CH395959A - Process for preparing 2-hydroxy-3-methyl-benzene-1-carbonamide - Google Patents

Process for preparing 2-hydroxy-3-methyl-benzene-1-carbonamide

Info

Publication number
CH395959A
CH395959A CH446761A CH446761A CH395959A CH 395959 A CH395959 A CH 395959A CH 446761 A CH446761 A CH 446761A CH 446761 A CH446761 A CH 446761A CH 395959 A CH395959 A CH 395959A
Authority
CH
Switzerland
Prior art keywords
methyl
hydroxy
benzene
carbonamide
preparing
Prior art date
Application number
CH446761A
Other languages
French (fr)
Inventor
Yves Mauvernay Roland
Original Assignee
Therapie Energetique Lab De
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Therapie Energetique Lab De filed Critical Therapie Energetique Lab De
Publication of CH395959A publication Critical patent/CH395959A/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • A61K31/566—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol having an oxo group in position 17, e.g. estrone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
    • A61K31/569—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone substituted in position 17 alpha, e.g. ethisterone
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides

Description

  

  Procédé de préparation de la     2-hydroxy-3-méthyl-benzène-1-carbonamide       La présente     invention    a pour objet un procédé  de préparation d'une nouvelle     carbonamide,    la 2  hydroxy-3-méthyl-benzène-1-carbonamide, de for  mule         NH2     OH       j_CHs       Ce     procédé        consiste    à hydrolyser le     2rhydroxy-          3-méthyl-benzoate    de méthyle par     l'ammoniac.     



  Le     2-hydroxy-3-méthyl-benzoate    de     méthyle    peut  avantageusement être préparé par simple     réaction          d'estérification        entre    l'acide     2-hydroxy-3-méthyl-          benzoique    et l'alcool     méthylique.     



  On obtient     ainsi    un     produit    fondant à 109  110,9 C. Il     cristallise    sous forme     d'aiguilles    blanches.  Il est     pratiquement        insoluble    dans l'eau, peu soluble       dans    l'éther de     pétrole,    soluble dans l'alcool, l'acé  tone et le benzène. Il donne une     coloration    bleue  intense avec le     perchlorure    de fer.  



  <I>Exemple</I>  Pour     obtenir    le produit de départ, on a     chauffé     30 h à reflux 50 g     d'alcool    méthylique, 50 g d'acide       2-hydroxy-3-méthyl-benzoïque    et 15 g     d'acide        sulfu-          rique        concentré.    Le mélange     réactionnel    a ensuite  été versé     dans    250     ml    d'eau, l'ester a été séparé     par          décantation    et lavé par une     solution        saturée    de bicar  bonate,

   puis à l'eau.  



  On a     procédé        ensuite    à une     distillation    sous vide:       (Ebo    =     113o-1150    C     sous    15     mm/Hg).    Le rendement  a     été        de        85        %.     



  30 g du précédent produit ont été     mis    en solu  tion dans 70 ml de méthanol. Le mélange a été saturé    en ammoniac à 00 C, puis     chauffé    en autoclave à       60         pendant    3 heures. On a chassé l'excès     d'ammo-          niac    et l'alcool     méthylique    sous vide.     On    a obtenu  la     2-hydroxy-3-méthyl-benzène-1-carbonamide    brute,  quia été lavée à l'eau et     recristallisée    dans le     benzène.     



  Le produit obtenu     conformément    à     l'invention          constitue    un agent     andinflammatoire    et     antipyrétique     très actif,     ainsi    que l'ont montré     les    études     cliniques     qui ont largement prouvé     l'action        antinflamrnatoire     du produit chez des     malades        atteints    de     rhumatisme     aigu d'une part,

   et de rhumatisme     inflammatoire    chro  nique d'autre part (polyarthrite chronique     évolutive          spondylarthrite        ankylosante).    Lesdites     études    ont éga  lement fait     apparaître        une        action        antipyrétique,    dans  des amygdalites, rhino-pharyngites et     grippes        saison-          nières.     



       Enfin,    le produit a     également    été     utilisé    comme       antalgique    dans les     céphalées        art    les     migraines,    les       algies    diverses et plus particulièrement     dans    les dou  leurs     accompagnant        les        rhumatismes        dégénératifs,          ainsi    que dans les lumbagos et     les        sciatiques.  



