FR2458546A1 - PROCESS FOR THE PRODUCTION OF RACEMIC ARYL-5 HYDANTOINS AND NEW PRODUCTS RESULTING THEREFROM - Google Patents

Abstract

THE INVENTION RELATES TO A PROCESS FOR MANUFACTURING ARYL-5 HYDANTOINS AND THE NEW PRODUCTS THEREFORE. THIS PROCESS CONSISTS OF REACTING, AT HOT, IN AN ACID MEDIUM, THE ALLANTOIN ON AN AROMATIC DERIVATIVE HAVING AT LEAST ONE NUCLEAR PROTON. APPLICATION OF THIS PROCESS TO OBTAINING NEW ARYL-5 HYDANTOINS.

Description

1. The present invention relates to a method of manufacture

  racemic aryl-5 hydantoins from allantoin and the new products

resulting calves.

  Aryl-5 hydantoins are valuable chemicals

  it has many applications, either in chemical synthesis to access certain racemic or split alpha-amino acids (FR 2 310 986), or in phytopharmacy to combat various plant growth disorders (US 2 891 069), or finally in therapeutic human or animal (LM Werbel

  and collaborators, J. Med. Chem. 20, 1569-72 (1977)).

  According to the prior art, aryl-5 hydan can be

  tonnes, either by cyclization of arylmalonamides according to C.K. Ingold and

  collaborators, J. Chem. Soc., 121, 1190 (1922), or arylcyanacetamides se-

  Thompson, T., et al., J. Amer. Chem. Soc., 47, 875 (1925), or

  of racemic aryl-2 hydantoic acids resulting from the action of an alkaline cyanate

  flax or urea on racemic alpha-arylglycines according to E.C. Wagner and

  collaborators, J. Chem. Educ. 13, 266 (1936) or alpha-aryl alphaureidoacid-

  tonitriles according to S. L. Ruskin et al., J. Amer. Chem. Soc., 60, 1471 (1938), or by the action of urea on an arylglyoxal according to J.J. Fisher et al., J. Amer. Chem. Soc., 64, 1434 (1942), either by the action of an alkaline cyanide in the presence of ammonium carbonate on benzaldehydes according to the method of Bergs-Bucherer or their bisulfitic combinations according to J. Klosa, Arch. Pharm., 285, 278 (1952) or on their cyanohydrin according to GB 936 664, or by alkylation of an aromatic with a 5-alkoxy hydantoin

  racemic according to D. Ben Ishai et al., Tetrahedron 1970, 1289-83.

  Some particular methods are described for prepa-

  5 racemic parahydroxyphenyl-5 hydantoin, either by the action of urea

  on racemic parahydroxymandelic acid according to the French patent application.

  78/22 989, either by the action of urea and glyoxylic acid on the

phenol according to BE 865 027.

  These methods require either the manipulation of alkaline cyanide, or the availability of difficult access raw materials, such as some substituted benzaldehydes or 5-alkoxy hydantoins, disadvantages

  troublesome for industrial manufacture.

  However, the Claimant has fortuitously discovered that the

  Tonne (5-ureidohydantoin racemic), in an acid medium, reacts with various aromatic structures to provide racemic aryl-5 hydantoins. The

  substitution in the acidic medium of the ureido group of allantoin by a group

  This aromatic reaction is unexpected and has never been reported in the literature 2.

  chemical to the knowledge of the Applicant. This arylation of the dioxio

  2,4-imidazolidine is all the more surprising since it is well known that

  lantoine is stable in acid medium, since it can be obtained in this medium

according to DE AS I 939 924.

  In addition, the invention provides access to new hyantoinoines which have never been described in the literature to the knowledge

of the Applicant.

  According to the process of the invention, the allantoin is reacted under hot conditions in an acidic medium on an aromatic derivative having at least one nuclear proton, in excess or not, in the presence, if necessary, of a solvent.

