Is the formation of imine a reversible reaction?
Formation of an imine--from an amine and an aldehyde--is a reversible reaction which operates under thermodynamic control such that the formation of kinetically competitive intermediates are, in the fullness of time, replaced by the thermodynamically most stable product(s).
What is the mechanism of imine formation?
As can be observed from the mechanism, imine formation is a reversible, acid-catalyzed process that begins with the nucleophilic addition of the primary amine to the carbonyl carbon, followed by transfer of a proton from nitrogen to oxygen to yield a neutral amino alcohol or also known as carbinolamine.
What are the imine reactions?
Imine reactions. Imines are susceptible to hydrolysis to the corresponding amine and carbonyl compound. An imine is reduced in reductive amination. An imine reacts with an amine to an aminal, see for example the synthesis of cucurbituril. An imine reacts with dienes in the Aza Diels-Alder reaction to a tetrahydropyridine.
How is an imine formed from RNH2?
With the general reaction shown above, it can be seen that an imine is formed by replacing the O of the C=O group with N-R of the RNH 2 while the lost O is combined with the H atoms of the primary amine, forming H 2 O.
How can I reverse the formation of my imine?
The reverse of imine formation is called imine hydrolysis, yielding the corresponding amine and carbonyl containing compound (aldehyde or ketone). In this process, the imine undergoes an addition of water.
Is imine hydrolysis reversible?
Reversibility of Imine Forming Reactions Imines can be hydrolyzed back to the corresponding 1o amine under acidic conditions.
What kind of reaction is imine formation?
Mechanism of Imine Formation Imine formation is a reversible process that starts with the nucleophilic addition of a primary amine to the carbonyl group of an aldehyde or ketone. Next, a proton transfer forms a neutral amino alcohol called a carbinolamine.
How is an imine formed?
Imines are formed when any primary amine reacts with an aldehyde or ketone under appropriate conditions. Imine formation requires an acid catalyst, otherwise the reaction is very slow. The acid is needed for the elimination of water.
Why is imine synthesis important?
The imine formation is one of the most important reactions in organic and medicinal chemistry [2]. For instance, imines are used as versatile components in the asymmetric synthesis of -aminonitriles [3], preparation of secondary amines by hydrogenation [4], and in cycloaddition reactions [5].
How do imines react?
Imines are widely used as intermediates in the synthesis of heterocycles. Aromatic imines react with an enol ether to a quinoline in the Povarov reaction. Imines react, thermally, with ketenes in [2+2] cycloadditions to form β-lactams in the Staudinger synthesis. Several variants have been described.
Is imine formation a condensation reaction?
The synthesis of imines is simple enough in most cases. A primary amine is added to a solution an aldehyde or ketone, water (H2O) is liberated and the corresponding imine is formed. You may recall that a reaction that forms water can be referred to as a condensation reaction. This is a classic example.
What makes an imine stable?
Stability is mostly substrate dependent. Sometimes reactions need to be heated for imine-product formation. I mean, if the reaction is kept under non-hydrolyzing conditions it should be stable up to a moderately high temperature. I have heated imine at 70 oC for 12 h without any decomposition.
What is the difference between imine and enamine?
Difference between Imine and Enamine An imine is an organic compound consisting of a C=N double bond. An enamine is an unsaturated organic compound with an amine group adjacent to the C=C double bond. 2. There is a pi bond between carbon and nitrogen.
Is reductive amination reversible?
In this organic reaction, the amine first reacts with the carbonyl group to form a hemiaminal species, which subsequently loses one molecule of water in a reversible manner by alkylimino-de-oxo-bisubstitution, to form the imine.
Is imine a functional group?
Imine (Schiff base): A functional group having a carbon-nitrogen double bond (C=N), or a molecule containing this functional group.
Can enamines be reduced?
Enamines are typically reduced to saturated amines either by hydride transfer to a previously formed iminium salt or by catalytic hydrogenation. The source of hydride ions can be from metal hydrides,2 formic acid,3 phosphorous acid,4 the Hantzsch ester,5 or secondary amines.
What conditions are used to hydrolyze an imine or an enamine?
Imine Hydrolysis Mechanism It starts by protonation of the nitrogen converting the imine into iminium ion which is very electrophilic and is attacked by water in the next step: After a proton transfer from the oxygen to the nitrogen (likely an intermolecular process), the ammonium ion is kicked out as a neutral amine.
Which catalyst is used in imine hydrolysis?
acid catalystDescription: Treatment of imines with water leads to their hydrolysis back to aldehydes (or ketones) and an amine. Notes: The reaction is assisted through the use of an acid catalyst. Notes: Note that the third example is intramolecular.
