the roots of organic development

P R E F A C E It seems to us, symbolic, important, and above all promising for the furore, that the year in which Rh6ne-Poulenc holds its centenary celebrations also sees the publication

Industrial Chemistry Library, Volume 8

The Roots of

Organic Development

Industrial Chemistry Library

Advisory Editor: S.T Sie, Faculty of Chemical Technology and Materials Science Delft University of Technology, Delft, The Netherlands

Progress in C1 Chemistry in Japan

(Edited by the Research Association for C 1 Chemistry)

Calcium Magnesium Acetate An Emerging Bulk Chemical for Environmental Applications

(Edited by D.L Wise, Y.A Levendis and M Metghalchi)

Advances in Organobromine Chemistry I

(Edited by J.-R Desmurs and B Gdrard)

Technology of Corn Wet Milling and Associated Processes (by P.H Blanchard)

Lithium Batteries New Materials, Developments and Perspectives (Edited by G Pistoia)

Industrial Chemicals Their Characteristics and Development (by G Again)

Advances in Organobromine Chemistry II

(Edited by J.-R Desmurs, B Gdrard and M.J Goldstein)

The Roots of Organic Development

(Edited by J.-R Desmurs and S Ratton)

Industrial Chemistry Library, Volume 8

The Roots of Organic

Development

Edited by

J e a n - R o g e r Desmurs

Rh6ne Poulenc Industrialisation, CRIT/Carrikres, 85 Avenue des Frbres Perret,

69192 Saint-Fons Cedex, France

S e r g e R a t t o n

Rh6ne Poulenc Organic Intermediates Enterprise, 25 Quai Paul Doumer,

92408 Courbevoie Cedex, France

1 9 9 6

ELSEVlER SCIENCE B.V

Sara Burgerhartstraat 25

P.O Box 211, 1000 AE Amsterdam, The Netherlands

ISBN: 0-444-82434-0

9 1996 Elsevier Science B.V All rights reserved

No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior written permission of the publisher, Elsevier Science B.V., Copyright & Permissions Department, P.O Box 521, 1000 AM Amsterdam, The Netherlands

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FOREWORD

It is our belief within RHONE-POULENC that the key to building long term customer relationship in our industry is superior technology backed up by outstanding service

Benefits of superior technology in Organic Chemistry are multiple : lower cost raw materials, shorter synthesis routes, improved yields, selectivity and kinetics, resulting in better productivity Higher transformation rates of less hazardous materials leads to healthier, cleaner operations with reduced waste disposal issues Last but not least, process safety is continually upgraded as more intimate knowledge of chemical reactions and other unit operations is achieved

For our worldwide customers such technical progress creates multifaceted value: reliability, shorter response time, more competitive economics, improved quality leading to faster registration, and safer and more environmentally responsible operations Furthermore, it enables us to extend the use of this expertise

to the adaptation of decisive physical or chemical properties of molecules to provide our customers with desired use properties

Making our overall skills available to customers to solve their problems is indeed the basis of our ,, Chimie Nouvelle ,, approach

In this spirit we expect and look forward to provide, along with our Organic Intermediates technology, whatever services are required to make our joint success complete : efficient pilot facilities, advanced analytical equipment with expert staff, toxicology and eco toxicology support, environmental services, formulation capabilities, we do this throughout the world

This is the way we aim to become your preferred partner in organic chemistry,

to gain your confidence and be able to participate early in your most important projects

May this book demonstrate to all our existing or potential partners our commitment to top level organic chemistry

We are proud of the achievements and expertise of our teams May our partners keep challenging them to build leaderships together

Bertrand LOUVET

Rh6ne-Poulenc Chemical Sector

Executive vice-President

Ted ZIEMANN President of Rh6ne-Poulenc Organic Intermediates Enterprise

This Page Intentionally Left Blank

P R E F A C E

It seems to us, symbolic, important, and above all promising for the furore, that the year in which Rh6ne-Poulenc holds its centenary celebrations also sees the publication of a scientific review, gathering together organic chemistry research carried out in common by groups from universities and other large organisations, and with Rh6ne-Poulenc research workers

