Baeyer-Villiger Reaction
Reaction mechanism
Peracid is first nucleophilic addition with carbonyl , and then an hydrocarbonyl on the ketone carbonyl group migrates with a pair of electrons to the oxygen atom in the -O-O-group directly connected to the carbonyl carbon atom, and O-O bond heterofracting occurs at the same time. Therefore, this is a rearrangement reaction
has optically active 3---phenylbutanone and peracid reaction. The configuration of the chiral carbon atom of the rearrangement product remains unchanged, indicating that the reaction belongs to the intramolecular rearrangement :
htm When l1 asymmetric ketone oxidation, both groups can migrate in the rearrangement step, but there is still a certain selectivity. According to the migration ability, the order is:
aldehyde oxidation mechanism is similar to this, but the migratory hydrogen negative ion is migrated to obtain carboxylic acid .
reaction example
ketone compounds are oxidized with peracids such as peracetic acid , peroxybenzoic acid, m-chlorperoxybenzoic acid or trifluoroperacetic acid , etc., and an oxygen atom can be inserted next to the carbonyl group to generate the corresponding ester, among which trifluoroperacetic acid is the best oxidant. This type of oxidant is characterized by a fast reaction rate, generally between 10 and 40℃, and a high yield.
Beckmann Rearrangement reaction
oxime is rearranged under the action of acids such as sulfuric acid, polyphosphoric acid, and phosphorus pentachloride , phosphorus trichloride , benzenesulfonyl chloride, thionyl chloride, etc., to produce corresponding substituted amides, such as cyclohexanone oxime rearrangement under sulfuric acid to generate caprolactam :
reaction mechanism
Under the action of acid, the oxime first protonated , and then removed a molecule of water. At the same time, the group in reverse position with hydroxyl migrated to the electron-deficient nitrogen atom, and the formed carbo-positive ion reacts with water to obtain amide .
Migration group If it is a chiral carbon atom, its configuration remains unchanged before and after migration, for example:
Reaction example
Cannizzaro When the reaction
When the aldehydes of α have no active hydrogen and concentrated NaOH or KOH water or alcohol solution interact, no aldehyde condensation or resinization occurs, and a disproportionation reaction occurs to form a mixture of acids (salts) and alcohols that are equivalent to the aldehydes. The characteristic of this reaction is that the aldehyde itself undergoes oxidation and reduction at the same time. One molecule is oxidized to an acid salt, and the other molecule is reduced to an alcohol:
fatty aldehyde , only formaldehyde and aldehydes with a tertiary carbon atom connected to the carbonyl group will occur. Other aldehydes and strong alkali liquid will undergo aldol condensation or further become resin-like substances.
aldehyde and formaldehyde with α-active hydrogen atom first undergo hydroxyaldehyde condensation reaction to obtain β-hydroxyaldehyde without α-active hydrogen atoms, and then cross-cannizzaro reaction with formaldehyde, such as acetaldehyde and formaldehyde reaction to obtain pentaerythritol:
Reaction mechanism
aldehyde is first nucleophilic addition to hydroxide negative ions to obtain negative ion , and then the hydrogen on the carbon carries a pair of electrons to the carbonyl carbon atom of another molecule in the form of hydrogen negative ions.
reaction example
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Claisen ester condensation reaction
esters containing α-hydrogen undergo condensation under the action of alkaline condensation agents such as sodium alkoxide, and lose one molecule of alcohol to obtain β-ketoate. For example, 2 molecules of ethyl acetate condensed under the action of metal sodium and a small amount of ethanol to obtain ethyl acetate . The lactone condensation of
dicarboxylic acid ester see Dieckmann condensation reaction.
Reaction mechanism
ethyl acetate has very weak α-hydroacidity (pKa-24.5), and sodium ethyl ethyl is a relatively weak base (pKa~15.9 of ethanol). Therefore, the negative ions formed by the action of ethyl acetate and sodium ethyl ethyl olefin are very few in the equilibrium system. However, since the final product ethyl acetoacetate is a relatively strong acid, it can interact with sodium ethyl oxide to form stable negative ions, thereby moving the equilibrium towards the product. Therefore, although the negative ion concentration of ethyl acetate in the reaction system is very low, it continues to react once it is formed, and the reaction can still be completed smoothly.
The commonly used alkaline condensants in addition to sodium ethylate, there are also potassium tert-butoxide , sodium tert-butoxide, potassium hydride , sodium hydride , sodium triphenylmethyl, lithium diisopropylamide (LDA) and Grignard reagents.
