Hohenlohe-Oehringen, K. published the artcile1-Methoxy-l-buten-3-one and primary amines, Application In Synthesis of 28056-87-3, the publication is Monatshefte fuer Chemie (1962), 586-99, database is CAplus.
MeOCH:CHAc (I) condensed with primary aliphatic amines and treated with HCl gave via the non-isolated alkylaminobutenones 40-50% N-alkyl2-methyl-5-acetylpyridinium salts (II). These were reducible directly or through intermediate stages to N-alkylcopellidines or N-alkylisocopellidines (1-alkyl-2-methyl-5-ethylpiperidines) (III). The structure of the II was proved by synthesis of the N-Me derivatives and the structure of the III by degradation. Homoveratrylamine (IIIa) (35 g.) in 90 ml. Et2O treated with 53 g. I, when the reaction subsided the solution kept 3 hrs. at room temperature, treated with Et2O-HCl, the gummy solid separated by decanting the supernatant solution, refluxed 2 hrs. in 100 ml. CHCl3, the solution diluted with 200 ml. Me2CO, and cooled gave 32 g. N-homoveratryl-2-methyl-5-acetylpyridinium chloride (IV), m. 220-30¡ã (decomposition); phenylhydrazone decompose 138-9¡ã (Me2CO). Aqueous IV poured into Me2CO containing NaI gave the corresponding iodide, m. 188¡ã. Aqueous IV treated with concentrated aqueous NH3 gave an unstable anhydro base, reconverted with Et2O-HCl into IV. IV (12 g.) in 50 ml. AcOH hydrogenated with Pd-C at room temperature and atm. pressure (970 ml. H absorbed), filtered, the filtrate evaporated in vacuo, and the residue recrystallized from EtOH-Me2CO gave 9.7 g. N-homoveratryl-2-methyl-5-(¦Á-hydroxyethyl)pyridinium chloride (V), m. 170¡ã. Alc.-V treated with Me2CO containing NaI gave the corresponding iodide, m. 175¡ã. IV (3.5 g.) in H2O treated with concentrated aqueous NH3, the precipitate filtered off, washed with H2O, dissolved in MeOH, the solution treated with MeI, heated 2 hrs. on a H2O bath in a glass autoclave, and cooled gave 1.6 g. unidentified compound, C19H24NO3I, m. 207¡ã (MeOH). IV (5 g.) and 10 ml. N2H4.H2O in 15 ml. EtOH boiled 45 min., evaporated in vacuo the residue treated with concentrated aqueous HCl, the mixture evaporated, the residue crystallized from EtOH, and the solid filtered off gave 3.1 g. compound, m. 170-92¡ã; evaporation of the mother liquor gave 2.1 g. IIa.HCl, m. 156¡ã (EtOH-Me2CO). PtO2 (2 g.) hydrogenated in 10 ml. H2O, the mixture treated with 15 g. IV in N HCl, hydrogenated at room temperature and atm. pressure (every 4 hrs. the mixture was shaken with air to reactivate the catalyst; after 30-40 hrs. 5300 ml. H was absorbed), the catalyst filtered off, extracted with boiling H2O, the extract filtered while hot, the combined filtrates evaporated in vacuo, and the residue crystallized from Me2CO gave 5.7 g. N-homoveratrylcopellidine-HCl (VI.HCl), m. 200¡ã (EtOH-Me2CO). VI.HCl in H2O treated with aqueous Na2CO3 gave VI, b7 160-70¡ã; HBr salt m. 212¡ã; HI salt m. 190¡ã; picrate m. 153¡ã. The Me2CO mother liquor from the above reduction kept several days at -20¡ã and the resulting solid (3.6 g.) repeatedly crystallized from EtOH-Et2O gave N-homoveratrylisocopellidine-HCl (VII.HCl) (isomeric with VI.HCl), m. 185¡ã; VII b7 160-70¡ã. Homoveratryl bromide [prepared by LiAlH4 reduction of 3,4-(MeO)2C6H3CH2CO2Et followed by treatment with PBr3] (2 g.) and 1 g. dl-coniine in 10 ml. C6H6 heated 4 hrs. on a H2O bath in a glass autoclave, cooled, filtered, the filtrate converted to bases, and the bases fractionated in vacuo gave N-homoveratrylconiine, b0.05 120¡ã, which was nonidentical with either VI or VII; HCl salt m. 95¡ã; picrate m. 104¡ã (EtOH). VI (2 g.) and