One Step Preparation of 1,4-Diketones from Methyl Ketones and α-Bromomethyl Ketones in the Presence of ZnCl2 · t-BuOH · Et2NR as a Condensation Agent

Abstract

1,4-Diketones have been prepared in one step from methyl ketones and a-bromomethyl ketones under the action of ZnCl 2 ·t-BuOH·Et 2 NR as a condensation agent with moderate to high yields. The mechanistic pathway of the reaction is proposed to go through aldol condensation of ketones followed by 1,3-dehydrobromination of aldol products and cleavage of activated cyclopropyl intermediates.1,4-Diketones are useful synthetic intermediates for the preparation of five-membered carbocyclic and heterocyclic compounds. 1 Among the most convenient methods for the synthesis of asymmetrical 1,4-diketones, 2-15 the Michael-Stetter addition of aldehydes to a,b-unsaturated ketones, 6-10 as well as alkylation of stabilized alkaline metal enolates, 10-13 enamines, 13,14 and tin enolates 15 by a-halocarbonyl compounds should be mentioned. However, to our knowledge, the Michael-Stetter method does not give satisfactory results with electron-poor aromatic substrates, 10 and the last three methods are restricted mainly by aromatic or symmetrical aliphatic starting nucleophiles, which should be prepared from the corresponding carbonyl compounds.Recently, we have reported a new simple and regioselective method for the preparation of 1,4-diketones directly from methyl ketones and a-bromo ketones. 16,17 This method is based on the thermodynamically controlled cross aldol condensation of methyl ketones with a-bromo ketones followed by 1,3-dehydrobromination of the aldol products and cleavage of the corresponding intermediate activated cyclopropyl derivatives to 1,4-diketones. Using this approach, we have developed two main preparative procedures. The first is based on the application of two separate stages: aldol condensation of methyl ketones with a-bromo ketones in the presence of magnesium bases, and subsequent conversion of the aldol products into 1,4-diketones by treatment with tertiary amine. 16 In the second procedure, we have succeeded in combining these both stages into one using titanium isopropoxide as the condensation agent. 17In this paper, we propose another simple one step procedure for the preparation of 1,4-diketones 5a-r from methyl ketones 1a-n and a-bromo ketones 2a-g, which gives better results for the synthesis of products with strong a Compounds 3−5: R 1 , R 2 , see Table 1.

Novel Catechol Derivatives of Arylimidamides as Antileishmanial Agents

“…For the preparation of the diamino compound 6 , bearing a pyrrole ring in the structure, Paal–Knorr synthesis was applied . The precursor 1,4‐diketone was prepared using the aldol condensation of 2‐bromo‐4′‐nitroacetophenone with 4′‐nitroacetophenone in the presence of zinc chloride‐diethylamine‐ t ‐butanol complex as the condensation agent . The resulted diketone then yielded 2,5‐bis(4‐nitrophenyl)pyrrole ( 5 ) in the Paal–Knorr reaction.…”

“…[24] The precursor 1,4-diketone was prepared using the aldol condensation of 2-bromo-4 0 -nitroacetophenone with 4 0 -nitroacetophenone in the presence of zinc chloridediethylamine-t-butanol complex as the condensation agent. [25] The resulted diketone then yielded 2,5-bis(4nitrophenyl)pyrrole (5) in the Paal-Knorr reaction. The nitro groups in compound 5 were reduced to amino moieties using catalytic hydrogenation in the presence of Pd/C to give the desired 2,5-bis(4-aminophenyl)pyrrole (6) in 81% yield (Scheme 2).…”

Peculiarities of the behavior of succinyl dichloride in Friedel-Crafts reaction with thiophenes*

“…It must also be assumed that, in the course of the reaction, there arise some kind of products other than the diketones 2 and keto acids 3 which previously simply could not be found or separated. In this paper we have carried out a detailed study of the composition of the products formed upon acylation of thiophenes 1a-c using succinyl dichloride in the presence of different amounts of AlCl 3 , as well as SnCl 4 and TiCl 4 , in order to optimize the synthesis of the diketones 2.…”

“…With regard to the most frequently used of these, the Stetter method is based on a Michael addition of aldehydes to the activated double bond of enones in the presence of cyanide or thiazolium salt [2,3]. Particularly promising for the preparation of unsymmetrical 1,4-diketones (although somewhat time consuming) is the method due to Kulinkovich et al based on the reaction of methyland -bromomethyl ketones [4]. The reactions of diesters or N,N,N',N'-tetrasubstituted succinic acid diamides with hetaryl lithium [5] or reaction of sodium acetylide with hetarenecarbaldehydes and subsequent conversion of the 1,4-dihetarylbut-2-en-1,4-diol to the corresponding 1,4-diketone in the presence of alcoholic alkali solution [6] are relatively simple but they give low yields.…”

Synthesis of Dicationic 2,5-Diarylpyrroles

“…Salt: Brown solid (0.33 g), mp 244-7 °C; 'H-NMR (DMSO-4,) δ 6.78 (s, 2H), 7.26-8.07 (m, 18H), 9.07 (br s, 1H), 9.13 (br s, 1H), 9.88 (br s, 1H), 9.94 (br s, 1 Η), 11.57 (br s, 1 Η), 11.66 (br s, 2H), 11.70 (br s, 2H); 13 C-NMR δ 2H), 11.14 (br s, 1H);13 C-NMR δ 151.9, 151.3, 148.1, 137.2, 134.7, 133.7, 133.3, 132.7, 132.6, 132.2, 129.5, 128.0, 127.6, 127.5, 127.2, 126.4, 126.0, 125.5, 124.9, 121.9, 121.3, 118.8, 118.3, 116.7, 107.6, 106.6; MS (GC/MS) m/z (rel. int.)…”