  Process for preparing 2-hydroxy-3-methyl-benzene-1-carbonamide The present invention relates to a process for preparing a novel carbonamide, 2-hydroxy-3-methyl-benzene-1-carbonamide, of for mule NH2 OH j_CHs This process consists in hydrolyzing methyl 2rhydroxy-3-methyl-benzoate with ammonia.



  Methyl 2-hydroxy-3-methyl-benzoate can advantageously be prepared by a simple esterification reaction between 2-hydroxy-3-methyl-benzoic acid and methyl alcohol.



  A product is thus obtained which melts at 109 110.9 C. It crystallizes in the form of white needles. It is practically insoluble in water, sparingly soluble in petroleum ether, soluble in alcohol, acetone and benzene. It gives an intense blue coloring with iron perchloride.



  <I> Example </I> To obtain the starting product, 50 g of methyl alcohol, 50 g of 2-hydroxy-3-methyl-benzoic acid and 15 g of sulphurous acid were heated for 30 h at reflux. - concentrated risk. The reaction mixture was then poured into 250 ml of water, the ester was separated by decantation and washed with a saturated solution of bicar bonate,

   then to water.



  A vacuum distillation was then carried out: (Ebo = 113o-1150 C under 15 mm / Hg). The yield was 85%.



  30 g of the preceding product were dissolved in 70 ml of methanol. The mixture was saturated with ammonia at 00 ° C., then heated in an autoclave at 60 for 3 hours. The excess ammonia and methyl alcohol were removed in vacuo. Crude 2-hydroxy-3-methyl-benzene-1-carbonamide was obtained, which was washed with water and recrystallized from benzene.



  The product obtained in accordance with the invention constitutes a very active andinflammatory and antipyretic agent, as shown by clinical studies which have largely proven the anti-inflammatory action of the product in patients suffering from acute rheumatism on the one hand,

   and chronic inflammatory rheumatism on the other hand (progressive chronic polyarthritis ankylosing spondylitis). Said studies have also shown an antipyretic action in tonsillitis, nasopharyngitis and seasonal influenza.



       Finally, the product has also been used as an analgesic in headaches, migraines, various types of pain and more particularly in pain accompanying degenerative rheumatism, as well as in lumbago and sciatica.

Claims (1)

REVENDICATION Procédé de préparation de la 2-hydroxy-3-méthyl- benzène-1-carbonamide, caractérisé en ce que l'on hydrolyse par l'ammoniac le 2-hydroxy-3-méthyl- benzoate de méthyle. SOUS-REVENDICATION Procédé selon la revendication, caractérisé en ce que l'on sature d'ammoniac, à basse température, CLAIM Process for preparing 2-hydroxy-3-methyl-benzene-1-carbonamide, characterized in that methyl 2-hydroxy-3-methyl-benzoate is hydrolyzed with ammonia. SUB-CLAIM Process according to claim, characterized in that ammonia is saturated at low temperature, une solution alcoolique de 2-hydroxy-3-méthyl-benzoate de méthyle après quoi la solution ainsi saturée est chauffée à l'autoclave. an alcoholic solution of methyl 2-hydroxy-3-methyl-benzoate after which the solution thus saturated is heated in an autoclave.
CH446761A 1960-07-05 1961-04-14 Process for preparing 2-hydroxy-3-methyl-benzene-1-carbonamide CH395959A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
FR832013A FR19M (en) 1960-07-05 1960-07-05 New anti-inflammatory and antipyretic product.

Publications (1)

Publication Number Publication Date
CH395959A true CH395959A (en) 1965-07-31

Family

ID=8734839

Family Applications (1)

Application Number Title Priority Date Filing Date
CH446761A CH395959A (en) 1960-07-05 1961-04-14 Process for preparing 2-hydroxy-3-methyl-benzene-1-carbonamide

Country Status (2)

Country Link
CH (1) CH395959A (en)
FR (1) FR19M (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4140769A (en) 1976-12-23 1979-02-20 Miles Laboratories, Inc. 3-Substituted salicylamides

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4140769A (en) 1976-12-23 1979-02-20 Miles Laboratories, Inc. 3-Substituted salicylamides

Also Published As

Publication number Publication date
FR19M (en) 1960-11-28

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