USOO6906214B2 (12) United States Patent (10) Patent No.: US 6,906,214 B2 Perichon et al. (45) Date of Patent: Jun. 14, 2005

(54) PREPARATION OF AROMATIC (56) References Cited ORGANOZINC COMPOUNDS AND U.S. PATENT DOCUMENTS COMPOSITION THEREFORE 6,211,380 B1 4/2001 Fantucci et al...... 548/101 (75) Inventors: Jacques Perichon, Savigny-sur-Orge 6.258,967 B1 * 7/2001 Blacker et al...... 556/121 (FR); Corinne Gosmini, 6,521,771 B2 * 2/2003 Frommeyer et al...... 556/121 Savigny-sur-Orge (FR); Hyacinthe 6,808,655 B1 * 10/2004 Perichon et al...... 252/519.2 Fillon, Thiais (FR) FOREIGN PATENT DOCUMENTS (73) Assignee: Rhodia Chimie, Boulogne Billancourt EP O 494 419 7/1992 ...... CO7C/65/05 (FR) WO WO 01/02625 1/2001 ...... C25B/3/12 OTHER PUBLICATIONS (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 Fillon, H et al; Tetrahedron Letters (2001), 42(23), U.S.C. 154(b) by 0 days. 3843-3846, XP004240102 The whole document. GoSmini, Corinne et al ; Journal of Organic Chemistry (21) Appl. No.: 10/482,319 (2000), 65(19), 6024–6026, XP002195474 the whole docu ment. (22) PCT Filed: Jul. 3, 2002 Buriez, O et al. ; Journal of Electroanalytical Chemistry (86) PCT No.: PCT/FR02/02319 (2001), 506(2), 162–169, XP002195473 the whole docu ment. S371 (c)(1), International Search Report (2002). (2), (4) Date: Jun. 18, 2004 * cited by examiner (87) PCT Pub. No.: WO03/004504 Primary Examiner Porfirio Nazario-Gonzalez PCT Pub. Date:Jan. 16, 2003 (57) ABSTRACT (65) Prior Publication Data The invention relates to a technique for preparing aromatic US 2004/0236155 A1 Nov. 25, 2004 organozinc compounds and to a composition therefore. This composition constitutes a reactant that can be used to carry (30) Foreign Application Priority Data out the Synthesis of organozinc compounds, and comprises Jul. 4, 2001 (FR) ...... O1 O888O a cobalt Salt, a Zinc Salt, a polar aprotic Solvent and elemental Zinc in divided form, the elemental Zinc being in Solid form, (51) Int. Cl...... C07F 3/06; CO9K3/00 the other elements being in a form dissolved in the solvent. (52) U.S. Cl...... 556/128; 556/121; 252/183.14 Application to organic Synthesis. (58) Field of Search ...... 556/121, 128; 252/183.14 10 Claims, No Drawings US 6,906,214 B2 1 2 PREPARATION OF AROMATIC Over the course of the study that led to the present ORGANOZINC COMPOUNDS AND invention, it was shown that it is preferable to avoid the use COMPOSITION THEREFORE of good cobalt complexing agents, and especially bidentate complexing agents Such as bipyridyls. Pyridine itself con This application is an application under 35 U.S.C. Sec 5 siderably slows down the reaction, favoring Side reactions. tion 371 of International Application Number PCT/FR02/ On the other hand, light complexing agents, Such as 02319 filed on Jul. 3, 2002. nitrile and possibly dinitrile functional groups, seem to favor The subject of the present invention is a novel method of the reaction. Synthesizing aryl organozinc derivatives. It relates more Thus, according to the present invention, it is preferable particularly to the Synthesis of aryl organozinc derivatives that the complexing agents of pyridinic type be less than two by a chemical route in the catalytic presence of the element times, preferably less than one times, the amount expressed cobalt. in moles of cobalt Salts. The reactivity of organozinc compounds, especially aryl It is desirable for the same rules to apply to the Strong organozinc compounds, has many Specific features that cobalt complexing agents, Such as optimally bidentate make them particularly useful in many organic Synthesis 15 amines and phosphines. operations. However, they are difficult to obtain and are This rule may be expressed in the following manner: the often prepared from organometallic compounds produced high molar ratio of cobalt to coordinating ligand, chosen with more electronegative, that is to