Reaction example
If there is only one hydrogen atom on the α-carbon of the ester, it is difficult to form negative ions with sodium ethyl ethyl . It is necessary to use a stronger base to turn the ester into negative ions. For example, ethyl isobutyrate can be condensed under the action of sodium triphenylmethyl, but cannot react under the action of sodium ethylate: two different esters can also be ester condensation. In theory, four different products can be obtained, called mixed ester condensation, which is not very meaningful in preparation. If one of the ester molecules has neither an α-hydrogen atoms nor an alkoxycarbonyl group is more active, only one condensation product is generated. Such as benzoate , formate, oxalate, carbonate , etc. When reacting with other α-hydrogen atoms, only one condensation product is produced.
In fact, this reaction is not limited to the condensation of the esters themselves. Both esters and compounds containing active methylene can undergo such a condensation reaction. This reaction can be represented by the following general formula:
Claisen—Schmidt Reaction
An aldehyde without α-hydrogen atom and an aliphatic aldehyde or ketone with α-hydrogen atom condensation reaction occurs in the presence of dilute sodium hydroxide aqueous solution or alcohol solution, and water loss is obtained to obtain α, β-unsaturated aldehyde or ketone:
Reaction mechanism
Reaction example
Claisen Rearrange
Allylaryl ether can be rearranged at high temperature (200°C) to generate allylphenol.
When the two ortho positions of the allyl aryl ether are not full by substituents, rearrangement mainly obtains ortho products. When both ortho positions are occupied by substituents, rearrangement obtains para-products. Such rearrangement reactions do not occur when both the alignment and the adjacent position are full.
cross-reaction experiment proves that Claisen rearrangement is the rearrangement of within the molecule of . Allyl ether labeled with g-carbon 14C is rearranged. After the rearrangement, the g-carbon atom is connected to benzene ring , and carbon-carbon double bond is displaced. The arylallyl phenol, which is substituted with both ortho-positions, is still connected to the benzene ring after rearrangement.
reaction mechanism
Claisen Rearrangement is a synergistic reaction, and a cyclic transition state is passed in the middle, so the electron effect of the substituents on the aromatic ring has no effect on the rearrangement.
rearranged from allylaryl ether to orthoallyl phenol undergoes a [3,3]s migration and a tautomer from ketone to enol formula; allylaryl phenol with both ortho-positions occupied by substituents is first moved through [3,3]s to ortho-positions (Claisen rearranged ). Since the ortho-position has been occupied by substituents, tautomer cannot occur. Then another [3,3]s migration (Cope rearranged ) occurs to the para-position, and then the para-allithophe is obtained through tautomer. When the allyl aryl ether substituted by
is rearranged, regardless of whether the original allyl double bond is Z-configuration or E-configuration, the configuration of the new double bond after rearrangement is E-type (trans) . This is because the six-circular transition state passed through the rearrangement reaction has the stable chair-type conformation .
Reaction Example
Claisen Rearrangement is universal. In ether compounds, if there is a structure in which an allyloxy group is connected to carbon and carbon, it is possible to occur.
Favorskii Rearrangement
a-halogenated ketone is heated and rearranged in aqueous sodium hydroxide to generate carboxylic acids containing the same number of carbon atoms; if it is a cyclic a-halogenated ketone, it will cause the ring to shrink.
If you use an alcohol solution of sodium in , you will get carboxylic acid ester:
This method can be used to synthesize four-membered rings with higher tension.
Reaction mechanism
Reaction example
Fries Rearrangement
Fries Rearrangement
phenolic ester is heated in the presence of Lewis acid, and an acyl rearrangement reaction can occur to generate a mixture of o-hydroxyl and para-hydroxyarosterone. The rearrangement can be performed in solvents such as nitrobenzene , nitromethane , or can be performed directly without the solvent. The ratio of para-parameter products depends on the structure of the phenolic ester, reaction conditions, catalyst, etc. For example, when catalyzed with polyphosphate , it mainly generates the para-local rearrangement product, and when catalyzed with titanium tetrachloride , it mainly generates the ortho-local rearrangement product. The reaction temperature has a greater impact on the ratio of ortho- and para-position products. Generally speaking, rearrangement at low temperature (such as room temperature) is conducive to forming para-position isomer products (kinetic control), and rearrangement at high temperature iso-position iso-position isomer products (thermodynamic control).