The development of an industrial group, especially one such as Rh6ne-Poulenc,

is directly linked to the possibility of innovation

For this, it is necessary to rely, not just on the groups own resources and strengths, but also on the research and discoveries made by external research bodies

The General Management of the Group, as far back as 1974, was aware of this need to have a closer association with upstream research, and so signed the first contract with the CNRS (National Research Centre)

This was only the first step, although an important one, and several years passed before Rh6ne-Poulenc opened its research doors to the outside world From 1981 until the present day, with the support and constant incitement of the Group managers, a network of collaborators has been set up, at first in France, and then abroad This has required, from everyone involved, efforts regarding mutual understanding, always within a climate of trust

The first organised meetings were RP-CNRS symposia based on themes, and focusing on problems directly related to the Groups chemical interests (homogeneous catalysis, chemical reactivity, regioselectivity ) during which our research workers and those of the CNRS exchanged information and results and initiated future collaborations Today these symposia have been replaced by ,, Journ6es RP-CNRS ,, where several themes are examined over a two day period, using a format akin to a seminar

It was then decided to modify these <, Journ6es Scientifiques ,,, originally reserved for Rh6ne-Poulenc research workers, by orienting them towards a particular theme (silicon chemistry, reactivity in organic chemistry, materials science, molecular biology, etc.) and by inviting, under the presidency of an internationaly renowned scientist, not only Rh6ne-Poulenc research workers, but also the best specialists from France and abroad, interested in the theme under examination, and by asking them to actively participate through written or oral presentations

The assessment of these ~ Journ6es ,, has been particularly positive, allowing on the one hand high-level research workers to discover our own research interests, and on the other, allowing the Group to take advantage of their expertise and to possibly have future Rh6ne-Poulenc scientists trained in their laboratories

At pratically the same time, Rh6ne-Poulenc set up a Scientific Council, assembling internationally renowned scientists, each working in the different areas

of research relevant to the Group

The role of this council is essentially to provide ideas and propositions concerning the great scientific problems, as well as an external and independant audit, ready at any moment to notify the General and Scientific Management of any new discoveries or advances likely to modify the direction of our research

In 1987, the organisation of the Scientific Management was improved, with directors being nominated for the following three areas : chemistry (J.M Lehn), physical-chemistry (P.G De Gennes) and biology (C H616ne), each being assisted

by an internal consultant, establishing permanently the opening of our research to the external scientific world

Today, always with this same preoccupation, under the impetus of Philippe Desmarescaux, General Manager, and of Claude H616ne, now Scientific Director, this collaboration has culminated in the Bio-Avenir programme, which represents a model for the interaction between public research and industry

But let us return to the various themes presented in this book They represent an image, albeit a rather incomplete one ; but an image which exemplifies this research

in common, and of the results achieved by such a methodology

It must also be noted that everything which has just been evoked, has only been possible because of the enthusiasm, support, trust and the willingness to persevere,

of all the research workers concerned, whatever their affiliation

Also, it must be added that the management of the large organisations, in particular the Management of the Chemical Sector of the CNRS, the Research Directors of our sectors as well as the group leaders of our Research Centres, have all contributed to this development through their encouragement and financial aid This continuing exciting adventure is a long term exercise Mutual respect, esteem and the desire to work together does not come over night Time is needed in order to know one another, to ~ tame one another ,, as the fox in the ~, Little Prince ,,

Today this long term policy is bearing fruit

We wish that this book be the first of many in the area of chemistry and perhaps

in other areas as well

Thank you, once again, to all those who made what was once only a wish, become a daily reality