say more reducing, from pyridines, phosphines and amines, is greater than 0.5, metals. advantageously equal to 1 and preferably 2. Furthermore, most of the techniques require the use of When a complexant is multidentate, the above rule will highly aprotic, and especially very dry, media. apply using the equivalents of complexing function and not Important advances have been recently made by the same the number of moles of complexing product function. authors as those of the present application, which advances It has also been shown that the presence of an aryl halide have formed the Subject of the patent application published can potentialize the reaction, especially when the ring car by virtue of the patent cooperation treaty under number WO 25 rying the X of Said ArX is at least as rich in electrons as a 01/02625 A1. The technique described in that patent pro phenyl. This potentialization is most particularly effected by poses an electrolytic Synthesis in the presence of Zinc Salts means of aryl halides of a ring less rich in electrons than that and in the presence of cobalt Salts. The cathodic reduction of of ArX, the Zinc compound of which it is desired to produce. the System results in the Synthesis of organozinc compounds To evaluate the electron richness of a ring, reference may with good coulumbic yields. This technique is also very be made to the Hammett constants taking as reference the Versatile. In this technique, metallic Zinc possibly present at Hammett constant O. This catalysis of the zinc by cobalt is the anode acts only as a source of zinc salt, the reaction Surprizing insofar as, usually, Zinc is capable of reducing in taking place at the cathode. metallic form, by a technique Sometimes called cementation, However, this technique has the drawbacks associated the element cobalt, which is leSS reducing than Zinc. with any electrolysis. 35 According to another aspect of the invention, it has also Thus, it is relatively expensive to implement Such a been shown that the presence of acid, advantageously an technique, and an electrolytic technique can be applied only organoSoluble acid, Significantly improves the yields. to expensive products. These acids may especially be carboxylic acids, fatty Another problem lies in the difficulty in producing large acids or halogenated, and even perhalogenated, acids. Per amounts in Small volumes by electrolytic techniques. 40 fluorinated acids are of particular interest because of their One of the objectives of the present invention is therefore Solubility in organic phases and of their relatively high to provide a method for obtaining organozinc derivatives acidity. with good yields, both reaction and conversion yields, and to Without this explanation being limiting, it is plausible do So without using an electrolytic technique. These that the role of these acids is to depassivate the Zinc used. objectives, and others that will appear later, are achieved by 45 The Solvents used are preferably Solvents of the polar aprotic the use of cobalt as catalyst for the reaction between metallic type, and especially those whose donor number is at least Zinc and an aryl halogen, and to do So without an electrolysis equal to 10 and preferably at most equal to 30, advanta device. geously between 20 and 30, the limits being inclusive. Thus the particle, or fragment taken in its entirety, of Zinc Said donor number corresponds to the AH (change in is not connected to any external electrolytic System, that is 50 enthalpy) expressed in kilocalories per mole of the combi to Say one in which the current Source is located outside the nation of Said polar aprotic Solvent with antimony pen reaction mixture, which therefore does not have the right to tachloride. This is described more precisely in the work by be called an “electrolytic bath' and does not act as anode. Christian Reichardt: “Solvents and Solvent effects in Organic The formation of an organozinc compound may be termed chemistry' VCH, page 19, 1988. On this page is found the chemical formation as no apparent current can be detected. 