  organic. This reaction is generally carried out in mineral acids

  such as concentrated hydrochloric acid, sulfuric acid, Nordhausen acid (fuming sulfuric acid) is

  aromatic structures susceptible to electrophilic attack only with structural

  aromatics deactivated by electro-acceptor groups. If ne

  necessary, and more particularly when the aromatic derivative used is a solid with a high melting point, it is preferred to carry out this condensation at

  within a conventional organic solvent such as C1 to C4 alcohols or

  of acetic. According to the process of the invention, the aromatic derivative may be phenol, alkylphenols such as cresols; diphenols such as the

  resorcinol, pyrocatechol, hydroquinone; triphenols such as pyridine

  rogallol and their ethers such as anisole, guaiacol, metametho-

  xyphenol, hydroquinone monomethyl ether; halogenated phenols such as

  parachlorophenol, 2,3-dichlorophenol, 2,5-dichlorophenol, di-

  2,4-chlorophenol, 3,5-dichlorophenol, nitrophenols; aromatics such as benzene, thiophene or their alkyl derivatives such as, for example,

  toluene, xylenes, mesitylene; benzoic acids, for example

  ple, gallic acid, syringic acid, trimethoxy-3,4,5 benzoic acid; halogenated aromatics such as chlorobenzene, dichlorobenzenes,

acetanilide, and the like.

  More specifically, the process of the invention consists in condensing

  heat, between 50 C and 100 C, for 6 to 48 hours, allantoin on an excess of aromatic derivative having at least one nuclear proton in the presence of a concentrated aqueous solution of strong mineral acid selected from the acid concentrated hydrochloric acid d = 1.18; sulfuric acid d = 1.83; Nordhausen acid or fuming sulfuric acid d = 1.88 and, if necessary, in the presence of an organic solvent such as acetic acid or isopropanol, then at the end of the reaction to isolate the desired product according to methods known per se, either by concentration under vacuum of the reaction medium and taken up with water when working in concentrated hydrochloric acid, or by taking up the medium.

  reaction with ice water, keeping the pH at 4 - 0.5 by addition

  of sodium hydroxide when working in the presence of sulphuric acid

  then filter the desired product when it crystallizes from the start in the water or is extracted with an organic solvent immiscible with water and

  finally, to purify it for recrystallization in a suitable solvent.

  The following examples are given for illustrative purposes and

limiting of the invention.

EXAMPLE 1

  The mixture is heated for 18 hours at 80 ° C., 0.5 mol (79 g) of allantoin and

  1 mole (124 g) of guaiacol in 50 g of isopropanol and 400 g of hydrochloric acid;

  that concentrated d = 1.18. Then the reaction medium is taken up with 100 cm3 of water.

  concentrated under vacuum. 55 g of (hydroxy-4-methoxy-3-phenyl) are thus isolated.

  racemic hydantoin having after recrystallization in three volumes of water a melting point of 200 ° C. (P.F. 276 ° C. literature with decomposition,

  H. R. Henze et al., J. Amer. Chem. Soc., 64, 522-3 (1942)).

Microanalysis CioH10N204

M.P. = 222.20 -

  Determination of water according to the method of K. Fischer 0,8%

C,% H,% N,%

  calculated with 0.8% water 53.61 4.59 12.51

found 53.3 4.6 12.5.

EXAMPLE 2

  The procedure is as in Example 1 but the ga {acol is replaced by 1 mole of phenol. Thus, after recrystallization from water, the racemic parahydroxyphenyl-5 hydantoin having a melting point of 265 ° C. with a yield of 70% of the theory calculated with respect to

  allantoin implementation (P.F. literature 269-270 C, E.K. Harvil and col-

  laborers, J. Org. Chem., 9, 21-30 (1944)).

Microanalysis C9H8N203

M.P. = 192.17

C,% H,% N,%

calculated 56.25 4.19 14.58

found 56.15 4.30 14.40.

EXAMPLE 3

  The procedure is as in Example I but guaiacol is replaced by 1 mole of paracresol. Thus, after recrystallization in a 9-1 (v / v) water-propanol mixture, racemic 5-hydroxy-2-methyl-5-phenyl-5-hydantoin 4. having a melting point of 258 ° C. in a yield of 70%

  of the theory calculated with respect to the allantoin used. At the

  birth of the Applicant, this product is not described in the literature.

Microanalysis C10H10N203

M.W. = 206.20

C,% H,% N,%

calculated 58.24 4.89 13.59

found 58.3 4.9 13.5.

EXAMPLE 4

  The procedure is as in Example I, but the guaiacol is replaced by one mole of metacresol. Thus, after recrystallization in a

  water-acetone mixture 9-1 (v / v) (2-hydroxy-4-methyl-phenyl) -5 hydantoin

  with a melting point of 244 - 3 C with a yield of 75%

  of the theory computed with respect to the allo-implementation. At the

  birth of the Applicant, this product is not described in the literature.

