Selective Reductions. V. The Partial Reduction of Tertiary Amides by Lithium Di- and Triethoxyaluminohydrides-A New Aldehyde Synthesis via the Dimethylamides

Abstract

A NEW ALDEHYDE SYNTHESIS via DIMETHYLAMIDES 1089 ~* O D 1.4042, and 2.5 g., 8.57, yield, of capronitrile, b . p . 73" a t 53-55 m m . , n z O~ 1,4070.C. Cyclohexanecarbonitrile.-Cyclohexanecarboxaldehyde, b.p. 63-66" a t 23-24 mm., n % 1.4507, was obtained in 71y0 yield.D . Benzonitri1e.-Benzaldehyde, b . p . 81-82' a t 31 mm., RZoD 1.5452, was obtained in 767? yield. E. p-Chlorobenzonitri1e.-Lithium triethoxyaluminohydride (0.238 mole) was prepared in 238 ml. of ether. Into this stirred solution was added 32.7 g . (0.238 mole) of p-chlorobenzonitrile all a t once a t ice-bath temperature. The reaction mixture was hydrolyzed, after an hour, with 200 ml. of 5 i V sulfuric acid.Ether was distilled and the resulting aqueous layer was steam distilled. p-Chlorobenzaldehyde, m . p . 47-47.5', was obtained (27.9 g , ) i n 8 3 . 5 ( 2 yield. Recrystallization from hot water did not change the m.p.Reduction with Lithium Tri-n-butoxyaluminohydride on a Preparative Scale .-The use of lithium tri-n-butoxyaluminohyiride is useful in cases where t h e removal of ethyl alcohol from the product offers difficulties.Cyclopropanecarbonitrile. -In a 1-1 ., three-necked, round-bottom flask equipped with a condenser, dropping funnel, and stirrer, flushed with nitrogen, was placed 0.3 mole of lithium aluminum hydride in 300 ml. of ether ( 1 M solution). T o this solution was added dropwise over a period of 75 min., 0.9 mole (66.6 9 . ) of 1butanol, maintaining the temperature a t -10 to -5 " . The reaction was stirred for another 15 min. T o this solution ( -10") was added 20.1 g . (0.3 mole) of cyclopropanecarbonitrile over 15 min., the temperature rising t o 8 " . The reaction was stirred for 1 h r . a t 3" (ice b a t h ) and then decomposed by 300 ml. of 5 AY sulfuric acid. The ether layer was separated and the heterogen-eous aqueous layer was extracted three times with 25-ml. portions of ether. T h e combined ether extracts were washed with sodium bicarbonate solution and water and then dried over sodium sul-

Reduction of N,N‐Dimethylcarboxamides to Aldehydes by Sodium Hydride–Iodide Composite

“…On the other hand, the reduction of simple N , N ‐dialkylamides to aldehydes needs use of modified hydride reagents such as LiAlH n (OEt) 4– n ( n = 1 or 2), disiamylborane, and lithium diisobutylpiperidinohydroaluminate . It should be noted that the Schwartz 's reagent [Cp 2 Zr(H)Cl] is capable of reducing a variety of amides (primary, secondary, and tertiary) to the corresponding aldehydes under very mild reaction conditions with wide functional group compatibility ( Scheme ,a ) .…”

Practical Synthesis of the Bicyclic Darunavir Side Chain: (3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-ol from Monopotassium Isocitrate

“…This observation is very similar to the lack of reaction in the LAH reduction of N , N -diisopropylbutyramide as report by Brown. 13 …”

“…This observation is very similar to the lack of reaction in the LAH reduction of N,N-diisopropylbutyramide as report by Brown. 13 It is well-known that Weinreb amides can be selectively reduced to aldehyde using LAH or diisobuytlaluminum hydride (DIBAL). 14 The tetrahedral intermediate resulting from the first hydride addition to Weinreb amide is stabilized by chelation and hence is unreactive to the addition of the second hydride.…”

EPC‐Synthesis of Tetrahydroisoquinolines by Diastereoselective Alkylation at the 1‐Position of Phenylalanine‐Derived Precursors. Synthesis of the Alkaloid (+)‐Corlumine

“…The correlation of the two alkylation products 5 and 6 with the parent (R)-1-methyland ( R ) -1-benzyltetrahydroisoquinoline 15 and 16, respectively, is outlined in Scheme 2. In the first step, the COOH corresponding nitril [21] or group is removed. Of the methods to do this (e.g.…”