Benzylamine and Dibenzylamine Revisited. Syntheses of N-Substituted Aryloxypropanolamines Exemplifying a General Route to Secondary Aliphatic Amines

References

• Henderson , W. A. Jr. and Schultz , C. J. 1962 . J. Org. Chem. , 27 : 4643 The direct conversion of primary to secondary amines by alkylation with electrophiles containing good leaving groups is generally complicated by multiple additions to a portion of the amine starting material. Simply employing an excess of amine usually will not remedy this situation since the desired secondary amines are typically superior nucleophiles to their precursor primary amines, especially when one or more of the nitrogen substitutents is relatively small (unbranched). Alternatively, monoalkylation of secondary amines to tertiary amines poses a lesser problem and when a primary amine contains a large substituent it is easier to control the degree of alkylation such that the secondary amine can be obtained in good yield depending upon the size of the added alkyl function. The kinetic influence of basicity, steric hinderance and solvation have been discussed with regard to the Menschutkin Reaction: W. P. Jeneks, “Catalysis in Chemistry and Enzymology”, McGraw-Hill, New York, 1969, Chapter 2; D. C. Wigfield and B. Lem, Tetrahedron, 31, 9 (1975); J. I. Seeman and J. F. Whidby, J. Org. Chem., 41, 3824 (1976). A discussion of the kinetic influence of these parameters concerning primary, secondary and tertiary aromatic amines has also appeared: P. Murti and G. Panagrahi, J. Ind. Chem. Soc., 44, 430 (1967); P. Radhakrishnamurti and G. Pnaigrahi, J. Ind. Chem. Soc., 46, 567 (1969).
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• Although the use of benzylamine to introduce an amino-group during chemical synthesis represents classical methodology, its introduction for the purpose of controlling the extent of amine alkylation during subsequent sequential reactions has not been significantly utilized
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• Marchini , P. , Liso , G. and Reho , A. 1975 . J. Org. Chem. , 40 : 3453 For example: RCO2H → RCOC1 → RCONHR′ → RCH2 NHR'; RCO2H + NaBH4 + RNH2 → RCH2NHR'RCHO + R'NH2 + NaCNBH3 → RCH2NHR' [R. Borch, M. Bernstein and H. Durst, J. Am. Chem. Soc., 93, 2897 (1971)]; Gabriel-like transformations via N-substituted trifluoroacetamides (J. E. Nordlander, D. B. Catalane, T. H. Eberlein, L. V. Farkas, R. S. Howe, R. M. Stevens and N. A. Tripoulas, Tet. Lett., 1978, 4987); organocopper reagents [H. Yamamoto and K. Maruoka, J. Org. Chem., 45, 2739 (1980)]; and organoborane reagents [M. W. Rathke, N. Inoue, K. R. Varma and H. C. Brown, J. Am. Chem. Soc., 88, 2870 (1966) and G. W. Kabalka, K. A. R. Sastry, G. W. McCollum and H. Yoshioka, J. Org. Chem., 46., 4296 (1981)].
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