Why are imines used in drugs?
Organic compounds containing a carbon-nitrogen double bond where a NITROGEN atom can be attached to HYDROGEN or an alkyl or aryl group....Imines.DrugDrug DescriptionMiglitolAn oral alpha-glucosidase inhibitor used to improve glycemic control by delaying the digestion of carbohydrates.14 more rows
Can amines be hydrolysed?
Hydrolysis of an amide in acid solution actually gives a carboxylic acid and the salt of ammonia or an amine (the ammonia or amine initially formed is neutralized by the acid). Basic hydrolysis gives a salt of the carboxylic acid and ammonia or an amine.
How are imines formed?
Imines are typically prepared by the condensation of ammonia or primary amines with aldehydes and ketones. The mechanism of imine formation will be further discussed in Section 8.02.3.2. Although this method of imine formation is reversible requiring long reaction times and the use of acid catalysts and dehydrating agents such as molecular sieves or azeotropic removal of water to drive the reaction to completion, it is still the most common method for preparation of imines. Aldimines and ketimines are the names given to imines derived from aldehydes and ketones, respectively. Another method of imine formation is the addition of metal alkyls or metal aryls (such as alkyl or aryl lithiums and Grignard reagents) to nitriles. The imine nitrogen in the crude product bears a metal cation [Li + or (MgX) + ]. A more recent procedure for preparation of imines is catalytic hydroamination of alkynes with ammonia or amines (see Table 1, entry 33). Many aliphatic imines (particularly R 2 C NH) display lower stability than the corresponding carbonyl derivatives and are usually prone to hydrolysis in the presence of water. These imines are best reduced directly and not isolated. Iminium ions (or salts) are derived from reaction of aldehydes or ketones with secondary amines and from protonation of imines (under acidic conditions). Iminium ions are more reactive toward reduction and nucleophilic attack than imines.
Why are imines more versatile than preformed iminium salts in reactions with active methylene compounds?
Imines are more versatile than preformed iminium salts in reactions with active methylene compounds because the product, a secondary Mannich base, has an additional site on the nitrogen for further elaboration (equation 11 ). Imine condensation reactions are also superior to the classical method for the synthesis of secondary Mannich bases because cross-condensation reactions do not occur, due to the absence of free aldehyde in solution. The major side reactions occurring in imine condensation reactions are abstraction of enolizable α-protons and self-condensation reactions of enolizable imines at elevated temperature.
What metals are reductively coupled with carbonyls, imines, and nitriles?
Pedersen and co-workers demonstrated that imine complexes of group 5 metals also reductively couple with carbonyls, imines, and nitriles. 71–3 These reactions led to 2-amino alcohols or vicinal diamines. For the reaction to form symmetric diamines ( 175 ), 72 an N -trimethylsilyl imine was added to NbCl 4 (THF) 2 ( 176) in 1:1 ratio to give a diimido complex, which was hydrolyzed to the amine ( 175) under basic conditions ( Scheme 42 ). This procedure gave good yields of organic products with very good diastereoselectivities observed in some cases. This method is restricted to the reaction of nonenolizable imines. An alternative synthesis of diamines uses the corresponding nitriles, which were treated with ( 176) in the presence of Bu 3 SnH to give analogous products ( 177 ). The nitrile reacts with an intermediate niobium hydride, providing an in situ source of coordinated imine complex ( 178 ). This method does not rely on the availability of imine starting materials and thus is a much more general route. One disadvantage of this method is that the diastereoselectivities are lower than when imines are used.
What are the imines that are used to condense?
Of the various imines known to condense with active methylene compounds, α-arylimines have been the most widely used, especially in earlier work, because of their stability, ease of preparation and the absence of enolizable protons. Aliphatic imines containing enolizable protons have broader synthetic applications but their use is more restricted because they are prone to deprotonation and self aldol type condensations. As will be discussed, new methods utilizing Lewis acids and the less basic boron enolates have been devised to overcome the problem of deprotonation. Other innovations that have extended the scope of imine condensations include in situ methods for the preparation of elusive formaldehyde imines (CH 2 =NR 2) and the utilization of N -heterosubstituted imines (N = Si, O and S) for the synthesis of primary Mannich bases and N -unsubstituted β-lactams, available via hydrolysis or reduction of the N_X bond.
How are nitrile imines formed?