Microanalysis C 0HlON203

M.W. = 206.20

C,% H,% N,%

calculated 58.24 4.89 13.59

found 57.8 5.0 13.45.

EXAMPLE 5

  The procedure is as in Example I but the gaZacol is replaced by 1 mole of orthocresol. Thus, after recrystallization from water-isopropanol 1-4 (v / v), the racemic (4-hydroxy-methyl-3-phenyl) hydantoin having a melting point of 242 ° C. in a yield of 90% is obtained.

  of the theory calculated with respect to the allantoin used. At the

  birth of the Applicant, this product is not described in the literature.

Microanalysis C 0H10N203

M.W. = 206.20

C,% H,% H,%

  calculated 58.24 4.89 13.59 found 57.9 5.2 13.0

EXAMPLE 6

  The procedure is as in Example 1, but the gaZacol is replaced by 1 mole of hydroquinone. Thus, after recrystallization in a

  acetone-water mixture 1-1 (v / v), 2,5-dihydroxy-phenyl-5 hydantoin

  decomposing at 170 C with a yield of 90% of the calculated

  in relation to the allantoin implemented. To the knowledge of the

5.

  this product is not described in the literature.

Microanalysis C9H8N204, H20

M.P. = 226.19

  bc,% H,% N,% H2, calculated 47.78 4.45 12.38 7.96 found 47.8 4.3 12.3 8, 4

  * determined by the method of K. Fischer.

EXAMPLE 7

  The procedure is as in Example 1, but the galacol is replaced by 1 mole of resorcinol. Thus, after recrystallization in a

  acetone-water mixture 1-1 (v / v), 2,4-dihydroxyphenylhydantoin

  having a melting point of about 300 C with a yield of 50%

  of the theory calculated with respect to the allantoin used. At the

  birth of the Applicant, this product is not described in the literature.

EXAMPLE 8

  The procedure is as in Example 1, but the galacol is replaced by 1 mole of pyrocatechol. Thus, after recrystallization from water, racemic (3,4-dihydroxy-3,4-phenyl) -5-hydantoin having a melting point of 240 ° C.-Cl with a yield of 70% of the theory calculated with respect to allantol is obtained. implementation (PF literature 231-232 C, R. Kuhn and

  co-workers, Annalen 662, 67-71 (1963)).

Microanalysis C9H8N204

M.P. = 208.18

C,% H,% N,%

calculated 51.92 3.88 13.46

found 52.0 4.0 13.4.

EXAMPLE 9

  The procedure is as in Example 1, but the ga; acol is replaced by 1 mole of 2,6-dimethylphenol. We thus obtain after recrystallization

  in water, racemic 5-hydroxy-3,5-dimethylphenyl-5-hydantoin possesses

  with a melting point of 248-1 C with a yield of 90% of theory calculated with respect to the allantois used. To the knowledge of

  Applicant, this product is not described in the literature.

Microanalysis C lH12N203

M.P. = 220.23

C,% H,% N,%

  calculated 59.99 5.49 12.72 found 59.9 5.4 12.5 6.

EXAMPLE 10

  We operate as in Example 1, but we replace the guaiacol

  with 1 mol of hydroquinone monomethyl ether. We thus obtain, after recrystallization

  in a water-dimethylformamide mixture 1-1 (v / v), 1 '(2-hydroxy-methoxy)

  5-phenyl) -5 racemic hydantoin decomposing at about 260 ° C. with a yield of 50% of the theory calculated with respect to the allantoin used. AT

  Applicant's knowledge, this product is not described in the literature.

  erature. Microanalysis C 10H10N204

M.P. = 222.20

C,% H,% N,%

calculated 54.05 4.54 12.61

found 53.9 4.6 12.6.

EXAMPLE 11

  The procedure is as in Example 1, but the ga! Acol is replaced by I mole of pyrogallol. Thus, after recrystallization in a

  ethanol-water mixture 1-1 (v / v), the (2,3,4-trihydroxy-phenyl) -5 hydanto does not

  with a melting point of 300 - 30C with a yield of 50%

  of the theory calculated with respect to the allantoin used. At the

  birth of the Applicant, this product is not described in the literature.

