FR2650588A1 - New 2-methylidenepyrrolidine derivatives, processes for their manufacture and their application as chemical precursors of pyrroles - Google Patents

Abstract

These derivatives have the general formula I: where Z1 and Z2 = or or -CN (R3 and R4 = aryl, alkyl or unsaturated C5-C7 heterocycle), which can be attached to the remainder of the molecule via a C1-C6 aliphatic chain, it being possible for either Z1 or Z2 to be replaced by H; or alternatively Z1 and Z2 form, with C to which they are attached, a ring having electron-withdrawing groups; R1 = H, alkyl, aryl, aralkyl or heterocycle; R2 = H, OH, OR5, NR6R7, COOH, COOR8 or CONR9R10; R5 = alkyl, aryl or Si(R11) 3 (R11 = alkyl or aryl); R6 and R7 = H, alkyl, aryl or heterocycle, it also being possible for R6 and R7 to form, with N to which they are attached, a C5-C7 heterocycle; R8 = alkyl, aralkyl or aryl; R9 and R10 = H, alkyl, aralkyl, aryl or heterocycle.

Description

NOVEL DERIVATIVES OF METHYLIDENE-2 PYRROLIDINE, THEIR
METHODS OF MANUFACTURE AND THEIR APPLICATION AS CHEMICAL PRECURSORS OF PYRROLES

 The present invention relates to novel 2-methylidene pyrrolidine derivatives and methods for making them. These derivatives are highly functionalized organic synthesis intermediates.

dans laquelle - Z1 et Z2 représentent chacun indépendamment

ou

ou -CN , avec R3 et R4 représentant chacun un groupe aryle éventuellement substitué ou un groupe alkyle, linéaire ou ramifié, éventuellement substitué, ou un groupement hétérocyclique insaturé comportant de 5 à 7 chaînons et étant éventuellement substitué, et pouvant par ailleurs être rattaché au reste de la molécule par une chaîne aliphatique comportant de 1 à 6 chaînons, l'un des deux radicaux Z1 et Z2 pouvant être remplace par H ; ou bien Zl et Z2 forment, conaointement avec l'atome de carbone auquel ils se rattachent, un cycle comportant des groupements attracteurs d'électrons R1 représente H, alkyle, linéaire ou ramifié, éventuellement substitué ou aryle éventuellement substitué ou araîkyle éventuellement substitué, ou un groupement hétérocyclique tel que celui entrant dans la définition de R3 et R4 ;
- R2 représente H, OH, OR5, NR6R7, COOH, COOR8 ou
CONR9R10, avec R5 représentant alkyle, linéaire ou
ramifié, éventuellement substitué ou aryle éventuelle
ment substitué, ou Si(R11)3 (avec R11 = alkyle linéaire
ou ramifié ou aryle) ;R6 et R7 représentant chacun
indépendamment H, alkyle, linéaire ou ramifié, éventuel
lement substitué, ou aryle éventuellement substitué, ou
un groupement hétérocyclique tel que celui entrant dans
la définition de R3 et R4, R6 et R7 pouvant également
former, conjointement avec l'atome d-'azote auquel ils
se rattachent, un hétérocycle ayant de 5 à 7 chaînons
R8 représentant alkyle, linéaire ou ramifié, éventuel
lement substitué ou araîkyle eventuellement substitué
ou aryle éventuellement substitué ;; Rg et R10 représen
tant H, alkyle, linéaire ou ramifié, éventuellement
substitué ou aralkyle éventuellement substitué ou aryle
éventuellement substitué ou un groupement hétérocycli
que tel que celui entrant dans la définition.de R3 et
R4, à l'exclusion des composés pour lesquels
R2 = COOCH3 ; R1 = H ; Z1 = H et Z2 = -COOCH3
-COOCH2C6H5 ; -CN ou bien Z1 = CN et Z2 = COOtBu ou
bien Z1 = COOC2H5 et Z2 = CN, ou bien Z1 et Z2 forment
ensemble un cycle d'acide de Meldrum, ou bien Z1 = Z2 =
COOCH3
2 = COOC2H5 ; R1 = H ; Z1 = COOC2H5 et Z2 = COOC2H5 ou
COC2H5
2 R2 = C9OtBu ; R1 = CH2C6H5 ; Z1 = COOCH3-et Z2 ~ H
2 R2 = 6H5 ; Z1 et Z2 forment ensemble un cycle
d'acide de Meldrum ; Z1 = H et Z2 = COOCH2C6H5.They are represented by the general formula (I):

in which - Z1 and Z2 represent each independently

or

or -CN, with R3 and R4 each representing an optionally substituted aryl group or an optionally substituted linear or branched alkyl group, or an unsaturated heterocyclic group having from 5 to 7 members and being optionally substituted, and which can also be attached to the the remainder of the molecule by an aliphatic chain having from 1 to 6 members, one of the two radicals Z1 and Z2 being able to be replaced by H; or Z1 and Z2 together with the carbon atom to which they are attached form a ring having electron-withdrawing groups R1 represents H, alkyl, linear or branched, optionally substituted or optionally substituted aryl or optionally substituted aralkyl, or a heterocyclic group such as that falling within the definition of R3 and R4;
R2 represents H, OH, OR5, NR6R7, COOH, COOR8 or
CONR9R10, with R5 representing alkyl, linear or
branched, optionally substituted or possible aryl
substituted, or Si (R11) 3 (with R11 = linear alkyl
or branched or aryl); R6 and R7 representing each
independently H, alkyl, linear or branched, if any
substituted or optionally substituted aryl, or
a heterocyclic group such as the one entering
the definition of R3 and R4, R6 and R7 can also
form, together with the nitrogen atom to which they
a heterocycle having 5 to 7 members
R8 represents alkyl, linear or branched, if any
substituted or optionally substituted
or optionally substituted aryl; Rg and R10 represent
both H, alkyl, linear or branched, optionally
substituted or optionally substituted aralkyl or aryl
optionally substituted or a heterocyclic group
such as that falling within the definition of R3 and
R4, excluding compounds for which
R2 = COOCH3; R1 = H; Z1 = H and Z2 = -COOCH3
-COOCH2C6H5; -CN or else Z1 = CN and Z2 = COOtBu or
Z1 = COOC2H5 and Z2 = CN, or Z1 and Z2 form
together a Meldrum acid cycle, or Z1 = Z2 =
COOCH 3
2 = COOC2H5; R1 = H; Z1 = COOC2H5 and Z2 = COOC2H5 or
COC2H5
R2 = C9OtBu; R1 = CH2C6H5; Z1 = COOCH3-and Z2 ~ H
R2 = 6H5; Z1 and Z2 together form a cycle
Meldrum acid; Z1 = H and Z2 = COOCH2C6H5.

ont été décrits par J.S. Petersen et coll. dans J. Am. Chem. * tBu = tertiary butyl
Formula compounds

have been described by JS Petersen et al. in J. Am. Chem.

Soc. 1984, 106, 4539.

ont été décrits par M.D. Buchi et coll. dans J. org. Chez.Compounds of formula

have been described by MD Buchi et al. in J. org. In.

1983, 48, 1439.

ont été décrits par T Nagasaka et coll. dans Heterocycles, 1986, 24 2015. Compounds of formula

have been described by T Nagasaka et al. in Heterocycles, 1986, 24 2015.

ont été décrits par H. Eritschi et coll., dans Angew. Chem.Compounds of formula

have been described by H. Eritschi et al., in Angew. Chem.

1986, 98, 1028.

a été décrit par B. Rigo et coll., dans-Synth. Commun. 1985, 15, 473..The compound of formula

has been described by B. Rigo et al., in-Synth. Common. 1985, 15, 473 ..

 The alkyl groups included in the definition of the substituents R3, R4, R1, R5, R11, R6, R7, R8, R8 and R10 are in particular C1-C10, preferably C1-C4, alkyl groups.

 The aryl groups used in the definition of these substituents are in particular the phenyl and naphthyl groups, and the unsaturated heterocyclic groups as defined above are; for example, furyl, pyridyl, thienyl, furylmethyl, pyridylmethyl, thienylmethyl; as for the aralkyl groups, they are, for example, benzyl or naphthylmethyl groups.

When these groups are substituted, it is understood that the substituents are chosen in particular from halogen atoms, in particular chlorine and fluorine, optionally halogenated alkyl groups, for example CF 3 and CC 13, alkoxy groups such as CH 3 O, nitre group. and ester or nitrile groups.

can also be cyclized by forming, for example, one of the following cycles
Meldrum Dimedone Acid
Barbituric acid

ou R8, Z1 et Z2 sont tels que définis ci-dessus, peuvent etre préparés par le procédé dont le schéma réactionnel global est le suivant

The compounds of formula (Ia)

or R8, Z1 and Z2 are as defined above, can be prepared by the process whose overall reaction scheme is as follows

 Thus, an iminoether is reacted with an active methylene compound of the formula Z1-CH2-Z2, preferably in the absence of a solvent and optionally in the presence of a weak base, such as triethylamine.

plus cher que l'iminoéther méthylique, ou à partir du thiolactame

Compounds analogous to the compounds (Ia) are already known from the publications mentioned above. They have generally been obtained from ethyl iminoether:

more expensive than methyl iminoether, or from thiolactam

R'8 is methyl, ethyl, tert.-butyl, benzyl (in this case, more steps are required with worse overall yields).