55 definition of the donor number. It will be assumed that one day an electrochemical With the exception of the particular case of nitrites, it is mechanism will be assigned to this reaction; the same parcel preferable for the donor character to be due neither to the of metal will then act at the Same time as cathode and as nitrogen nor to the phosphorus, but instead due to oxygen. anode. In the case of Solvents with amide functional group, it This chemical nature of the reaction is demonstrated by 60 will be assumed that the donor aspect is due to the oxygen the divided form of the introduction of the metal-the Zinc linked by a double bond to the carbon of the amide func is introduced in divided form, for example powder, machin tional group. Thus, amides form part of the Solvents capable ing chips, shot, etc. and is brought into contact with no of giving good results in the case of the reaction according current Source. There is no electrical connection between the to the invention. Zinc and a current Source external to the medium, which is 65 The solvent must be sufficiently polar to dissolve the consequently not an “electrolytic' medium but Simply a metals, or more precisely the Salts of the metals used, and reaction mixture. must be sufficiently lipophilic to at least partly dissolve the US 6,906,214 B2 3 4 Substrates of which it is desired to form the organozinc end of the reaction, not to exceed the Solubility of Said Zinc compound. It is preferable to use Solvents that are Suffi Salt in the media. ciently Scarcely acidic (it is desirable for their pKa to be at It is possible to dispense with a Zinc Salt, but the reaction, least equal to 16, advantageously at least equal to 20 and in all cases in its starts, will become autocatalytic, the Zinc preferably at least equal to 25) for the reactions with Salts being formed during the reaction. It is thus preferable hydrogen to be as Scarcely pronounced as possible. Thus, to have a zinc salt concentration of at least 10M, prefer primary alcohols are too acidic to give good results. ably at least 10°M. If there is need for acidity, it is then necessary to control Aryl halides, that potentialize or act as adjuvant for the its amount using the acids that were mentioned above, and reaction, are especially denoted in the examples by ArX, especially carboxylic acids Such as trifluoroacetic acid and where X" represents the halide in question. The amounts of acetic acid itself. Fatty acids may also be used, whether or adjuvant halide (Ar"X") may be very low, but it is preferable not they are perhalogenated (in general perfluorentated) on for them to be at least equal to 10M. It is also preferable the carbon carrying the carboxylic functional group. for its concentration to be at most equal to, and even leSS Returning to the solvents, it will be preferable more than, that of the cobalt expressed in moles per liter. This is Specifically to use what are called polar aprotic Solvents Such 15 because if it is greater than that of cobalt, organozinc as, for example, by themselves or as a mixture: compounds of the adjuvant are present that may constitute purely oxygen-type Solvents, particularly ethers, prefer an impurity with regard to the desired organozinc com ably polyetherS Such as 1,2-dimethoxy ethane, or cyclic pound. X may take the same values as X (especially ethers. Such as THF or dioxane; chlorine, bromine, iodine), but ordinarily X is chosen to be equal to X. amides or ureas (DMF, N-methyl-2-pyrrollidone, When Ar"X" remains less than the amount of cobalt imidazolidone, tetramethylurea, dimethoxypropylene, present (expressed in moles per liter), the possible interme etc.); diate