C JEANMART

Correspondant Member of

the Academy of Sciences

J.M LEHN Nobel Prize Winner Presidem of the Sciemific Council

A C K N O W L E D G E M E N T S

We would like to thank the Rh6ne-Poulenc Organic Intermediates Enterprise for the financial backing that has enabled this book to be published, and especially Ted Ziemann, president of Rh6ne-Poulenc Organic Intermediates Enterprise

We would also like to thank :

- M r s Th6r6se Fessetaud who co-ordinated all the authors and the company Proman

- T h e Mrs Marthe Di Rollo, Dominique Trouillet, Laurence Ouled and Elisabeth

Di Rollo from Proman who did all the typing for this work

- Mrs Tavernier for her help in translating various articles

- T h e Mrs St6fanie de Rouville and Martine Pinard from the communications management of the chemicals sector for their help and advice

Lastly, we would like to thank all the authors for their work that enabled the publication of this book

Bismuth (III) salts in the Friedel-Crafts acylation

J.R Desmurs, M Labrouill6re, J Dubac, A Laporterie,

H Gaspard, F Metz 15

Friedel-Crafts acylation of aromatics using zeolites

M Spagnol, L Gilbert, D Alby 29

COC12 catalyzed trifluoroacetylation of aromatics using trifluoroacetic anhydride

J Ruiz, L Gilbert, D Astruc 39

ALKYLATION

Catalysis by rare earth phosphate II 9 Selective O-methylation of phenols by methanol in vapor phase

L Gilbert, M Janin, A.M Le Govic, P Pommier, A Aubry 48

Catalysis by rare earth phosphate III : Characterisation of samarium phosphate and samarium phosphate-cesium hydrogenophosphate as key catalysts for O-alkylation

of phenols

A.M Le Govic, P Pommier, A Aubry, L Gilbert, M Janin 62

AROMATIC FUNCTIONALISATION

Selective functionalisation of fluoroaromatics via organosilicon intermediates

B Bennetau, P Babin, J Dunogues 75

Arylation of amines and alcohols catalyzed by nickel, copper or palladium complexes

H.J Cristau, J.R Desmurs, S Ratton,

S Rignol, M Taillefer 90

The isomerisation of 1,2,4-trichlorobenzene : a theoretical study

S Firkins 107

CARBOXYLATION

Carboxylation of hydroxy aromatic compounds

I Bonneau-Gubelmann, M Michel, B Besson,

S Ratton, J.R Desmurs 116

E Cerbelaud, M.C Bontoux, F Foray, D Faucher,

S Levy-Schil, D Thibaut, F Soubrier, J Crouzet, D P6tr6 189

B Langlois, L Gilbert, G Forat 244

4-Fluorophenol : a key intermediate for agrochemicals and pharmaceuticals

C Mercier, P Youmans 293

Fluorodecarboxylation of arylchloroformate : a new access to fluoroaromatics

H Garcia, L Gilbert, M.C Perrod, S Ratton, C Rochin 301

Mild trifluoromethylation of organic compounds

C Wakselman, M Tordeux 313

FORMYLATION

Formylation of aromatic compounds in superacidic medium

L Saint-Jalmes, C Rochin, R Janin, M Morel 325

Selective access to hydroquinone ,, Fuchsone ,, route

M Costantini, E Fache, D Michelet, D Manaut 350

NITRATION

The mechanisms of nitration of phenol

P M6tivier, T Schlama 368

O X I D A T I O N

Oxidation of alkylphenols to hydroxybenzaldehydes

E Fache, D Laucher, M Costantini, M Beclere,

G Perrin-Janet 380

Large pore Ti-Beta zeolite with very low aluminium comem : an active and

PEPTIDE SYNTHESIS

Peptide synthesis by SAPPHO technology

J.M Bernard, K Bouzid, J.P Casati, M Galvez,

C Gervais, P Meilland, V P6v6re, M.F Vandewalle,

NMR under high gas pressure

F Metz, M Lanson, A Merbarch, U Frey 528

Lactic derivatives : methods for determining the optical purity of various intermediates

