Reduction of 2-chloro-N-phenylpropanamide and 2-methyl-N-phenylaziridine with lithium aluminium hydride.

The reduction of 2-chloro-N-phenylpropanamide with LiAlH(4) has been re-examined. In contrast to previous findings, we obtain in almost equal quantities two amines from this reaction, namely N-propylaniline and the rearranged product N-isopropylaniline. 2-Methyl-N-phenylaziridine is an intermediate in the reduction and can be isolated from reactions with less LiAlH(4). Reduction of 2-methyl-N-phenylaziridine itself proceeds non-regioselectively to provide a mixture of propyl- and isopropylanilines. Formation of the amines by reduction of the aziridine is much slower than formation by reduction of the 2-chloropropanamide, which indicates that Lewis acid catalysis (by aluminium chlorohydrides) facilitates the reduction of the aziridine. In addition, Lewis acid catalysis increases the relative yield of the propylamine product. The reduction of 2-chloro-N-phenylpropanamide furnishes 2-phenylamino-1-propanol as a by-product, rather than the previously proposed 1-phenylamino-2-propanol.

[1]  R. Verhé,et al.  Reaction of secondary N-1-(2-chloroalkylidene)amines with lithium tetrahydridoaluminate: Synthesis and rearrangement of 1,2,2-trisubstituted aziridines† , 2010 .

[2]  R. Verhé,et al.  Reactivity of α,α‐Dihalogenated Imino Compounds. Part IX Rearrangement of N‐2‐ (1, 1‐Dichloroalkylidene) Anilines with Lithium Aluminium Hydride , 2010 .

[3]  R. Verhé,et al.  On the mechanism of the rearrangement of N-aryl α,α-dichloroketimines with lithium aluminium hydride† , 2010 .

[4]  N. de Kimpe,et al.  Synthesis and reactivity of C-heteroatom-substituted aziridines. , 2007, Chemical reviews.

[5]  A. Yudin,et al.  Preparation and Reactivity of Versatile α-Amino Ketones , 2007 .

[6]  Takuya Kumamoto,et al.  Ring‐Opening Reactions of 3‐Aryl‐1‐benzylaziridine‐2‐carboxylates and Application to the Asymmetric Synthesis of an Amphetamine‐Type Compound , 2007 .

[7]  R. Di Fabio,et al.  Asymmetric synthesis of 2-(2-pyridyl)aziridines from 2-pyridineimines bearing stereogenic N-alkyl substituents and regioselective opening of the aziridine ring. , 2006, The Journal of organic chemistry.

[8]  U. Holzgrabe,et al.  Aziridine-2,3-dicarboxylate inhibitors targeting the major cysteine protease of Trypanosoma brucei as lead trypanocidal agents. , 2006, Bioorganic & medicinal chemistry letters.

[9]  A. Chakraborti,et al.  Lithium Bromide, an Inexpensive and Efficient Catalyst for Opening of Epoxide Rings by Amines at Room Temperature under Solvent‐Free Condition , 2004 .

[10]  José Ramón Suárez,et al.  Synthesis and stereoselective lithiation of enantiopure 2-(1-aminoalkyl)aziridine-borane complexes. , 2004, Angewandte Chemie.

[11]  J. Metzger,et al.  Fat‐Derived Aziridines and Their N‐Substituted Derivatives: Biologically Active Compounds Based on Renewable Raw Materials , 2003 .

[12]  J. Sweeney.  Aziridines: epoxides' ugly cousins? , 2002, Chemical Society reviews.

[13]  R. S. Coleman,et al.  SYNTHESIS OF NATURALLY OCCURRING ANTITUMOR AGENTS : STEREOCONTROLLED SYNTHESIS OF THE AZABICYCLIC RING SYSTEM OF THE AZINOMYCINS , 1999 .

[14]  J. Bae,et al.  Synthesis of substituted (D)-phenylalanine derivatives by regioselective reduction of enantiomerically pure cis-2,3-disubstituted aziridines , 1998 .

[15]  D. Tanner,et al.  Regioselective nucleophilic ring opening of epoxides and aziridines derived from homoallylic alcohols , 1997 .

[16]  A. Otaka,et al.  Palladium-catalyzed reductive ring opening with formic acid of aziridines bearing an α,β-unsaturated ester group , 1997 .