organozinc compound is essentially converted into a Sulfones (for example Sulfolane) or Sulfoxides (such as hydrogenated derivative corresponding to the adjuvant aryl DMSO). However, it will then be necessary, in these 25 halide. cases too, to check that the Zinc is not able, under the When the adjuvant aryl halide is such that the halogen is reaction conditions, to reduce these Solvents, close (in the ortho or equivalent position) to a functional compounds with a nitrile functional group (for those that group that complexes, even weakly, cobalt, the organozinc are preferred, see below); and compound corresponding to Ar"X may form, which may be nitriles; in order to be used these must preferably be liquid problematic during Synthesis. In general therefore, they are at the reaction temperature (as goes without saying), not used as adjuvant aromatic halide. but polynitriles may also be used, and especially bis On the other hand, such compounds may, without an nitriles. These bis-nitriles are of particular interest adjuvant aromatic, be easily converted into organozinc com because they are Scarcely complexing. They may be pounds. used as Solvent, coSolvent or light complexing agent, 35 The acid concentration is advantageously at least equal to without lowering the yield. 10M, advantageously 5x10M. The upper value is essen It is desirable, in order to avoid the medium becoming too tially limited by the amount of metallic zinc in the medium. acidic, for the bis-nitriles, that constitute the Solvent, part of The amount of acid must be less than that needed to dissolve the solvent or the coordinate, to be such that two nitrile all of the metallic Zinc and leave enough metallic Zinc for the functional groups are Separated by at least two carbons, 40 reaction. advantageously by three carbons, via the most direct path. According to the present invention, it is possible to Dinitriloalkylenes whose alkylene group contains from 2 replace in the equivalent amounts (expressed in moles) by to 8 carbon atoms give good results. Mention may be made iodine (I2). in particular of glutaronitrile, methylglutaronitrile, In general, whether iodine or acids, it is preferable to be adiponitrile, pimelonitrile and Suberonitrile. 45 at a relatively low level in order to avoid Spurious reactions, The cobalt may be introduced into the reaction mixture in especially the formation of hydrocarbon instead of the various ways and above all in various forms, but it is desired organozinc compound. In general therefore, amounts preferable for it to be introduced in the form of a salt, of acid or of iodine of less than 10%, advantageously at most preferably a cobaltous Salt. Cobaltic Salts may also be used, equal to 5%, for the aromatic constituting the precursor but they will cause additional consumption of Zinc. 50 Substrate of the organozinc compound expressed in moles To be effective, it is desirable for the cobalt to be present are used. in a minimum concentration, at least equal to 10M. To be The concentration of an ArX to be converted into a zinc economic, it is preferable for the cobalt not to be too compound, where X represents the halide or pseudohalide of concentrated-therefore the cobalt content is at most equal said aryl (pseudo)halide and where Ar represents the aro to 0.2 M. It has been shown during the present study that 55 matic residue, is not critical. However, it is preferable to be Zinc Salts can be useful at Start-up of the reaction. It is in a concentration range lying between 10°M and 2 M, therefore preferable to add Zinc Salts to the initial reaction preferably between 2x10°M and 1.5M. mixture. These Zinc Salts may be any kind of Salt, but it is The pressure is virtually of no importance in the reaction. often more practical to introduce them in the form of a On the other hand, the temperature may be a factor in halide, and especially of the halide corresponding to the 60 reducing the yield; in particular, it is preferable to have the halides of the Substrates of which it is desired to form the temperature as low as possible, in general between the organozinc compound. melting point of the reaction mixture at 100 C., advanta The same applies to cobalt. However, it is necessary to geously at a temperature of at most 80 C. and even at most avoid a multiplicity of anions in the mixture in order to be 50° C. able more easily to treat the reaction Solutions. 