F Marcenac, D Bernard, F Boyer, J Chabannes,

Y Danion, M Minfray, N Peyre, E Zandanel, M Hillairet,

J.C Marsault, E Pilot 536

A U T H O R INDEX 550

S U B J E C T INDEX 552

INTRODUCTION

JEAN-ROGER DESMURS a)

AND SERGE RATTON c~

, CLAUDE H E L E N E b), DANIEL MICHELET b)

a) Rh6ne-Poulenc Industrialisation, Centre de Recherche, d'Ing6nierie et de Technologie, 85 Avenue des Fr~res Perret, 69192 Saint-Fons Cedex, France b) Direction Scientifique, 25 Quai Paul Doumer, 92408 Courbevoie Cedex, France

c) Interm6diaires Organiques, 25 Quai Paul Doumer, 92408 Courbevoie Cedex, France

This book is a collection of papers dealing with various aspects of inorganic chemistry:

- from exploratory work on the reactivity and selectivity of new reactions to studies

on the reaction mechanisms of well known reactions,

-from work highlighting the potential of certain technologies for new reactions (bioconversion, organometallic catalysis, etc.), to studies illustrating the potential for synthesis of certain reactants (e.g sodamide),

-from work on the choice and development of industrial synthesis pathways for new Fine Chemical intermediates, to studies aimed at understanding chemical phenomena linked to process Safety,

- from work dealing with the treatment and formation of organic solids in order to tailor their properties, to development of analytical techniques enabling detection of the origin of products,

- and work on the development of new analytical methods in order to provide better characterisation of reaction processes and products

The diversity of topics covered in this book clearly shows the scope required nowadays, in terms of fields of knowledge and expertise, to enable the development

of new processes and to the industrialisation and commercialisation of new intermediates

The speed with which the complex new process or product development procedure must take place, starting from exploratory research right through to the launch of the industrial production process, implies the contribution of numerous scientific disciplines, in other words the existence of major centres of competency,

as well as perfect harmony between all the experts involved

The major centres of competency in Organic Chemistry, the foundation of Rh6ne-Poulenc Group Chemicals Sector's technical activity, are the fruit of many years of basic research

This type of research is often initiated by Rh6ne-Poulenc Group's Sciemific Direction or benefits from its support before being fully taken over by the Chemicals sector for confirmation of new concepts and scientific orientation towards high potential targets

Fundamental type research is often performed in association with the CNRS and internationally renowned university laboratories

This book contains a certain number of articles written by joint RP - University Laboratory teams, which is a good illustration of the spirit of trust that motivates researchers who are getting to know and appreciate one another more and more

F R I E D E L - C R A F T S A C Y L A T I O N : I N T E R A C T I O N S B E T W E E N L E W I S ACIDS / A C Y L C H L O R I D E S AND L E W I S ACIDS / ARYL K E T O N E S

REBECCA ASHFORTH AND JEAN-ROGER DESMURS

Rh6ne-Poulenc Industrialisation, Centre de Recherche, d'Ing6nierie et de Technologie, 85 Avenue des Fr6res Perret, B.P 62, 69192 Saint-Fons Cedex, France

The use of stoichiometrical quantities of Lewis acid results in the formation of a complex at the end of the reaction between the aryl ketone formed and the Lewis acid

~ _ _ C / ? MCln

To resolve the effluent problem, much work has been performed investigating the conditions or catalysts that enable the Friedel-Crafts acylation to be performed with catalytic quantities of Lewis acid

Whilst the Friedel-Crafts acylation mechanism remains

determined (ref 6) it is reasonable to postulate four stages

The Friedel-Crafts acylation with catalytic quantities of Lewis acid requires a knowledge of the equilibria (2) and (5)

