GB1586095A

GB1586095A - Process for the preparation of lower alkyl 2-(n-r'-pyrryl)-a-lower alkanoic acid esters

Info

Publication number: GB1586095A
Application number: GB3476077A
Authority: GB
Original assignee: McNeilab Inc; McNeil Laboratories Inc
Current assignee: Janssen Pharmaceuticals Inc
Priority date: 1976-08-23
Filing date: 1977-08-18
Publication date: 1981-03-18
Also published as: FR2362835B1; ATA608177A; DE2737946A1; FR2362835A1; CH634833A5; CA1076586A

Abstract

2-(N-R'-pyrryl)- alpha -alkanoic acid lower alkyl esters, wherein R' is hydrogen or lower primary alkyl, are obtained isomer-selectively and in high yield and purity if, in the reaction of N-R'-pyrrole with an alpha -diazoalkanoic acid lower alkyl ester, a copper(II) complex of the formula <IMAGE> or <IMAGE> is employed as a promoter, the symbols used being defined in Patent Claim 1. Novel complexes of this type, namely acetylacetonato-copper(II) trifluoromethylsulphonate are obtained by reacting copper acetylacetonate with trifluoromethylsulphonic acid.

Description

(54) PROCESS FOR THE PREPARATION OF LOWERALKYL 2-(N-R'-PYRRYL)-a-LOWERALKANOIC ACID ESTERS (71) -We, McNEIL LABORATORIES, INCORPORATED, a Corporation organised and existing under the laws of the State of Pennsylvania, United States of America, of Camp Hill Road, Fort Washington, State of Pennsylvania, United States of America, do hereby declare the invention for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement: The present invention relates to a process for the preparation of loweralkyl 2-(N-R'pyrryl)-a-loweralkanoic acid esters and, more particularly, for the preparation of loweralkyl 2-(N-methylpyrryl) acetic acid esters.

Lower alkyl 2-(N-R -pyrryl-a-loweralkanoic acid esters comprise a very useful class of compounds, being intermediates for the preparation of phenothiazine derivatives (see, for example, British Patent No. 823,733) and for the synthesis of the well-known antiinflammatory agent tolmetin and its analogues (see, for example, U.S. Patent No.

3,752,826), and are represented by the following generic formula:

wherein R is a loweralkyl group; R' is a hydrogen atom or a primary loweralkyl group; and R" is a hydrogen atom or a loweralkyl group.

The prior art method for the preparation of compounds of this type is by the decomposition of a loweralkyl a-diazoloweralkanoate of formula (II), in the presence of an N-R'-pyrrole of formula (III), with copper bronze as a catalyst or promoting agent. See, for example, H. Rapoport and E. Jorgensen, J. Org. Chem., 14, 664(1949). By the term "promoting agent" as used herein is meant a material which effects or facilitates a chemical reaction even when employed in a much less than a stoichiometric amount (i.e., which functions as a catalyst, in the usual sense of the term, but which may be chemically altered during the course of the reaction). Given the chemical modification of the promoting agent, it necessarily differs from a true catalyst, which by definition remains unchanged by the reaction that it induces.

It has recently been discovered that this prior art preparative procedure does not yield only the desired 2-isomer but also yields some of the 3-isomer of formula (IV), as a by-product. This prior art process is illustrated by the following:

CH-COOR 1 N2iCOOR coDer.bronze) (I) + (III) (11) wherein R, R', and R" are as previously defined.

As these two isomers are practically inseparable it is desirable to have a process whereby one obtains a reaction product as enriched as possible in the desired 2-isomer (as "pure" as possible). As used herein, the term "pure" refers specifically to the degree of enrichment in the favored 2-isomer (i.e., to the relative amount of the desired 2-isomer compared to the undesired 3-isomer). The greater the ratio of 2-isomer to 3-isomer, the more "pure" the product mixture is said to be. Throughout the present application, this "purity" will be represented as the percent of the total amount of loweralkyl (N-R'-pyrryl)-a-loweralkanoic acid ester which is the desired 2-isomer.