65 When the reaction rate is high enough, it is advantageous There is no clear-cut maximum amount of Zinc Salts to be for the temperature to be close to room temperature, and used, but it is preferable to arrange for the Zinc Salt, after the even O. C. US 6,906,214 B2 S 6 The Substrates (ArX) that can be converted into orga Thus the aryl groups may in particular be chosen from the nozinc compounds by the present invention represent a following formulae: broad range of compounds. In general, the halides are halides corresponding to the relatively heavy halogens, that is to say to the halogens heavier than fluorine. It may also be pointed out that, when the halogen (X) is linked to an aromatic ring depleted in electrons, it is pref erable to use bromine or chlorine as halogen, chlorine being reserved for rings that are particularly depleted in electrons. where Z is chosen from the same meanings as those given If the condition is fulfilled by six-membered heterocycles, in for Z. the case of homocyclic aryl compounds, in order to use a The radicals R, R, R are chosen from the abovemen chlorine it is preferable for the sum of the Hammett con tioned Substituents and especially: stants O of the Substituents (not taking into account the electron-withdrawing groups, in particular acyl groups, leaving halide) to be at least equal to 0.40, preferably at least 15 equal to 0.50. In contrast, rings that are particularly rich in nitrile groups, Sulfone groups, carboxylate groups, tri electrons may use iodine as halide. fluoromethyl groups or, more generally, perfluoroalkyl For more details about Hammett constants, the reader groups and halogens of lower rank than the halide that may refer to the 3' edition of the manual written by will be converted into an organozinc compound; Professor Jerry March “Advanced Organic Chemistry” donor groups, especially aryloxyl and alkyloxyl groups, (pages 242 to 250) published by John Wiley and Sons. hydrocarbyl groups, Such as aryl and alkyl (the latter The Substrates (ArX) having, as aromatic ring carrying X, word being taken in its etymological sense) and amine five-membered heterocycles, which include a chalcogen groups, including those that are monoSubstituted and (Such as furan and thiophene) as heteroatom, exhibit high 25 disubstituted with alkylamine hydrocarbon groups. convertibility into Zinc compound, show exceptional reac It is desirable for the Substrates to have at most 50 carbon tivity and are always easily convertible into Zinc compound. atoms, advantageously at most 30 carbon atoms and pref The electron depletion of the ring may be due either to the erably at most 20 carbon atoms. presence of electron-withdrawing groups as Substituents or, Among the Substrates that are particularly useful are aryl in the case of six-membered rings, by the replacement of a halides, preferably aryl chlorides, or more particularly aryl carbon with a heteroatom. In other words, the electron bromides, especially those carrying, in the meta position, an depleted ring may be a six-membered heterocyclic ring, aliphatic (i.e. sp.) carbon carrying at least two fluorines, for especially heterocyclic rings having an atom from the nitro example trifluoromethylaryl halides, preferably trifluorom gen column, and more particularly nitrogen. ethylaryl chlorides. Among electron-withdrawing groups