Alkene stereochemistry present in ( 170b) was retained in the cyclization product. It is noteworthy that nitrile imines typically fail to cycloadd intermolecularly to unactivated alkenes. The nitrile imine ( 171 ), presumably formed by reaction of the corresponding chlorohydrazone with base , failed to cyclize, probably owing to a reduced entropic advantage. The nitrile imine ( 172) also failed to cyclize, presumably because the dipole and dipolarophile could not approach on parallel planes. 90 Nor did ( 172) give a 1,1-cycloadduct, although it did undergo intermolecular cycloaddition.
What are imines in chemistry?
Imines are compounds containing a carbon-nitrogen double bond > C N having substituents that can be the same or different at the carbon and nitrogen atoms. Imines typically result from the condensation reaction of a carbonyl compound and NH 3 or an amine. The compounds formed with NH 3 are not stable while those formed with amines, particularly when the substituent to the nitrogen is an aromatic ring, are stable; they are known as Schiff bases. When the Schiff base is formed with an aromatic molecule such as aniline, the resulting compound is also known as an anil. Little information is available in the literature regarding thermal stability of Schiff bases. However, the compounds appear to be relatively stable to heating. For example, the anils of keto acids generate by pyrolysis a Schiff base eliminating CO 2, which is an indication that the carboxyl group in the specified compound is less stable than the imine group [1]. The reaction is shown below:
What are the names of the imines?
Aldimines and ketimines are the names given to imines derived from aldehydes and ketones, respectively. Another method of imine formation is the addition of metal alkyls or metal aryls (such as alkyl or aryl lithiums and Grignard reagents) to nitriles.
How are imines formed?
Imines are typically prepared by the condensation of primary amines and aldehydes and less commonly ketones. In terms of mechanism, such reactions proceed via the nucleophilic addition giving a hemiaminal -C (OH) (NHR)- intermediate, followed by an elimination of water to yield the imine (see alkylimino-de-oxo-bisubstitution for a detailed mechanism). The equilibrium in this reaction usually favors the carbonyl compound and amine, so that azeotropic distillation or use of a dehydrating agent, such as molecular sieves or magnesium sulfate, is required to push the reaction in favor of imine formation. In recent years, several reagents such as Tris (2,2,2-trifluoroethyl)borate [B (OCH 2 CF 3) 3 ], pyrrolidine or titanium ethoxide [Ti (OEt) 4] have been shown to catalyse imine formation.
What is the structure of an imine?
The general structure of an imine. An imine ( / ɪˈmiːn / or / ˈɪmɪn /) is a functional group or chemical compound containing a carbon – nitrogen double bond. The nitrogen atom can be attached to a hydrogen (H) or an organic group (R).
What is the name of the imine that is attached to both hydrocarbyls?
A primary imine in which C is attached to both a hydrocarbyl and a H is called a primary aldimine ; a secondary imine with such groups is called a secondary aldimine. A primary imine in which C is attached to two hydrocarbyls is called a primary ketimine; a secondary imine with such groups is called a secondary ketimine. Primary aldimine .
What reacts with ketenes in Staudinger synthesis?
Imines react, thermally, with ketenes in [2+2] cycloadditions to form β-lactams in the Staudinger synthesis. An imine can be oxidized with meta-chloroperoxybenzoic acid (mCPBA) to give an oxaziridine. A tosylimine reacts with an α,β-unsaturated carbonyl compound to an allylic amine in the Aza-Baylis–Hillman reaction .
What are imines used for?
Imines are widely used as intermediates in the synthesis of heterocycles. Aromatic imines reacts with an enol ether to a quinoline in the Povarov reaction. The C=N bond in imines is reactive toward cycloadditions. Imines react, thermally, with ketenes in [2+2] cycloadditions to form β-lactams in the Staudinger synthesis. An imine can be oxidized with meta-chloroperoxybenzoic acid (mCPBA) to give an oxaziridine
How are imines related to ketones?
Imines are related to ketones and aldehydes by replacement of the oxygen with an NR group. When R = H, the compound is a primary imine, when R is hydrocarbyl, the compound is a secondary imine. Imines exhibit diverse reactivity and are commonly encountered throughout chemistry. When R 3 is OH, the imine is called an oxime, ...
What is the formula for aldimines?
An aldimine is an imine that is an analog of an aldehyde. As such, aldimines have the general formula R–CH=N–R'. Aldimines are similar to ketimines, which are analogs of ketones .
Is an imine a reversible reaction?
Formation of an imine--from an amine and an aldehyde--is a reversible reaction which operates under thermodynamic control such that the formation of kinetically competitive intermediates are, in the fullness of time, replaced by the thermodynamically most stable product(s). For this fundamental reas …
Is an imine bond reversible?
