Imines from amides

The a is L-lysine, as in the case of piperidine, but the f3 is different. The /3 is a-aminoadipic acid 6-semialdehyde. The q> is L-pipecolic acid, which is synthesized in plants from piperideine-6-carboxylic acid. In the case of many other organisms, the obligatory intermedia (q>) is derived from the /3. The

ring structure. The indolizidine nucleus will be formed only in the synthesis of the x- The deep structmal change occms when

Claisen reaction with acetyl or malonyl CoA (Cra/mCoA) and the ring closme process (by amide or imine) to 1-indolizidinone, which is the x- The second obligatory intermedia ( k ) only has the indolizidine nucleus. 

We might first think of removing the structural heteroatom—the ring nitrogen. With reductive amination in mind we might consider imines from 52 or amides from 53. But these compounds have four different carbonyl groups and obviously problems of selectivity arise. 

Some reactions of munchnones occur via acylamino ketenes, the covalent valence tautomers of the betaines. The ketenes are intermediates in the thermolysis (see Scheme 22) and in the formation of azetidinones from imines (equation 69) they are thought to be involved in the aminolysis of the mesoionic compounds, which results in amides of a-acylamino acids, and in the formation of the benzodioxin (247) by the combined action of acetic anhydride and tetrachloro-o-benzoquinone on Af-benzoylalanine (equation 70). 

Diaryl-l,2,4,5-tetrazines, when treated with bulky amides such as lithium di-isopropylamide, undergo two competing reactions. In the first, tetrazine is reduced with concomitant formation of an imine from the amide. The imine is then attacked further by amide to give a pyridazine. For example, 3,6-diphenyl-l,2,4,5-tetrazine is converted with lithium diethylamide into 3,6-diphenylpyridazine in low yield. With lithium di-isopropylamide, 4-methyl-3,6-diphenylpyridazine is obtained in moderate yield [83JCS(P1)1601]. 

In the covalent approach, the print molecules are covalently coupled to polymerisable molecules prior to polymerisation (see Chapter 4). The covalent bonds have to be relatively easy to break to allow cleavage of the print molecules after polymerisation. Print molecules have been coupled to monomers through the formation of boronic, carboxylic and phosphonic ester bonds, amide bonds, imines and ketals. After copolymerisation with a high degree of cross-linker, the print molecules are cleaved from the polymer. A representative example of the covalent approach is shown in Fig. 17.1. 

The fragmentation of amines, amides, and imines, may be profoundly influenced by a hydroxy-group, even when the two groups are situated far apart in the molecule. Fragmentation is initiated by transfer of hydrogen from the hydroxy-group to nitrogen. 

Adducts (6) and (7) from amides and chlorophosphoric acid aiyl esters or dichlorophosphoric acid aryl esters respectively are well known. - The adducts are formed in a 1 1 ratio. They have been applied to the synthesis of mixed anhydrides from diarylphosphoric acids and carboxylic acids, as well as mixed substituted esters of pyrophosphoric acid. The adduct formation between primary or secondary carboxamides and dichlorophosphates has been used to prepare nitriles and isonitriles respectively. The adduct from DMF and phenyldichlorophosphate is a useful reagent for the preparation of carboxylic acid esters from the corresponding acids and alcohols, 3-lactams from imines and carboxylic acids," carboxylic acid anhydrides, carboxylic acid esters and thiol esters. Adducts of amides with ester amides or diamides of chlorophosphoric acid have been studied. ... 

Lithium aminoborohydrides are obtained by the reaction of -BuLi with amine-boranes [FF2, FH5, NT2]. They can be generated in situ as THF solutions or as solids when formed in diethylether or hexane (n-BuLi must then be used in sub-stoichiometric amounts). They are stable under dry air and are slowly decomposed by water [NT2] or methanol so that workup of the reactions mixtures can be carried out with 3M HCl. They reduce alkyl halides (Section 2.1), epoxides (Section 2.3), aldehydes, and ketones (Section 3.2.1) (in the latter case with an interesting stereoselectivity [HFl]), and esters to primary alcohols (Section 3.2.5). a,(3-Unsaturated aldehydes, ketones, and esters are reduced to allyl alcohols (Section 3.2.9) [FF2, FS2]. Depending on the bulkiness of the amines associated with the reagent and to the substrate, tertiary amides give amines or alcohols (Section 3.2.8) [FFl, FF2]. Amines are also formed from imines (Section 3.3.1) [FB1 ] and from azides (Section 5.2) [AFl]. However, carboxylic acids remain untouched. 