giving good results, 35 This method of Synthesizing organozinc compounds may mention should be made of acyl groups, nitrile groups, Sulfone groups, carboxylate groups, trifluoromethyl groups be extended, on the one hand, to all those in which the or, more generally, perfluoroalkyl groups and halogens of organozinc groups are linked to sp-hybridized carbon lower rank than the halide that will be converted into an atoms and especially to the Synthesis of organozinc com 40 pounds from Vinyl halides, most particularly when these are organozinc compound. When the Substituents are halogens conjugated with aromatic rings. In general, the Substrate is of the same rank, a diorganozinc compound is generally added last to the reaction mixture. formed. Among donor groups, that is to say those giving mediocre Another Subject of the present invention is a composition results with chlorine but good results with bromine, mention forming a reactant that can be used to carry out the Synthesis may be made of alkyloxyl groups, alkyl groupS and amine 45 of organozinc compounds, characterized in that it comprises and dialkylamine groups. a cobalt Salt, a Zinc Salt, a polar aprotic Solvent and elemental The aromatic derivative, namely the substrate of the Zinc in divided form, the elemental Zinc being in Solid form, present method, advantageously Satisfies the following for the other elements being in a form dissolved in the solvent. mula: This composition furthermore includes an acid or molecular 50 iodine. The constituents of the reactant may be added in various orders of addition. According to a Standard but nonobligatory method of implementation, the salts used (cobalt Salt, if this is 55 provided, Zinc Salt and optionally other salts), the adjuvants where: (Such as iodine or acid) for activating the metallic Zinc and the optional Ar"X" (or the ArX, or a portion of ArX, when Z represents a trivalent-C(R)=link, an atom of Column V, advantageously a nitrogen; there is no Ar"X") are introduced into the solvent, followed 60 secondly by the zinc and finally by the ArX (when there is X represents the leaving halogen; and an Ar"X", or when all of the ArX has not yet been A represents either a link chosen either from ZH groups introduced). or from chalcogens, advantageously of a rank at least AS teaching, through the example (paradigm), the reader equal to that of sulfur, or from two-membered divalent may refer to the general experimental conditions that give an unsaturated groups CR=CR, N=CR or CR=N. 65 order of introduction of the components of the reactant. If they are carried by adjacent atoms, two of the radicals These general operating conditions were used in the R, R, R2 and R may be linked to form rings. examples. US 6,906,214 B2 7 8 General Experimental Conditions: EXAMPLE 2 The following mixture was initially prepared: Nature of the Halide Linked to the Zinc 1) 20 ml acetonitrile solvent, or 20 ml acetonitrile +0.5 ml With ZnBr: adiponitrile (1.5 equivalents relative to the CoBr), or 20 s ml acetonitrile+MVK (1.5 equivalents relative to the CoBr-)-methyl vinyl ketone (MVK) is stable under the % ArX operating conditions. FG X % Ar % Arar remaining % ArZnX Powdered Zn: 50 mmol (3.3 eq/ArX) 1O p-OCN Br O O O 1OO CF,COOH: 0.0125 to 0.025M p-CH Br 9 2O 71 PhBr(Ar"X): 0.10 eq/ArX CoBr: 0.10 eq/ArX With ZnCl:

ZnBr: 0.10 eq/ArX. 15 Once the release of Ar"H was over, in general 4 of an hour after the above mixture was produced, the Substrate % ArX ArX was added in an amount equal to 15 mmol. FG X % Ar % Arar remaining % ArZnX 2) Arbr: 15 mmol p-OCN Br O O O 1OO Reaction: With Zn(CHSO):

where FG represents the substituent under investigation of 25 % ArX the aromatic. FG X % Ar % Arar remaining % ArZnX The following nonlimiting examples illustrate the inven p-CH Br 50 3 47 tion.