 In the process according to the invention, the iminoether methyl previously considered unstable is used and no solvent is used; the reaction times are decreased and the yields increased.

on peut mentionner que les imino-éthers pyroglutamiques sont connus depuis longtemps (N. Kolocouris, Thèse, Lille (1971)) ; ils étaient alors obtenus avec un réactif coûteux: le triéthyl oxonium fluoroborate, et l'iminoéther méthylique décrit ici a été publié (T. Nagasaka et Col., Heterocycles, 24, 2015 (1986)) comme étant un produit instable dont la synthèse doit être faite à froid et dont l'isolement nécessite un passage en milieu aqueux.Concerning compounds of formula

it may be mentioned that the pyroglutamic imino-ethers have been known for a long time (N. Kolocouris, Thesis, Lille (1971)); they were then obtained with an expensive reagent: triethyloxonium fluoroborate, and the iminoether methyl described here was published (T. Nagasaka et al., Heterocycles, 24, 2015 (1986)) as being an unstable product whose synthesis must be made cold and whose isolation requires passage in an aqueous medium.

et l'on neutralise in situ le.sel d'imlnoéther formé avec une amine tertiaire, telle que la triéthylamine, cette réaction et cette neutralisation pouvant être conduites sans purification des composés intermédiaires et pouvant être mises en oeuvre directement pour effectuer la réaction précitée conduisant au composé (Ia). According to the invention, it is proposed to prepare these compounds according to the reaction scheme given in Example C below, for R 8 = methyl). Thus, the above iminoether is prepared by reacting methyl sulfate with a pyroglutamic ester of formula

and neutralizing in situ the salt of imminoether formed with a tertiary amine, such as triethylamine, which reaction and neutralization can be carried out without purification of the intermediate compounds and can be carried out directly to effect the aforesaid reaction leading to to the compound (Ia).

 Thus, the neutralization with triethylamine avoids the passage in an aqueous medium and provides an iminoether mixture plus triethylamine salts directly usable in the following steps; the iminoether can also be isolated with the same yield as if it had been worked cold and neutralized in an aqueous medium.

 To obtain the compounds (Ia), the pyroglutamic acid can also be reacted with. methanol to chloroform solvent, removing the reaction water as a ternary azeotrope, the compound obtained (methyl pyroglutamate) can be used directly to carry out the above reaction leading to the compounds (la).

 The modification made with respect to the known synthesis consists in using chloroform as a co-solvent for the reaction, which makes it possible to distil the ternary azeotrope MeOH-H 2 O -CHCl 3 which can be either removed or dried on molecular sieves 30 nm (3 A ) before being recycled.

As a result, virtually quantitative yields of colorless product are obtained which do not require purification before further use.

ou R81 Z1 et Z2 étant tels que définis ci-dessus et R'1 représente alkyle ou aryle ou aralkyle ou groupement hétérocyclique tels que définis en liaison avec la formule (I), peuvent etre préparés par le procédé dont le schéma réactionnel global est généralement le suivant

avec
- X = halogène
- ATP = agent de transfert de phase.The compounds of formula (lob)

or R 81 Z 1 and Z 2 being as defined above and R 1 represents alkyl or aryl or aralkyl or heterocyclic group as defined in connection with formula (I), may be prepared by the process whose overall reaction scheme is generally the following

with
- X = halogen
ATP = phase transfer agent.

 The compounds (Ia) are alkylated using a mobile halogen compound R'1X, preferably under solid-liquid phase transfer conditions, the preferred base being solid The phase transfer agent is advantageously prepared in situ by reacting R'1X with triethylamine.

ont déjà été décrites, mais ces synthèses ont toujours été effectuée avec une base très forte (NaH, nBuLi). Le type de réaction qui est décrit selon la présente invention est différent en ce sens qu'on utilise une base faible K2C03 et un agent de transfert de phase (sel d'ammonium quaternaire), qui peut être avantageusement du Et MeOSO3G, formé in situ par réaction entre la triéthylamîne et du sulfate de méthyle. Le solvant peut être n'importe quel solvant comme du diméthylformamide, de l'acétone ou du glyme.Several alkylations with nitrogen of enaminoesters

have already been described, but these syntheses have always been performed with a very strong base (NaH, nBuLi). The type of reaction which is described according to the present invention is different in that a weak base K 2 CO 3 and a phase transfer agent (quaternary ammonium salt), which may advantageously be EtO.sub.3O.sub.3, formed in situ, are advantageously used. by reaction between triethylamine and methyl sulfate. The solvent may be any solvent such as dimethylformamide, acetone or glyme.

The compounds of formula (Ib) can also be obtained starting from an N-substituted amino ether salt according to the following reaction scheme

<tb><SEP><SEP> / <SEP>% 1 <SEP> base <SEP> \ <SEP><
<tb><SEP> A <SEP> COR8 <SEP> + <SEP> base <SEP> / -COR8
<tb> R120 <SEP> -O <SEP> Z2 <SEP> Low <SEP> Z2 <SEP> N <SEP> O
<tb><SEP> R <SEP> 1 <SEP> A <SEP>R'1
<tb> with
- R12 = inter alia, lower alkyl, such as methyl,
ethyl;
- A # = anion, such as BF4 or CH30S0355.

 This reaction is conducted in the presence of a weak base, such as sodium methoxide.

The starting iminoether salt can be prepared by the reaction

The closest compound of which the applicant is aware is the following compound (P. Martin, E. Steiner,
J. Streith, T. Winkler and D. Bellus, Tetrahedron 41 4057 (1985)):

 In this case, the reaction is carried out with triethyl oxonium fluoroborate (EtOBF4-). According to the invention, the same reagent can be used, but it has the disadvantage of costing more than methyl sulphate.

avec R8 = R'1 = alkyle, notamment méthyle, peut être préparé par le procédé dont le schéma réactionnel est le suivant

The compound of formula

with R8 = R'1 = alkyl, in particular methyl, may be prepared by the process whose reaction scheme is as follows

<tb><SEP> Agent <SEP> of alky- <SEP> K2C03 <SEP> by <SEP> ex.
<Tb>

<SEP> station <SEP> such <SEP> as <SEP> ATP <SEP> M
<tb> / \ <SEP> + <SEP>R'ICL<SEP>R'iCt<SEP> OR <SEP> SE <SEP> CO-R8
<tb> O <SEP> O <SEP>2CR'1) 2SO4 <SEP> O- <SEP> W '<SEP> O
<tb><SEP> H <SEP> R1
<Tb>
The pyroglutamic acid is reacted with the alkylating agent in the presence of a solid-liquid phase transfer agent, the preferred base being solid potassium carbonate, the phase transfer agent being advantageously prepared in situ. reacting (R'1) 2SO4 with triethylamine.

 Methyl N-methyl pyroglutamate, for example, has always been synthesized in two stages, from methyl pyroglutamate. The process according to the invention consists in carrying out the esterification and the N-methylation in one step, thanks to the use of a phase transfer agent (ATP), manufactured in situ (Et3NMe + MeOSO3-). Methyl N-methyl pyroglutamate is one of the most used pyroglutamic derivatives in organic synthesis in this series.

peut être préparé par le procédé dont le schéma réactionnel est le suivant, dans les mêmes conditions qu la réaction précédente.

The compound of formula

can be prepared by the process whose reaction scheme is as follows, under the same conditions as the previous reaction.

<Tb>

<SEP> X <SEP> -CO-R8 <SEP> + <SEP>(R'1) 2S 4 <SEP> ATP <SEP> X <SEP> -CO-R8
<tb> O '<SEP> N <SEP> O <SEP>O'NO18
<tb><SEP> H <SEP> by <SEP> ex. <SEP>R'1
<Tb>
The alkylation of methyl pyroglutamate has hitherto been practically always carried out in the presence of a strong base. The modification provided according to the invention consists of using K 2 CO 3 (weak base) at low temperature (20 ° -400 ° C.) in the presence of a strong base. a phase transfer agent (ATP) itself obtained in situ by reacting the triethylamine with the alkylating agent. It can work in solvents such as acetone, glyme or DMF. A small amount of water (-5) is favorable. It should be mentioned that this reaction is general for other alkylating agents than Me 2 SO 4, for example substituted benzyl halides.
Compounds of formula (Ic)

R'1 being as defined for the compounds (Ib), can be prepared by the process whose overall reaction scheme is as follows

est une liaison fragile qui
peut s'hydrolyser si les conditions de travail sont
trop sévères - les groupes Z1 et Z2 sont fréquemment des groupes hydrolysables (C-N,

etc) ; et
- les acides ainsi obtenus présentent souvent une
solubilité non négligeable dans l'eau.<tb> Z1 <SEP> TO-COR8 <SEP> 1) <SEP> Base <SEP> Strong <SEP> Z1 <SEP>,
<tb><SEP> \ <SEP> C R8 <SEP> ~ / <SEP>><SEP> \ <SEP> X <SEP> r <SEP> C-OH
<tb> Z2 <SEP> \ N <SEP><SEP> 2) <SEP> Strong <SEP> Strong <SEP> Z2 <SEP> N <SEP> O
<tb>'2<SEP> I <SEP>R'1
<tb><SEP> R <SEP> 1 <SEP> a <SEP> 1
<Tb>
Three main difficulties existed to lead this synthesis :: - the double bond

is a fragile bond that
can hydrolyze if the working conditions are
Z1 and Z2 are frequently hydrolysable groups (CN,

etc); and
the acids thus obtained often have a
significant solubility in water.

 This saponification is carried out by treatment of the above esters with the aid of a strong base, preferably sodium hydroxide, followed by a treatment with a strong acid, preferably hydrochloric acid.