I N T E R A C T I O N S W I T H L E W I S ACIDS OF M E T A L H A L I D E T Y P E

Complexation of acid chlorides

D.E.H Jones and J.L Wood (ref 7) used infrared spectroscopy to study the chloride complexes of acidic A1CI 3 The study of the complexation of acetyl chloride by the various metal halides (Table 1) was performed by measuring the variation of the vibration intensity (CO) at 1808 cm -1

Table 1 Complexation of acetyl chloride in equimolar mixtures of CH3COC1 and metal halides

94 Insoluble

79

13 Insoluble

89

84

21

22 a) 0.2 M solution in CHzC12

b) Precipitation after 30 minutes

These results obtained using IR are confirmed with NMR in accordance with the

Table 2 NMRS3C of acetyl chloride in equimolar mixtures of CH3COC1 and metal halides a)

1,OM

Lewis acid

A1C13 SnC14 TIC14

~13C (C " 0 ) p p m

170.3 207.4 170.8 171.0

A~13C (C = 0)ppm

36.7 0.2 0.7

Table 3 Complexation of p-4-methyl acetophenone 1 with equimolar mixtures of (1) and metal

Table 4 NMR13C of 4-methyl acetophenone 1 with equimolar mixtures of 1 and metal halides

Fig 1

$13C of the CO in 4-methyl acetophenone as a function of the aluminium chloride / 4-

A similar change is also seen in NMR of 27A1 (Fig 2)

These observations could be due to the existence of several complexes of different stoichiometry and geometry as suggested by various pieces of work (refs 9,10)

COMPLEXATION OF LEWIS ACIDS

N M R and IR studies have enabled us to show that equilibria (2) and (5) were strongly shifted towards the complex form,

Table 5 The degree of complexed 4-methyl acetophenone measured by infrared in an equimolar

mixture of 4-methyl acetophenone and acetyl chloride

Table 6 Degree of complexed 4-methyl acetophenone measured by infrared using a mixture of

acetyl chloride (5 eq.), 4-methyl acetophenone (1 eq.)

To make Lewis acids catalytic for the Freidel-Crafts reaction various solutions can be considered :

9 Finding weaker metal halides such as BiC13 (ref 11) in order to limit the complexation with aryl acetone and favour complexation with the chlorine in the acid chloride,

9 Using solid catalysts in order to hinder aryl ketone complexation (ref 12),

9 Using less complex forming salts than metal halides with aryl acetone in the same way as rare earth triflates (refs 13, 14),

9 Increasing acylation temperature (ref 4) but this is often a source of secondary reactions

References

1 C Friedel, J.M Crafts, Bull Soc Chim Fr., 27,482, (1877)

2 C Friedel, J.M Crafts, Bull Soc Chim Fr., 27,530, (1877)

3 A Noguchi, T Ikawa, Y Shimada, J Org Syn Chem Japan, 39, 714, (1966)

4 I.P Tsukervanik, N.V Veber, Dold Akad Navk SSSR, 180, 892, (1968)

5 J.J Scheele in "Electrophilic Aromatic Acylation", Thesis, Delf, (1991)

6 J March in "Advanced Organic Chemistry, Reactions, Mechanisms and Structure" 4 ed., J

7 D.E.N Jones, J.L Wood, J Chem Soc (A), 3132, (1971)

8 F Bigi, G Casmati, G Sartori, G Predieri, J Chem Soc Perkin Trans II, 1319, (1991)

9 S Starowieyski, S Pasynkiewicz, A Sporzynski, A Chwojnowski, I Organometal Chem.,

94, 361 (1975)