Microanalysis C9H8N205

M.P. = 224.18

C,% H,% N,%

  calculated 48.22 3.6 12.5 found 48.0 4.1 11.6

EXAMPLE 12

  The procedure is as in Example 1, but the gaZacol is replaced by 1 mole of 2,6-dimethoxyphenol. We thus obtain after recrystallization

  in water the racemic 5-hydroxy-3,5-dimethoxy-phenyl-5 hydantoin possessed

  melting point close to 265 C with a yield of 40% of theo-

  calculated in relation to the allantoin used (P.F. literature 261-

  261 C., G. Schmidt et al., Annalen 1976, 126-39).

CIlH12N205 Microanalysis

M.P. = 252.23

C,% H,% N,%

calculated 52.38 4.8 11.11

found 52.2 4.9 11.1.

7.

EXAMPLE 13

  The procedure is as in Example 1, but the galacol is replaced by 1 mole of orthochlorophenol. We thus obtain after recrystallization

  in an ethanol-water mixture 1-2 (v / v) (3-chloro-4-hydroxy-phenyl) -5-hydanol

  racemic tolme having a melting point of 222 3 C with a yield

  80% of the theory caleulée compared to the allantoine implemented.

  (P.F. Literature 240-242 C, B. Bognar et al., Antibiotiki, 9, 875-

(1964)).

Microanalysis C9H7C1N203

M.P. = 226.63

  C,% H,% Ci,% N,% calculated 47.70 3.11 15.65 12.36

found 47.8 3.1 15.5 12.25.

EXAMPLE 14

  The procedure is as in Example I but the gamacol is replaced by 1 mole of 2,6-dichlorophenol. Thus, after recrystallization in a 1-2 ethanol-water mixture (v / v), the racemic (3,5-dichloro-4-phenyl) -5 hydantoin having a melting point of about 264 ° C. with a yield of 50% of the theory calculated with respect to the allantoin used. To the knowledge of the Applicant, this product is not described in

Literature.

  Microanalysis C9H6C12N205 PoM. = 261.07 C,% H,% Ci,% N,% calculated 41, 4 2.32 27.16 10.73

found 41.4 2.5 27.05 10.8.

EXAMPLE 15

  The procedure is as in Example 1, but the galacol is replaced by 1 mole of beta-naphthol. This gives, after recrystallization in ethanol-water mixture 1-2 (v / v) racemic (2-hydroxy-2-naphthyl) hydantoin racemic

  having a melting point (with decomposition) to 300 C with a yield of

  of 60% of the theory calculated with respect to the allantois used.

  To the knowledge of the applicant, this product is not known in the literature.

erature. Microanalysis C13H10N203

M.P. = 242.23

C,% H,% N,%

calculated 64.45 4.16 11.57

found 64.5 4.3 11.5.

  8. Physical NMR analysis of the proton at 60 MHz in deuterated DMSO (TMS internal reference), 9 ppm 1H singlet CH 7.6 ppm 6H aromatic solid 10, 3 ppm 1H singlet OH 8.0-10.8 ppm 2H solid NH

EXAMPLE 16

  We operate as in Example 1, but we replace the galacol

  by I mole of anisole. In this way, after recrystallization in a

  water-methanol 9-1 (v / v) paramethoxyphenyl-5-hydantoin racemic pos-

  sedating a melting point of 196 C with a yield of 50% of the theory calculated with respect to the allantois used (P.F. literature 195 C,

  E. K. Harvill et al., J. Org. Chem., 9, 21-30 (1944)).

Microanalysis C10H1oN203

M.W. = 206.20

C% H% N%

calculated 58.20 4.89 13.59

found 58.3 5.0 13.6.

EXAMPLE 17

  The mixture is heated for 24 hours at 80 ° C., 0.5 mol (79 g) of allantoin, g of thiophene in 50 g of acetic acid and 200 g of concentrated sulfuric acid of 1.83. At the end of the reaction, the reaction medium is poured onto 500 g of crushed ice while maintaining the pH at 4 - 0.5 by simultaneous addition of sodium hydroxide solution and the resulting suspension is then extracted with ethyl acetate. The organic extraction phases are then washed with water and then

  removes the solvent under vacuum. The residue obtained is recrystallized from

  1,2-chloroethane. This isolated racemic (thienyl-2) -5 hydantoin possesses

  seducing a melting point of 78-80 C with a yield of 70% of the theory calculated with respect to the allantois used (product described: U.S.

3,198,804).