 The procedure chosen to carry out this reaction has been adapted to take account of these criteria: the ester is mixed with very little water, and concentrated sodium hydroxide is slowly added as the saponification proceeds .

par le procédé dont le schéma réactionnel global est le suivant

Compounds of formula (Id) can be prepared

by the process whose overall reaction scheme is as follows

 This reaction preferably takes place in a solvent medium and, preferably, in the presence of an acid catalyst.

par le procéde dont le schéma réactionnel global est le suivant

The compounds of formula (Ie) can be prepared

by the procedure whose global reaction scheme is as follows

avec B+ = cation alcalin tel que Na+,K+,Li+.

with B + = alkaline cation such as Na +, K +, Li +.

This reaction makes it easy to replace the Meldrum cycle in these compounds by a group

This gives access to another series of compounds capable of undergoing the electrochemical reaction described below.

avec R'1, R5, Z1 et Z2 tels que définis ci-dessus, par la réaction électrochimique dont le schéma général est le suivant

The compounds of the formulas can be prepared

with R'1, R5, Z1 and Z2 as defined above, by the electrochemical reaction whose general scheme is as follows

<tb> Z1 <SEP> electro- <SEP> ZI \ <SEP> / <SEP> \
<tb><SEP> / <SEP> -COH <SEP> + <SEP> R5OH <SEP> or <SEP> -OH
<tb> Z2 <SEP> N <SEP> O <SEP> or <SEP> H2o <SEP> Chemistry <SEP> Z2 <SEP> -OR5
<tb><SEP> I <SEP> I
<tb><SEP>R'1<SEP>R'1
<Tb>
This electrochemical decarboxylation is conducted between the above acid and a compound R 50 H or H 2 O in the presence of a basic catalyst and optionally a carrier electrolyte, the basic catalyst being in particular a small amount of sodium hydroxide or an alcoholate. and the supporting electrolyte is a quaternary ammonium salt.

The electrodes may be carbon rods 1 cm apart from each other; the intensity of the current is set at a value between 0.1 A and 1 A, so as to obtain a potential of between about 3 and 20 volts. Preferably an undivided cell is used.

aiors que pour un vinylogue d'amide, on introduit une-double liaison supplémentaire

It is the first time that such an electrochemical decarboxylation reaction is used with amide vinylogues: it is classical with amides

while for an amide vinylogue an additional double bond is introduced

 Furthermore, the products thus obtained have a certain mobility of the OR5 or OH group thus introduced.

It is therefore possible to dehydrate or replace the OR5 or OH group with a -ZA group (Z = electronegative atom;
A = alkyl, etc.).

 These compounds of formula (If) or (Ig) therefore represent a new class of organic chemistry intermediates, highly functionalized.

avec -YR = -OR5 ou -NR6R7, par la réaction d'échange dont le schéma général est le suivant, en présence de H-

The compounds of formula (1h) can be obtained

with -YR = -OR5 or -NR6R7, by the exchange reaction whose general scheme is as follows, in the presence of H-

avec -RY = -OR'5 ou -NR6R7, R'5 ayant une signification choisie parmi celles données pour R5.The compounds of formula (Ih), with Z1, Z2, R'1 and -YR having the same meaning as above, can also be obtained by the exchange reaction, the general scheme of which is as follows:

with -RY = -OR'5 or -NR6R7, R'5 having a meaning chosen from those given for R5.

The compounds of formula (I) according to the present invention are chemical precursors of pyrroles (R2 =
OH or OR5) or compounds leading to these precursors.

 These methods make it possible to obtain a certain number of products which would not be accessible directly by electrochemical reaction.

 The following examples illustrate the present invention without, however, limiting its scope.

Example A
Preparation of Methyl Pvro4lutamate
Reaction scheme

. Operating mode
A mixture of 500 g (3.87 mol) of pyroglutamic acid, 15 g of para-toluenesulfonic acid and 1000 ml of chloroform is refluxed for 24 hours. The solvent vapors are condensed and the condensed liquid is passed through 1500 g of 30 nm molecular sieve (3) before being recycled. After cooling, the solvents are evaporated. An almost quantitative yield of crude methyl pyroglutamate is obtained which can be used for the following reactions. It is possible to distil the ester, which is then obtained pure in a yield of 90%.

Example B1 Pretaration of methyl N-methyl pvroslutamate. Scheme - Reaction Scheme

Operating mode
12.9 g (0.1 mol) are strongly mixed using a Polytron stirrer. of pyroglutamic acid, 0.7 ml (0.005 mole) of triethylamine, 41.5 g (0.3 mole) of
K2CO3 and 50 ml of acetone, then 29 ml (0.305 mole) of methyl sulfate are slowly added, and stirring is continued for 6 hours, keeping the temperature at 400 ° C. by means of a thermostatic bath. The K 2 CO 3 is filtered, rinsed with 200 ml of acetone, and the acetone is evaporated at room temperature.
Rotavapor. The acetone obtained can be reused in another reaction.

 The residue is distilled under vacuum. E = 900C (6.67 Pa, 0.05 mmHg). Yield: 85%.

Example B2
Preparation of N-Methyl Methyl Pvroalutamate
Reaction scheme

. Operating mode
71.7 g (0.5 mol) of methyl pyroglutamate, 3.5 ml of water, 3.5 ml of triethylamine, 500 ml of dimethyl ether and a mixture of poly (methylene chloride) are mixed well with a Polytron stirrer. 124.4 g (0.9 mol) of K 2 CO 3, then 87.5 ml (0.93 mol) of (CH 3) 2 SO 4 are added slowly, and stirring is continued for 7 hours, keeping the temperature at 100.degree. using a thermostatic bath. The K 2 CO 3 is filtered and rinsed with 1 l of dimethyl ether. The solvent, evaporated at
Rotavapor, can be reused.

 The residue is distilled under vacuum. E = 900C (6.67 Pa, 0.05 mmHg). Yield: 82%.

Example C
Preparation of Methoxy-2-methyl-2-carboxylic acid methyl-5-carboxylate
Reaction scheme

Operating mode
94.5 ml (1 mole) of methyl sulfate are added dropwise, with good stirring, to 143 g (1 mole) of methyl pyroglutamate maintained at 600 ° C. with the aid of a bain-marie, and the mixture is maintained at room temperature. stirring and heating for 5 hours. The NMR yield is 92% in iminoether salt.

 100 ml of methylene chloride are added to the preceding salt, and it is slowly added with good stirring to 1.05 mol (106 g) of triethylamine and 1250 ml of ether, at 50 ° C., stirring is continued for 1 h 30, the ethereal phase is separated, and the extraction is repeated twice with 1250 ml of ether each time. The ethereal phases are combined and evaporated, providing 81% yield of crude iminoether.

Example D
Preparation of 2-methoxy-2-ethoxycarbonyl-5-pyrrolinium-2-sulfate
Reaction scheme

. Operating mode
For 40 hours, a mixture of 10 g (0.07 mol) of
Methyl N-methyl pyroglutamate and 6 ml (8 g, 0.063 mol) of methyl sulfate. We get a return
NMR 70%. It is pointed out that the reaction is balanced and can not be shifted to the right (eg by removing unreacted methyl methyl pyroglutamate).

Example la
Preparation of methyl (5-cyano) methoxycarbonyl methylene 5-prolinate from iminoether methylene
Reaction scheme

. Operating mode
A mixture of 1 molar equivalent of ininoether and 1 molar equivalent of methyl cyanomalonate, without solvent, is stirred at 800 ° C. for 1.5 hours. After cooling, the product is precipitated by addition of water (5 times the volume of the cyanoacetate), filtered, washed with water, dried and recrystallized from an ether / methylene chloride mixture. The yield is 75%.

Example lb
Preparation of methyl (α-cyano-methoxycarbonyl methylene) -prolinate from methyl pyroglutamate.

without isolation of intermediate products
Reaction scheme

. Operating mode
473 ml (5 moles) of methyl sulfate are added over a period of 30 minutes to 4 moles (572 g) of
methyl pyroglutamate, and heated to 600C
8 hours.

 696 ml (5 moles) of triethylamine are cooled to 50.degree. C. and the temperature of the preceding iminoether salt is added over a period of 40 minutes, with good mechanical stirring.

 406 g (4 moles) of methyl cyanomalonate are added to the mixture obtained over a period of 40 minutes, and the mixture is heated for 1 hour at 800 ° C. with stirring.

 After cooling, 1.25 liters of water are added to the solution and the mixture is stirred for 1/2 hour before filtering, washing with water and drying in an oven.

 The yield is 82%.

Examples 2 to 18
In the same two ways as in Examples 1a and 1b, the compounds of Examples 2 to 18, as defined in Table I, were prepared. In the latter, the physical characteristics of the compounds thus synthesized were reported.