It is also desirable to have a process which produces as much of the desirable 2-isomer as possible, regardless of the purity thereof. This characteristic will be referred to as the "yield" of the reaction and will be based upon the limiting reagent loweralkyl a-diazoloweralkanoate.

The prior art procedure is less than desirable in both the purity and the yield of the product. For example, the prior art preparative method for N-methylpyrrole acetic acid ethyl esters generally produces a product mixture having a purity of about 82% of the desired 2-isomer and a yield of the desired 2-isomer of about 32%, based on the ethyl diazoacetate. It should be noted at this point that, for this particular product, the literature often reports yields based upon N-methylpyrrole rather than ethyl diazoacetate. these yields appear considerably larger than those as calculated herein because they are not based upon the limiting reagent, ethyl diazoacetate. For valid comparison of two percentage yields, they must both be based on the same starting material. Throughout this application all yields are based on the amount of loweralkyl a-diazoloweralkanoate consumed in the reaction.

It is known in the chemical art that the effect of different types of catalysts on an individual reaction, or on related reactions, is very difficult to predict. A given catalyst may be ineffective in one reaction, while being the catalyst of choice in a closely related reaction.

Different catalysts may result in different products or different ratios of products from the same starting materials. This unpredictability with respect to copper catalysts in diazo compound reactions is discussed, for example, on page 251 of "The Reaction of Diazoacetic Esters with Alkenes, Alkynes, Heterocyclic and Aromatic Compounds", Chapter 3, in Organic Reactions, 18, 217 (1970), by V. Dane and E.W. Warnhoff.

It has now surprisingly been discovered that the yield of the desired 2-isomer can be significantly increased and, in some cases, the purity of the product improved through the use of the copper (II) 1,3-diketonate, copper (II) salicylaldehyde, copper (II) monoamino1,3-diketonate, and copper (I1) salicylaldimine complexes of the invention as promoting agents.

According to the present invention there is provided a process for preparing a loweralkyl 2-(N-R'-pyrryl)-a-loweralkanoic acid ester of the formula:

wherein R is a loweralkyl group, R' is a hydrogen atom or a primary loweralkyl group, and R" is a hydrogen atom or a loweralkyl group, which process comprises reacting an N-R'-pyrrole of the formula:

wherein R' is as above defined with a loweralky a-diazoloweralkanoate of the formula:

wherein R and R" are as defined above, in the presence of a copper complex of the formula;

wherein: n is the integer 1 or 2; X is an anion derived from a monoprotic strong acid, lower-alkoxy or phenoxy;

is a 1 ,3-diketonate or salicylaldehyde ligand capable of forming a bidentate complex with copper (II); and

is a monoamino-1,3-diketonate or salicylaldimine ligand capable of forming a bidentate complex with copper (II) wherein R12 is a hydrogen atom, or a lower alkyl; loweralkoxy; hydroxy; loweralkylamino; diloweralkylamino; phenyl substituted with from one to three members which are each independently a loweralkyl or loweralkoxy group, or a halogen atom; phenylloweralkyl; phenylloweralkyl in which said phenyl is substituted with from one to three members which are each independently a loweralkyl or loweralkoxy group, or a halogen atom; phenylamino, and phenylamino in which said phenyl is substituted with from one to three members which are each independently a loweralkyl or loweralkoxy group or a halogen atom; provided that the R12 groups on both ligands taken together may also be:

wherein a and b are integers such that a + b is from 1 to 6, and R13 is a hydrogen atom, a loweralkyl, phenyl, or phenyl group substituted with from one to three members which are each independently a loweralkyl or loweralkoxy group or a halogen atom;

wherein c is an integer from 3 to 5; (iii) o-phenylene or o-phenyline substituted with from one to three members which are each independently a loweralkyl or loweralkoxy group or a halogen atom; or (iv) -(CH2)d-[NR14-(CH2),If-NR1S-(CH2)g, wherein d, e, and g are each 2 or 3,f is0 or 1, and R14 and R15 are each independently a hydrogen atom or a loweralkyl group.

