Crotonates amines

Primary fatty amines also add (Michael addition) to esters of acryUc acid, H2C=CHCOOH, methacrylic acid, H2C=C(CH2)COOH, or crotonic acid, CH2CH=CHC00H. Hydrolysis of the Michael ester forms an amphoteric surfactant. Crotonic acid can be used to form the amphoteric compound... 

Amine-containing cellulose esters, eg, the acetate A/A/-diethylaminoacetate (36) and propionate morpholinobutyrate (35), are of interest because of their unique solubiHty in dilute acid. Such esters are prepared by the addition of the appropriate amine to the cellulose acrylate crotonate esters or by replacement of the chlorine on cellulose acrylate chloroacetate esters with amines. This type of ester has been suggested for use in controlled release, mmen-protected feed supplements for mminants (36,37). 

Butyl hypochlorite, warning, 44, 26 N-chlorination of amines with, 41, 82 n-Butyl isocyanide, 41,14 /er/-Butyl isocyanide, 41,14 -Butylmagnesium bromide, 41, 61 reaction with rec-butyl crotonate, 41, 61... 

Chiral fl-amino esters. The conjugate addition of primary amines to alkyl crotonates proceeds in satisfactory yield when carried out under high pressure. French chemists have recently examined this reaction using crotonates derived from chiral alcohols. Thus addition of diphenylmethylamine to 8-phenylmenthyl croton-ate proceeds in 85-90% chemical yield and in 60% de. Optical yields are increased... 

The second major class of enamines contains the enamino ketones, made from ammonia or an amine and a 1,3-diketone. By this route the same 1,3-diketone can provide both halves of the resulting pyridine such an example is provided by the synthesis of 5-benzoyl-2-phenylpyridine (444) (54YZ259). As in the case of the crotonates, the first examples of the condensation of an enamino ketone with an a,/ -unsaturated ketone were provided by Knoevenagel and Ruschhaupt (1898CB1025), who prepared the range of 3-acetyldihy-dropyridines (445) to (447). Similarly, Mumm and Bohme obtained the 3-acetyl- and 3-benzoyl-2,6-dimethylpyridines (448) and (449) from ethyl acetylpyruvate (21CB726). 

Amino-1,2,4-triazolo[l,5-a]pyrimidine derivatives (115) were prepared from 3,5-dihalo-l,2,4-triazoles (111) by amination followed by reaction with acrylic or crotonic ester (113) and then amination without the isolation of 112 and 114 [87T2497 88JAP(K)63/267782] (Scheme 22). 

Acrylic acid esterified with cross-linked hydroxymethyl polystyrene or Wang resin reacts smoothly with primary or secondary aliphatic amines at room temperature (Entries 1 and 2, Table 10.6). Only sterically demanding amines or amines of low nucleophilicity (anilines, a-amino acid esters) fail to add to polystyrene-bound acrylate. Support-bound acrylamides are less reactive than acrylic esters, and generally require heating to undergo addition with amines (Entries 4 and 5, Table 10.6). a, 3-Unsaturated esters with substituents in the 3-position (e.g. crotonates, Entry 3, Table 10.6) react significantly more slowly with nucleophiles than do acrylates. The examples in Table 10.6 also show that polystyrene-bound esters are rather stable towards aminolysis, and provide for robust attachment even in the presence of high concentrations of amines. Entry 10 in Table 10.6 is an example of the alkylation of a resin-bound amine with an electron-poor alkene to yield a fluorinated peptide mimetic. 

Chiral a,(3-unsaturated sulfoxides also produce predominately one diastereomer on addition of heteronucleophiles (equation 96).104 Kinetic protonation of the anion (440 Scheme 59), generated by addition of thiophenoxide to the nitroalkene (233), followed by trapping with formaldehyde, produced a 87 13 mixture of diastereomers favoring (441).10S Finally, the use of high pressure can increase the dia-stereoselectivity of the addition of amines to chiral crotonates.,06a... 

While sluggish under thermal conditions,274-275 the asymmetric conjugate addition of amines to alkyl crotonates is achieved at room temperature under high pressure (15 kbar).276 Thus, benzylamine can be added to the crotonate derived from 8-p-naphthyl menthol, with virtually complete diastereoselectivity. A related intramolecular 1,4-addition of an amine to a chiral enoate was used in a total synthesis of the alkaloid (-)-tylophorine.277 Additions of amines to chiral iron complexes of type (116) proceed with excellent selectivity and allow the preparation of homochiral p-lactams.l27128,l3() l32 In contrast, the addition of amine nucleophiles to chiral vinylic sulfoxides278-2811 and to chiral vinylsulfoximines281 proceeds with comparably low selectivities. 