Table I

<tb> Ex. <SEP> Formula <SEP> Point <SEP> of <SEP> RHW <SEP> (ppm)
<tb><SEP> merge <SEP> (soLvant)
<tb><SEP> C <SEP> C)
<tb><SEP> NC <SEP> / ~ \
<tb><SEP> / <SEP>, CO-CH3 <SEP> 120 <SEP> (CDCL3): <SEP> 2-2.6 <SEP> (m, <SEP> 2H), <SEP> 2, 7-3.2 <SEP> (m, <SEP> 2H),
<tb> (a <SEP> and <SEP> b) <SEP> CH3-0-C <SEP> N <SEP> O <SEP> 3.70 <SEP> (s, <SEP> 3H), <SEP > 3.73 <SEP> (s, <SEP> 3H),
<tb><SEP> O <SEP> H <SEP> 4.3-4.7 <SEP> (m, <SEP> 1H), <SEP> 9 <SEP> (s, <SEP> 1H)
<tb><SEP> HCI / <SEP> / -O-tH3 <SEP> 118 <SEP> (CDCt3): <SEP> 1.32 <SEP> (t, <SEP> 3H), - <SEP> 2 , 1-2.7 <SEP> (e, <SEP> 2H),
## EQU1 ## , <SEP> 3.78 <SEP> (s, <SEP> 3H),
<tb><SEP> CZH50-C
<tb><SEP> δ <SEP> H <SEP> 4.25 <SEP> (q, <SEP> 2H), <SEP> 4.4-4.7 <SEP> (m, <SEP>;) ,
<tb><SEP> 9.1 <SEP> (s, <SEP> 1H)
<tb> 3 <SEP>. <SEP> -OH <SEP> 144 <SEP> (DZD * NaOD): <SEP> 1.26 <SEP> (t, <SEP> 3H), <SEP> 1.8 -2.6 <SEP> (n-, <SEP> 2),
<tb> / \ <SEP> ~
<tb><SEP> C2HS-sC <SEP> -6 <SEP> 5-OC <SEP> W <SEP> O <SEP> 2,6-3,2 <SEP> (m, <SEP> 2H), <SEP> 4.2 <SEP> (q, <SEP> 2n),
<tb><SEP> O <SEP> H <SEP> 4.3-4.5 <SEP> Cm, <SEP> 1H)
<tb><SEP> WC
<tb> 4 <SEP> - <SEP> COC <SEP> 2H5 <SEP> 86 <SEP> (COCL3): <SEP> 1.30 <SEP> (t, <SEP> 3H), <SEP> 1, 9-2.6 <SEP> (m, <SEP> zou),
<tb><SEP> CH3-OC <SEP> N <SEP> O <SEP> 2,6-3,2 <SEP> (m, <SEP> 2free), <SEP> 3,73 <SEP> Ca, <SEP> 3H),
<tb><SEP> O <SEP> H <SEP> 4.24 <SEP> (q, <SEP> 2hui, <SEP> 4.3-4.8 <SEP> (, <SEP> 1H),
<tb><SEP> 9.05 <SEP> (s, <SEP> 1H)
<tb>"--OH<SEP> 168 <SEP> (Duo): <SEP> 1.5-2.6 <SEP> Cm, <SEP> 2H), <SEP> 2.6-3.2 <SEP> Cm, <SEP> 2H),
<tb> tHg-O-CT \ <SEP> N '<SEP> O <SEP> 3.74 <SEP> ts, <SEP> 3H). <SEP> 4.25 <SEP> (t, <SEP> 1H)
<tb><SEP> CH3-OC <SEP> H <SEP> 3.74 <SEP> Ca, <SEP> 3H), <SEP> 4.25 <SEP> (t, <SEP> 1H)
<tb><SEP> O <SEP> H
<tb><SEP> o
<tb><SEP> o # ff
<tb> 6 <SEP>><SEP> CO-CH3 <SEP> 140 <SEP> (CDCl3): <SEP> 1.7 <SEP> (s, <SEP> 6H), <SEP> 2.2- 2.7 <SEP> Cm, <SEP> 2H),
<tb><SEP>:<SEP> o <SEP> 3, t-3.7 <SEP> Cm, <SEP> 2H), <SEP> 3.7 <SEP> (s, <SEP> 3H),
<tb><SEP>'0<SEP> O <SEP> H <SEP> 4,4-4,9 <SEP> (t, <SEP> 1H), <SEP> 10,1 <SEP> (s, <SEP> 1H)
<tb><SEP> 0
<tb><SEP> OS
<tb> 7 <SEP> / C0H <SEP> - <SEP> 192 <SEP> (btONaOD): <SEP> 1.75 <SEP> (s, <SEP> 6H), <SEP> 2-2.5 <SEP> (m, <SEP> 2H),
<tb><SEP> O <SEP> / <SEP> 0 <SEP> 3-3.4 <SEP> (m, <SEP> 2H)
<tb><SEP> OH
<Tb>
Table 4 (continued)

<tb> Ex. <SEP>Fc; ule <SEP><SEP> Point of <SEP> RHW <SEP> (ppm)
<tb><SEP> fusion <SEP> (solvent)
<tb><SEP> (OC)
<tb><SEP> H <SEP> O
<tb><SEP> 8 <SEP> oXf <SEP> -CO-CH3 <SEP>> 260 <SEP> (DHS0d6): 1.8-2.6 <SEP> (m, <SEP> 2H), <MS> 2.95-3.45 <SEP> (m, <SEP> 2H)
<tb><SEP>,<SEP> T <SEP> Ni <SEP><SEP> S, 65 <SEP> (s, <SEP> 3H), <SEP> 4.35-4.6 <SEP> Cm, <SEP> 1H),
####
<tb><SEP> 0
<tb><SEP> 9 <SEP> t <SEP> -CO-CH3 <SEP> (CDC13): <SEP> 0.99 <SEP> (s, <SEP> 3H), <SEP> 1, T1 <SEP> (s, <SEP> 3H),
<tb><SEP> O ~ - <SEP> N <SEP> i-, 58 <SEP> (s, <SEP> 3H), <SEP> 2-2,4 <SEP> (m, <SEP> 2H )
<tb><SEP> O <SEP> H <SEP> 2.1-2.68 <SEP> (m, <SEP> 2H), <SEP> 3.1-3.6 <SEP> (2H),
<tb><SEP> 3.75 <SEP> (s, <SEP> 3H), <SEP> 4.4-4.8 <SEP> (m, <SEP> 1H),
<tb><SEP> 7.1-7.6 <SEP> (m, <SEP> 1H)
<tb> 10 <SEP> H, M <SEP>,> CO-CH3 <SEP> 93 <SEP> (CDCl3): <SEP> 2-2.8Cm, <SEP> 4H), <SEP> 3.63 <SEP> (s, <SEP> 3H),
<tb><SEP> CH3-0-C <SEP> \ <SEP> N <SEP> O <SEP> 3.75 <SEP> (s, <SEP> 3H), <SEP> 4.25-4, 7 <SEP> (m, <SEP> 2H),
<tb><SEP> O <SEP> H <SEP> - <SEP> 8.1 <SEP> (s, <SEP> 1H)
<tb> Hr <SEP> NC-OH <SEP> 146 <SEP> (D20 + NaOD) - <SEP> 1.6-2.8 <SEP> (m, <SEP> 4H), <SEP> 3, 6 <SEP> (s, <SEP> 3H),
<tb><SEP> CH3-DC? <SEP> 0 <SEP> 4.1-4.45 <SEP> (m, <SEP> 1H),
<tb><SEP> dH
<tb><SEP> 0
<tb><SEP> CH3 <SEP> -C
<tb> 12 <SEP>'<SEP> C-O-CH3 <SEP> 97 <SEP> (CDCl3): <SEP> 2-2.25 <SEP> Cm, <SEP> 8H), <SEP> 2 , 8-3.3 <SEP> (m, <SEP> 2H),
<tb><SEP> CH3-C / ^ \ <SEP> N <SEP> Ó <SEP> ~ <SEP> 3.77 <SEP> (s, <SEP> 3H), <SEP> 4,2B-4 , 59 <SEP> (m, <SEP> 1H)
<tb><SEP> O <SEP> H
<tb><SEP> 9
<tb><SEP> ca3-oc <SEP> H3.O, C
<tb> 13 <SEP> ~ <SEP>, 1C-o-CH3 <SEP> 79- <SEP> (COCl3 ?: <SEP> 2-2.25 <SEP> Cm, <SEP>5H);<SEP> 3-3.4 <SEP> Cm, <SEP> 2H),
## EQU1 ## > 3.75 <SEP> (s, <SEP> 3H),
<tb><SEP> O <SEP> H <SEP> 4.3-4.7 <SEP> Cm, <SEP> 1H), <SEP> 9 <SEP> (s, <SEP> 1H)
<tb><SEP> O
<tb><SEP> C <SEP> H3 <SEP> - <SEP> O- <SEP> C / 5
<tb> 14 <SEP> Z <SEP> COH <SEP> 198 <SEP> (duo, <SEP> NaOD): 1.4-2.1 <SEP> (m, <SEP>2H>,<SEP> 2.32 <SEP> (s, <SEP> 3H),
<tb><SEP> Ch3-C <SEP> x <SEP> tl <SEP> O <SEP> 2.7-3.4 <SEP> Cm, <SEP> 2H), <SEP> 3.75, (s,. <SEP> 3H)
<tb><SEP> O <SEP> O <SEP> H
<Tb>
Example 15a Preparation of methyl N-methyl (α-cyano-methoxycarbonyl) methyl prolinate from the enaminoester of Example la
Reaction scheme

. Operating mode
620.5 g (2.77 mol) of cyanoester, 2.3 liters of glycol dimethyl ether, 18.7 ml (13.6 g, 0.13 mol) of triethylamine are mixed with a Polytron-type apparatus. 483 g (3.5 moles) of potassium carbonate are then added, the mixture is mixed again and 343 ml (457 g, 3.63 moles) of sodium sulfate are added in the course of 1 hour while maintaining stirring. The stirred mixture is then heated at 400 ° C. for 16 hours, the excess methyl sulfate is neutralized with 18.7 ml of triethylamine, filtered and the solid residue is extracted twice with 1 each time. 2 liters of dimethyl ether glycol, with good stirring, the whole of the organic phases are evaporated (the solvent can be reused for another operation); the precipitate obtained is washed with water. A quantitative yield of N-methylation product is obtained.