Microanalysis C7H6N202S, H20

M.P. = 200.21

C,% H,% N,% S,% 2 '%

  calculated 41.99 4.03 14.00 16.01 9.00 found 42.0 3.95 13.95 16.1 8.9

  * determined according to the method of K. Fischer.

EXAMPLE 18

  The procedure is as in Example 17, but the thiophene 9 is replaced by 200 g of parachlorophenol. Thus, after recrystallization from 2-1 (v / v) ethanol-water, racemic (5-chloro-5-hydroxy-phenyl) hydantoin having a melting point of 280 ° C. with decomposition in a yield of 60%. of the theory calculated with respect to the allantois used (PF literature 255-257 C, US 3,410,865). Microanalysis C9H7ClN203

M.P. = 226.63

  C,% H,% Ci,% N,% calculated 47.7 3.11 15.65 12.36

found 47.9 3.2 15.7 12.3.

EXAMPLE 19

  The procedure is as in Example 17 but the thiophene is replaced by 200 g of 2,4-dichlorophenol. We thus obtain after recrystallization

  in a 4-1 (v / v) ethanol-water mixture, (3,5-dichloro-2-hydroxyphenyl)

  Racemic 5-hydantoin having a melting point of 300-5 C with decomposition

  position with a yield of 80% of the theory calculated with respect to the allantol implemented. To the knowledge of the Applicant, this product

  is not described in the literature.

Microanalysis C9H6C12N203

C9 6 2 2 3

M.P. = 261.07

  C,% H,% Ci,% N,% calculated 41.40 2.32 27.16 10.73

found 41.4 2.35 26.9 10.7.

EXAMPLE 20

  The procedure is as in Example 17, but the thiophene is replaced by 200 g of 3,5-dichlorophenol. Thus, after recrystallization in

  an acetone-water mixture 2-1 (v / v), (2,6-dichloro-4-hydroxyphenyl) -5-hydanol

  toine having a melting point with decomposition at about 300 C with a

  60% of the calculated theory in relation to the allantol

  fever. To the knowledge of the Applicant, this product is not described in

Literature.

EXAMPLE 21

The procedure is as in Example 17, but the thiophene is replaced by 200 g of 2,3-dichlorophenol. Thus, after recrystallization in ethanol-water mixture 1-1 (v / v), (dichloro-3,4-hydroxy-2-phenyl) hydantoin having a melting point with decomposition at 260 ° C. with yield of 70% of the theory calculated with respect to the allantois used. To the knowledge of the Applicant, this product is not described

in the litterature.

10. Microanalysis C9H6C12N203

M.P. = 261.07

  C,% H,% Cl,% N,% calculated 41.40 2.32 27.16 10.73 found 40.9 2.5 26.4 10.7.

EXAMPLE 22

  The procedure is as in Example 17 but the thiophene is replaced by 200 g of benzene. Thus, after recrystallization in water containing 10% of isopropanol, the racemic phenyl-5-hydantoin having a melting point of 170-1 ° C. with a yield of 88% of the theory calculated with respect to allantoin is obtained. implementation, (PF literature 179-180 C, D.

Ben Ishal, Chem. Comm., 1969, 376).

Microanalysis C9H8N202

M.P. = 176.18

C,% H,% N,%

calculated 61.35 4.58 15.90

found 61.5 4.7 15.9.

EXAMPLE 23

  The process is carried out according to Example 17, but the thiophene is replaced by 200 g of 2,5-dichlorophenol. Thus, after recrystallization in a dimethylformamide-water mixture 1-2 (v / v), the racemic (4-dichloro-2,5-hydroxy-phenyl) -5-hydantoin having a melting point with decomposition at 270qC with a yield of 80% of the theory calculated with respect to the allantois used. To the knowledge of the Applicant, this product

  is not described in the literature.

Microanalysis C9H6C12N203

M.P. = 261.07

  C,% H,% Cl,% N,% calculated 41.40 2.32 27.16 10.73

found 41, o 2.6 26.8 10.5.

EXAMPLE 24

  We operate according to Example 17, but we replace the thiophene

  per 200 g of toluene. In this way, after recrystallization in a

  acetone-water 1-1 (v / v), the racemic paratolyl-5 hydantoin having a melting point of 180 C (capillary tube) with a yield of 80% of

  the theory computed in relation to the allantoin used.

