef in 1894. The Nef reaction consists in the hydrolysis of acyl forms of nitro compounds (nitronic acids), and therefore primary and secondary aliphatic and alicyclic nitro compounds can enter into it.
The Nef reaction makes it possible to obtain dicarbonyl compounds with a yield of up to 80-85%. To do this, the reaction is carried out at pH=1, since in a less acidic medium, nitronic acids isomerize back into a nitro compound with a decrease in the conversion of the nitro compound, and in a more acidic one, the formation of by-products increases. This reaction is carried out at t=0-5 0 C .
Interaction of ketones with acid chlorides in the presence of piperidine
Acid chlorides are easily reduced to primary alcohols under the action of lithium aluminum hydride. But if the enamine obtained from the ketone under the action of piperidine is reacted with acid chlorides, then after the hydrolysis of the initially obtained salt, b-diketones are formed.
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.