Example 15b
Preparation of N-methyl (-N'-cyano-methoxycarbonyl methylene) -5 methylprolinate from the iminoether salt of Example D
Reaction scheme

. Operating mode
3.4 g (0.034 mol) of methyl cyanomalonate are added rapidly to a solution of 0.032 mol of sodium methoxide in methanol (16 ml), then heated to 600 ° C. and 9 g (0.032 mol) are added dropwise. ) of iminoether salt. After 15 minutes, the reaction medium is solidified; it is cooled, water is added and the white product obtained is filtered off; yield: 41%
The physical characteristics of the compound obtained according to Examples 15a and 15b are as follows:

<tb> Ex. <SEP> Formula <SEP> Point <SEP> of <SEP> RMW <SEP> (ppm)
<tb><SEP> fusion <SEP> (solvent)
<tb><SEP> C <SEP> 0C)
<sep>SEP><SEP> 0-CH3 <SEP> 104 <SEP> (CDCt3): <SEP> 1.8-2.6 <SEP> (m, <SEP> 2H) , <SEP> 2.7-3.6 <SEP> (m, <SEP> 2H),
<tb> (a <SEP> and <SEP> b) <SEP> CH3-OC <SEP> N <SEP> o <SEP> 3.41 <SEP> (s, <SEP> 3H), <SEP> 3 , 73 <SEP> (s, <SEP> 3H),
<tb><SEP> O <SEP> CH3 <SEP> 3.80 <SEP> (s, <SEP> 3H), <SEP> 4.14.5 (<SEP> 1H)
<Tb>
Example 16
Preparation of N-methyl (&alpha; -cyano &alpha; methoxycarbonyl methylene) -proline
Reaction scheme

Operating mode
A suspension of 640 g (2.68 moles) of ester, previously reduced to a fine powder, in 1.5 liters of water is thoroughly mixed at ambient temperature and, over a period of 3 hours, 2 7 moles (540 ml) of 5N sodium hydroxide solution. The solution obtained is acidified by addition, with vigorous stirring over 45 minutes, of 1 equivalent (275 ml) of concentrated hydrochloric acid. The product obtained can be recrystallized from water. In the raw state, it is usable for electrochemical decarboxylation reactions.

The physical characteristics of the compound obtained according to Example 16 are as follows:

<tb> Ex. <SEP> Formula <SEP> Point <SEP> of <SEP> NMR <SEP> (ppm)
<tb><SEP> fusion <SEP> (solvent)
<tb><SEP> (OC)
<tb> 16 <SEP> NC <SEP><SEP> oc-GH <SEP> 96 <SEP> (D20 + aOG): <SEP> 1,5-2,5 <SEP> (m, <SEP> 2H),
<tb><SEP> CH3-0-CX <SEP> N- / <SEP> O <SEP>. <SEP> 2.5-3.4 <SEP> (m, <SEP> 2H), <SEP> 3.32 <SEP> (a, <SEP> 3H),
<tb><SEP> o <SEP> CH3 <SEP> 4.1-4.5 <SEP> (m, <SEP> 1H)
<Tb>
Example 17
Preparation of Isopropylaminocarbonyl-2 (x-cyano-methoxycarbonylmethylene) -5-pyrrolidine
Reaction scheme

- Operating mode
5.4 g of ester (2 × 10 -2 mol) are dissolved in 6.8 ml of isopropylamine (8 × 10 -2 mol, ie 4 equivalents).

The mixture is refluxed for 13 hours. In NMR, the disappearance of the ester function is observed. The precipitate obtained is filtered and weighed: 5.9 g of crude product, ie a yield of 100%. It is recrystallized from 100 ml of absolute ethanol. It is stored for 24 hours in the refrigerator and then for 2 hours in the freezer. Five streams of recrystallization give 4.3 g of recrystallized product (yield = 72t).

In the same way as in Example 17, the compounds according to Examples 18 to 21 defined in
Table II. In the latter, the physical characteristics of the compounds 17 to 21 thus synthesized have been reported.

Table II

+ 2 NaCl +

+ acétone
. ode opératoire
Dans 150 ml de CH30H, on ajoute 20 g d-'ester (7,4 x 10-2 mole) et 27 g d'une solution à 30% de CH30-NaX dans le CH30H, soit 14,8 x 10-2 -2 mole (2 équivalents).Le mélange est porté à reflux pendant 24 heures. Après avoir laissé refroidir, on neutralise le CH3O Na+ par 14,3 ml d'HCl (14,8 x 10-2 mole). On évapore le méthanol et on ajoute du CH2C12 afin de faire précipiter les sels minéraux qui sont ensuite filtrés. La phase organique est séché par du sulfate de sodium, filtrée et evaporée. On ajoute 5 ml de CH3CN au résidu. Apres une nuit au réfrigérateur.et 6 heures au congélateur, on filtre.<tb> Ex. <SEP> Formula <SEP> Point <SEP> of <SEP> RMH <SEP> (ppm)
<tb><SEP> fusion <SEP> (solvent)
<tb><SEP> C <SEP> 0C)
<tb><SEP> o
<tb><SEP> 0-)
<tb> 17 <SEP>> t <SEP>><SEP> / <SEP> C-NHiPr <SEP> 196 <SEP> (CDCl3): <SEP> 1.1 <SEP> (s, <SEP> 3H) ), <SEP> 1.2 <SEP> (s, <SEP> 3H),
<tb><SEP> H <SEP> to <SEP> 0 <SEP> 1.69 <SEP> (s, <SEP> 6H), <SEP> 2.05-2.6 <SEP> (m, <SEP> 2H),
<tb><SEP> O <SEP> H <SEP> 3,1-3,6 <SEP> (t, <SEP> 2H), <SEP> 3,7-4,2 <SEP> Cm, <SEP > .1H),
<tb><SEP> 3,7-4,65 <SEP> (m, <SEP> 1H)
<tb><SEP> (iPr <SEP> = <SEP> isopropyl)
<tb><SEP> 0
<tb><SEP> oA
<tb> 18 <SEP> V <SEP> C-HH-CH <SEP> 159 <SEP> (COCI3): <SEP> 1.60 <SEP> (s, <SEP> 6H), <SEP> 1, 8-2.7 <SEP> (m, <SEP> 2H),
<tb><SEP><SEP><SEP> 3-3.6 <SEP> (m, <SEP> 2H), <SEP> 4,2-4,65 <SEP> (m, <SEP> 3H) ,
<tb><SEP> O <SEP> H <SEP> 7.26 <SEP> (s, <SEP> 5H), <SEP> 10.25 <SEP> (s, <SEP> 1H)
<tb><SEP> O
<tb> 19 <SEP> C-HCCH3) 2 <SEP> 211 <SEP> (titi3): <SEP> 1.64 <SEP> (s, <SEP> 6H), <SEP> 2-2.5 <SEP> (m, <SEP> 2H),
<tb><SEP> H <SEP> N <SEP> O <SEP> 2.95 <SEP> (s, <SEP> 3H), <SEP> 3.05 <SEP> (s, <SEP> 3H) ,
<tb><SEP> O <SEP> H <SEP> 3,4 <SEP> (t, <SEP> 2H), <SEP> 4,6-5 <SEP> (s, <SEP> 1H),
<tb><SEP> 10.18 <SEP> (s, <SEP> 1H)
<tb><SEP> CF3
<tb> 20 <SEP> - <SEP> OX <SEP> C-HH-01 <SEP> 223 <SEP> (C0CL3 + 5% OMSOd6): <SEP> 1.7 <SEP> (s, <SEP> 6H),
<tb><SEP> 0XC <SEP> N / <SEP> 2.1-2.7 <SEP> (m, <SEP> 2H), <SEP> 3.2-3.65 <SEP> (m, <SEP> 2H),
<tb><SEP> O <SEP> H <SEP> 4.5-4.9 <SEP> (m, <SEP> 1H), <SEP> 7.6-7.9 <SEP> (m, <SEP> 4H)
<tb><SEP> H <SEP> 0
<tb> 21 <SEP>(SEP> N <SEP> C <SEP> -0-CH3 <SEP>'<SEP>> 260
<tb><SEP> pt1 <SEP> U <SEP> O
<tb><SEP> H <SEP> O <SEP> H
<Tb>
Example 22
Preparation of methyl methoxycarbonylmethyl-5-prolinate
Reaction scheme

+ 2 NaCl +

+ acetone
. Operative ode
In 150 ml of CH 3 OH, 20 g of ester (7.4 × 10 -2 mol) and 27 g of a 30% solution of CH 3 OH-Na 2 in CH 3 OH are added, ie 14.8 × 10 -2 -2 mole (2 equivalents). The mixture is refluxed for 24 hours. After allowing to cool, the CH 3 O Na + was neutralized with 14.3 ml of HCl (14.8 × 10 -2 mol). The methanol is evaporated and CH 2 Cl 2 is added in order to precipitate the mineral salts which are then filtered. The organic phase is dried with sodium sulfate, filtered and evaporated. 5 ml of CH3CN is added to the residue. After a night in the refrigerator and 6 hours in the freezer, filter.

We obtain:

<tb> 10 <SEP> jet <SEP>: <SEP> 3.9 <SEP> g <SEP> or <SEP> 26% <SEP>
<tb> 20 <SEP> jet <SEP>: <SEP> 2.6 <SEP> g <SEP> or <SEP> 17% <SEP> 52% <SEP> Yield
<tb> 30 <SEP> jet <SEP>: <SEP> 1.4 <SEP> g <SEP> is <SEP> 9%
<Tb>
Example 23 to 28
The compounds defined in Table III below have been prepared according to one or more of the routes in accordance with Examples 19 to 22. The physical characteristics of the compounds obtained are also included in this specification.
Board.