  155 C, F. P. Doyle, J. Chem. Soc., 1962, 1440).

Microanalysis C1 0H10N202

M.P. = 190.20

II.

C,% H,% N,%

calculated 63.15 5.30 14.73

found 62.7 5.4 14.6.

EXAMPLE 25

  The procedure is as in Example 17, but the thiophene is replaced by 200 g of mesitylene. Thus, after recrystallization in a methanol-water mixture 1-2 (v / v), the racemic mesityl-5 hydantoin having a melting point of 218 C with a yield of 90% of the theory calculated

  compared to the allantoin implemented. To the knowledge of the

  This product is not described in the literature.

Microanalysis C12H14N202

M.P. = 218.25

C,% H,% N,%

calculated 66.04 6.46 12.84

found 65.8 6.6 12.65.

EXAMPLE 26

  48 hours at 70 ° C., 0.5 mol (79 g) of allantoin and 500 g of chlorobenzene are heated in 200 g of concentrated sulfuric acid of 1.83 and

  g of Nordhausen fuming sulfuric acid d = 1.88. Then we pay half

  reaction place on 500 g of crushed ice keeping the pH to 4 - 0.5 by simultaneous addition of sodium hydroxide solution. The product is then wrung

  crystallized obtained. After drying at constant weight, under vacuum at 60.degree.

  crystallization in a methanol-water mixture, parachlorophenyl-

  hydantoin having a melting point of 142 C with a yield of 88%

  of the theory computed in relation to the allantoin used (literary P.F.

  142-144 C., D. Ben Ishai et al., J. Heterocyclic Chem., 7,

1289-93, (1970)).

Microanalysis C9H7C1N202

M.P. = 210.63

  C,% H.% Cl,% N,% calculated2 51.32 3.35 16.84 13.30

found 51.4 3.1 16.9 13.0.

EXAMPLE 27

  The procedure is as in Example 26, but the chlorobenz is replaced.

  zen per 500 g of parahydroxybenzoic acid. Thus, after recreating

  in 2- (2-v / v) 2-hydroxyethyl (2,4-dioxo-5-imidazolidin-5-yl) benzoic acid with a yield of 40% of the theory calculated relative to allantoin implementation. At the 12.

  Applicant's knowledge, this product is not described in the literature.

ture. Microanalysis C10H8N205

M.P. = 236.19

  C,% H,% N,% H20,% t calculated 50.85 3.42 11.86 found 49.8 3.6 11.4 1, 2 calculated in 1.2% water 50.24%, 51 11.72 1.2

  * determined by the K. Fischer method.

EXAMPLE 28

  The procedure is as in Example 26, but the chlorobenz is replaced.

  zen per 500 g of acetanilide. Thus, after recrystallization in

  an ethanol-water mixture 1-1 (v / v), racemic (acetamido-4-phenyl) -5-hydantoin

  having a melting point greater than 300 C with a yield of

  40% of the theory calculated with respect to the allantoin used (P.

  2500C literature, R. Kuhn et al., Annalen, 662, 67-71 (1963)).

EXAMPLE 29

  The procedure is as in Example 27, but the chlorobenz is replaced.

  zen per 500 g of paranitrophenol. We thus obtain after recrystallization

  in a dimethylformamide-water mixture 2-1 (v / v), (5-nitro-2-hydroxyphenyl)

  racemic hydantoin having a melting point with decomposition to

  250 C with a yield of 50% of the theory calculated with respect to the

  to'ne implement. To the knowledge of the applicant, this product is not

not described in the literature.

EXAMPLES 30, 31 and 32

  The procedure is as in Example 26, but the chlorobenz is replaced.

  zen per 500 g of trimethoxy-3,4,5 benzoic acid. We thus obtain, after

  recrystallization from a methanol-water mixture 10-1 (v / v), the acid (dioxo2,4-

  2-trimethoxy-3,4,5-benzoic acid having a melting point of 230-3 ° C with decomposition with a yield of 90% of the

  theory calculated with respect to the alloimplementation. To the knowledge

  that of the Applicant, this product is not described in the literature.

Microanalysis C13H14N207

M.P. = 310.26

C,% H,% N,%

calculated 50.32 4.55 9.03

found 50.3 4.5 9.1.