Reaction mechanism
Reaction example
Hofmann rearrangement (degradation)
amide treated with bromine (or chlorine) under alkaline conditions and converted into primary amine :
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Reaction mechanism
Reaction example
Knoevenagel reaction
Knoevenagel reaction
Compound containing active methylene and aldehydes or ketones are condensed in the presence of weakly basic catalysts (ammonia, primary amine, secondary amine, pyridine and other organic bases) to obtain a,b-unsaturated compound.
Reaction mechanism
Reaction example
Reaction example
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Gabriel Synthesis method
phthalimide and potassium hydroxide are converted into phthalimide salt. This salt reacts with haloalkyl to form N-alkyl phthalimide, and then hydrolyzes under acidic or alkaline conditions to obtain primary amine and phthalic acid. This is a method for to prepare pure primary amine .
hydrolysis is difficult in some cases, and can be replaced by hydrazine dehydration of :
Reaction mechanism
phthalimide salt and halogenated alkyl are nucleophilic substitution reactions, and the hydrolysis process of the substitution reaction products is similar to the hydrolysis of amides.
Mannich reaction
aldehydes and ketones containing a-active hydrogen react with formaldehyde and amines (primary amine, secondary amine or ammonia). As a result, an a-active hydrogen is replaced by amine methyl . This reaction is also called amine methylation reaction, and the obtained product is called Mannich base.
Reaction mechanism
Reaction example
Oppenauer Oxidation
secondary alcohol under the action of tert-butanol or aluminum isopropoxide and acetone , oxidation becomes the corresponding ketone, while acetone is reduced to isopropoxide . This reaction is equivalent to the reverse reaction of the Meerwein-Ponndorf reaction.
reaction mechanism
reaction example
Pinacol-PinacoloneRearrangement Rearrangement Rearrangement
When the pellet alcohols are heated and dehydrated in the presence of dilute H2SO4, a special internal rearrangement reaction occurs to generate pelletketone. If hydrochloric acid, oxalic acid, I2/CH3COOH, CH3COOH and other dehydration-transposition agents are used to replace H2SO4, the same outcome can be obtained:
Reaction mechanism
The key to the reaction is to generate carbohydrate positive ion :
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Reaction Example
Reformatsky reaction
aldehyde or ketone reacts with a-halogenated ester and zinc in an inert solvent , and after hydrolysis, b-hydroxy acid ester is obtained.
Reaction mechanism
First, the reaction of a-halogenated acid ester and zinc to generate intermediate Organic zinc reagent , and then the organic zinc reagent is added to the carbonyl group of aldehyde ketone, and then hydrolyzed:
Reaction Example
Reimer-Tiemann reaction
Hot and chloroform are heated in an alkaline solution to generate ortho- and para-hydroxybenzoic acid. This reaction can also be performed by heterocyclic compounds such as quinoline , pyrrole , indene, etc.
The commonly used alkali solution is sodium hydroxide, potassium carbonate , and sodium carbonate aqueous solution. The product is generally the ortho-position of , and a small amount is the para-position product. If both neighbors are occupied, they enter the alignment. Compounds that cannot react in water can be performed in pyridine. At this time, only the ortho- product is obtained.
Reaction mechanism
First, chloroform forms dichlorocarbene , it is an electron-deficient electrophile reagent, which undergoes electrophilic substitution with the negative ions of phenol (II) to form intermediate (II), (III) and (III) obtain a proton from the solvent or reaction system, while the α-hydrogen of the carbonyl leaves to form (IV) or (V), and (V) obtains aldehyde through hydrolysis.
Reaction Examples
1 phenolic hydroxyl group has a substituent or para-position, by-product 2,2- or 4,4-disubstituted cyclohexadiene is often produced. For example:
Sandmeyer reaction
diazo salt cumber chloride or or cumber bromide to obtain chlorine or bromine aromatic hydrocarbon:
This reaction can also be achieved with fresh copper powder and HCl or HBr (Gattermann reaction).
Reaction mechanism
Reaction example
Wittig reaction
Wittig The reagent undergoes nucleophilic addition reaction with the carbonyl groups of aldehydes and ketones, forming olefin :
Reaction mechanism
Reaction example
Wagner-Meerwein Rearrange
When the b-carbon atom of the alcohol hydroxyl group is a secondary carbon atom (secondary carbon atom) or tertiary carbon atom (third-order carbon atom), in the acid-catalyzed dehydration reaction, a rearrangement reaction often occurs to obtain the rearrangement product:
Reaction mechanism