Table III

<tb> Ex. <SEP> Formula <SEP> Point <SEP> of <SEP> NMR <SEP> (ppm)
<tb><SEP> fusion <SEP> (solvent)
<tb> (Oc)
<tb><SEP> H <SEP> n
<tb> 23 <SEP> / <SEP> CO-CH3 <SEP> 42 <SEP> (cDC13): <SEP> 2.4 <SEP> (m, <SEP> 2H), <SEP> 2.8 <SEP> (s, <SEP> 3H),
## EQU1 ## s, <SEP> 3H),
<tb><SEP> O <SEP> CH3 <SEP> 3.75 <SEP> (s, <SEP> 3H), <SEP> 4.4.3 <SEP> Cm, <SEP> 1H),
<tb><SEP> 4.6 <SEP> (s, <SEP> 1H)
<tb><SEP> o
<tb> o <SEP><SEP> / ~ COOCH <SEP> 159 <SEP> tCDCi3): <SEP> 1.64 <SEP> (s, <SEP> 6H), <SEP> Z, 1-2 , 55 <SEP> tm, <SEP> 2H),
<tb><SEP> O- <SEP> N <SEP> OX <SEP> 3,2-3,6 <SEP> (m, <SEP> 2H), <SEP> 4,4-4,75 <SEP > (m, <SEP> 1h,
<tb><SEP> O <SEP> CH2- <SEP> T <SEP> 5.15 <SEP> (s, <SEP> 2H), <SEP> 7.32 <SEP> (5H)
<tb><SEP> O
<tb><SEP> AT / H
<tb> 25 <SEP>'-<SEP></<SEP> CN- (CH3) 2 <SEP> 207 <SEP> (tDCL3): 1.66 <SEP> (s, <SEP> 6H), <SEP> 2-2.5 <SEP> (m, <SEP> 2H),
<tb><SEP> o- \ <SEP> \. <SEP> N <SEP> 0 <SEP> 2.97 <SEP> (s, <SEP> 3H), <SEP> 3.03 <SEP> ( s, <SEP> 3H),
<tb><SEP> O <SEP> CH3 <SEP> 3,2-3,65 <SEP> (m, <SEP> 2H), <SEP> 4,6-4,95 <SEP> Cm, <SEP > 1H)
<tb><SEP> 0
<tb><SEP> O <SEP>;; nA
<tb> 26 <SEP>><SEP> ~ <SEP> CO-CH3 <SEP> 160 <SEP> tCDCI3): <SEP> 1.71 <SEP> (s, <SEP> 6H), <SEP> 2 , 1-2.7 <SEP> (m, <SEP> 2H),
## EQU1 ## > (m, <SEP> 2H),
<tb><SEP> O <SEP> CH3 <SEP> 4.3-4.6 <SEP>(m;<SEP> 1H)
<tb><SEP> 110
<tb> 27 <SEP> \ <SEP> -OH <SEP> 129 <SEP> (D2O + NaOD): <SEP> 1.70 <SEP> (s, <SEP> 6H), <SEP> 2-2 , 4 <SEP> (m, <SEP> 2H),
<tb><SEP> ff <SEP> O <SEP> ~ <SEP> \ <SEP> N <SEP><SEP> 3.05 <SEP> (s, <SEP> 3H), <SEP> 2.7 -3.15 <SEP> (m, <SEP> 2H),
<tb><SEP> 3
<tb><SEP> NC <SEP> n
<tb> 28 <SEP>><SEP> 2 <SEP> CO-C2H <SEP> (COCI3): <SEP> 1.31 <SEP> (t, <SEP> 3H), <SEP> 1.9- 2.6 <SEP> (m, <SEP> 2H),
<tb><SEP> -O-C1 <SEP> N / O "
<tb><SEP> CH3 <SEP> N <SEP><SEP> - <SEP> 2.7-3.6 <SEP> (m, <SEP> 2H), <SEP> 3.42 <SEP> ( s, <SEP> 3H),
<tb><SEP> O <SEP> CH3 <SEP> 3.73 <SEP> (s, <SEP> 3H), <SEP> 4.25 <SEP> (m, <SEP> 1H),
<tb><SEP> 4.25 <SEP> tq, <SEP> 2H)
<Tb>
Example 29 Preparation of (5-cyano-methoxycarbonyl methalel-5-methoxypyrrolidine
Reaction scheme

<tb><SEP> NC <SEP> g \ <SEP> electro
<tb><SEP> i. <SEP> + <SEP> CH30H <SEP> - \ N
<tb> CH30-C <SEP> N <SEP> CH3OH <SEP> Chemistry <SEP> CH30-C <SEP> v <SEP> N
<tb> CH3O-C
<tb><SEP> O <SEP> H <SE> O <SEP> H
<Tb>
.Operating mode
In a reactor of 3 liters, undivided, provided with a nitrogen sparge, and in which dip 25 anodes and 25 cathodes of 5 mm diameter in carbon, 1 cm apart, are introduced 141.8 g (0.675 mol) ) of acid, 2.5 g of sodium methylate, 2.5 g of tetrabutylammonium hydrogen sulfate and 2500 ml of methanol. Magnetic stirring is carried out and electrolysis is carried out at 500 mA (initial voltage: 3.8 volts, final voltage: 3.9 volts). After 79h20 (1.03 times the amount of theoretical current), the solvent is evaporated and 72% of the desired product is recovered.

<tb> Ex. <SEP> Formula <SEP> Point <SEP> of <SEP> RMH <SEP> (ppm)
<tb><SEP> fusion <SEP> (solvent)
<tb><SEP> C <SEP> 0C)
<tb><SEP> MC <SEP> n
<tb> 29 <SEP>, T-CU) - <SEP> 144 <SEP> 44 <SEP> (CDCl3): <SEP> 1.9-2.4Cm, <SEP> 2H), <SEP> 2 , 7-3.2 <SEP> (m, <SEP> 2H),
<tb><SEP> tH3-l <SEP> \ <SEP> N <SEP> / <SEP> 3.30 <SEP> (s, <SEP> 3H), <SEP> 3.74 <SEP> (s , <SEP> 3H),
<tb><SEP> 5.1 <SEP> (m, <SEP> 1H)
<Tb>
Example 30
Preparation of N-methyl (alpha-cyano-alpha-methoxycarbonyl methylene) -5-hydroxy-2-pyrrolidine Reaction Scheme

<tb><SEP> NCC-OH <SEP> + <SEP> electro- <SEP> NC
<tb><SEP> N <SEP> H20
<tb><SEP> CH30-1C <SEP> N <SEP> 2 <SEP> Chemistry <SEP> CH30-C <SEP> \ <SEP> N
<tb> t <SEP>,
<tb><SEP> O <SEP> CH3 <SEP> O <SEP> CH3
<Tb>
Operating mode
In a reactor identical in design to the previous one, the electrodecarboxylation of 0.134 mol (30 g) of acid in 1000 ml of water containing 0.3 g of pearl NaOH is carried out. The reaction is stopped when 1.44 times the theoretical amount of current is passed; after evaporation of the solvent, 87% yield of the desired alcohol is obtained.

<Tb>

Ex. <SEP> Formula <SEP> Point <SEP> of <SEP> NMR <SEP> (ppm)
<tb><SEP> merge <SEP> (soLvant)
<tb><SEP> (0C)
<tb><SEP> NC <SEP> r7
<tb> 30 <SEP> H / H <SEP> F <SEP> oh <SEP> 110 <SEP> (CDCL3): <SEP> 1.5-2.6 <SEP> (m, <SEP> 2H) , <SEP> 1.9-3.5 <SEP> (m, <SEP> 2H),
<tb><SEP> CH3-OC <SEP> 3.39 <SEP> (s, <SEP> 3H), <SEP> 3.71 <SEP> (s, <SEP> 3H),
<tb><SEP> o <SEP> 0 <SEP> CH3 <SEP> 4.7 <SEP> (s <SEP> Large, <SEP> 1H)
<tb><SEP> 4.9-5.4 <SEP> (s <SEP> wide, <SEP> 1H)
<Tb>
Example 31
Preparation of (> -cwano-methoxycarbonylmethylene-5) hydroxypropyl pyrrolidine
Reaction scheme

. Operating mode
A solution of 10 g (0.051 M) of methyl ether and 150 ml of water containing 10 drops of concentrated hydrochloric acid is refluxed for 15 minutes.

The desired alcohol precipitates on cooling; 85% yield.

The alcohol is recrystallized from acetonitrile and then washed with toluene. It is identical to that obtained by electrochemical reaction.

<Tb>

Ex. <SEP> Formula <SEP> Point <SEP> of <SEP> NMR <SEP> (ppm)
<tb><SEP> fusion <SEP> (solvent)
<tb><SEP> (C)
<tb><SEP> (0C)
<tb> 31 <SEP>, <SEP> OH <SEP> 162 <SEP> C00 <SEP> 1,4-2,5 <SEP> (m, <SEP> 2H), <SEP> 2,6-3 -2 <SEP> Cm, <SEP> 2H)
<tb><SEP> 31 <SEP>><SEP> H <SEP> 162 <SEP> 3,71 <SEP> 1,4-2,5 <SEP> (s, <SEP> 3H), <SEP> 5.73 <SEP> (t, <SEP> 1H)
<tb><SEP> CH <SEP> -OC
<tb><SEP> O <SEP> H
<Tb>
Example 32 Preparation of N-Methyl (-cyano-methoxycarbonyl methylene) -5-methoxy-2-pyrrolidine
Reaction scheme

<tb><SEP> NC <SEP> CH3OH <SEP> Reflux <SEP> NC
<tb><SEP> / <SEP> OH <SEP> + <SEP> CH30H <SEP>-><SEP> I <SEP><SEP> / SEP> OCH3
<tb> CH3O-C1N <SEP> H <SEP> H + <SEP> CH30-C
<tb><SEP> O <SEP> CH3 <SEP> O <SEP> CH3
<Tb>
Operating mode
A solution of 9.8 g (0.05 mol) of alcohol in 200 ml of methanol containing 20 drops of concentrated hydrochloric acid is refluxed. An NMR yield of 100% is obtained in methyl ether identical to that obtained by electrochemical reaction.