10 N.L Chikina, Yu V Kobdazhnyl, G.A Osipov, Zh OBBshch Khim, 45, 1354, (1975)

11 J.R Desmurs, M Labrouill6re, J Dubac, A Laporterie, H Gaspard, F Metz This book

12 M Spagnol, L Gilbert, D Alby This book

13 A Kawada, S Mitamura, S Kabayashi, J Chem Soc., Chem Commun 1157, (1993)

14 L Hachiya, M Moriwaki, S Kobayashi Tetrahedron Lett 36, 409, (1995)

B I S M U T H (III) SALTS IN F R I E D E L - C R A F T S A C Y L A T I O N

FRAN(~OIS METZ a~

a) Rh6ne-Poulenc Industrialisation, Centre de Recherche, d'Ing6nierie et de Technologie des Carri6res, 85, Avenue des Fr6res Perret, BP 62, 69192 Saint-Fons Cedex, France

b) H6t6rochimie Fondamentale et Appliqu6e (URA CNRS 477), Universit6 Paul-Sabatier, 118 route de Narbonne, 31062 Toulouse Cedex, France

INTRODUCTION

The acylation reaction is one of the most important reactions in organic chemistry (ref 1) (eqn 1) The substituted atom Y is generally hydrogen, but can be an organometallic group of silyl type (refs 2, 3)

II

0 This reaction involves an acylating reagent (acyl halides, carboxylic acids or anhydrides) in the presence of an activator, usually a Lewis acid However, as

a result of the complexation of this Lewis acid with the formed ketone, more than one mole of catalyst is required per mole of reagent It cannot be reused because the ketone is isolated after hydrolysis of the complex Such is the dilemma of Friedel-Crafts acylation (refs 4-6) in the presence of the traditional catalyst, aluminum chloride (eqn 2)

ArH + RCOX + A1C13 ~ A r ~ C - - R + HX

Consequently, a lot of research has been carried out in this area in order to find convenient catalysts, i.e those able to activate the acylating reagent while giving labile complexes with ketones, in particular in hot conditions Ferric chloride is the most common catalyst when the reaction is achieved in this manner (refs 7, 8) With this same view, Friedel-Crafts acylation in the presence of small quantities of catalysts (for example FeC13), is strongly activated by microwave irradiation, in particular when the catalyst is on a graphite substrate (ref 9)

Other recent works concerning the catalytic acylation of aromatic ethers concern :

- t h e use of Lewis acid-lithium or silver salt (AgC104 or AgSbF6) systems (ref 10), boron (ref 11) or metallic triflates (ref 12), the latter being reusable catalysts, or also zinc chloride on a clay substrate ("Clayzic") (ref 13) ;

- the study of the regiochemistry of the acylation of 2-methoxynaphtalene in the presence of metallic chlorides (ref 14) ;

- and the preparation of 4-alkanoylaryl-benzylethers (ref 15)

Catalysis by Br6nsted acids requires very strong concentrations (refs 4-6), and is restricted to the more stable reagents and substrates In this respect, anisole is not acylated with a good yield in presence of 1 % of triflic acid (ref.tl6)

R E C E N T RESULTS CONCERNING CATALYSIS BY BISMUTH (HI) SALTS

Whilst numerous metallic salts are used in catalysis, some of them have been relatively little studied Such is the case of bismuth (III) salts including the chloride Bismuth, relatively inexpensive, with a metallic character marldedly more pronounced than that of As or Sb, and giving much less toxic derivatives (ref 17), might play an increasing role in catalysis, in particular for the substitution of some industrial catalysts affected by stricter standards on wastes Many works concern Bi (V) compounds in stoichiometric oxidations involving the BiV/Bi m redox pairing (ref 18) The use of Bi (III) compounds in organic reactions is less developed, but the literature includes some references,

Concerning BiC13, this weak Lewis acid proved an unexpected catalyst in the Mukaiyama-cross aldol and -Michael reactions from enoxysilanes (ref 28), because other metallic chlorides (TIC14, A1C13, SnC14 ) and stronger Lewis acids, are required in stoichiometric proportion for these reactions (ref 29) On the other hand, more recently, i has been shown that :

- the BiC13 catalytic activity in these reactions could be considerably enhanced

by addition of some metallic iodides (ref 30) ;

