Double bonds aldehyde amination

Primary and secondary amines, double bonds, aldehydes, sulfides and certain aromatic and dihydroaroraatic systems are also oxidized by chromium VI reagents under standard hydroxyl oxidizing conditions. Amines are commonly protected by salt formation or by conversion to amides. Aldehydes and... 

A 2° amine reacts with an aldehyde or ketone to give an enamine. Enamines have a nitrogen atom bonded to a double bond zSkene + amine = enamine). 

Oxidation. Potassium ferrate (VI) is a reagent for selective oxidation of primary alcohols and amines to aldehydes and of secondary alcohols to ketones. Double bonds, aldehyde functions, tertiary hydroxyl groups, and tertiary amino groups are resistant to oxidation. The reaction is carried out at room temperature either in water or in aqueous solvents. In fact water is essential for oxidation. The reaction is carried out at an initial pH of 11.5 the final pH is 13.5. In a typical procedure K.2pe04 (0.(X)2 mole)... 

Secondary amines react with aldehydes and ketones to form enamines. The name enamine is derived from -en- to indicate the presence of a carbon-carbon double bond and -amine to indicate the presence of an amino group. An example is enamine formation between cyclohexanone and piperidine, a cyclic secondary amine. Water is removed by a Dean-Stark trap (Figure 16.1), which forces fhe equilibrium to the right. 

The reaction conditions applied are usually heating the amine with a slight excess of aldehyde and a considerable.excess of 2d-30hydrochloric acid at 100 °C for a few hours, but much milder ( physiological ) conditions can be used with good success. Diols, olefinic double bonds, enol ethers, and glycosidic bonds survive a Pictet-Spengler reaction very well, since phenol and indole systems are much more reactive than any of these acid sensitive functional groups (W.M. Whaley, 1951 J.E.D. Barton, 1965 A.R. Battersby, 1969). 

Secondary amines are compounds of the type R2NH They add to aldehydes and ketones to form carbmolammes but their carbmolamme intermediates can dehydrate to a stable product only m the direction that leads to a carbon-carbon double bond... 

Generally, isolated olefinic bonds will not escape attack by these reagents. However, in certain cases where the rate of hydroxyl oxidation is relatively fast, as with allylic alcohols, an isolated double bond will survive. Thepresence of other nucleophilic centers in the molecule, such as primary and secondary amines, sulfides, enol ethers and activated aromatic systems, will generate undesirable side reactions, but aldehydes, esters, ethers, ketals and acetals are generally stable under neutral or basic conditions. Halogenation of the product ketone can become but is not always a problem when base is not included in the reaction mixture. The generated acid can promote formation of an enol which in turn may compete favorably with the alcohol for the oxidant. 

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. 

Aldehydes, formates, primary, and secondary alcohols, amines, ethers, alkyl halides, compounds of the type Z—CH2—Z, and a few other compounds add to double bonds in the presence of free-radical initiators/ This is formally the addition of RH to a double bond, but the R is not just any carbon but one connected to an oxygen or a nitrogen, a halogen, or to two Z groups (defined as on p. 548). The addition of aldehydes is illustrated above. Formates and formamides " add similarly ... 

The reaction with bromine is very rapid and is easily carried out at room temperature, although the reaction is reversible under some conditions. In the case of bromine, an alkene-Br2 complex has been detected in at least one case. Bromine is often used as a test, qualitative or quantitative, for unsaturation. The vast majority of double bonds can be successfully brominated. Even when aldehyde, ketone, amine, so on functions are present in the molecule, they do not interfere, since the reaction with double bonds is faster. 

Compounds containing carbon-nitrogen double bonds can be hydrolyzed to the corresponding aldehydes or ketones. For imines (W = R or H) the hydrolysis is easy and can be carried out with water. When W = H, the imine is seldom stable enough for isolation, and hydrolysis usually occurs in situ, without isolation. The hydrolysis of Schiff bases (W = Ar) is more difficult and requires acid or basic catalysis. Oximes (W = OH), arylhydrazones (W = NHAr), and, most easily, semicarbazones (W = NHCONH2) can also be hydrolyzed. Often a reactive aldehyde (e.g., formaldehyde) is added to combine with the liberated amine. 

Polar C=Y double bonds (Y = NR, O, S) with electrophilic carbon have been added to suifinic acids under formation of sulfones. As in the preceding section one must distinguish between carbonyl groups and their derivatives on the one hand, and carboxylic acids (possessing leaving groups at the electrophilic carbon) on the other. Aldehydes " of sufficient reactivity—especially mono-substituted glyoxals - —and their aryl or arylsulfonyl imines have been added to suifinic acids (in a reversible equilibrium) to yield a-hydroxy or a-amino sulfones the latter could also be obtained from the former in the presence of primary amines (equation 26). 

Derivatives of hydrazine, especially the hydrazide compounds formed from carboxylate groups, can react specifically with aldehyde or ketone functional groups in target molecules. Reaction with either group creates a hydrazone linkage (Reaction 44)—a type of Schiff base. This bond is relatively stable if it is formed with a ketone, but somewhat labile if the reaction is with an aldehyde group. However, the reaction rate of hydrazine derivatives with aldehydes typically is faster than the rate with ketones. Hydrazone formation with aldehydes, however, results in much more stable bonds than the easily reversible Schiff base interaction of an amine with an aldehyde. To further stabilize the bond between a hydrazide and an aldehyde, the hydrazone may be reacted with sodium cyanoborohydride to reduce the double bond and form a secure covalent linkage. 

Benzotriazol-l-yl)methyl]triphenylphosphonium chloride 848 reacts with BunLi and aldehydes to give l-(alken-l-yl)benzotriazoles 849. Addition of bromine to the double bond of derivatives 849 followed by a reaction with amines furnishes amides 850. A variety of primary or secondary amines can be used. This way aldehydes are conveniently homologated and converted to amides with a one-atom longer chain (Scheme 136) <2004ARK(ix)44. 

FIGURE 5.6 Reaction of ninhydrin (trioxohydrindene hydrate) with the amino group of a bound residue (A) generates the Schiff s base. Hydrolysis after shift of the double bond generates the aldehyde and another amine which reacts (B) with a second molecule of ninhydrin to give an equilibrium mixture of the anion depicted and its tetraoxo form with a maximum of absorbance at 570 nm. 

C—Organic bases are, in general, amines (contain N). An ether would have an oxygen single-bonded to two carbons (R groups). An aldehyde has oxygen double-bonded to a carbon at the end of a chain. Aldehydes (RCHO) and... 

Since then, optically active a-aminophosphonates have been obtained by a variety of methods including resolution, asymmetric phosphite additions to imine double bonds and sugar-based nitrones, condensation of optically active ureas with phosphites and aldehydes, catalytic asymmetric hydrogenation, and 1,3-dipolar cycloadditions. These approaches have been discussed in a comprehensive review by Dhawan and Redmore.9 More recent protocols involve electrophilic amination of homochiral dioxane acetals,10 alkylation of homochiral imines derived from pinanone11 and ketopinic acid,12 and alkylation of homochiral, bicyclic phosphonamides.13... 

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