Perfluorinated resin-sulfonic acid (Nafion-H): an efficient, environment friendly and recyclable heterogeneous catalyst for the one-pot multicomponent synthesis of β -acetamido ketones

Multi component condensation of an aryl aldehyde, acetyl chloride, acetonitrile and enolisable ketone in presence of Nafion-H, as an efficient, environment friendly heterogenous and recyclable catalyst for the one-pot synthesis of β -acetamido ketones in high yields is described.


Introduction
β-Acetamido ketones are considered as versatile intermediates as their basic skeleton exist in a number of biologically or pharmacologically important compounds. 1,2These compounds are also useful in the synthesis of other important organic molecules like 1,3-amino alcohols 3,4 units common in natural nucleoside peptide antibiotics, e.g., nikkomycines or neopolyoxins. 5,6ynthetic strategies based on one-pot multicomponent reactions overriding the conventional linear type synthesis and considered as powerful tools in the modern drug discovery process. 7arlier reports on the synthesis of β-acetamido ketones through multi component reactions is mainly using catalysts like CoCl 2 , 8 montmorillonite K10 clay, 9 BiCl 3 , 10 silica sulphuric acid, 11,12 and solid acid Hβ-zeolite. 13he interest is continuously growing in recent years on the use of eco-friendly and recyclable catalysts due to environmental legislations.Perfluorinated resin sulfonic acid (Nafion-H) 14 an acid catalyst extensively used for alkylation's, 15 acylation, 16 nitration, 17 acetal synthesis 18 and in Diels-Alder reaction. 19The Nafion-H catalyst, an insoluble resin is inert to corrosive environments, stable up to 201 0 C, easy to recover and to reuse.Nafion-H is used as a catalyst for multi component condensation reaction for the first time and found to be an efficient catalyst to obtain β-acetamido ketones under mild conditions.

Results and Discussion
In a typical reaction, the enolisable ketone (acetophenone) was reacted with various aldehydes in presence of acetyl chloride in acetonitrile medium using Nafion-H as catalyst.The catalyst is the source of protons which protonates aldehyde and acetonitrile to form a six membered intermediate.Subsequently, the enolisable ketone attacks methine carbon and give β-acetamido ketones.The probable mechanism for sequence of reactions 8,10, 12 is represented in Scheme 2.

Scheme 2
The role of substituents in phenyl ring of aldehyde and in CH 3 of ketone on rate of reaction and yield of products is studied in detail.It is found that the reaction is smooth in almost all the cases irrespective of substituent used.Similarly reactions with aliphatic aldehydes, aliphatic ketones and also nitriles than acetonitriles were independently tried and found to be no reaction.
The catalyst is recovered and recycled with different proportions five times for entry 1 (Table 2) and found to have no loss of activity.In case of entry 1, the reaction is up scaled to 5 m moles with 94% yield.The results are tabulated in   The number of compounds prepared have been tabulated in Table 2.  Similarly propiophenone (α-substituted enolisable ketone) is reacted with various aromatic aldehydes under given conditions resulted two diasteriomeric products in definite proportions.In all the cases anti isomer is formed in major quantity.The 1 H NMR pattern is interesting in that in a specific example of entry 3 (table 3) shows a doublet of doublet for CHCO proton with coupling constant values (J) 7.7 Hz for syn isomer and 13.7 Hz for trans isomer.The products are tabulated in table   a Ratio of syn and anti isomers is estimated with 1 H NMR for methine proton (CHCO) based on coupling constants.b Isolated yields.
In conclusion, we have developed an efficient method for the preparation of β-acetamido ketones using an environment friendly heterogeneous catalyst.The recycle of catalyst and versatility of reaction is established.

Table 2 .
Reaction of substituted acetophenones with various aryl aldehydes