- the coupling of aldolisation and halogenation reactions, giving 13-haloketones

or -esters, is possible owing to these catalytic systems (ref 31) ;

- these Bi (III) halide systems allow strong Lewis acid sensitive compounds to

be used (furane cpds) (ref 32)

Moreover, BiC13 on its own acts as catalyst for the Knoevenagel reaction (ref 33) and is a strong activator of the Si-C1 bond (ref 34)

Associated with some metals (A1, Fe, Zn), BiC13 gives Bi(0) which is a catalyst for the allylation of aldehydes and amines (ref 35), and for the reduction of aromatic nitro compounds to azoxy compounds (ref 36) When associated with sodium borohydride, BiC13 gives an efficiem system for the selective reduction of nitroarenes and azomethines (ref 37)

As far as catalysis of acylation is concerned, BiC13 has been little studied Two references report the use of this salt for the acetylation of toluene (ref 38) and for the benzoylation of anisole (ref 39), with average results for the latter, but poor for toluene More recently, Le Roux and al showed that BiC13- metallic iodide systems efficiently catalyze the acylation reaction of enoxysilanes and allylsilanes for which they represent the first known catalysts (refs 30b, 40)

Although involving organosilanes, these last results encouraged us on to investigate the catalytic approach of Friedel-Crafts acylation using bismuth (III) salts, on their own, associated with co-catalysts, or on a substrate We present here our initial results (ref 41)

BISMUTH (III) SALTS IN THE FRIEDEL-CRAFTS ACYLATION OF

A R O M A T I C E T H E R S

Anisole is a reactive aromatic substrate for acylating reagents For large extent, the recent works of Scheele (ref 42) focus on this compound Therefore, in order to give good comparison, we have chosen to carry out our first tests on Friedel- Crafts acylation using anisole 1 (eqn 3)

M e O - ~ RCOX_ HX -~ M e O ~ C R + M e O - ~

RC [I

Acylation of anisole by acyl chlorides

The reaction between anisole and acyl chlorides (eqn 3, Z = C1) was carried out with an excess of aromatic substrate, without solvent (Table 1)

Table 1 Acylation of anisole by acyl chlorides (eq 1, E = C1) a

a Without solvent; anisole / RCOC1 = 4/1; heating in an oil bath

b Temperature of the oil bath

c Conversion toward RCOCI ; 2_ a,b,c,e / 3 a,b,c,e > 90/10

d Yield in isolated product after aqueous workup

e BiC13 / K 10 Montmorillonite prepared as "Clayzic" (ref 13)

f 5% mol in BiC13

The Bi (III) salts, used bath chloride and oxide, gave comparable or often better results to those previously described in the literature For instance, in the same experimental conditions Scheele observed 40 to 50% conversion of acetyl chloride in presence of 25 % mol of catalyst (FeC13, TiCI4, SnCI4) (ref 42)

We have obtained 60 % conversion of acetyl chloride with only 10 % mol of BiC13 (Table 1, entry 1) With a less volatile reagent, isobutyryl chloride, the reaction temperature can be increased, and the conversion was quantitative after 6h of heating at 85~ (Table 1, emry 2) In this case, 1 % mol of BiC13 led to

40 % conversion (entry 3) Isovaleryl chloride and benzoyl chloride also gave high yields (entries 4, 5) With the oxide Bi203, the yields are comparable to those obtained with the chloride (entries 9, 10)

Deposited on K 10 Montmorillonite ("Claybis"), BiC13 becames more active than ZnC12 (ref 13), the acylation reaction takes place at lower temperature and with a shorter reaction time (entries 7, 8), with only 5 % mol of BiC13- equivalent

Furthermore, some experiments with various Bi (III) salts and organometallic derivatives (for example : bismuth oxychloride, -acetate, - salicylate, -carbonate oxide, -zirconate, -germanium oxide, triphenylbismuth) have shown that these derivatives are also catalysts for the acylation of anisole

by acyl chlorides (ref 41)