Formation of an imine--from an amine and an aldehyde--is a reversible reaction which operates under thermodynamic control such that the formation of kinetically competitive intermediates are, in the fullness of time, replaced by the thermodynamically most stable product(s). For this fundamental reason, the imine bond has emerged as an extraordinarily diverse and useful one in the hands of synthetic chemists. Imine bond formation is one of a handful of reactions which define a discipline known as dynamic covalent chemistry (DCC), which is now employed widely in the construction of exotic molecules and extended structures on account of the inherent 'proof-reading' and 'error-checking' associated with these reversible reactions. While both supramolecular chemistry and DCC operate under the regime of reversibility, DCC has the added advantage of constructing robust molecules on account of the formation of covalent bonds rather than fragile supermolecules resulting from noncovalent bonding interactions. On the other hand, these products tend to require more time to form--sometimes days or even months--but their formation can often be catalysed. In this manner, highly symmetrical molecules and extended structures can be prepared from relatively simple precursors. When DCC is utilised in conjunction with template-directed protocols--which rely on the use of noncovalent bonding interactions between molecular building blocks in order to preorganise them into certain relative geometries as a prelude to the formation of covalent bonds under equilibrium control--an additional level of control of structure and topology arises which offers a disarmingly simple way of constructing mechanically-interlocked molecules, such as rotaxanes, catenanes, Borromean rings, and Solomon knots. This tutorial review focuses on the use of dynamic imine bonds in the construction of compounds and products formed with and without the aid of additional templates. While synthesis under thermodynamic control is giving the field of chemical topology a new lease of life, it is also providing access to an endless array of new materials that are, in many circumstances, simply not accessible using more traditional synthetic methodologies where kinetic control rules the roost. One of the most endearing qualities of chemistry is its ability to reinvent itself in order to create its own object, as Berthelot first pointed out a century and a half ago.
Template-directed synthesis employing reversible imine bond formation
The imine bond – formed by the reversible condensation of an amine and an aldehyde – and its applications as a dynamic covalent bond in the template-directed synthesis of molecular compounds, will be the focus of this tutorial review.
Abstract
The imine bond – formed by the reversible condensation of an amine and an aldehyde – and its applications as a dynamic covalent bond in the template-directed synthesis of molecular compounds, will be the focus of this tutorial review.
What is the bond formation of imine?
Imine bond formation is one of a handful of reactions which define a discipline known as dynamic covalent chemistry (DCC), which is now employed widely in the construction of exotic molecules and extended structures on account of the inherent ‘proof-reading’ and ‘error-checking’ associated with these reversible reactions.
Is synthesis under thermodynamic control?
While synthesis under thermodynamic control is giving the field of chemical topology a new lease of life, it is also providing access to an endless array of new materials that are, in many circumstances, simply not accessible using more traditional synthetic methodologies where kinetic control rules the roost.
Is an imine bond reversible?
Formation of an imine —from an amine and an aldehyde —is a reversible reaction which operates under thermodynamic control such that the formation of kinetically competitive intermediates are, in the fullness of time, replaced by the thermodynamically most stable product (s). For this fundamental reason, the imine bond has emerged as an extraordinarily diverse and useful one in the hands of synthetic chemists. Imine bond formation is one of a handful of reactions which define a discipline known as dynamic covalent chemistry (DCC), which is now employed widely in the construction of exotic molecules and extended structures on account of the inherent ‘proof-reading’ and ‘error-checking’ associated with these reversible reactions. While both supramolecular chemistry and DCC operate under the regime of reversibility, DCC has the added advantage of constructing robust molecules on account of the formation of covalent bonds rather than fragile supermolecules resulting from noncovalent bonding interactions. On the other hand, these products tend to require more time to form—sometimes days or even months—but their formation can often be catalysed. In this manner, highly symmetrical molecules and extended structures can be prepared from relatively simple precursors. When DCC is utilised in conjunction with template-directed protocols—which rely on the use of noncovalent bonding interactions between molecular building blocks in order to preorganise them into certain relative geometries as a prelude to the formation of covalent bonds under equilibrium control—an additional level of control of structure and topology arises which offers a disarmingly simple way of constructing mechanically-interlocked molecules, such as rotaxanes, catenanes, Borromean rings, and Solomon knots. This tutorial review focuses on the use of dynamic imine bonds in the construction of compounds and products formed with and without the aid of additional templates. While synthesis under thermodynamic control is giving the field of chemical topology a new lease of life, it is also providing access to an endless array of new materials that are, in many circumstances, simply not accessible using more traditional synthetic methodologies where kinetic control rules the roost. One of the most endearing qualities of chemistry is its ability to reinvent itself in order to create its own object, as Berthelot first pointed out a century and a half ago.
