Imine primary amines

Aldebyde Ammonia or ketone Imine Primary amine... 

Direct aldols of ketones and glyoxylates (RC0C02Me) give high ee using axially chiral diimine catalysts (55) in acetic acid media, but MS and other evidence suggests that the related imine-primary amine (56) - formed by acid-catalysed equilibration - is the immediate catalytic species. °... 

Reaction with primary amines (Section 17 10) Isolated product is an imine (Schiff s base) A carbinolamine inter mediate is formed which undergoes de hydration to an imine... 

Primary amines undergo nucleo philic addition to the carbonyl group of aldehydes and ketones to form carbinol amines These carbinolamines dehydrate under the conditions of their formation to give N substituted imines Secondary amines yield enamines... 

Imines are formed by nucleophilic addition of a primary amine to the carbonyl group of an al dehyde or a ketone The key step is formation of a carbinolamine intermedi ate which then dehy drates to the imine... 

Reactions with Amines and Amides. Hydroxybenzaldehydes undergo the normal reactions with aUphatic and aromatic primary amines to form imines and Schiff bases reaction with hydroxylamine gives an oxime, reaction with hydrazines gives hydrazones, and reactions with semicarbazide give semicarbazones. The reaction of 4-hydroxybenzaldehyde with hydroxylamine hydrochloride is a convenient method for the preparation of 4-cyanophenol (52,53). 

Reductive amination of cyclohexanone using primary and secondary aHphatic amines provides A/-alkylated cyclohexylamines. Dehydration to imine for the primary amines, to endocycHc enamine for the secondary amines is usually performed in situ prior to hydrogenation in batch processing. Alternatively, reduction of the /V-a1ky1ani1ines may be performed, as for /V,/V-dimethy1 cyclohexyl amine from /V, /V- di m e th y1 a n i1 i n e [121 -69-7] (12,13). One-step routes from phenol and the alkylamine (14) have also been practiced. 

One characteristic of this reaction that can cause problems is that secondary and tertiary amines are produced in addition to the primary amine. It has been proposed that these side reactions occur through reaction of the imine iatermediate with the product amine, followed by the loss of ammonia and further hydrogenation (10). 

Schiff bases, also known as imines, ate formed by the condensation of carbonyl compounds with ammonia or primary amines. Hydrogenation of the resulting Schiff bases forms amines, such as benzylamine and dibenzylamine. 

FORSTER - DECKER Amine Synthesis Selective monoalkylation of primary amines via imines An altemativa method is the reaction ol 1 and 2 in the preserve of NaCNBH4 or tnaceloxyborohydride (Borch reduction)/... 

The kinetics of the hydrolysis of some imines derived from benzophenone anc primary amines revealed the normal dependence of mechanism on pH with ratedetermining nucleophilic attack at high pH and rate-determining decomposition of the tetrahedral intermediate at low pH. The simple primary amines show a linear correlation between the rate of nucleophilic addition and the basicity of the amine Several diamines which were included in the study, in particular A, B, and C, al showed a positive (more reactive) deviation from the correlation line for the simple amines. Why might these amines be more reactive than predicted on the basis of thei ... 

The addition of primary amines to fluoroolefins under anhydrous conditions yields imines The hexafluoropropene dimer, perfluoro-2-methyl-2-pcntcne, and ten butylamine react to yield a mixture of two compounds m a 9 4 ratio [4] (equation 3) rather than just the major keteiiimme-imine, as previously reported [5] It IS claimed that this result is possible by means of isomerization to the terminally unsaturated difluoromethylene isomer prior to nucleophilic attack Secondary amines add to fluoroolefins under anhydrous conditions to give fluonnated ternary amines m good yields If the fluoroolefin is added to the amine without cooling the reaction mixture, or if an excess of the secondary armne is used, there is a tendency toward dehvdrofluonnation of the ternary amine The products... 

A class of nitrogen-containing compounds that was omitted from the section just discussed includes imines and their- derivatives. Irnines are formed by the reaction of aldehydes and ketones with ammonia. Imines can be reduced to primary amines by catalytic hydrogenation. 