A. Complexes with dioxo ligands In the dioxo copper (II) salicylaldehyde and 1,3-diketonate complexes (promoting agents) of the formula:

wherein n is as above defined, and X is an anion derived from a monoprotic strong acid, such anions may be, for example, -OSO2CF3, picrate, hexafluorophosphate, nitrate, perchlorate, halide, loweralkylsulfonate, arenesulfonate, such as benzenesulfonate, toluenesulfonate and naphthalenesulfonate, fluoborate, trifluoracetate or fluorosulfate.

The group

is intended to encompass all salicylaldehyde and 1 ,3-diketonate ligands capable of forming bidentate complexes with copper (II), whatever the substitution thereon. When n is 2, the two ligands may be the same or different.

It should be understood that certain 1 ,3-diketonate ligands, because of their molecular geometry, are incapable of forming bidentate complexes with copper (II). Examples of 1,3-diketones which are unsuitable for making such copper complexes are

Since the keto groups on these compounds are directed away from each other due to the molecular geometry, these compounds cannot function as bidentate ligands.

The expression "1,3-diketonate" includes, for example, compounds of formula

wherein R1 and R3 are each independently a loweralkyl, loweralkoxy, perfluoroloweralky, phenyl, 2-thienyl or ss-naphthyl groups and R2 is a hydrogen atom or a loweralkyl group.

Also included within the expression "1,3-diketonate" are the semicyclic 1,3-diketonates exemplified by the following:

wherein R4 is a loweralkyl, loweralkoxy, phenyl or perfluoroloweralkyl group; m is 0 or 1; and R5 is a loweralkyl or perfluoroloweralky group.

The expression "salicylaldehyde" includes, for example, compounds of formula

wherein R6 and R, are each independently a hydrogen or halogen atom, or a nitro, lower alkoxy or loweralkyl group; provided that R6 and R7 are oriented meta to each other if both are other than hydrogen atoms; and R8 is a hydrogen atom, a loweralkyl or perfluoroloweralkyl group.

Also included within the expression "salicylaldehyde" is the bicyclic compound of formula:

wherein R8 is as previously defined.

By the terms "loweralkyl' and "loweralkoxy" as used herein are meant straight or branched chain saturated aliphatic hydrocarbon radicals having from one to six carbon atoms such as, methyl, ethyl, isopropyl or pentyl, and methoxy, ethoxy, isopropoxy or pentoxy. By the term "primary loweralkyl" is meant a loweralkyl group in which the bonding carbon atom is unbranched such as, methyl, ethyl, isobutyl or pentyl, but excluding, for example, isopropyl and sec-butyl.

By the term "perfluoroloweralkyl" is meant a loweralkyl group in which all of the hydrogen atoms have been replaced by fluoro such as, trifluoromethyl or tetrafluoroethyl. The term "halo" includes fluoro, chloro, bromo, and iodo; and the term "halide" includes fluoride, chloride, bromide, and iodide.

The 1,3-diketones useful for preparation of the copper (II) 1,3-diketonate complexes are generally known or may be readily prepared according to the procedures described in Org.

Syn., Coll. Vol. 3, 16, 17, 251(1951) or C. R. Hauser, Org. Reactions, 8, 59 (1954). The salicylaldehydes useful for the preparation of the said complexes are also generally known.

The preferred copper (II) 1 ,3-diketonate and copper (II) salicylaldehyde complexes (promoting agents) may be represented by the following formulae:

wherein Rg and R10 are each independently a loweralkyl, perfluoroloweralkyl, phenyl, loweralkoxy, or 2-thienyl group.

wherein Xis a OSO2CF3 or OCH3 group; and

wherein R11 is a hydrogen or halogen atom, or a nitro or loweralkoxy group.

Certain of the complexes of formula (XIV) are novel (e.g., those wherein X' is -OSO2CF3). They may be prepared by metathesis of an appropriate complex of formula (X) with one equivalent of a suitable strong acid such as HOSO2CF3.

The remaining dioxo complexes are generally known or may be readily prepared according to the procedures described by, for example, E. W. Berg and J. T. Truemper, J.

