Chatterjee, A.; Bose, S.; Srimany, S. K. published an article in 1959, the title of the article was Constitution, stereochemistry, and synthesis of aegeline, an alkaloidal amide of Aegle marmelos.Synthetic Route of 456-12-2 And the article contains the following content:
cf. CA 47, 10544g. Aegeline (I), C18H19NO3, was shown to be N-β-hydroxy-β-p-methoxyphenylethylcinnamamide by degradation and synthesis and its trans configuration established spectrometrically. Powd. sun-dried leaves of A. marmelos (5 kg.) extracted 72 hrs. with 8 l. Et2O and the deep green extract concentrated to 500 ml., washed with 1% HCl and 5% aqueous NaOH and the dried concentrate refrigerated 2 weeks, the precipitate (3.6 g.) triturated with C6H6 and Me2CO and the residue crystallized from alc. gave I, m. 173-5°. The mother liquors evaporated and the residue chromatographed in C6H6 on 4 kg. Al2O3, the column eluted with 200 ml. EtOAc and the fraction (2.4 g.) recrystallized (alc. and EtOAc) yielded pure I, m. 176°; mono-Ac derivative, m. 124°. I (0.3 g.) in 30 ml. aldehyde-free alc. hydrogenated 2 hrs. with 0.09 g. prereduced PtO2 and the filtered solution evaporated gave dihydroaegeline, C18H21NO3, m. 140° (alc. and EtOAc). I (0.25 g.) in 10 ml. EtOAc and 2 ml. AcOH ozonized 50 min. at -75° and the ozonide decomposed reductively overnight with 0.5 g. Mg powder in 10 ml. 1:1 AcOH-H2O, the mixture diluted with 50 ml. H2O and shaken 3 times with 30 ml. CHCl3, the organic layer washed twice with 2N HCl and once with H2O and the dried (anhydrous Na2SO4) solution evaporated (N atm.), the residual oil taken up in 2 ml. alc. and treated 40 hrs. with Brady’s reagent, the precipitate taken up in 1:1 C6H6-AcOEt and chromatographed over Al2O3, eluted with C6H6 and the fraction recrystallized 3 times from alc. gave authentic 2,4-(O2N)2C6H3NHN:CHPh (II), m. 235°. I (0.15 g.) in 150 ml. MeOH treated 4 hrs. with 2 g. HIO4 and the mixture steam-distilled, the distillate (800 ml.) extracted 4 times with 250 ml. Et2O and the extract washed with aqueous NaHSO3, the iodine-free extract evaporated and the residue treated with 2,4-(O2N)2C6H3NHNH2, the precipitate (m. 225-47°) chromatographed in 15 ml. 1:1 C6H6-EtOAc over Al2O3 and eluted with 45 ml. C6H6 yielded 80 mg. II. Further elution with 30 ml. EtOAc gave 40 mg. 2,4-(O2N)2C6H3NHN:CHC6H4OMe-p (III), m. 250°. I (0.5 g.) in 5 ml. alc. and 5 ml. concentrated HCl heated 60 hrs. in a sealed tube at 120° (oil bath) and the cooled mixture diluted with 50 ml. H2O, extracted 3 times with 100 ml. Et2O and the aqueous phase evaporated, the residue decomposed with alkali and the evolved gas adsorbed in 10 ml. 2N aqueous HCl, the solution evaporated and the residue taken up in 1 ml. H2O, treated with a few drops of aqueous picric acid gave H2NMe picrate, m. 209°. The H2O-washed Et2O layer shaken with aqueous NaHCO3 and the alk. solution acidified with HCl gave 0.159 g. PhCH:CHCO2H. The acid-free Et2O evaporated and the residue taken up in 3 ml. alc., the solution treated with 2,4-(O2N)2C6H3NHNH2 and the precipitate (60 mg.) chromatographed in 10 ml. EtOAc over Al2O3 and eluted with 45 ml. C6H6 and 30 ml. EtOAc gave III from the latter eluant. I (1 g.) fused 30 min. with 6.0 g. KOH in a Ni crucible at 250° with evolution of MeNH2 and the cooled mass digested in 200 ml. H2O containing 10.0 g. NH4Cl, the filtered solution shaken 5 times with 100 ml. Et2O and the cooled aqueous solution acidified with HCl, extracted 3 times with 100 ml. Et2O and the washed and dried extract evaporated gave a mixture of 30 mg. p-MeOC6H4CO2H and 170 mg. BzOH. The probability that I suffered hydramine fission and that the basic fragment was a p-MeOC6H4CH(OH)CH2NH2 derivative was finally substantiated by a simple straight forward synthesis. Prolonged hydrolysis of ω-phthalimido-p-methoxyacetophenone with refluxing concentrated HCl gave p-MeOC6H4COCH2NH2.HCl, taken up (1 g.) in 3 ml. H2O and treated with 3 ml. aqueous solution of 1.24 g. SnCl4.4H2O containing 1 ml. HCl, the mixture stirred and the crystalline precipitate (2.0 g.) taken up in 20 ml. hot H2O, the solution cooled to 37° and stirred with 2.0 g. molten PhCH:CHCOCl, the mixture treated dropwise with 25 ml. 10% aqueous KOH until red and the stirring continued until the solution became colorless, the addition of alkali resumed and the alternate process continued until the red coloration persisted, the pyrazine-free solution stored 2 hrs. and the H2O-washed crystals recrystallized (EtOAc), gave ω-cinnamoylamino-p-methoxyacetophenone, m. 153-4°. The ketone (0.5 g.) in 50 ml. MeOH treated with 5.0 g. NaBH4 and the mixture kept 24 hrs., the solution concentrated and diluted with 100 ml. H2O, extracted 3 times with 200 ml. Et2O and the washed and dried extract evaporated yielded 60% authentic I, m. 176° (EtOAc). The absorption maximum λ 217, 223, 275 mμ (log ε 4.5328, 4.5177, 4.6053) were indicative of a trans double bond to the carboxyamide group and this assignment was in agreement with the strong absorption in the infrared spectrum at “trans-band region” (intense band at 982 cm.-1 with a shoulder at 990 cm.-1). Comparative data for other trans α,β-unsaturated amides were tabulated (compound and ν in cm.-1 given): I, 3250, 3060, 2830, 1665, 1627, 1580, 1520, 1062, 1040, 990, 982; trans-N-2-p-methoxyphenylethyl-N-methylcinnamamide, 1655, 1610, 1576, 1509, 1036, 1027, 991, 982; trans-N-methylcinnamamide, 3280, 3100, 2860, 1660, 1625, 1580, 1500, 953. I contained an asym. C atom but was optically inactive and it seemed that the linkage of the trans-cinnamoyl group to the optically active N-β-hydroxy-β-p-methoxyphenylethylamine caused an inversion at the asym. center. The experimental process involved the reaction of N-(2-Hydroxy-2-(4-methoxyphenyl)ethyl)cinnamamide(cas: 456-12-2).Synthetic Route of 456-12-2
N-(2-Hydroxy-2-(4-methoxyphenyl)ethyl)cinnamamide(cas:456-12-2) belongs to amides. Amides are pervasive in nature and technology. Proteins and important plastics like Nylons, Aramid, Twaron, and Kevlar are polymers whose units are connected by amide groups (polyamides); these linkages are easily formed, confer structural rigidity, and resist hydrolysis. Synthetic Route of 456-12-2
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics