Sterically Congested Molecules, 16 A Convenient Synthesis of Di‐tert‐butyl Ketone via its Imine, 2,2,4,4‐tetramethyl‐3‐pentanimine

Abstract

2,2,4,4-Tetramethyl-3-pentanimine (3)is efficiently prepared by a Barbier-type reaction of pivalonitrile (1) with an excess of tert-butyl chloride (2) and metallic lithium in ether. Its pu-rification by extraction into aqueous acid and slow hydrolysis permit an inexpensive and very simple production of di-tertbutyl ketone (4).Numerous possible applications of 2,2,4,4-tetramethyl-3-pentanone (4) as a source of gem-di-tert-butyl compounds call for a ready access to this ketone. But despite a variety of published preparations, the commercial substance 4 is sold at an exorbitantly high price (currently at least DM 2400 per mol), perhaps indicative of severe problems in production or purification. We are now able to remedy this situation by communicating the following simple and efficient route to di-tert-butyl ketone (4).

Kinetics of α-(2,6-Dimethylphenl)vinyllithium: How To Control Errors Caused by Inefficient Mixing with Pairs of Rapidly Competing Ketones

“…Based on the conveniently slow butylation (section ) of 2 with its coproduct n -BuBr in Et 2 O, a simplified general procedure could be used for derivatizations of 2 with rapidly reacting interceptors: The Br/Li interchange reaction of 1 (Scheme ) was carried out in t -BuOMe or Et 2 O with not more than a small excess of n -BuLi, whereupon the crude product was not purified but treated directly with a ketone or aldehyde. In order to explore the limit of steric hindrance, we added the sterically shielded di- tert -butyl ketone ( t -Bu 2 CO, 8a ) to 2 in t -BuOMe and obtained the precipitating lithium alkoxide 10 (Scheme ) of the expected adduct 9a . This smooth addition reaction was very slowly reversible at rt in THF as the solvent: In the presence of dicyclopropyl ketone ( 8d ), only 58% of 10 decayed within 15 h, generating the fragment 2 that was trapped by 8d to produce the Li alkoxide 13 of 9d .…”

Deuterium Quantification through Deuterium‐Induced Remote1H and13C NMR Shifts

“…Scheme displays the formulae of the investigated compounds 1 – 6 with their deuterium‐induced 1 H and 13 C NMR isotope shifts Δ in units of ppb (=10 −3 ppm). We prepared perdeuteriopivalonitrile ( 1 ) from commercial (D 3 C) 3 CCl by the one‐step method4 (yield 22 %),5 and converted it into tert ‐butyl [D 9 ] tert ‐butyl ketone ( 2 ) using a Barbier‐type procedure 6. Compounds 3 – 6 were studied as mixtures7 of these isotopomers ( 3 / 4 and 5 / 6 ) and isotopologues ( 3 being the main component) with the parent unlabeled acyloin (H 3 C) 3 CC(O)C(OH)[C(CH 3 ) 3 ] 2 , namely, 4‐ tert ‐butyl‐4‐hydroxy‐2,2,5,5‐tetramethylhexan‐3‐one.…”

Shorter and Easier Syntheses of Di‐tert‐butylketene and Relatedgem‐Di‐tert‐butyl Compounds

“…The easier approach to the alkoxide 17 (Scheme ) consists of the generation of dichloromethyllithium ( 16 ) in THF through deprotonation of CH 2 Cl 2 in the presence of di‐ tert ‐butyl ketone3 ( 1 ), a strategy13 that appeared to us to be an argument against the use of carbanionic bases that might add across the C=O double bond of 1 14a. Because the recommended13b base lithium dicyclohexylamide can give annoying problems with the poorly soluble dicyclohexylammonium salt during the aqueous workup, we replaced it with lithium diisopropylamide13b (LDA), which was added dropwise to a THF solution of 1 and CH 2 Cl 2 stirred at –70 °C: LiCHCl 2 was formed and efficiently trapped by the ketone 1 ,14b as shown through final quenching with acids at –70 °C or 0 °C and subsequent isolation of the chlorooxirane 18 (86 %) as the only product.…”

“…2,2‐Di‐ tert ‐butyl‐3‐chlorooxirane (18): A two‐necked flask (500 mL) was fitted with an internal thermometer, a magnetic stirring bar, and a large pressure‐equalizing addition funnel with an argon bubbler. The flask was loaded with dry THF (70 mL), di‐ tert ‐butyl ketone ( 1 , 17.06 g, 120.0 mmol),3 and dry dichloromethane (23.16 mL, 30.69 g, 361.4 mmol) and was then cooled with stirring at –70 °C. A solution of LDA (241 mmol), prepared by addition of n BuLi (103 mL in hexanes, 240 mmol) to diisopropylamine (241 mmol) in dry THF (70 mL) at 3 °C, was added (not vice versa!)…”

“…Di‐ tert ‐butylketene ( 14 , Scheme ) is noted for its very low reactivity:1 unlike other ketenes,2 it does not dimerize and adds neutral water very slowly to produce the acid 11 . The following routes (Scheme ) to this persistent ketene, starting either from di‐ tert ‐butyl ketone3 ( 1 ) or its imine3 3 , have been published.…”