Comparative tests were carried out with some catalysts under the same experimental conditions (Table 2) BiC13 is the most efficient of the 4 metallic chlorides used (Table 2, entries 1-6), but the difference is more pronounced with the oxides (entries 7-10), a point that will be turned to account and discussed further

Table 2 Acylation of anisole by

catalysts a

hexanoyl chloride Comparative tests with various

a Without solvent 9 anisole / RCOCI = 4/1 9 heating at 80~ in an oil bath

b In isolated product after aqueous workup; 2 d / 3 d > 90/10

A study of solvents (Table 3) shows that dichloromethane associated with ether (10/1) gives acceptable yields, but benzene, not acylated in these conditions, and nitromethane give better yields BiC13 is soluble in these last two solvents, at room temperature in MeNO2, and the reaction proceeds in homogeneous conditions

Acylation of anisole by acid anhydrides

Table 4 reports the results using 10 % tool of BiC13 with acetic and isobutyric anhydrides as reagents (eq 3, Z = OC(O)R) The acetylation of anisole by (MeCO)20 is outstanding (Table 4, entries 1,2), particularly by refluxing, towards acylation by MeCOC1 (Table 1, entries 1,6) On the other hand, acylation with (MezCHCO)20 is more difficult than with MezCHCOC1 The oxide Bi203 is not an acylation catalyst with an acid anhydride as reagent However, the addition of chlorine-mobile agent to Bi203 gives an efficient catalytic system, for example Bi203,6 MeCOCI (5 % mol) or BieO 3, 6 Me3SiC1 (5 % mol)

In the acylation of anisole by acetic anhydride, bismuth trichloride appears

as a better catalyst than iron and zinc chlorides (Table 4, entries 2,5,6)

Table 3 Acylation of anisole by acyl chlorides RCOC1 in the presence of a solvent a

70

85 9 68 c 90" 80 c

A c y l a t i o n of v e r a t r o l e

The acylation of 1,2-dimethoxybenzene or veratrole was carried out in the same conditions as those of anisole, either using acyl chlorides or acid anhydrides (eqn 4) (Table 5)

Table 4 A c y l a t i o n of anisole by acid anhydrides (eq 1, Z = OC(O)R) a

Bismuth chloride is a good catalyst for veratrole acylation by RCOC1 (entries 1,2), but the crude product may contain about 5 % of an impurity idemified (GC-MS) as compound 6, which would arise from cleavage of an ether group by HC1 The reaction is more difficult with acid anhydrides (entries 4,5) relative to anisole (Table 4, entries 2,4)

MeO

Table 5 Acylation of veratrole a

a Without solvent; veratrole / acylating agent = 4/1 ; heating in an oil bath

b Temperature of the oil bath

c Conversion of 5 toward acylating agent

d Yield in isolated product after aqueous workup

Mechanistic aspects

The mechanistic aspects of Friedel-Crafts acylation have been widely developed, in particular concerning identification of the intermediate complexes between the acylating reagent and the catalyst (refs 1, 5, 6, 43) The general opinion is that these species exist in solution as an equilibrium mixture of ionic (oxocarbenium salts) and molecular (donor-acceptor complexes) forms whose relative concentrations depend on solvent and temperature

As a result of the insolubility of bismuth chloride in chloromethanes, a spectrometric study of RCOC1-BiC13 mixtures has been carried out in nitromethane

An equimolecular mixture of MeCOC1-BiC13 in MeNO2 (0.2 mol 1-1) analyzed by infrared spectrometry showed the lack of characteristic absorptions

of oxocarbenium ions around 2200-2300 cm -1 (refs 43, 44), but a marked modification of the carbonyl stretching absorption Two bands at 1715 and 1756

of acetyl chloride-BiC13 system (Table 6) Experiments using carbon 13 labelled acetyl-13C2 chloride in CD3NO 2 prove the existence of only one coordination