J ~ N U A R Y1961
261
NOTES
Acknowledgments. The author is indebted to Dr. A. R. Hanze for his interest in this work, and to Mr. M. F. Grostic for interpretation of the infrared spectra.
The scope of the project involved only the walkyl halides from one to seven carbon atoms. The N,N-di-n-octyl compound was isolated from the intermediate secondary amine when the latter was produced. DEPARTMENT OF CHEMISTRY The elemental analyses and physical properties THEUPJOHN.COMPANY KAIAMAZOO, MICH. are given in Tables I and 11. It is worthy to note confirmation of the atomic factor value for the methylene group (D line) for the series synthesized. Synthesis of Some N-Benzyl-N-alkyl-N-n- Calculations from the observed molecular ref ractivities over the range of one to eight carbon atoms octylamines give an MD value of 4.617, while the generally accepted value is 4.61fA4 P. J. APICE~ Several attempts to prepare.the usual derivatives of the tertiary amines of this series have thus far Received April 29, 1960 been unsuccessful. This difficulty is probably due A recent research program of this laboratory mainly to steric effects. involved the preparation of some new tertiary EXPERIMENTAL^ amines from the intermediate N-benzyl-N-n-octylamine. In general, the intermediate N-benayl-NN-BenzyGN-woctyEamine. This base was obtained aa the n-octylamine can be prepared via reduction of the main product by the following process: Beneykmine, 286 g. corresponding Schiff basel2 or by the reaction of (2.67 moles), was mixed with n-octyl bromide, 257 g. (1.33 TABLE I ELEMENTAL ANALYSES Alkyl
Formula
HCHaCzHrTL-C~HF n-C4Hg7&5H11-
n-CsHir n-C7Hi5Z-CgHir
CILHZSN CieHz7N CI7HZ9N CiiHnN CioHaaN CzoH3nN CniHnN C2&9N CIJH~IN
Yield, % 68 39 73 61 64 59 64 66
-
Carbon, yo Calcd. Found
Hydrogen, % Calcd. Found
83.23 82.99 83.01 83.00 83.23 83.47 82.81 83.31 83.53
82.12 82.34 82.53 82.69 82.84 82.97 83.10 83.20 83.31
11.49 11.66 11.81 11.95 12.07 12.19 12.29 12.39 12.46
11.59 11.63 11.78 11.97 12.18 12.25 12.42 12.45 12.46
-Nitrogen, % Calcd.
Found
6.39 6.00 5.66 5.36 5.09 4.84 4.61 4.41 4.23
6.13 5.92 5.78 5.19 5.12 4.80 4.50 4.21 4.11
TABLE I1 PHYSICAL PROPERTIES Alkyl
B.P.,/Mm.
HCHaGHSn-C3Hr n-C4H9n-CSH11n-C&rn-C7Hlr n-CaHir
159-161.5/10 150-151.5/9 155.5-157/9 167-169/11 166-169/8 178.5-180.5/9 185-187.5/8 195-197/8 211-212/9
Sp. Gr.
20 20
0.8914 0.8825 0.8796 0.8758 0.8722 0.8702 0.8688 0.8682 0.8679
benzylamine with an n-oxtyl halide, or vice versa. In this work the second method was employed. This method is similar to that used by King and Work3 in preparing various secondary and tertiary benzylamines. (1) Present address: Plastics and Coal Chemicals Division, Allied Chemical Corporation, Technical Department, Edgewater, N. J. (2) R. E. Lutz, et al., J. Org. Chem., 12,760 (1947).
ny 1.4945 1.4909 1.4886 1.4857 1.4850 1.4835 1.4823 1.4818 1.4815
Molecular Refractivity Calcd. Obs. 71.54 76.50 81.12 85.73 90.28 94.97 99.59 104.21 108.82
71.70 76.57 81.16 85.66 90.43 95.09 99.65 104.23 108.89
moles), in a large beaker and allowed to stand at room temperature. The reaction is midly exothermic, and after 45 min. benzylamine hydrobromide was deposited as a white slush. The mixture was heated on a boiling water bath for 1 hr., cooled, diluted with dry ether, and the benzylamine (3) H. King and T. S. Work, J. Chem. Soc., 401 (1942). (4) H. Gilman, Organic Chemistry, An Advanced Treatise, Vol. IZ, John Wiley and Sons, Inc., New York, N. Y., 1943, p. 1751. (5) All melting and boiling points are corrected.