Phys. Chem., 64, 487 (1960); J. H. Bertrand and R. L. Kaplan, Inorg. Chem., 4, 1657 (1965); or K. Clarke, J. Chem. Soc. 245 (1963). This latter reference teaches the preparation of the following complexes.

wherein A is a chlorine, bromine or iodine atom or a nitro group; and B is a methoxy or nitro group or a chlorine atom.

B. Complexes with oxoamino ligands In the oxoamino copper (II) complexes of the formula: the radical

is as defined above.

These oxoamino copper (II) salicylaldimine and copper (II) monoamino-1.3-diketonate complexes and the ligands from which thev are made are generally known or may be readily prepared according to the procedures described bv R. H. Holm. et al: Prog. in Inorg.

Chem.. 7. 83(1966) and references contained therein. The ligands are conveniently prepared by reacting the appropriate corresponding dioxo ligand with an equivalent amount of the appropriate amine.

Preferred oxoamino copper (II) complexes may be represented by the following formula:

wherein R12 is as above defined.

The complexes wherein both R12 groups are taken together may be illustrated by the following: selected from class (i) above:

wherein a and b are as previously defined.

More preferred oxoamino copper (II) complexes ma! be represented by the following formulae:

wherein: Rt. R-. Rs. and Rl2 are as previously defined.

Most preferred copper (II) salicylaldimine complexes (promoting agents) may be represented by the following formula:

wherein R12 is a hydrogen atom or a loweralkyl; phenyl or phenyl group substituted with from one to three members which are each a loweralkyl or loweralkoxy group, or a halogen atom or a phenylloweralkyl group.

In one embodiment of the method of the present invention the N-R'-pyrrole is present in excess, preferably about three equivalents for every equivalent of the loweralkyl a-diazoloweralkanoate. The promoting agent is a compound of formula (V) or (XVI), and is present in an amount of from 0.1 to 2 mol percent, but preferably 1 mol percent based on the loweralkyl a-diazoloweralkanoate. The reaction may be conducted in the N-R'-pyrrole as solvent; a halogenated hydrocarbon, such as methylene chloride, chloroform, bromoform, carbon tetrachloride or 1,2-dichloroethane; an aliphatic hydrocarbon, such as cyclohexane or heptane; or an aromatic hydrocarbon, such as benzene, toluene or xylene.

The preferred solvent is the N-R'-pyrrole itself, or a halogenated hydrocarbon, which is convenient for attainment of the required reaction temperature. The reaction mixture may be heated up to as high as 110 C., but a convenient operating temperature range is from 30 to 800C. The preferred operating temperature depends upon the particular promoting agent used.

A small portion of the loweralkyl a-diazoloweralkanoate is added initially for reasons of safety; i.e., to prevent an accumulation of the reagent which could result in the violent and sudden production of heat and nitrogen gas. Once nitrogen evolution has begun, the remainder of the loweralkyl a-diazoloweralkanoate is added drop by drop maintaining a temperature sufficient for smooth and steady nitrogen evolution by warming or cooling as needed. Subsequent to addition of the loweralkyl a-diazoloweralkanoate, the mixture may be heated to ensure completion of the reaction, but this is frequently unnecessary.

The mixture of the desired 2-isomer and the undesired 3-isomer may be isolated by known techniques, for example by distillation.

A preferred process of the invention is that wherein the N-R'-pyrrole is N-methylpyrrole.

A more preferred process of the invention is that wherein the promoting agent is a compound of formula (XI) wherein Rg is a methyl group and Rlo is a phenyl group or Rg and Rlo are both loweralkyl groups, a compound of formula (XII), a compound of formula (XIV) wherein Xis a methoxy group, and compounds of formula (XX) wherein R12 is a hydrogen atom, or an isopropyl, p-chlorophenyl or benzyl group. These more preferred processes result in very high purity of the desired 2-isomer.

