Aldehyde to form imines

Primary amines react with ketones and aldehydes to form imines. In the case of formaldehyde (R = H), these products are typically cyclic trimers. 

Formation of C—Nu The second mode of nucleophilic addition, which often occurs with amine nucleophiles, involves elimination of oxygen and formation of a C=Nu bond. For example, aldehydes and ketones react with primary amines, RNH2, to form imines, R2C=NR. These reactions proceed through exactly the same kind of tetrahedral intermediate as that formed during hydride reduction and Grignard reaction, but the initially formed alkoxide ion is not isolated. Instead, it is protonated and then loses water to form an imine, as shown in Figure 3. 

A novel guanidinium ylide-mediated procedure has recently been reported by Ishi-kawa [62]. Though not an imine transformation, it does employ an imine precursor in the fonn of an aldehyde. Guanidinium ylides react with aldehydes to form aziridines (Scheme 1.35). The mechanism for the formation of the aziridine is believed to involve [3+2] cycloaddition between the guanidinium ylide 112 and the aldehyde, followed by stereospecific extrusion of the urea with concomitant aziridine formation. 

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

Abstract Aldehydes obtained from olefins under hydroformylation conditions can be converted to more complex reaction products in one-pot reaction sequences. These involve heterofunctionalization of aldehydes to form acetals, aminals, imines and enamines, including reduction products of the latter in an overall hydroaminomethylation. Furthermore, numerous conversions of oxo aldehydes with additional C.C-bond formation are conceivable such as aldol reactions, allylations, carbonyl olefinations, ene reactions and electrophilic aromatic substitutions, including Fischer indole syntheses. 

Primary nitramines react with amines in the presence of an aldehyde to form 1,3-amino-nitramines in a reaction analogous to the Mannich condensation. In these reactions the amine and aldehyde component combine to form an intermediate imine which is then attacked by the nitramine nucleophile. 

The reaction is exactly analogous to the chemical aldol reaction (also shown), but it utilizes an enamine as the nucleophile, and it can thus be achieved under typical enzymic conditions, i.e. around neutrality and at room temperature. There is one subtle difference though, in that the enzyme produces an enamine from a primary amine. We have indicated that enamine formation is a property of secondary amines, whereas primary amines react with aldehydes and ketones to form imines (see Section 7.7.1). Thus, a further property of the enzyme is to help stabilize the enamine tautomer relative to the imine. 

The heat of formation of [MolCOlg] has been determined as -960 + 12 kJ mol by measuring its heat of decomposition. The Mossbauer parameters for the 100 keV transition of in [W(CO)g] and some tungsten(vi) complexes have been measured and discussed in terms of known bonding and structure. Secondary ions [M (CO) ] (M = Mo, m = I or 2 M = W, m = 1—4 n = 0—14) formed by ion-molecule reactions have been observed in the mass spectra of the hexacarbonyls. A mixt u re of [Cr(CO) ] and [MolCO) ] vapours affords [CrMo(CO) ] ( = 5—7). [MofCOl ] and [WICO) ] catalyse the condensation of isocyanates with aldehydes to give imines in high yields. ... 

In enamine-catalyzed aldol reaction, the donor aldehyde or ketone first forms an enamine and then reacts with another aldehyde to form the aldol product. If imines instead of aldehydes are used as acceptors, the end result is the formation of a... 

Primary amines add to aldehydes and ketones to form imines, R-N=CR2-Secondciry cimines react to form enamines, R 2C=CR(NR2). Hydroxylamine reacts to form an oxime, R2C=NOH. Hydrazine reacts to form a hydrazone,... 

Glycoproteins, such as horseradish peroxidase, are coupled selectively to other proteins or NH2-groups bearing molecules via oligosaccharide side chain oxidation. The vicinal OH groups of oligosaccharide residues are oxidized by periodate to aldehyde groups, which react with amines to form imines (Schiff bases). 

Aliphatic ketones react more slowly than aldehydes with amines to form imines (see Table VII). Higher reaction temperatures, longer reaction times, and the removal of water aid in giving high yields of imines (80-95 %). Steric-ally hindered ketones react slowly. Methyl ketones require mild acid catalyst and are more prone to aldol condensation by-products than are methylene ketones [3]. 

Aliphatic and aromatic aldehydes condense with aliphatic and aromatic primary amines to form JV-substituted imines. The reaction is catalyzed by acids and is generally carried out by refluxing the amine and the carbonyl compound with an azeotroping agent in order to separate the water formed. The aliphatic imines (C5-C10) are obtained in good yield but are unstable and must be used directly after their distillation [2b], Tertiary aliphatic and aromatic aldehydes at room temperature react readily and nearly quantitatively with amines to give the imines without the aid of catalysts [la]. Primary aliphatic aldehydes tend to give polymeric materials with amines as a result of the ease of their aldol condensation [3]. The use of low temperatures and potassium hydroxide favors the formation of the imine product [4a, b]. Secondary aliphatic aldehydes readily form imines with amines with little or no side reactions [5]. 