The formation of bicyclic imines (263,264) from piperidine enamines and y-bromopropyl amines may appear at first sight to be a simple extension of the reactions of enamines with alkyl halides. However, evidence has been found that the products are formed by an initial enamine exchange, followed by an intramolecular enamine alkylation. Thus y-bromodiethylamino-propane does not react with piperidinocyclohexene under conditions suitable for the corresponding primary amine. Furthermore, the enamine of cyclopentanone, but not that of cyclohexanone, requires a secondary rather than primary y-bromopropylamine, presumably because of the less favorable imine to enamine conversion in this instance. 

A trifluoromethylsulfonamide can be prepared from a primary amine to allow monoalkylation of that amine. The triflamide is not stable to strong base, which causes elimination to an imine, but when used to protect an indole, it is cleaved with K2CO3 in refluxing methanol. ... 

The cyclization of the imine 158 is believed (81UK1252) to involve the addition of the second formamide molecule to C-3 (at least primary amines readily add in a similar manner to such systems). 

One of the most popular orally active penicillins in present clinical use is amoxicillin (12). Its oral effectiveness and broad spectrum of activity against common pathogens as well as its better absorption than its closest precedent competitor, ampicillin (14), largely accounts for this. Higher blood and tissue levels of antibiotics is another means of dealing with resistance. In an attempt to achieve yet further improvements in oral bioavailability and hence blood and ti.ssue levels of amoxicillin, the prodmg fumoxicillin (13) is prepared from amoxicillin (12) by treatment with furfural [3]. The imine moiety is less basic than the primary amine so that the isoelectric point of fumoxicillin is more on the acid side than is that of amoxicillin. 

Nitriles and oximes are considered together because of common features. Both functions are reduced to primary amines, both undergo coupling reactions to secondary amines, and both are subject to reductive hydrolysis. These similarities arise from a common intermediate, an imine. The imine is... 

A common technique for minimizing secondary amine formation is to carry out the hydrogenation in the presence of ammonia (21,23,42). Ammonia is thought to complete with the primary amine in attack on the intermediate imine. Anhydrous ammonia is preferred to prevent hydrolysis reactions,... 

Solvents influence the hydrogenation of oximes in much the same way as they do hydrogenation of nitriles. Acidic solvents prevent the formation of secondary amines through salt formation with the initially formed primary amine. A variety of acids have been used for this purpose (66 ), but acids cannot always be used interchangeably (43). Primary amines can be trapped also as amides by use of an anhydride solvent (2,/5,57). Ammonia prevents secondary amine formation through competition of ammonia with the primary amine in reaction with the intermediate imine. Unless the ammonia is anhydrous hydrolysis reactions may also occur. 

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. 

Primary amines, RNH2, add to aldehydes and ketones to yield imines, R2C=NR. Secondary amines, R2NH, add similarly to yield enamines, R2N—CR=CR2 (ene + amine = unsaturated amine). 

Mechanism of imine formation by reaction of an aldehyde or ketone with a primary amine. 

Reaction of an aldehyde or ketone with a secondary amine, R2NH, rather than a primary amine yields an enamine. The process is identical to imine formation up to the iminium ion stage, but at this point there is no proton on nitrogen that can be lost to form a neutral imine product. Instead, a proton is lost from the neighboring carbon (the a carbon), yielding an enamine (Figure 19.10). 

An aldehyde or ketone reacts with a primary amine, RNH.2, to yield an imine, in which the carbonyl oxygen atom has been replaced by the =N-R group of the amine. Reaction of the same aldehyde or ketone with a secondary amine, R2NH, yields an enamine, in which the oxygen atom has been replaced by the -NR2 group of the amine and the double bond has moved to a position between the former carbonyl carbon and the neighboring carbon. 

Imine formation is reversible. Show all the steps involved in the acid-catalyzed reaction of an imine with water (hydrolysis) to yield an aldehyde or ketone plus primary amine. 

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