A second more preferred process of the invention is that wherein the promoting agent is a compound of the formula (XI) wherein Rg is a methyl group and Rlo is a perfluoroloweralkyl group or Rg and Rlo are both perfluoroloweralkyl groups, a compound of formula (XIV) wherein X' is an OSO2CF3 group, and compounds of formula (XV) wherein R11 is a chlorine or hydrogen atom, or a nitro group. These more preferred processes result in a large increase in yield of the desired 2-isomer.

Better yield and generally better purity are obtained through use of the promoting agents and processes of the invention. The purity of the reaction mixture is as high as 93-94% in some cases and generally the same as or better than in the prior art, while the yield of the desired 2-isomer is increased by at least 10% and by as much as 50% over the yield in the prior art methods.

The present invention is further illustrated by the following examples: EXAMPLE I Ethyl 2- (N-methylpyrryl) acetate In a flask is placed 9.72 grams (120 mmol) N-methyl pyrrole and 158 mg (.016 mmole; 1.5 mol%) Cu(acetylacetonate)2 abbreviated herein as "Cu(acac)2". The mixture is heated to 50"C. after which a few drops of the 4.56 grams (40 mmol) ethyl diazoacetate are added with stirring. Nitrogen gas is evolved after about 1 minute and the mixture darkens, whereupon the remainder of the ethyl diazoacetate is added drop by drop over a period of 15 minutes. The reaction mixture is then heated and stirred for a further 45 minutes to insure completion of the reaction.

The excess and unreacted N-methylpyrrole is recovered by distillation of the product mixture in vacuo, after which the residue is flash distilled at a pot temperature of 80-100 C.

(0.5 torr) to yield 2.40 grams of yellow liquid (36% yield based on ethyl diazoacetate) comprising 91% of the desired ethyl 2-(N-methylpyrryl) acetate.

EXAMPLE II Ethyl 2-pyrrylacetate Following the procedure of Example I, but substituting an equivalent amount of pyrrole for the N-methylpyrrole used therein, resulted in 50% yield (based on ethyl diazoacetate) of the desired ethyl 2-pyrrylacetate in 94% purity. For comparison, the prior art process using copper bronze as the promoting agent resulted in only 38% yield (based on ethyl diazoacetate) of the desired ethyl 2-pyrrylacetate in 92% purity.

EXAMPLE III The purity and yields of the desired 2-isomer ethyl 2-(N-methylpyrryl)acetate obtained following the procedure of Example I but using equivalent amounts of illustrative catalysts of the invention for the Cu(acac)2 used therein are shown in the following table, wherein Y and P stand for percentage yield and percentage purity, respectively: Formula R9 R10 X' R11 R12 Y P (XI) CH3 phenyl - - - 37 90 CH3 CF3 - - - 43 79 t-butyl t-butyl - - - 36 89 CF3 CF3 - - - 44 78 phenyl phenyl - - - 37 87 CH3 OC2H5 - - - 41 84 2-thienyl CF3 - - - 40 83 (XII) - - - - - 40 89 (XIII) - - - - - 39 86 (XIV) - - OSO2CF3 - - 47 81 - - OCH3 - - 40 90 Formula R9 R10 X' R11 R12 Y P (XV) - - - Cl - 48 80 - - - H - 45 83 - - - NO2 - 47 75 - - - OCH3 - 42 83 (XX) - - - - H 46 91 - - - - OH 42 82 - - - - CH(CH3)2 47 94 - - - - benzyl 44 94 - - - - p-ClC6H4 47 90 - - - - -CH2CH2-* 37 89 - - - - -(CH2CH2)2NH* 37 89 - - - - -(CH2CH2NHCH2)2* 38 89 *both R12 groups taken together PREPARATION I Bis(S-chlorosalicylaldehyde) Copper(ll) To a solution of 1.61g of copper (II) nitrate trihydrate and 1.25g of sodium acetate in 25 ml of deionized water is added a warm solution of 2.08g of 5-chlorosalicylaldehyde in 25 ml of 95% ethanol. The mixture is stirred at 450-500C for 15 minutes, cooled, and filtered.

The yellow-green solid which results, Bis(5-chlorosalicylaldehyde) copper (II), is rinsed with water and 95% ethanol and dried in vacuo.

