Synthesis Of α-aminoammides By Addition Of Carbamoylsilane To Imines

This article has three parts.The first part briefly introduces the research progress in the synthesis and properties of carbamoylsilane α-aminoamide.The second part introduces the reaction of carbamoylsilane 1and a series of N-Boc imine plus,generate the corresponding α-aminoamide.The third part introduces the carbamoylsilane method for synthesis of α-amino secondary amide reaction 3and a series of N-Boc imines.α-aminoamide exists widely in nature,It is widely used in organic synthesis and clinical medicine.It can be used to synthesize natural products and drugs,and its derivatives can also be used to treat diseases such as headache.Therefore,the research on the synthesis method ofα-aminoamide is very important.The synthetic methods of α-aminoamide method is used Ugi reaction and the new Ugi reaction,but this method also has some shortcomings.In order to develop a simple and efficient method for the synthesis of the α-aminoamide.Our group use carbamoylsilane and imine to react,and get a good yield,on the basis of the study,we synthesised α-amino secondary amide project,a simple and efficient method to provide for the organic synthesis method.In this paper,we first use the aldehyde,carbamate,sodium benzene sulphinate and formic acid synthesised N-Boc imine,such as aldehyde N-Boc imine(11),isobutylaldehyde N-Boc imine(12),4-dimethylamino benzaldehyde N-Boc imine(13),aubepine N-Boc imine(14),methyl benzaldehyde N-Boc imine(15),benzaldehyde N-Boc imine(16),parachlorobenzaldehyde N-Boc imine(17),p-nitrobenzaldehyde N-Boc imine(18),2-furan aldehyde N-Boc imine(19),2-thiophene N-Boc aldehyde imine(20),2-pyridine aldehydeN-Boc imine(21),cinnamyl aldehyde N-Boc imine(22)reacts with carbamoylsilane 1.We obtain α-(N-Boc)amino-N,N-dimethyl-valeramide(31),α-(N-Boc)amino-N,N-dimethylis opropylamide(32),α-(N-Boc)amino-N,N-dimethyl-(4-dimethylamino)acetamide(33),α-(N-Boc)amino-N,N-dimethyl-N,N-(4-methoxy amide)phenylacetamide(34),α-(N-Boc)am ino-N,N-dimethyl-(4-methyl)phenylacetamide(35),α-(N-Boc)amino-N,N-dimethyl phenylacetamide(36),α-(N-Boc)amino-N,N-dimethyl(4-methyl chloride)phenyl acetamide(37),α-(N-Boc)amino-N,N-dimethyl(4-methyl)phenyl acetamide(38),α-(N-Boc)amino-N,N-dimethyl-(2)-furylacetic amide(39),α-(N-Boc)amino-N,N-dimethyl thiophene acetamide(40),α-(N-Boc)amino-N,N-dimethyl pyridinium acetamide(41),α-(N-Boc)amino-N,N-dimethyl-4-phenyl-2-butryumid(42).By comparing the experimental results.When there is anelectron withdrawing group attached to the imine,the stronger the electron withdrawing ability is,the shorter the reaction time is,the higher the yield is,and the longer the reaction time is,the larger the steric hindrance of the N-Boc imine group is.After discovery this synthetic method,we have reacted with carbamoylsilane 3 and N-Boc imine 11-22 respectively,and the corresponding product α-(N-Boc)amino-N-methyl-N-methoxy methyl valeramide(51),α-(N-Boc)amino-N-methyl-N-methoxy methyl-isopropyla mide(52),α-(N-Boc)amino-N-methyl-N-methoxy-methyl-(4-dimethylamino)acetamide(53a),α-(N-Boc)amino-N-propyl-N-methoxy-methyl-(4-dimethylamino)acetamide(53b),α-(N-Boc)amino-N-cyclohexyl-N-methoxy-methyl-(4-dimethylamino)acetamide(53c),α-(N-Boc)amino-N-benzyl-N-methoxy-methyl-(4-dimethylamino)acetamide(53d),α-(N-Boc)amino-N-methyl-N-methoxymethyl-N,N-(4-methoxyamide)-phenylacetamide(54),α-(N-Boc)amino-N-methyl-N-methoxy methyl-(4-methyl)phenylacetamide(55a),α-(N-Boc)amino-Npropyl-N-methoxy methyl-(4-methyl)phenylacetamide(55b),α-(N-Boc)amino-N-cyclohexy l-N-methoxy methyl-(4-methyl)phenylacetamide(55c),α-(N-Boc)amino-N-benzyl-N-methox y methyl-(4-methyl)phenylacetamide(55d),α-(N-Boc)amino-N-methyl-N-methoxy-methyl phenylacetamide(56),α-(N-Boc)amino-N-methyl-N-methoxymethyl-(4-methylchloride)phenyl-N-methyl-N-methoxyacetamide(57a),α-(N-Boc)amino-N-cyclohexyl-N-methoxymethyl-(4-m ethylchloride)phenyl-N-propyl-N-methoxyacetamide(57b),α-(N-Boc)amino-N-methyl-N-methoxymethyl-(4-methylchloride)phenyl-N-cyclohexyl-N-methoxyacetamide(57c),α-(N-Boc)ami no-N-methyl-N-methoxymethyl-(4-methylchloride)phenyl-N-benzyl-N-methoxyacetamide(57d),α-(N-Boc)amino-N-methyl-N-methoxymethyl-(4-methyl)phenylacetamide(58),α-(N-Boc)a mino-N-methyl-N-methoxymethyl-(2)-furylacetic amide(59),α-(N-Boc)amino-N-methyl-Nmethoxy methyl thiophene acetamide(60),α-(N-Boc)amino-N-methyl-N-methoxy-methyl pyridinium acetamide(61),α-(N-Boc)amino-N-methyl-N-methoxy methyl-4-phenyl-2-butry umid(62).has been obtained,and a higher yield was obtained.Finally,we dissolve the α-amino amide 53-57,59 to hydrolysis,and then convert it intoα-amino amide: 73-77,79,the hydrolysis yield is higher.Through the experiment,carbamoylsilane is an efficient introduction of amide organosilicon reagents,we synthesized without catalyst under the conditions,a series of high yield α-amino tertiary amide and α-amino secondary amide were synthesized,synthesis of amino acid,protein and drug intermediates provides a simple and efficient method.