A further strategy used to prepare amides on insoluble supports is based on the Ugi reaction (Figure 13.8). Simple mixing of an amine, an aldehyde, an acid, and an isonitrile can lead to the formation of a-amino acid amides. The mechanism of this remarkable reaction is outlined in Figure 13.8. Sometimes, the amine is first condensed with the aldehyde to form an imine, which is then combined with the acid and the isonitrile. 

Innine ligation of unprotected peptides is based on the chemoselectivity between a weak base and an aldehyde to form either a stable imine or an imino intermediate that can isomerize rapidly to a more stable product. Whereas the thiol ligations are optimally performed at neutral or basic pH, imine ligations are performed under acidic conditions, which is highly desirable because under acidic conditions the basic side-chain nucleophiles of an unprotected peptide are protonated to be excluded from the reaction. Furthermore, these two reaction conditions can be exploited for ligating dissimilar peptide chains to a core to form heteromeric peptide dendrimers.11401... 

The addition of nucleophiles to the carbonyl group may be catalysed by acids obtained by the protonation of the carbonyl oxygen (equilibrium 26). Acid catalysis can also occur during the elimination step which follows the addition step. For example, the reactions of aldehydes with amines (and of all the ammonia derivatives) to form imines are generally assumed to occur in two steps the first is the addition of nucleophile to yield a gem amino alcohol, the second includes the elimination of water from the tetrahedral adduct 138 (see Scheme 45). This elimination is usually thought to be catalysed by electrophiles171,212. 

Aniline is a primary amine and undergoes nucleophilic addition to aldehydes and ketones to form imines. 

The first step is probably the condensation of ammonia with the aldehyde to form an imine ... 

Alcohols and aldehydes are also suitable materials for the creation of an alkyl amine. In addition to the aforementioned formation of alkyl chloride as an intermediate, alcohols can be directly converted to amines under hydrogenation conditions in the presence of ammonia while aldehydes are prereacted to form imine followed by hydrogenation [13]. Selectivity of the primary amine with these techniques is difficult and this process is more typically utilized for the preparation of tertiary amines where the reaction can be driven to completion. In certain cases, alcohols and aldehydes provide structural elements which are not attainable from natural sources. An example is the formation of a hydrogenated tallow 2-ethyl hexyl amine. The amine is prepared as shown below in eqn 6.1.8 using a hydrogenated tallow amine reacted with 2-ethyl hexanal [14, 15] ... 

This reaction proceeds by initial reaction of ammonium chloride with the aldehyde to form an imine (see Section 18.8). Then cyanide adds to the imine in a reaction that is exactly analogous to the addition of cyanide to an aldehyde to form a cyanohydrin (see Section 18.4). The final step in the Strecker synthesis is the hydrolysis of the nitrile to a carboxylic acid (see Section 19.5). 

Ketones and aldehydes also condense with other ammonia derivatives, such as hydroxyl amine and substituted hydrazines, to give imine derivatives. The equilibrium constants for these reactions are usually more favorable than for reactions with simple amines. Hydroxylamine reacts with ketones and aldehydes to form oximes hydrazine and its derivatives react to form hydrazones and semicarbazide reacts to form semicarbazones. The mechanisms of these reactions are similar to the mechanism of imine formation. 

Aldehydes and ketones can undergo nucleophilic addition reactions. In particular, aldehydes and ketones can react with amines to form imines and enamines, reactions that might compete with formation of amide bonds between amino acids. Because of this reactivity, aldehydes and ketones are unlikely to be found in amino acid side chains. 

Aldol-type reactions. In the presence of I r. h, these ketals condense with aldehydes to form p-hydroxy carboxylic acids (equation 1) ir with imines to form P-lactams (equation 11). 

Fig. 16) If weak allylic or benzylic C—H groups are present, a lactone product may form through an acyloxyl radical, while amino acids may go on to form imines or aldehydes (99,100). 

A useful variation of this reaction involves lithium enolates derived from esters. - They react with imines derived from non-enolizable aldehydes to form -lactams (equations 44 and 45). ... 

Aldehydes and ketones react with 1° amines to form imines and with 2° amines to form enamines. Both reactions involve nucleophilic addition of the amine to the carbonyl group to form a carbinolamine, which then loses water to form the final product. 

An alternate strategy to identify the upstream kinase responsible for phosphorylating a particular phosphoserine protein also was reported (22). In this scheme, a bis aryl aldehyde ATP analog was designed to form an imine with the lysine (Lys 72 in PKA) essential for orienting the a/fi phosphates of ATP. The substrate of interest, with its target serine mutated to cysteine, provides a nucleophile to attack the imine, which then cyclizes with a second aldehyde to form a stable isoindole adduct that links kinase and substrate (Fig. 8b). 

As adenosine antagonists, a great number of 8-substituted xanthines with varying substitution patterns in the 1- and 3-position have been prepared. As starting materials, l,3-dialkyl-5,6-di-aminouracils are used, which are transformed to the 1,3,8-trisubstituted xanthines by one of three methods. The first consists of condensing diaminouracil with an aldehyde to form the imine which is oxidatively cyclized by treatment with diethyl azodicarboxylate (DEAD) in a modification of a reported general procedureto give the appropriate xanthine derivative, e.g. formation of 10. 

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