  In the same way, syringic acid is used.

  obtained with a yield of 71%, the acid (2,4-dioxo-imidazolidinyl-5) -2-

  racemic 4-dimethoxy-4-hydroxybenzoic acid having a melting point with

  decomposition towards 250 C after recrystallization in a dimethylfor-

mamide-acetic acid 1-1 (v / v).

  In the same way, using gallic acid, we get

  with a yield of 70%, the acid (2,4-dioxo-5-imidazolidinyl-5) trihydroxy-

  3,4,5 benzoic racemic having a low melting point around 250 C

  after recrystallization in water.

  To the knowledge of the Applicant, these products are not

not described in the literature.

  It goes without saying that the present invention has been described only for explanatory and non-limiting purposes and that any useful modification can be made without departing from its scope as defined by the

claims below.

24585 4 <6

14.

Claims (8)

CLAIMS V E N D I C A T I 0 N S   1. - Method for producing racemic aryl-5-hydantoins   characterized by reacting, under heat, in an acid medium, the   lantoine on an aromatic derivative, having at least one nuclear proton.   2. - A process for producing 5-aryl hydantoins racemic according to claim 1, characterized in that it is reacted hot,   in a strong mineral acid in aqueous solution and possibly in   organic solvent, allantoin on an aromatic derivative at least one nuclear proton.   3. - Process according to claim 2, characterized in that the strong mineral acid is concentrated hydrochloric acid, concentrated sulfuric acid, Nordhausen fuming sulfuric acid or a mixture of these acids.   4. - Method according to claim 2, characterized by the   that the aliphatic organic solvent possibly present in the middle   reaction locus is acetic acid or aliphatic alcohols containing of! at 4 carbon atoms.   5. - Method according to claim 2, characterized by   that the reaction is carried out at a temperature of not less than 50 C.   6. - Process according to any one of claims 1 to   characterized in that the aromatic derivative is selected from the following: phenol, alkylphenols such as cresols; diphenols such as the   resorcinol, pyrocatechol, hydroquinone; triphenols such as pyro-   gallol, as well as other ethers such as anisole, galacol, metamethoxy   phenol, hydroquinone monomethyl ether; halogenated phenols such as   parachlorophenol, 2,3-dichlorophenol, 2,5-dichlorophenol, dichlorobenzene   2,4-phenol, 3,5-dichlorophenol, nitrophenols; aromatics such as benzene, thiophene or their alkyl derivatives such as toluene, xylenes, mesitylene, benzoic acids such as gallic acid, syringic acid, 3,4-trimethoxy acid; Benzolque; halogenated aromatics such as chlorobenzene, dichlorobenzenes, Acetanilide, and the like.   7 - Aryl-5 racemic hydantoins, characterized by the fact   that they are maintained by the process according to any one of the claims tions 1 to 7.   8. - New racemic aryl-5 hydantoins according to claim 7, characterized in that they are: - (2-hydroxy-5-methyl-phenyl) hydantoin, 15. - (2-hydroxy-4-methyl-phenyl) -5 hydantoin, - (3-hydroxy-3-methyl-phenyl) hydantoin, - (2,5-dihydroxyphenyl) -5 hydantoin, (2,4-dihydroxyphenyl) -5 hydantoin, - (4-hydroxy-3,5-dimethylphenyl) ) -5 hydantoin, - (2-hydroxy-5-methoxyphenyl) -5-hydantoin, - (2,4-trihydroxy-3,4-phenyl) hydantoin, - (3,5-dichloro-4-hydroxyphenyl) -5 hydantobne - (2-hydroxy-1-naphthyl) hydantoin, - (3,5-dichloro-2-hydroxy-phenyl) -5 hydantoin, - (2,6-dichloro-4-hydroxy-4-phenyl) hydantoin, - (dihydrochloride) 3- (4-hydroxy-2-phenyl) hydantoin, - (2,5-dichloro-4-hydroxy-4-phenyl) hydantoin, - 5-mesityl hydantoin, 4-hydroxy-4-hydroxy-2,4-dioxo-5-imidazolidinyl) - 3-benzoic acid, - (5-nitro-2-hydroxyphenyl) hydantoin, - (2,4-dioxo-5-imidazolidinyl) -2,4,5-trimethoxybenzoic acid, (dioxo-2 acid, 4 imidazolidinyl-5) -2 dim 3,5-ethoxy-4-hydroxy benzoic acid,   2,4-dioxo-5-imidazolidin-5-yl-3,4,5-trihydroxybenzoic acid.