Would my interpretation of this article be correct if I'd conclude that a new route to butanamines is within reach?
The article reacts a carbonitrile with isobutyl magnesium chloride; they obtain a phenethylamine with an isobutyl chain at the alfa-carbon. Hence I'd think that reacting the same carbonitrile with e.g. ethyl magnesium bromide would yield the corresponding butanamine.
I think the carbonitriles can easily be prepared from scratch. Rhodium's site holds an article that describes the synthesis of carbonitriles from benzyl alcohols: https://www.thevespiary.org/rhodium/Rhodium/chemistry/pea.benzyloh.html (https://www.thevespiary.org/rhodium/Rhodium/chemistry/pea.benzyloh.html)
However, the same benzyl alcohols can be prepared from the corresponding substituted benzene and formaldehyde. Instead of using the benzyl alcohol as intermediate, a direct halomethylation can be applied equally well. Only problem is NaCN... :(
EtBr is rather cheap. Preparing the Grignard reagent and reacting it with the previously synthesized carbonitrile might yield an imine, which after reduction with NaBH4 might yield the butanamine.
Comments?
Quite like https://www.thevespiary.org/rhodium/Rhodium/chemistry/amphetamine.html (https://www.thevespiary.org/rhodium/Rhodium/chemistry/amphetamine.html)
isn't it? Phenylacetonitrile could be even prepared from toluene through benzyl bromide, see Post 468077 (missing)
(moo: "Oxidations and brominations w/ H2O2/Br2/HBr", Methods Discourse). :)
Also, I consider relevant to this thread what is described hereinafter :P :
Hydrogenating ketiminomagnesium intermediates with lithium aluminum hydride to produce amines
Pohland, Albert (Eli Lilly & Co.)
Patent US2772311 (http://l2.espacenet.com/dips/viewer?PN=US2772311&CY=gb&LG=en&DB=EPD)
EXAMPLE 2
Preparation of 2-amino-1-phenylbutane
A Grignard reagent was prepared from 38.0 g. (0.30 mol.) of benzyl chloride, 19.0 g. (0.78 mol.) of magnesium and 300 ml. of ether. The solution of the Grignard reagent was stirred and 13.8 g. (0.25 mol.) of propionitrile were added dropwise. The reaction mixture was refluxed for two hours, and 7.6 g. (0.2 mol.) of lithium aluminum hydride in 100 ml. of tetrahydrofuran were added thereto. The resulting mixture was refluxed for about sixteen hours, and thereafter decomposed, with cooling, by the addition of successive portions of 8 ml. of water, 6 ml. of 20 percent aqueous sodium hydroxide and 28 ml. of water. The precipitated salts were removed by filtration and washings were dried over magnesium sulfate and fractionally distilled in vacuo. The 2-amino-1-phenylbutane formed in the reaction was collected and found to boil at about 98-99° C. at a pressure of 10 mm. of mercury. There were obtained 21 g. (yield 47%) of 2-amino-1-phenylbutane having the following index of refraction: nD25=1.5128.
Lithium aluminum hydride reduction of Grignard-nitrile adducts to primary amines
Pohland, A.; Sullivan, H. R.
Journal of the American Chemical Society 75, 5898-9 (1953)
Abstract
The prepn. of 5 disubstituted carbinamines by the LiAlH4 reduction of Grignard-nitrile adducts is described. EtCN (13.8 g.) added with stirring dropwise to PhMgBr from 47.3 g. PhBr, 7.2 g. Mg, and 300 cc. Et2O, the mixt. refluxed 2 hrs., treated slowly with a slurry of 11.4 g. LiAlH4 in 100 cc. tetrahydrofuran, refluxed 18 hrs., and decompd. carefully with cooling with 12 cc. H2O, 9 cc. 20% aq. NaOH, and finally 42 cc. H2O, the solid filtered off and washed with Et2O, and the combined filtrate and washing dried with MgSO4 and distd. gave 27.1 g. (80%) EtPhCHNH2 (I), b7 78-80 Deg, nD25 1.5186. In another run, the org. layer obtained after the decompn. of the mixt. with H2O and base was added to 200 cc. dil. HCl, concd. in vacuo to 75 cc., and treated with 50% aq. NaOH to give 26.5 g. (78%) I, b7 78-9 Deg, nD25 1.5185. In a similar run with only 3.8 g. LiAlH4, 2.8 g. (8%) I and 15.8 g. (51%) EtPhCHN:CEtPh (II), b3.4 156-7 Deg, were obtained; with 7.6 g. LiAlH4, 19.5 g. (62%) I, b10 84-5 Deg, nD25 1.5182, and 3.2 g. (10%) II, b2.8 100-50 Deg, were formed. Similarly were prepd. PhCH2CH(NH2)Et, 26.2 g. (71%) (Yield based on benzyl chloride instead of the nitrile is 59%), b9.5 96-7 Deg, nD25 1.5130, from PhCH2MgCl from 38 g. PhCH2Cl, 19 g. Mg, and 300 cc. Et2O; PhCH(NH2)Am, 23.6 g. (54%), b0.9 82-3 Deg, nD25 1.5070, from 24.3 g. AmCN; Et2CHNH2, 4.8 g. (23%), nD25 1.4030 [HCl salt, m. 215-16 Deg (from MeOH-EtOAc)], from EtMgBr and EtCN; Et2N(CH2)3CHPhNH2, 27.5 g. (62%), b0.8 115-16 Deg, nD25 1.5081, from 28 g. Et2N(CH2)3CN. BzEt (26.8 g.), 26.8 g. I, 4.8 g. NaH, and 150 cc. C6H6 refluxed overnight did not give the imine; a similar run with 6 g. Et3N was also unsuccessful. EtPhCHNHMgBr prepd. in the usual manner from 13.8 g. EtCN and treated dropwise with 33.8 g. I, the mixt. stirred 3 hrs., decompd. by 4 cc. H2O, 3 cc. 20% aq. NaOH, and finally 24 cc. H2O, and stirred 2 hrs. at room temp., and the Et2O soln. decanted, dried with MgSO4, and distd. gave 46.0 g. (74%) II, b0.6 125-6 Deg, nD25 1.5552. II (7.0 g.) in 100 cc. dil. HCl refluxed 1 hr., the resulting oil dissolved in Et2O, the Et2O removed, and the residue treated with 2,4-(O2N)2C6H3NHNH2 gave 2.0 g. 2,4-(O2N)2C6H3NHN:CEtPh, m. 188-9 Deg; the acid aq. phase evapd. to dryness in vacuo gave 3.6 g. I.HCl, m. 193-4 Deg (from MeOH-EtOAc). II (10.0 g.) in 200 cc. EtOH hydrogenated over 200 mg. PtO2, the mixt. filtered, the filtrate concd. in vacuo, the residual oil dissolved in Et2O, the soln. treated with dry HCl, and the cryst. ppt. fractionally crystd. from MeOH-EtOAc gave 0.8 g. a-form of (EtPhCH)2NH, m. 252-3 Deg, and 2.7 g. more sol. b-form, m. 242-3 Deg; mixed m.p., 215-17 Deg.