262
VOL.26
NOTES
hydrobromide collected. Recrystallization of the hydrobromide from ethanol gave a material, m.p. 222-223'. Anal. Calcd. for GHIoNBr:Br, 42.49. Found: Br, 42.43 and
from the concentrated reaction products with a solvent in which it is sparingly soluble, e.g., methanol. Where mentioned, the #?-alaninethus obtained 42.46. The ethereal solution waa shaken with 150 ml. of 10% is claimed to be of high purity. aqueous sodium hydroxide solution, separated, and dried Preliminary investigations in this laboratory of over potassium hydroxide. The ether was removed by syntheses of @-alanineby the interaction of aqueous vacuum, and fractionation of the main material through a Vigreux column under reduced pressure gave: Benzylamine, ammonia and either ethyl or methyl acrylate2at 125 21 g., b.p. 62-67"/&9 mm.; N-benzyl-N-n-octylamine, 220 to 190°, or ethylene cyanohydrin4 at 180 to 190°, showed, however, that quite impure @-alaninewas g., b.p. 140-175°/11-12 mm.; and N-benzyl-N,N-di-noctylamine, 45 g., b.p. 191-213°/10 mm. Separate redis- invariably produced. In some instances, the product tillations through the Vigreux column of the latter two cuts contained less than 70% of B-alanine. The pregave the desired products. (See Tables I and I1 for analyses scribed isolation procedures214were followed in each and physical properties.) case. General method for preparing the N-benzyl-N-alkyl-N-w octylamines. N-Benzyl-N-n-octylamine (21.9 g., 0.1 mole), The impure products were found by titration to alkyl halide (0.11 mole), and potassium hydroxide (7.7 g.) contain acidic and basic functions in almost equi-' were added to a suitable flask and refluxed for 5 hr. The product was then cooled, shaken with 50 ml. of 10% aqueous valent amounts; moreover, the neutralization sodium hydroxide solution, and separated. Fractionation of equivalents determined were only slightly greater the colorless oily material through a Vigreux column under than those calculated for @-alanine.Combined amreduced pressure gave essentially the desired tertiary amine. monia' (in the form of ammonium salts) was, howThe main product collected waa then redistilled through ever, present in appreciable quantities. No unthe Vigreux column to give the N-Benzyl-N-alkyl-N-noctylamine. (See Tables I and I1 for analytical data and saturated compounds or tertiary amines were detected. These results, together with an analysis physical properties.) specific for the primary amino group,* indicated Acknowledgment. The author wishes to express that the major impurity was probably the monohis thanks to Mr. Anthony Cristino of the Plastics ammonium salt of 3,3'-iminodipropionic acid (I). Division, Allied Chemical Corporation, Technical Department, Edgewater, N. J., for the elemental CHzCHnCOOR / analyses. Gratitude is also expressed to Prof. S. P. HN Gimelli, Fairleigh Dickinson University, for making \ CHzCHzCOOH the overall research program possible. CHEMISTRYDEPARTMENT FAIRLEIGH DICKINSON UNIVEREITP TEANECK, N. J.
I. R = NH, 11. R = H
Pertinently, Forde has pointed out that the monoammonium salt (I) and acid (11) are probable byproducts in @-alaninesyntheses of the type under discussion. Compounds I and I1 have solubilities Improved Syntheses of &Alanine similar to that of #?-alaninein water and methan01,~ F. POPPELSDORF AND R. C. LEMON the solvents employed for the isolation. Consequently, if these by-products are formed in large Received May 12,1960 enough quantity they will crystallize with the #?alanine. Furthermore, the similarity of solubilities One important group of @-alaninesyntheses in- makes purification by fractional crystallization cludes preparative procedures which involve the tedious and impractical. interaction at elevated temperatures and pressures A simple purification procedure for #?-alanine of aqueous ammonia and acrylonitrile,' esters of made by syntheses based on an acrylate ester or acrylic acid,2or compounds RCH2CH2Xwhich can ethylene cyanohydrin has now been found. Reyield acrylonitrile or acrylic acid by a simple, fluxing of either diisopropylamine or triethylamine usually base-catalyzed, elimination r e a ~ t i o n ~ - ~with , an aqueous solution of the crude @-alanineconCH2= CHX (X = CN or verted the impurities into methanol-soluble prodRCH2CH2X+ RH COOH). These reactions have generally been car- ucts but did not affect the #?-alanine.Because @ried out between 125 and 250'. In each case, the @- alanine is sparingly soluble in methanol, the amine alanine was directly isolated by precipitating it treatment followed by precipitation with methanol enabled the direct isolation of the amino-acid in a (1) G. H. Carlson and C. N. Hotchkiss, U. S. Patent good degree of purity (95 to 98%). One crystalliza2,377,401 (1945). tion of this product from water gave @-alaninein a (2) S. H. Babcock, Jr., and B. R. Baker, U. S. Patent purity of 99.9%.
+
2,376,334 (1945). (3) P. M. Kirk, U. S. Patent 2,334,163 (1943). (4) P. M. Kirk and J. H. Paden, U. S. Patent 2,364,538 (1944). (5) J. H. Paden, U. S. Patent 2,414,389 (1947). (6) P. M. Kirk, U. S. Patent 2,416,630 (1947).
(7) Determined by the method of K. G. Mizuch and A. Y. Savchenko [Org. Chem. Znd. (U.S.S.R.),7 , 2 4 (1940)l. (8) F. E. Critchfield and J. B. Johnson, Anal. Chem., 29, 1174 (1957). (9) J. H. Ford, J . Am. Chem. Soc., 67,876 (1945).