excess MeI in Et2O kept 16 hrs. at room temperature and the oily precipitate crystallized from MeOH gave VI.MeI, m. 146¡ã. VI.Mel (1 g.) in 40 ml. H2O shaken 1 hr. with Ag2O (from 2 g. AgNO3), filtered, the filtrate evaporated in vacuo, the residue distilled in vacuo (H2O pump), and the distillate worked up gave a neutral (VIII) and basic (IX) fraction; VIII treated with Et2O-picric acid gave N-methylcopellidine (X) picrate (XI), X. 169¡ã; IX was identified as 3,4-(MeO)2C6H3CH:CH2 by its spectrum, by formation of its bromide, m. 101¡ã, and by KMnO4 oxidation to veratric acid, m. 178-80¡ã. MeNH2 (3.1 g.) and 20 g. I in 100 ml. Et2O kept 4 hrs. at room temperature and treated with Et2O-HCl gave 2.7 g. 2-methyl-5-acetylpyridine-MeCl (XII.MeCl) sesquihydrate, decompose 207-15¡ã (EtOH-EtOAc); phenylhydrazone hemihydrate decompose 237¡ã. I (170 g.) in 300 ml. Et2O cooled to -20¡ã, the solution mixed with a cooled (-20¡ã) solution of 35 ml. MeNH2 in 100 ml. Et2O, kept 1 hr. in an ice-salt mixture and then 15 min. at room temperature, treated with Et2O-HCl, the precipitate separated by decanting the supernatant Et2O solution, dissolved in AcOH, and the solution treated with AcOH-Br at 10-15¡ã gave 112 g. perbromide (XIII), needles [HCONMe2 (XIV)-AcOH], decomposing slowly at room temperature and rapidly at 70¡ã. XIII in XIV treated portionwise with PhOH in XIV with cooling and diluted with Et2O gave 61 g. XII.MeBr, m. 204¡ã (decomposition). XIII heated above 70¡ã (HBr was evolved; self-bromination occurred) gave a Br derivative of XII.MeBr hydrate, m. 200¡ã (decomposition) (H2OMe2CO). XII.MeBr was stable in neutral and acid solution and towards oxidation agents, but was unstable in the alk. range, forming in aqueous NaHCO3 a carmine-red dye. XII.MeBr heated with MeI and NaHCO3 gave the carmine-red dye mentioned above; if the NaHCO3 was omitted, XII.MeI, m. 157¡ã, was formed. XII.MeBr (20 g.) in 40 ml. H2O and 12 ml. HCl hydrogenated with 3 g. PtO2 at room temperature and atm. pressure (the catalyst was frequently reactivated by shaking with air; after 35 hrs. 11,200 ml. H was absorbed), filtered, the filtrate evaporated in vacuo, the residue dissolved in a little H2O, the solution treated with KOH, extracted with Et2O, the extract evaporated, the residual base (XV) dissolved in 50 ml. EtOH, the solution treated with warm EtOH containing 19 g. picric acid and the product (25 g.) recrystallized twice from EtOH gave 21 g. XI, m. 169¡ã (EtOH). XV treated with Et2O-HCl gave X.HCl, m. 205¡ã (sublimed above 160¡ã) (EtOH-Et2O); X.HBr m. 198-200¡ã. XI in aqueous suspension treated with dilute aqueous NaOH gave X, b7 60¡ã, mol. weight (mass spectrometry) 141. The mother liquor of XI (m. 169¡ã) concentrated, the residue dissolved in petr. ether, and the solution kept 24 hrs. deposited 8 g. N-methylisocopellidine (XVI) picrate (XVII), m. 98¡ã (EtOH-Et2O); XVI b7 60¡ã. XII.MeBr (15 g.) in 50 ml. H2O containing 8 g. NaOAc.3H2O hydrogenated 6 hrs. with Raney Ni at 150-60¡ã and 100 atm., the catalyst filtered off, washed with EtOH, the combined filtrate and washing treated with HCl, evaporated in vacuo, the residue dissolved in H2O, the solution made strongly alk. with KOH, the product isolated with Et2O, and distilled gave 3.3 g. isomer of X and XVI, C9H19N, b7 54-6¡ã [picrate m. 205-10¡ã (EtOH)], and 3.5 g. 1,2-dimethyl-b-(¦Á-hydroxyethyl)piperidine (XVIII), b7 115-17¡ã [picrate m. 158¡ã (EtOH Et2O)]. XVIII (1 g.) treated with Et2O-HCl, the resulting XVIII.HCl dissolved in excess SOCl2, the solution boiled 1 hr., evaporated, the residue treated