PREPARATION II Following the procedure of Preparation I,but substituting for the 5-chlorosalicylaldehyde used therein, an equivalent amount of the suitable starting material, there are prepared the following representative complexes: Bis(benzoylacetonato) Copper(II); Bis(2-acetyltetralonato) Copper(II); Bis(2-acetylcyclohexanonato) Copper(II); Bis 1,1,1,2,2,3,3 ,-heptafluoro-7 ,7-dimethyloctane-4,6-dionato) Copper(II); Bis(3-trifluoroacetylcamphorato) Copper(II); Bis(2,4-heptanedionato) Copper(II); Bis(1,1,1-trifluoropentane-2,4-dionato) Copper(II); Bis[1 ,1,1,5,5 ,5-hexafluoropentane-2 ,4-dionato] Copper(II); Bis(3-methylpentane-2,-dionato) Copper(II); Bis(ethylacetoacetato) Copper(II); Bis(3-pivaloyl camphorato Copper(II); Bis(2-furoylacetonato) Copper(II); and Bis dibenzoylmethanato) Copper(II).

PREPARATION III (Acetylacetonato) Copper(ll) trifluoromethylsulfonate A suspension of 262 mg. (1 mmole) of Cu(acac)2 in 3 ml of dichloromethane is treated dropwise with stirring with 150 mg (1 mmole) of trifluoromethyl sulfonic acid. The resulting green solution is decanted from a small amount of residual solid and diluted with hexane, whereupon a green precipitate, (acetylacetonato) Copper(II) trifluoromethylsulfonate, results, m.p. 182"C.

PREPARATION IV Following the procedure of Preparation III, but substituting for the Cu(acac)2 and the trifluoromethylsulfonic acid used therein, the equivalent amount of suitable starting materials, there are prepared the following complexes: (Acetylacetonato) Copper (II) trifluoroacetate; (Benzoylacetonato) Copper (II) fluorosulfate; (Acetylacetonato) Copper (II) picrate; (Acetylacetonato) Copper (II) hexafluorophosphate; (Acetylacetonato) Copper (II) nitrate; (Acetylacetonato) Copper (II) perchlorate; (Acetylacetonato) Copper (II) chloride; (Acetylacetonato) Copper (II) ethylsulfonate; (Acetylacetonato) Copper (II) benzenesulfonate; (Acetylacetonato) Copper (II) fluoborate.

PREPARATION V Bis- ( -salicylaldiminoethyl) amine Copper (II) To a solution of 2.44g (20 mmol) of salicylaldehyde in 20 ml of absolute ethanol was added 1.03g (10 mmol) of diethylenetriamine and the whole was allowed to stand at ambient temperature for one hour. A solution of Copper (II) acetate (from 2.42g of Cu(NO3)2.3H2O and 1.7g of sodium acetate) in 20 ml of deionized water was added, and the whole was allowed to stand for 18 hours. The resulting purple crystals were collected by filtration, washed with 75% aqueous ethanol, and dried in vacuo at 70" to yield Bis-( -salicylaldiminoethyl)amine Copper(II); m.p. ca. 240"C (dec).

PREPARATION VI Following the procedure of Preparation V, but substituting an equivalent amount of triethylenetetramine for the diethylenetriamine used therein, there is prepared: 1,2-Bis(P-salicylaldiminoethylamino)ethane Copper (II); m.p. ca. 240"C (dec).

EXAMPLE IV Following the procedure of Example I, but substituting for the N-methylpyrrole and ethyl diazoacetate used therein equivalent amounts of the appropriate starting materials, the following 2-pyrrylacetic acid esters are produced in increased yield or yield and purity over the prior art process: Methyl 2-(N-methylpyrryl)acetate; Methyl 2-(N-ethylpyrryl)acetate; Ethyl 2-(N-ethylpyrryl)acetate; n-Propyl 2-(N-methylpyrryl)acetate; Isopropyl 2-(N-methylpyrryl)acetate; Methyl 2-(N-methylpyrryl)-a-propionate; Butyl 2-(N-ethylpyrryl)-α-propionate; Ethyl 2-(N-n-propylpyrryl)-α-isovalerate; and Methyl 2-(N-isobutylpyrryl)-α-acetate.