A second-order dependence on crotonic acid has been observed in its Os(VIII)-catalysed oxidation with CAT in alkaline solution. The reaction rate varied linearly with the concentration of Os(VIII). A mechanism has been proposed.140 The kinetics of the ruthenium(III)-catalysed oxidation of the secondary amines with CAT in acidic medium have been obtained and mechanisms have been postulated.141 Uncatalysed and Ru(III)-catalysed oxidation of ethylenediamine, diethylenetriamine, triethylenete-tramine, aminoethylpiperazine, and isophoronediamine with CAT in HC1 solution showed a fractional dependence on the amine, hydrogen ions, and Ru(III), and it is independent of CAT concentration. TSNH2CI has been postulated as the reactive species and a mechanism has been suggested.142... 

Das and co-workers have described the generation of a-aminoalkyl radicals from cyclic secondary amines using anthraquinone-photocatalysis [95JCS(P1)1797]. The conjugate addition of the a-aminoalkyl radical to enoates has been examined. The cyclized compound is obtained directly from the reaction. The chemical yield of 149 is low and it is accompanied by 148, a product arising from nucleophilic addition of the amine to the crotonate. 

These materials are the reaction product of a primary amine and either acrylic acid, an ester of acrylic acid such as methyl acrylate, ethyl acrylate or crotonic acid. Either 1 or 2 mol of acrylate is used. If 1 mol is added, an N-alkyl (3-alanine is produced (Figure 6.6) and if 2 mol of acrylate per mole of amine is used, the corresponding carboxyethyl (3 -alanine derivative is produced (Figure 6.7). 

In addition to the above-mentioned monomers, various acrylic and methacrylic esters, methacrylonitrile, itaconic acid, crotonic acid, methyl vinyl ketone, allyl alcohol, allyl amine etc., have been studied by Fischer... 

Hydroperoxide-n-Butyllithium gives 50% de. Chiral 3-amino esters of 8-phenylmenthol have been prepared in 50-60% de by the addition of amines to the re face of 8-phenylmenthyl crotonate under 14-15 kbar pressures (eq 2). Much higher (75 to >99%) de is obtained using 8-0-naphthyl)menthol crotonate. The 3-amino esters obtained are of the proper configuration for conversion to biologically active 3-lactams. ... 

Two different chiral auxiliary approaches have been applied to the synthesis of NPS 1407 and it s enantiomer (119) (147). NPS 1407 is an antagonist of the glutamate NMDA receptor that has in vivo activity in neuroprotection and anti-convulsant assays. The J2-en-antiomer was synthesized in four steps from (116)with the chiral center introduced by. a completely stereoselective alkylation of hydra-zone (117). The chiral auxiliary, jS-( )-l-ami-no-2-(methoxylmethyl)pyrrolidine (SAMP), was introduced by condensation with aldehyde (116) and removed by catalytic hydro-genolysis. In the second method, the S-enan-tiomer was formed in a four-step sequence with the chiral center installed by the Michael addition of chiral amine (121) (formed in one step from the readily available a-methylben-zylamine) to benzyl crotonate (120). NPS 1407 (123) was found to be 12 times more potent than it s enantiomer (119)at the NMDA receptor in an in vitro assay. 

Action of Hydrogen and of Ammonia.— Another reaction of aceto acetic ester should be mentioned. When hydrogen (sodium amalgam), ammonia or alkyl primary amines react with aceto acetic ester, crotonic acid (p. 173) CHs—CH = CH—COOH, or derivatives of it are obtained. The fact that crotonic acid contains a double bond seems to indicate the presence of a double bond in aceto acetic ester, and would be evidence for the enol form. 

Ethyl 3-formylbutyrate (61) was prepared in 15% overall yield from ethyl crotonate (56) by sequential hydrobromination, cyanation, reductive amination with 7V,7V -diphenylethylenediamine (59) in the presence of Raney nickel catalyst, and acid-catalyzed hydrolysis as shown in Scheme... 

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