The amide or imine from reaction of 2-aryl-ethanamines with an acid derivative or with an aldehyde, can be ring-closed to a 3,4-dihydro- or 1,2,3,4-tetrahydroisoquinoline respectively. Subsequent dehydrogenation can produce the aromatic heterocycle. 

The newly formed resin bound amides are liberated from the solid phase by acidic conditions to provide the free amides (28) in good yield without further purification. It has also been shown that carboxylic acids containing an aldehydic moiety (i.e., 4-formyl benzoic acid) give the expected amides (no imine formation) in 90% yield and with 95% purity (e.g., where R = phenethyl). 

Amides from N-Acyl Imines and Related Heterodienes in [4+2]-Cycloaddition Reactions"... 

The dicarbonyl compoimd 51 was oxidized to the anhydride 52, which subsequently reacted with primary or secondary amines to form a-amino acids, a-amino amides and dipeptides 53 (Scheme 14) [48]. 3-Hydroxy j8-lactams obtained from imines derived from carbohydrates [49,50] or prepared via the Sharpless AD reaction [51-53] were directly oxidized to anhydrides by treatment with NaOCl and TEMPO. Anhydrides 54-56 were used for the synthesis of compounds related to the family of polyoxins represented by 57 (Scheme 15) [49-53]. 

NH+ in cations derived from aromatic azine systems and from imines Amides and related structure NH moieties in aromatic azole systems Protonated nitriles, R—C=NH... 

The modifications of the Gilman-Speeter reaction include the activation of zinc by tri-methylsilyl chloride (TMSCl) and the application of lithium ester enolate" or lithium thioester enolate as the substitute for the traditional Reformatsky reagent. In these modifications, it was found that TMSCl-activated zinc is much more effective in promoting the reaction between ethyl bromoacetate and Schiff bases. In addition, in the presence of a chiral ether ligand, the reaction between lithium ester enolate and imines affords 0-lactams of high enantiomeric excess, probably due to the formation of a ternary complex reagent. " The enantioselectivity and reactivity of the ternary complex depend on the size and nature of the lithium amide used. For example, the lithium amide from 2,2,6,6-tetramethylpiperidine (LTMP) is unfavorable for this reaction." ... 

Radovic et al. (1996) investigated the effects of nitriding the surface on adsorption from solution. Reacting with ammonia at elevated temperatures introduced pyridine functional groups on carbon. Reaction at 200 °C forms amides, imides, imines, amines, and nitriles while reaction at 250 °C results in bonding of ammonia to the carbon double bonds (Vinke et al., 1994). The effects of nitriding (at 250 °C) were similar to that of oxidation. Nitriding also hindered the adsorption of benzoate and aliphatic anions, oxalate, and fumarate. 

The enolate, perhaps the most versatile synthetic intermediate of all, lends itself well to asymmetric synthesis via chiral auxiliaries. There are three principal sites for the installation of an auxiliary. A either on C-1 of the enolate or on the nitrogen atom of the aza-enolates derived from imines or amides ... 

As can be seen from the stmcture of the compound 142, the o-aminostyryle substituent and the C(2), C(3) atoms of the amide and imine fragments of the pyrazine ring of quinoxalin-2(l//)-one 143 (Scheme 6.61) are involved in the constmction of two new heterocyclic systems. In this case, the formation of the pyridine ring of the quinoline system occurs as a result of the proceeding new rearrangement (Hassner and Namboothiri 2012 Mamedov and Zhukova 2013). As can be seen from Table 6.16, the atoms C(2) and C(3) of the quinoxalin-2(l//)-one system become the atoms C(2 ) and C(2) of the benzimidazole and quinoline systems of the compounds 142 respectively. 

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