PREPARATION VII Bis(Salicylaldimino) Copper (11) Following the procedure of S. V. Sheat and T. N. Waters, Inorg. Nucl. Chem., 26, 1221 (1965), 500 mg of bis(salicylaldehyde) copper (II) was combined with 5 ml of 10% ammonium hydroxide and the mixture was stirred vigorously for one hour. The solid was filtered off and dried in air, affording 410 mg of pale green powder identified by its ultraviolet spectrum as bis(salicylaldimino) copper (II).

PREPARATION VIII Bis(N-isopropylsalicylaldimino) Copper (II) Following the procedures of L. Sacconi et al, J. Chem. Soc., 1964, 274, 1.22g of salicylaldehyde (10 mmol) in 10 ml of absolute ethanol was treated with 590 mg of isopropylamine (10 mmol) at ca. 150. The reaction was stoppered to prevent loss of the volatile amine and allowed to stand for one hour. A solution of 1.21g of Cu (NO3)2.3H2O and 0.85g of sodium acetate in 10 ml of deionized water was added with stirring. Filtration afforded bis(N-isopropylsalicylaldimino) copper (II) as a brown solid (air-dried); m.p.

140-143.

PREPARATION IX Following the procedure of Preparation VIII, but substituting equivalent amounts of the appropriate salicylaldehyde or 1,3-diketone and amine or hydrazine for the salicylaldehyde and isopropylamine used therein, the following are prepared: Bis(N-hydroxysalicylaldimino) Copper (II); Bis(N-benzylsalicylaIdimino) Copper (II); Bis[N-(p-chlorophenyI)salicylaldimino Copper Bis N- n-hexyl)salicylaldimino] Copper (II); Bis[N-(p-tolyl)salicylaldimino] Copper (II); Bis[N-(p-chlorobenzyl)salicylaldimino] Copper (II); Bis[N-methoxysalicylaldimino] Copper (II); Bis[N-methylaminosalicylaldimino] Copper (II); Bis[N-(dimethylamino)salicylaldimino] Copper (II) Bis[N-(phenylamino)salicylaldimino] Copper (II); Bis[N-(p-chlorophenylamino)salicylaldimino] Copper (II); The above Examples have been provided by way of illustration and not to limit the scope of the present invention, which scope is defined by the following claims.

Claims

WHAT WE CLAIM IS:

1. A process for preparing a loweralkyl 2-(N-R'-pyrryl)-a-loweralkanoic acid ester of the formula:

wherein R is a loweralkyl group; R' is a hydrogen atom or a primary loweralkyl group; and R" is a hydrogen atom or a loweralkyl group, which process comprises reacting an N-R'-pyrrole of the formula:

wherein R' is as above defined with a loweralkyl a-diazoloweralkanoate of the formula:

wherein R and R" are as defined above, in the presence of a copper complex of the formula:

wherein: n is the integer 1 or 2; X is an anion derived from a monoprotic strong acid, loweralkoxy or phenoxy;

is a monoamine-1, 3-diketonate or salicylaldimine ligand capable of forming a bidentate complex with copper (II) wherein R12 is a hydrogen atom, or a loweralkyl; loweralkoxy; hydroxy; loweralkylamino; diloweralkylamino; phenyl substituted with from one to three members which are each independently a loweralkyl or loweralkoxy group, or a halogen atom; phenylloweralkyl; phenylloweralkyl in which said phenyl is substituted with from one to three members which are each indpendently a loweralkyl or loweralkoxy group, or a halogen atom; phenylamino, and phenylamino in which said phenyl is substituted with from one to three members which are each independently a loweralkyl or loweralkoxy group or a halogen atom; provided that the R12 groups on both ligands taken together may also be:

wherein c is an integer from 3 to 5; (iii) o-phenylene or o-phenyline substituted with from one to three members which are each independently a loweralkyl or loweralkoxy group or a halogen atom; or (iv) -(CH2)d- [NR14-(CH2)e] f-NR15-(CH2)-,wherein d, e, and g are each 2 or 3, f isO or 1, and R14 and R15 are each independently a hydrogen atom or a loweralkyl group.