3O EXAMPLE 3 EXAMPLE 1. Moment of Introduction of the Zinc Salt (Here Nature of the Solvent ZnBr.) In solvent: 20 ml CHCN+1.5 eq/CoBra adiponitrile In solvent: 20 ml CHCN 35 ZnBr in the first step

FG X % ArH % Arar 76 ArX remaining % ArznX FG X % ArH % Arar 76 ArX remaining % ArznX p-OCH Br 1O 4 9 78 40 p-OCH Br 16 13 O 71 p-CHSOCO Br 1O 17 O 73 m-CF, Br 12 3 O 8O m-CF Br 6 1O O 84 p-COCH, Br 15 34 O 52 p-CHSOCO Br 11 12 O 76

In solvent: 20 ml CHCN+1.5 eq/CoBradiponitrile 45 In solvent: 20 ml CHCN+1.5 eq/CoBra adiponitrile ZnBr in the Second step

FG X % ArH % Arar 76 ArX remaining % ArznX p-OCH Br 16 13 O 71 50 FG X % ArH % Arar 76 ArX remaining % ArznX p-CHSOCO Br 11 12 O 76 p-OCH Br 11 O O 89 m-CF Br 12 3 O 8O p-CHSOCO Br 13 9 O 76 p-CN Br 3 2 O 95 p-COCH, Br 15 34 O 52

In solvent: 20 ml CHCN+1.5 eq/CoBr MVK 55 The results obtained are Substantially the same as those obtained according to the usual procedure. EXAMPLE 4 FG X % ArH % Arar 76 ArX remaining % ArznX Nature of the Halide Linked to the Zinc p-OCH Br 14 34 O 52 60 Either ZnBr or ZnCl2 is used, the results are the Same: in p-CHOCO Br 7 8 O 85 the cases of p-BrPhCN, 100% p-BrZnPhCN was obtained in p-CN Br 5 O O 95 both cases. EXAMPLE 5 The results obtained from these various Solvents vary 65 Nature of the Activant for the Powdered Zinc from one Species to another; it was therefore chosen to work In solvent: 20 ml CHCN+1.5 eq/CoBra adiponitrile Acti in a 20 ml CHCN+1.5 eq/CoBra adiponitrile mixture. vant: CFCOOH US 6,906,214 B2 9 10 EXAMPLE 7

FG X % ArH % Arar 76 ArX remaining % ArznX Influence of the Presence of the Pyridine

5 1) Same conditions as those of example 6-1 with,s as Solvent s toCO R g 7. the CHCN/pyridine (20 ml/2.5 ml) mixture, without adiponitrile. With ArBr being p-BrPhOCH and Ar"X" being PhBr, it In solvent: 20 ml CHCN+1.5 eq/CoBra adiponitrile Acti- was observed that the reaction was greatly slowed vant: I 1O down. 2) Same conditions as 1), but with no PhBr. Starting from p-BrPhOCH, practically no FG X % ArH % Arar 76 ArX remaining % ArznX p-BrZnPhOCH, was obtained in 24 H, whereas in the absence of pyridine the reactions lasted from 15 to 20 p-OCH Br 12 O O 88 15 min. p-CHSOCO Br 7 19 O 75 3) Same conditions as 2) with ArBr=p-BrPhCOEt. 60% ArBr converted into p-BrZnPhCOEt in 24 H. Thus, In solvent: 20 ml CHCN+1.5 eq/CoBradiponitrile Acti- the presence of pyridine greatly slows down the for vant: acetic acid mation of organozinc compounds whose ring is rich in 2O electrons. EXAMPLE 8 FG X % ArH % Arar 76 ArX remaining % ArznX Studv of the Vari Substrat udy oI une various SubSurates -OCH B 22 O O 77 Roco E. 16 14 O 70 25 The following working conditions were chosen: 1) Solvent: 20 ml acetonitrile+0.5 ml adiponitrile Powdered zinc: 50 mmol (3.3 eq/Arx) improved.If the activant is I, the Zinc derivative yields are CFCOOH: (0.0125 to 0.025M) 30 PhBr(ArX): 0.10 eq/ArX EXAMPLE 6 CoBr: 0.10 eq/ArX ZnBr: 0.10 eq/ArX. Replacement of PhBr with Other Aromatic Halides 2) Arbr: 15 mmol in the First Phase of the Reaction 35 The reactions were carried out at room temperature. The Whether Ar"X", p-BrPhCOOEt, p-BrPhCN, m-BrPhCF, results obtained were the following: o-BrPhCN, or 3-bromopyridine was used, results identical to those obtained with PhBr were obtained. All these halides were converted into Ph.H., except in the case of o-BrPhCN, % ArX which was partly converted into o-BrZnPhCN. 40 FG X % ArH % Arar remaining % ArznX 1) Choice of aromatic halide (Ar'Br) Conditions: CHCN (20 ml), adiponitrile (0.5 ml), CoBra m-OCH Br 7 23 O 70 (0.1 eq), ZnBr (0.1 eq), CFCOOH (0.0125 to O-OCH Br 6 7 O 87 0.025M), powdered zinc (3.3 eq), Ar'Br (0.1 eq), addi- E; OCO i g 7. tion of 15 mmol of ArBr (1 eq) when all the Ar'Br has 45 cf. Br 12 3 O 8O been consumed. ArBr is p-BrPhOCH. The following p-Cl Br 6 5 O 89 Ar"Xp-BrPhCO.Et, compounds p-BrPhCN, were testedm-BrPhCF, one after o-BrPhCN, another: 3 p-FES" BBr is9 s21 gO 70 BrPyridine. RN Br 4 O O 96 The results obtained (p-BrZnPhOCH, yields from 65 to CN Br O O O 1OO 72%) are similar to those obtained with PhBr. All the Role 29 s 6 i Ar'Br compounds were converted into ArH, except for p-CHOCO Cl 23 O 71 6 o-BrPhCN, which was partly converted into p-OCH I 8 3 O 88 O-BrZnPhCN. p-CHSOCO I 14 11 O 75 2) Influence of the Ar'Br/CoBr ratio 55 Riseh. 