<Tb>

Ex. <SEP> Formula <SEP> Point <SEP> of <SEP>. <SEP> NMR <SEP> (ppm)
<tb><SEP> fusion <SEP> (solvent)
<tb><SEP> C <SEP> 0C)
<tb><SEP> NC <SEP> n
<tb> 32 <SEP>><SEP> O-CH3 <SEP> 88 <SEP> (CDCL3): <SEP> 1.8-2.3 <SEP> (m, <SEP> 2H), <SEP> 3-3.5 <SEP> (m, <SEP> 2H),
<tb><SEP> CH3-OC <SEP>><SEP> N <SEP> / <SEP> 3.28 <SEP> (s, <SEP> 3H), <SEP> 3.40 <SEP> (s , <SEP> 3H),
<tb><SEP> Ó <SEP> CH3 <SEP> 3.70 <SEP> (s, <SEP> 3H), <SEP> 4, S-5.05 <SEP> (m, <SEP> 1H)
<Tb>
Example 33
Preparation of N-methyl (α-cyano-alpha-methoxycarbonylmethyl) -5-aminophenylpyrrolidine
Reaction scheme

<tb><SEP> NC <SEP> GNH <SEP> CH2Cl2 <SEP> NC
<tb><SEP> NC <SEP> o <SEP> OH <SEP> + <SEP> 9 <SEP> NH2
<tb>CH30C'N<SEP> Reflux
<tb><SEP> Reflux
<tb><SEP> O <SEP> CH3 <SEP> H + <SEP> O- <SEP> CH3
<Tb>
. Operating mode
A solution of 2 g (0.01 mol) of alcohol in 5 ml of methylene chloride containing 3 drops of concentrated hydrochloric acid and 0.9 g (0.01 mol) of aniline is refluxed for 5 hours. . At the end of the reaction, add sludge, extract with methyl chloride, dry over sodium sulfate and evaporate the solvent. 63t of the desired amine is obtained.

Reaction scheme b

. Operating mode
0.2 ml (2.3.10 mol) of triflic acid is slowly added to a magnetically stirred mixture of 2.1 g (10-2 mol) of ether and 1.8 g (10-2 mol) of aniline silylated. The reaction is instantaneous and exothermic. The NMR yield is 100%. The mixture is filtered and the solid is washed with a 95/5 v / v ether / methylene chloride mixture and 2.2 g of product are obtained. Evaporation of the solvents provides 0.35 g of product. The yield is 94% crude product, identical to that obtained according to reaction scheme a.

Examples 34 to 36
The compounds defined in Table IV below were prepared according to the preparation veils similar to that of the Example. The physical characteristics of the compounds obtained are also shown in this Table.

Table IV

<tb> Ex. <SEP><SEP> Path of <SEP> Formula <SEP> Point <SEP> of <SEP> NMR <SEP> (ppm)
<tb><SEP> Prepa- <SEP> merge <SEP>. <SEP> (solvent)
<tb><SEP> ration <SEP> (Oc)
<tb><SEP> O
<tb><SEP> Û
<tb> 34 <SEP> oO-CH3 <SEP> 126 <SEP> (CDCl3): 1.7 <SEP> (s, <SEP> 6H), - 2-2.4 <SEP> (m, <SEP > 2H),
<tb><SEP> - <SEP> f
<tb><SEP>0'H<SEP> \ N <SEP> 3,2-3,5 <SEP> (m, <SEP> 5H), <SEP> 5,05-5,25 <SEP> ( m, <SEP> 1H)
<tb><SEP> i. <SEP> f
<tb><SEP> OH
<tb><SEP> O
<tb><SEP> r
<tb><SEP> O-!
<tb> 35 <SEP> 90 <SEP> 0-CH3 <SEP> tCDC13): <SEP> 1.7 <SEP> (s, <SEP> 6H), <SEP> 2-2.3 <SEP> ( m, <SEP> 2H),
<tb><SEP> 3.1 <SEP> 1 <SEP> N <SEP> 3.1 <SEP> (s, <SEP>3H>,<SEP> 3.2-3.6 <SEP> (m , <SEP> SH),
<tb><SEP> O <SEP> CH3 <SEP> 4.95-5.2 <SEP> Cm, <SEP> 1H)
<tb> 36 <SEP> r <SEP> SNHS3 <SEP> 150 <SEP> (CDCL3): <SEP> 1.6-2.9 <SEP> (m, <SEP> 2H), <SEP> 3- 3.6 <SEP> (m, <SEP> 2H),
<tb> P \ 1WH <SEP> (s,
<tb><SEP> CH3-OC <SEP>''<SEP> 3.35 <SEP> (s, <SEP> 3H), <SEP> 3.71 <SEP> (s, <SEP>3H>,
<tb><SEP> O <SEP> CH3 <SEP> 4.2 <SEP> (s, <SEP> 1H), <SEP> 5.27 <SEP> (t, <SEP> 1H),
<tb><SEP>6; 3-7.5 <SEP> (m, <SEP> 5H)
<tb><SEP> O
<tb> 37 <SEP>, / <SEP>><SEP> SOH <SEP> 188 <SEP> (COCI3): <SEP> 1.69 <SEP> (s, <SEP> 6H), <SEP> 1 , 9-2.5 <SEP> (m, <SEP> 2H),
<tb><SEP> O <SEP> N <SEP> WOH <SEP> 3,2-3,6 <SEP> (m, <SEP> 2H), <SEP> 5,6-5,9 <SEP> Cm, <SEP> 1H),
<tb><SEP> O <SEP> H <SEP> - <SEP> 10.4 <SEP> Cm, <SEP> 1H)
<tb><SEP> O
<tb><SEP> CH3-C,
<tb> 38 <SEP> 3 <SEP>> OCH3 <SEP> 68 <SEP> (COCI3) -. <SEP> 1.8-2.2 <SEP> (m, <SEP> 2H), <SEP> 2.4 <SEP> (s, <SEP> 3H),
<tb><SEP> CH3-OC <SEP> N <SEP> 2.9-3.4 <SEP> (m, <SEP> 2H), <SEP> 3.3 <SEP> (s, <SEP> 3H),
<tb><SEP> O <SEP> H <SEP> 3.7 <SEP> (s, <SEP> 3H), <SEP> 4.9-5.2 <SEP> Cm, <SEP> 1H),
<tb><SEP> 8.5-9 <SEP> (m, <SEP> 1H)
<Tb>
Example (al)
Preparation of N-Methylcyclohexyl-2 pyrrole
Reaction scheme

<tb><SEP> NCff <SEP> NC
<tb><SEP> OH <SEP><<SEP><SEP> + <SEP> + (CH3C0) 20 / CH3tOOH / <SEP> CH <SEP> \ <SEP> HC-CH2
<tb> CH30-C <SEP> NI <SEP> Pyridine <SEP> CH30C, <SEP> N <SEP> | - <SEP> N
<tb><SEP> O <SEP>, <SEP> O <SEP> Cl3 <SEP>(<SEP> CH3
<Tb>
.Operating mode
A mixture of 20 g (0.102M) of alcohol, 13.6 ml of pyridine, 11.1 ml of acetic anhydride and 36.5 ml of acetic acid is refluxed. After 30 minutes, the intermediate product was formed; 2.8 g of water are added and the reflux is continued for 5 hours. It is cooled, 25 ml of water are added, the mixture is extracted with methyl chloride, washed with dilute sodium hydroxide and distilled under vacuum. 73% of the desired pyrrole is obtained: E = 55 (5.33 Pa, 0.04 mmHg).

Example (a2)
Preparation of N-methyl-2-pyrroline
Reaction scheme

<tb><SEP> HC <SEP> HO, <SEP>-><SEP> Nt-tH2
<tb> CH <SEP> O-CH3 <SEP> O <SEP> CH3Co2H / Pyridin / <SEP> OC <SEP> H <SEP> 2 /
<tb> 1 <SEP> cl3 <SEP> INH3 <SEP> H20 <SEP> ICH3.00 <SEP> CH3 | <SEP> CH30I
<tb><SEP> O <SEP> 0 <SEP> CH <SEP> CH
<Tb>
. Operating mode
A mixture of 20 g (0.095 mmol) of ether, 2.6 ml of water, 11.5 ml of pyridine and 50 ml of acetic acid is refluxed for 5 hours. After extraction, washing, drying and distillation, a yield of 71% of desired pyrrole is obtained.

Example (b)
Preparation of methylene (N-methyl pyrrolyl) cyanomalonate
Reaction scheme

.Operating mode
Refluxed for 2 h 10, a mixture of 20 g (0.095 M) of ether, 5.7 ml of acetic acid (0.1 M) and 28.3 ml (0.3 My of acetic anhydride. It is extracted and washed in the usual manner, and a yield of 71% in desired pyrrole is obtained, E = 950 (8 Pa, 0.06 mmHg).