2. A process as claimed in claim 1 wherein

is: (a) a compound of formula

wherein R1 and R3 are each, independently, a loweralkyl, loweralkoxy, perfluoroloweralkyl, phenyl, 2-thienyl or ss-naphthyl group; and R2 is a hydrogen atom or a loweralkyl group; (b) a compound of formula

wherein R4 is a loweralkyl, loweralkoxy, phenyl or perfluoroloweralkyl group; and m is 0 or 1; (c) a compound of formula

wherein R5 is a loweralkyl or perfluoroloweralkyl group; or (d) a compound of formula

wherein R6 and R7 are each independently a hydrogen or halogen atom, or a nitro, loweralkoxy or loweralkyl group; provided that R6 and R7 are oriented meta to each other if both are other than hydrogen atoms; and R8 is a hydrogen- atom, a loweralkyl or perfluoroloweralkyl group.

3. A process as claimed in claim 1 wherein

is the group:

wherein R6, R7, and R8 are as defined in claim 2 and R12 is as defined in claim 1.

4. A process as claimed in claim 1 wherein the copper (II) complex is selected from:

wherein Rg and R10 are each independently a loweralkyl, perfluoroloweralkyl, phenyl, loweralkoxy, or 2-thienyl group; Xis a OSO2CF3 or OCH3 group; R11 is a hydrogen or halogen atom, or a nitro or loweralkoxy group; and R12 is a hydrogen atom, or a loweralkyl, phenyl or phenyl group substituted with from one to three members which are each independently a loweralkyl or loweralkoxy group or a halogen atom; or a phenylloweralkyl group.

5. A process as claimed in claim 4 wherein the copper (II) complex is:

wherein Rg and R10 are each independently a loweralkyl, perfluoroloweralkyl, phenyl, loweralkoxy or 2-thienyl group.

6. A process as claimed in claim 4 wherein the copper (II) complex is:

7. A process as claimed in claim 4 wherein the copper (II) complex is:

8. A process as claimed in claim 4 wherein the copper (II) complex is:

wherein X' is a OSO2CF3 or OCH3 group.

9. A process as claimed in claim 4 wherein the copper (II) complex is:

wherein R11 is a hydrogen or halogen atom, or a nitro or loweralkoxy group.

10. A process as claimed in claim 4 wherein the copper (II) complex is:

wherein R9 is methyl group and Rlo is a phenyl group or R9 and R10 are both t-butyl groups; and R12 is a hydrogen atom, or an isopropyl, p-chlorophenyl or benzyl group.

11. A process as claimed in claim 4 wherein the copper (II) complex is:

wherein R9 is a methyl or trifluoromethyl group; Rlo is a trifluoromethyl group, and Rii is a chlorine or hydrogen atom, or a nitro group.

12. A process as claimed in any one of the preceding claims wherein the N-R'-pyrrole is present in excess, based on the loweralkyl a-diazoloweralkanoate.

13. A process as claimed in any one of the preceding claims wherein the copper (II) complex is present in an amount of 1 mol percent of the amount of loweralkyl a-diazoloweralkanoate.

14. A process as claimed in any one of the preceding claims wherein the reaction mixture is heated to a temperature in the range of from 30 to 80"C during the reaction.

15. A process as claimed in any one of the preceding claims wherein the N-R'-pyrrole is N-methylpyrrole.

16. A process as claimed in any one of the preceding claims wherein the N-R'-pyrrole acts as a solvent for the reaction.

17. A process as claimed in any one of claims 1 to 15 wherein the reaction is carried out in a halogenated hydrocarbon solvent.

18. A process as claimed in claim 1 substantially as hereinbefore described with reference to any one of the Examples.

19. A loweralkyl 2-(N-R'-pyrryl)-a-loweralkanoic acid ester whenever prepared by a process as claimed in any one of the preceding claims.