43 g s d The operating conditions were the same as those of 1), X-Ph-SO, Cl 23 O 37 41 with ArBr being p-BrPhOCH and Ar'X' being PhBr. p-COCH Cl 23 O 71 6 Three Ar"X"/CoBr ratios were examined experimen- p-NH. Br 52 O 8 40 tally. 60 *CoBr: 0.20 eq/ArX; The Ar'Br/CoBr ratio of /2(0.05 eq)/(0.1 eq) gave the ZnBr: 0.20 eq/ArX. same result as with a ratio of 1 ArX=CoBr=0.1 eq, namely a p-BrZnPhOCH yield ranging from 68 to EXAMPLE 9 70%. A ratio of 2 (0.2 eq)/0.1 eq) gave the same result. In this 65 Split Addition of CoBre case however, it was established that about 50% of the Same conditions as in example 6 but without Ar'Br and PhBr was converted into PhZnBr. without ArBr and CoBr=0.01 eq. The mixture was left for US 6,906,214 B2 11 12 30 min, then 0.09 eq of CoBra and 1 eq of ArBr What is claimed is: (p-BrPhCOEt) were added. 1. A process for the Synthesis of aryl organozinc com A p-BrZnPhCOEt yield of 60% (reaction yield) was pounds from areaction mixture comprising a metallic Zinc obtained. and an aryl halide of the formula:

EXAMPLE 10 AX Two-step Reactions wherein Aris an aromatic residue and X is a halogen heavier than fluorine, Said proceSS comprising the Step of using Identical conditions to example 6, but in two steps: cobalt as catalyst. 1 step: no ArBrand no ZnBr. 2. The proceSS as claimed in claim 1, wherein the cobalt 2" step: after 10 to 30 minutes, Zn Bra (0.1 eq) and ArBr (1 is introduced into the reaction mixture in the cobaltous State. eq) were added. 3. The process as claimed in claim 1, wherein the cobalt Results: is weakly coordinated. 15 4. The process as claimed in claim 1, wherein the Syn thesis is carried out in the presence of an adjuvant aromatic Arr % Ar % Ar-Air % ArZnX halide of the formula:

p-BrPhCO.Et 13 8 76 A-X p-BrPhCOCH, 14 12 74 p-BrPhOCH, 11 O 89 p-BrPhCH, 14 19 67 wherein X" represents a halogen heavier than fluorine, and Ar' represents an aromatic derivitive whose ring carrying the halogen X is less electron-rich than the radical Ar. Results Substantially the same as those obtained according 5. The process as claimed in claim 4, wherein the the to the standard procedure, except with p-BrPhCOCH where 25 aromatic of formula Ar"X" is present in a content, expressed the yield is markedly increased (74% of ArZnX in 10 in moles per liter, is at most equal to the cobalt concentration minutes), but at 20° C. this Zinc compound decomposes and in the reaction mixture. is progressively converted into Ar-Ar. 6. The process as claimed in 1, wherein the reaction EXAMPLE 11 mixture furthermore includes an acid Soluble in the mixture, or molecular iodine. Influence of the Temperature 7. The process as claimed in claim 1, wherein the Sub strate ArX is added last. Conditions identical to example 6, but the reactions were 8. The process as claimed in claim 1, wherein the halide carried out at 0° C. and without adiponitrile. 35 X of ArX is bromine or iodine, advantageously bromine. 9. A composition forming a reactant that can be used to carry out the Synthesis of organozinc compounds, compris % ArX Time ing a cobalt Salt, a Zinc Salt, a polar aprotic Solvent and Arr % ArH % Ar-Ar remaining % ArznX (min) elemental Zinc in divided form, the elemental Zinc being in 40 Solid form, the other elements being in a form dissolved in p-BrPhCHO 9 44 23 23 8O the solvent. p-BrPhCOCH, 8 23 1O 59 25 10. The composition as claimed in claim 9, further com prising an acid or molecular iodine. In both cases, progression toward Ar-Ar when the temperature increases.