Example (c)
Preparation of (N-methyl pyrrolyl-2) acetamide
. Reaction scheme

. Operating mode
Refluxed for 2 h 10, a mixture of 10 g (0.047 M) of ether, 2.8 ml of acetic acid (0.05 M) and 14.2 ml (0.15 M) of acetic anhydride. It is extracted and washed in the usual manner, the solvents are evaporated off and the residue is boiled for 2 hours in 48 ml of 2N sodium hydroxide. After cooling, it neutralizes with concentrated hydrochloric acid; the precipitate obtained is washed with water; the aqueous phase is extracted with methylene chloride; the organic phase is dried and evaporated and the.

residue combined with the preceding precipitate. Yield 63%.

The amide can be purified by distillation. E = 1350C (26.67 Pa, 0.2 mmHg).

Claims (18)

 1 - Derivatives of 2-methylidene pyrrolidine represented by the general formula (

 in which  Z1 and Z2 each independently represent -C-R3 or O  -C-O-R4 or -CN, with R3 and R4 each representing O  an optionally substituted aryl group, or a group  alkyl, linear or branched, optionally substituted,  or an unsaturated heterocyclic group containing  5-7 membered and optionally substituted, and  can also be attached to the rest of the  molecule by an aliphatic chain having from 1 to  6 links, one of the two radicals Z1 and Z2 being  be replaced by H; or  Z1 and Z2 together with the carbon atom  to which they relate, a cycle comprising  electron attracting groups  R1 represents H, alkyl, linear or branched, optional  substituted or optionally substituted aryl or  optionally substituted aralkyl, or a group  heterocyclic such as that falling within the definition  R3 and R4  R2 represents H, OH, OR5, NR6R7, COOH, COOR8 or  CONR9R10, with R5 representing alkyl, linear or  branched, possibly substituted or possible aryl  substituted, or Si (R11) 3 (with R11 = linear alkyl  or branched or aryl); R6 and R7 representing each  independently H, alkyl, linear or branched, if any  substituted or optionally substituted aryl, or  a heterocyclic group such as the one entering  the definition of R3 and R4, R6 and R7 can also  form, together with the nitrogen atom to which they  a heterocycle having 5 to 7 members  R8 represents alkyl, linear or branched, if any  substituted or optionally substituted aralkyl  or optionally substituted aryl; Rg and R10 represent  both H, alkyl, linear or branched, optionally  substituted or optionally substituted aralkyl or aryl  optionally substituted or a heterocyclic group  that such as that falling within the definition of R3 and  R4, excluding compounds for which  R2 = COOCH3; R1 = H; Z1 = H and Z2 CO = -COOCH3  -COOCH2C6H5; -CN or else Z1 = CN and Z2 = COOtBu or  Z1 = COOC2H5 and Z2 = CN, or Z1 and Z2 form  together a Meldrum acid cycle, or Z1 = Z2 =  COOCH 3  R2 = COOC2H5; R1 = H; Z1 = COOC2H5 and Z2 = COOC2H5 or  COC2Hs;  . R2 = COOtBu; R1 = CH2C6H5; Z1 = COOCH3 and Z2 = H  . R2 = COOCH2C6H5; Z1 and Z2 together form a cycle  Meldrum acid; Z1 = H and Z2 = COOCH2C6H5.  2 - Compound according to claim 1, characterized in that the alkyl groups falling within the definition of the substituents R3, R4, R1, R5, R11, R6 to R10 are C1-C10 alkyl groups, preferably C1-C4.  3 - Compound according to claim 1, characterized in that the aryl groups falling within the definition of the substituents R3, R4, R1, R8, R11, R6 to R10 are phenyl or naphthyl groups.  4 - Compound according to claim 1, characterized in that the heterocyclic unsaturated groups falling within the definition of substituents R3, R4, R1; R5, Roll, R6 to R10 are furyl, pyridyl, thienyl, furylmethyl, pyridylmethyl or thienylmethyl.  5 - Compound according to claim 1, characterized in that the aralkyl groups falling within the definition of the substituents R3, R4, R1, R5, R11, R6 to R10 are benzyl or naphthylmethyl groups.  6 - Compound according to claim 1, characterized in that

 can be cyclized by forming one of the following cycles Meldrum Dimedone Acid Barbituric acid

 7 - Process for preparing the compounds of formula (Ia)

 in which R8, Z1 and Z2 are as defined in claim 1, characterized in that a methyl iminoether of formula

 wherein R8 is as defined above, on an active methylene compound of formula Z1-CH2-Z2, wherein Z1 and Z2 are as defined in claim 1, preferably in the absence of solvent optionally in the presence of a weak base, such as triethylamine.  8 - Process according to Claim 7, characterized in that the iminoether is prepared by reacting dimethyl sulphate with a pyroglutamic ester of formula

 and the iminoether salt formed is neutralized in situ with a tertiary amine, such as triethylamine, which reaction and neutralization can be carried out without purification of the intermediate compounds and can be carried out directly to carry out the aforesaid reaction leading to compound (Ia).  9 - Process according to claim 7, characterized in that, to obtain the compounds (Ia), as defined in claim 7, the pyroglutamic acid is reacted with methanol chloroform solvent, removing the water of reaction in the form of a ternary azeotrope, the compound obtained, namely methyl pyroglutamate, which can be used directly to carry out the aforementioned reaction leading to the compounds (Ia).  10 - Process for preparing the compounds of formula (Ib)

 or  - R8, Z1 and Z2 are as defined in the claim  1; and  R'1 represents alkyl or aryl or aralkyl or  heterocyclic group as defined in  Claim 1 in conjunction with formula (I), characterized in that the compound of formula

 wherein Z1, Z2 and R8 are as defined above, with the compound  R 'lx, or  X represents a halogen; and  R'1 is as defined above, preferably under solid-liquid phase transfer conditions, the preferred base being solid potassium carbonate, the phase transfer agent being advantageously prepared in situ by reacting R'1X with triethylamine.  li - Process for the preparation of compounds of formula (lob)

 or R'1, R8, Z1 and Z2 are as defined in claim 10, characterized in that an N-substituted iminoether salt of formula

 with  - R12 = in particular lower alkyl, such as methyl,  ethyl;  G- = cation, such  - A- = anion, such as RF4- or CH3OS 3 this reaction being conducted in the presence of a weak base, such as sodium methoxide.  12 - Process according to claim 11, characterized in that the starting iminoether salt is prepared by reaction of the compound of formula

 or R1 and R8 are as defined in claim 10, on (CH3) 2SO4 or C2H5C + BF4- or other salt corresponding to the anion  13.Procédé according to claim 12, characterized in that the compound of formula is prepared:

 with R 8 R 9 alkyl, especially methyl, by reacting pyroglutamic acid with a dialkyl sulphate (R '1) 2 SO 4 in the presence of a solid-liquid phase transfer agent, the preferred base being potassium carbonate sium solid, the phase transfer agent being advantageously prepared in situ by reacting (R'1) 2SO4 with triethylamine  14.Procedure according to claim 12, characterized in that the compound of formula:

 with R8 = R '1 = alkyl, especially methyl, by reacting the compound of formula:

 on an alkylating agent such as R'lCl or (R'1) 2SO4, in the presence of a solid-liquid phase transfer agent, la. preferred base being solid potassium carbonate, the phase transfer agent being advantageously prepared in situ by reacting (R'1) 2SO4 with triethylamine.  15 - Process for preparing the compounds of formula (Ic)

 in which Z17 Z2 and R1 are as defined for the compounds (Ib), to claim 10 or 11, characterized in that the saponification of the esters of formula

 wherein Z17 Z2, R'1 and R8 are as defined above, using a strong base, preferably sodium hydroxide, followed by treatment with a strong acid, preferably hydrochloric acid.  16 - Process for preparing compounds of formula (Id)

 in which Z17 Z2 Rg and R10 are as defined in claim 1, and R'1 is as defined in claim 10, characterized in that the compound of formula

 or R8 is as defined in claim 1, on the compound of formula NR9R10, this reaction taking place, preferably in a solvent medium, and preferably in the presence of an acid catalyst.  17 - Process for preparing the compounds of formula (Ie) or (Ie)

 where R4, R8, Rg and R10 are as defined in claim 1, and R'1 is as defined in claim 10, characterized in that the compound of formula

  on the compound of formula R4O-B + with L10 +. with BÇ = alkaline cation, such as Nazi  18 - Process for preparing the compounds of formula (If) or cil

 with R5, Z1 and Z2 as defined in claim 1, and R '1 as defined in claim 10, characterized in that an electrochemical decarboxylation of the compound of formula

 on a compound of formula R 50 H or H 2 O respectively, in the presence of a basic catalyst and optionally of a support electrolyte, the basic catalyst being in particular a small quantity of sodium hydroxide or an alcoholate, and the supporting electrolyte being a salt quaternary ammonium, the intensity of the current being set at a value between 0.1 A and 1 A, so as to obtain a potential of between 3 and 20 volts  19 - Process for preparing the compounds of formula (Ih)

 with -YR = -OR5 or NR6R7, R5, R6 and R7 being as defined in claim 1, Z1 and Z2 being as defined in claim 1; and R'1 being as defined in claim 10, characterized in that an exchange reaction, in the presence of H +, is carried out between the compound of formula

 and the compound of formula RYH.  20 - Process for preparing the compounds of formula (Ih)

 with RY, Z1, Z2 and R'1 as defined in claim 19, characterized in that an exchange reaction is carried out between the compounds of formula

 on the compound RYSi (R11) 3 with -RY = -OR'5 or -NR6R7, R61 R7 and R11 being as defined in claim 1, and R'5 having a meaning chosen from those given for R5.  21 - Use of the compounds of formula (I) as defined in claim 1 as a pyrrole precursor agent or as a compound leading to these precursors.