[17]  G. Molander,et al.  Reduction of 2-acylaziridines by samarium(II) iodide. An efficient and regioselective route to β-amino carbonyl compounds , 1997 .

[18]  D. Tanner,et al.  Studies of regio- and stereoselectivity in some nucleophilic ring opening reactions of N-tosyl-3-phenyl-2-aziridinemethanols and derivatives , 1995 .

[19]  M. Yus,et al.  N,2-Dilithioalkylamines from Aziridines by Naphthalene-Catalyzed Reductive Opening. Synthetic Applications , 1994 .

[20]  D. Tanner,et al.  Regioselective nucleophilic ring opening of 2,3-aziridino alcohols , 1992 .

[21]  D. Tanner,et al.  An aziridine route to chiral β-lactams a novel entry to (+)-thienamycin , 1987 .

[22]  R. PfisterJurg.  A One-Pot Synthesis of Aziridines from 2-Aminoethanols , 1984 .

[23]  Kunio Suzuki,et al.  Reductive Rearrangement of 2-Chloroalkanamides with Lithium Aluminum Hydride Leading to α-Methyl-Branched Aliphatic Amines , 1983 .

[24]  R. Verhé,et al.  Synthesis of 2,2-dichloro-1,3-diarylaziridines by reduction of trichloroacetophenone imines , 1981 .

[25]  R. Verhé,et al.  Stereospecific synthesis of N-substituted cis-2-aryl-3-alkylaziridines , 1980 .

[26]  C. Gey,et al.  Stereochimie en serie aziridine—XIII: N-chloration d'aziridines secondaires, reduction de n-chloroaziridines cetoniques , 1979 .

[27]  R. Verhé,et al.  A Facile Synthesis of 1,2-Disubstituted Aziridines , 1975 .

[28]  Jean-Louis Pierre,et al.  Stereochimie en serie aziridine—XIII , 1974 .

[29]  Shi-chow Chen.  Molecular Rearrangements in Lithium Aluminum Hydride Reduction , 1974 .

[30]  T. Okada,et al.  Kinetics and Mechanism of Aziridine Synthesis from Ketoxime with Lithium Aluminum Hydride , 1973 .

[31]  M. Ohta,et al.  Umwandlung von Aldehyden in 2-monosubstituierte Aziridine. Reduktion von α-Chlor, Brom- und Sulfonyloxynitilen mit Lithiumaluminiumhydrid , 1970 .

[32]  K. Kotera,et al.  Conversion of 2-isoxazolines into aziridines by lithium aluminum hydride reduction , 1970 .

[33]  D. Arnold,et al.  Mercury photosensitized extrusion reactions for the preparation of heterocycles , 1970 .

[34]  F. W. Fowler,et al.  Stereochemistry. XLI. Reduction of .beta.-iodo azides. Stereospecific synthesis of aziridines , 1969 .

[35]  T. Okada,et al.  Aziridine formation by lithium aluminum hydride reduction of oximes , 1968 .

[36]  T. Okada,et al.  Stereochemistry of aziridine formation by reduction of oximes with lithium aluminum hydride on aralkyl alkyl ketoximes and their tosylates , 1968 .

[37]  T. Okada,et al.  Aziridine formation by reduction of ketoximes with lithium aluminium hydride , 1968 .

[38]  M. Ohta,et al.  Eine neue Synthese von Aziridinen durch Reduktion von α-Chlornitrilen mit Lithiumaluminiumhydrid , 1967 .

[39]  T. Okada,et al.  Formation of aziridines by lithium aluminum hydride reduction of ketoximes , 1965 .

[40]  D. Delmonte,et al.  The Mechanism of Halide Reductions with Lithium Aluminum Hydride. VI. Reduction of Certain Bromohydrins and Epoxides1,2 , 1958 .

[41]  D. Delmonte,et al.  ANOMALOUS REDUCTION OF EPOXIDES WITH LITHIUM ALUMINUM HYDRIDE , 1956 .

[42]  E. Schlittler,et al.  Eine neue Methode zur Reduktion eines Amids zum Amin mit der gleichen Anzahl von Kohlenstoffatomen , 1948 .