with C in Me2CO-H2O, the solution hydrogenated with Raney Ni at room temperature, after H absorption ceased the mixture filtered, the filtrate treated with a few ml. HCl, evaporated, the residue made alk., the product isolated with Et2O, and treated with pieric acid gave XI, m. 169¡ã (EtOH). XII.MeBr (9.5 g.) in AcOH hydrogenated with Pd-C at room temperature and atm. pressure (after 1 hr. 1300 ml. H was absorbed, when absorption ceased), filtered, and the filtrate evaporated in vacuo gave crude 1,2-dimethyl-5-(¦Á-hydroxyethyl)pyridinium bromide (XIX), which could not be crystallized Crude XIX refluxed 3 hrs. with excess SOCl2, the solution evaporated in vacuo on a H2O bath, the residue heated 1 hr. at 100¡ã in vacuo, and the product recrystallized from EtOHEt2O gave dichloropyridinium chloride compound (XX), C9H12Cl3N, having the double m.p. 160¡ã and 169¡ã. XX in H2O hydrogenated with Pd-C at room temperature and atm. pressure, filtered, the filtrate evaporated, the residue dissolved in a little EtOH, the solution treated with some Me2CO, decanted from precipitated oily byproducts, and diluted with Et2O gave 1,2-dimethyl-5-ethylpyridinium chloride, very hygroscopic; picrate m. 112¡ã (EtOH). XI (12 g.) suspended in 50 ml. H2O, treated with dilute NaOH (from 3 g. NaOH), steam distilled, the distillate treated with Et2O, the Et2O phase separated, and kept 1 day at room temperature with excess MeI gave 8.2 g. X.MeI, m. 230-3¡ã (EtOH-Me2CO). X.MeI (4.5 g.) in 50 ml. H2O shaken 0.5 hr. at room temperature with Ag2O (from 8 g. AgNO3), filtered, the filtrate evaporated in vacuo, and the residue distilled in vacuo (80 mm.) and 140¡ã (bath temperature) gave CH2:CH(CH2)2CHEtCH2NMe2 (XXI); picrate (XXII) m. 69¡ã (EtOH-Et2O); methiodide (XXIII) m. 190-2¡ã (Me2COEt2O). XVII (20 g.) converted as above to XVI.MeI [m. 286-8¡ã (decomposition)] and the latter subjected to similar Hofmann degradation gave 5.7 g. XXI (XXII m. 69¡ã; XXIII m. 193¡ã); these products from XVI.MeI were identical with the analogous products obtained from X.MeI. XXI (2 g.) in 15 ml. dilute HCl hydrogenated with Pd C at room temperature and atm. pressure (H absorption ceased after 0.5 hr.), filtered, the filtrate made alk., the product isolated with Et2O, and distilled gave Me(CH2)3CHEtCH2NMe2, b7 62¡ã; methiodide (XXIV) m. 217¡ã (Me2CO-EtOAc). XXIV (10 g.) in 200 ml. H2O shaken 0.5 hr. with Ag2O (from 15 g. AgNO3), filtered, the filtrate evaporated in vacuo, the residue decomposed at 155¡ã (bath temperature) and atm. pressure (Widmer column), the distillate diluted with Et2O, the solution extracted with dilute HCl, dried, and fractionated gave 1.2 g. Me(CH2)3CEt: CH2 (XXV), b. 117¡ã/740 mm. XXV (0.5 g.) in EtOAc ozonized at -15¡ã until no more O3 was absorbed, the solution hydrogenated with Pd-C at room temperature and atm. pressure until H absorption ceased, filtered, the EtOAc filtrate and the catalyst extracted with H2O, and the combined extracts treated with dimedon in EtOH gave 0.65 g. dimedon derivative of CH2O, m. 192¡ã. XXV (0.6 g.) in 5 ml. HCO2Me hydrogenated with Pd-C at 50 atm. and room temperature, filtered, and the filtrate fractionated gave Me(CH2)3CHMeEt, b. 116¡ã/740 mm. Infrared and ultraviolet spectral data were presented.
Monatshefte fuer Chemie published new progress about 28056-87-3. 28056-87-3 belongs to catalysis-chemistry, auxiliary class Amine,Aliphatic hydrocarbon chain, name is 2-Ethyl-N,N-dimethylhexan-1-amine, and the molecular formula is C10H23N, Application In Synthesis of 28056-87-3.
Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia