CH433240A - Process for the preparation of alicyclic carboxamides - Google Patents
Process for the preparation of alicyclic carboxamidesInfo
- Publication number
- CH433240A CH433240A CH263263A CH263263A CH433240A CH 433240 A CH433240 A CH 433240A CH 263263 A CH263263 A CH 263263A CH 263263 A CH263263 A CH 263263A CH 433240 A CH433240 A CH 433240A
- Authority
- CH
- Switzerland
- Prior art keywords
- group
- ch2ch2
- ethylene
- nitrile group
- intermediate compound
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 8
- -1 alicyclic carboxamides Chemical class 0.000 title description 5
- 238000002360 preparation method Methods 0.000 title description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 15
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 11
- 150000001875 compounds Chemical class 0.000 claims description 8
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims description 6
- 125000002560 nitrile group Chemical group 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 230000003301 hydrolyzing effect Effects 0.000 claims description 4
- LFAGQMCIGQNPJG-UHFFFAOYSA-N silver cyanide Chemical compound [Ag+].N#[C-] LFAGQMCIGQNPJG-UHFFFAOYSA-N 0.000 claims description 4
- 229940098221 silver cyanide Drugs 0.000 claims description 4
- 239000000725 suspension Substances 0.000 claims description 4
- 229910015900 BF3 Inorganic materials 0.000 claims description 3
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 3
- 125000005392 carboxamide group Chemical class NC(=O)* 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 229910001385 heavy metal Inorganic materials 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims 4
- PJQCANLCUDUPRF-UHFFFAOYSA-N dibenzocycloheptene Chemical compound C1CC2=CC=CC=C2CC2=CC=CC=C12 PJQCANLCUDUPRF-UHFFFAOYSA-N 0.000 claims 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 235000011149 sulphuric acid Nutrition 0.000 claims 1
- 230000001131 transforming effect Effects 0.000 claims 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- APBVLLORZMAWKI-UHFFFAOYSA-N 6,11-dihydro-5h-dibenzo[1,2-a:1',2'-e][7]annulene-11-carboxamide Chemical compound C1CC2=CC=CC=C2C(C(=O)N)C2=CC=CC=C21 APBVLLORZMAWKI-UHFFFAOYSA-N 0.000 description 4
- GWYPDXLJACEENP-UHFFFAOYSA-N 1,3-cycloheptadiene Chemical compound C1CC=CC=CC1 GWYPDXLJACEENP-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- CHVJITGCYZJHLR-UHFFFAOYSA-N cyclohepta-1,3,5-triene Chemical compound C1C=CC=CC=C1 CHVJITGCYZJHLR-UHFFFAOYSA-N 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000002198 insoluble material Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- KWRDSAWYEAFHAE-UHFFFAOYSA-N 1-chloro-1h-dibenzo[1,2-a:1',2'-d][7]annulene Chemical compound C1=CC=C2C=CC=CC2=C2C(Cl)C=CC=C21 KWRDSAWYEAFHAE-UHFFFAOYSA-N 0.000 description 1
- VMJNTFXCTXAXTC-UHFFFAOYSA-N 2,2-difluoro-1,3-benzodioxole-5-carbonitrile Chemical group C1=C(C#N)C=C2OC(F)(F)OC2=C1 VMJNTFXCTXAXTC-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- AVHZJNMNRXOVLP-UHFFFAOYSA-N cyclohepta-1,4,6-triene-1-carboxamide Chemical compound NC(=O)C1=CCC=CC=C1 AVHZJNMNRXOVLP-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- GTVRLHPVICIJFQ-UHFFFAOYSA-N hexane;tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl.CCCCCC GTVRLHPVICIJFQ-UHFFFAOYSA-N 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 229960005152 pentetrazol Drugs 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C61/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C61/16—Unsaturated compounds
- C07C61/39—Unsaturated compounds containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/45—Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/08—Preparation of carboxylic acids or their salts, halides or anhydrides from nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/15—Preparation of carboxylic acids or their salts, halides or anhydrides by reaction of organic compounds with carbon dioxide, e.g. Kolbe-Schmitt synthesis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/58—Preparation of carboxylic acid halides
- C07C51/60—Preparation of carboxylic acid halides by conversion of carboxylic acids or their anhydrides or esters, lactones, salts into halides with the same carboxylic acid part
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Procédé de préparation de carboxamides alicycliques
La présente invention a pour objet un procédé de préparation de carboxamides alicycliques de formule
EMI1.1
dans laquelle Z représente le groupe éthylène-CH2CHg- ou le groupe vinylidène-CH=CH-, Rl et R2 représen- tent chacun de l'hydrogène, un halogène (de préférence du chlore) ou un groupe alcoyle inférieur (de préférence méthyle).
Ces composés sont capables, à faible dose orale ou parentérale, de protéger contre les convulsions provoquées par l'administration de pentylènetétrazole ou par l'électrochoc. Ces effets, associés à une très faible toxicité, indiquent que les composés de formule ci-dessus sont utiles comme agents anti-convulsivants.
Les composés de formule ci-dessus sont préparés par la suite de réactions ci-après : On fait réagir un 5 chloro-dibenzocycloheptène (décrit par Van der Stelt,
Harms et Nauta, J. Med. Pharm. Chem. 4,335 [1961] et par G. Berti, Gazz. Chim. Ital. 87, 293 [1957]) avec un cyanure de métal lourd, de préférence du cyanure d'argent, avantageusement dans un solvant inerte anhydre, par exemple un hydrocarbure aromatique, de préfé- rence du benzène, ou de l'acétonitrile, à chaud et de préférence à la température de reflux du mélange, pendant plusieurs heures, pour obtenir un 5-cyano-di benzoeycloheptène intermédiaire.
Ensuite, on transforme directement le groupe 5nitrile en groupe carboxamide par traitement du composé intermédiaire avec un agent hydrolysant. On peut utiliser un agent hydrolysant alcalin, tel qu'un hydroxyde de métal alcalin, par exemple l'hydroxyde de sodium ou de potassium, dans un solvant approprié, de préférence un alcanol inférieur, à la température de reflux du mélange et laisser agir l'agent hydrolysant pendant 10 à 30 heures. Les 5-carboxamides désirés sont ainsi obtenus en bon rendement par évaporation du solvant et peuvent tre purifiés par cristallisation.
On peut également faire agir du trifluorure de bore gazeux ou de l'acide sulfurique sur un mélange du composé 5-cyano correspondant et d'acide acétique aqueux, à chaud. Les 5-carboxamides peuvent en outre tre obtenus, en faible quantité, par action directe d'acide sulfurique aqueux chaud sur les composés 5-cyano correspondant.
Exemple 1
Le 5-chlorodibenzo [a, d] [1, 4] cycloheptadiène peut tre préparé par action de chlorure de thionyle sur le 5-hydroxydibenzo [a, d] [1, 4] cycloheptadiène dans du benzène comme décrit par Mychajlyszyn et Protiva dans
Coll. Czech. Chem. Commun. 24, 2955 (1959) ou, plus commodément, en saturant une solution benzénique du carbinol avec du gaz chlorhydrique, suivant le procédé de van der Stelt, Harms et Nauta, J. Med. Pharm. Chem., 4, 335 (1961).
A une suspension agitée de 56,5 g (0,42 mole) de cyanure d'argent dans 350 ml d'acétonitrile anhydre, on ajoute 70, 0 g (0,31 mole) du composé 5-chloro ci-dessus et on chauffe le mélange à reflux pendant 12 heures.
On sépare la matière insoluble du mélange chaud par filtration et on la lave avec de l'acétonitrile frais. On chasse le solvant des filtrats réunis par évaporation sous vide et on recristallise le résidu dans un mélange étherhexane ou tétrachlorure de carbone-hexane. On a ainsi obtenu 55,7g de 5-cyano-dibenzo [a, d] [1, 4] cycloheptadiène, p. f. 92-93"C.
L'analyse a confirmé la formule brute CI6Ht3N.
a) On chauffe à reflux 26,2g de 5-cyano-dibenzo [a, d] [1, 4] cycloheptadiène pendant 5 heures et demi avec 160ml d'acide sulfurique aqueux à 57 /o, en agitant rapidement. On refroidit le mélange, on le dilue à l'eau et on recueille le précipité. On agite ce dernier avec un excès d'une solution d'hydroxyde de sodium, on sépare la matière insoluble-par filtration et on la recristallise dans de l'acétonitrile, obtenant ainsi 4,0 g de dibenzo [a, d] [1, 4] cycloheptadiène-5-carboxamide, p. f. 193194 C.
L'analyse a confirmé la formule brute C16Hl5NO.
b) On fait passer un courant de trifluorure de bore sur la surface d'une suspension agitée de 11,0 g (0,05 mole) de 5-cyano-dibenzo [a, d] [1, 4] cycloheptadiène dans 60 ml d'acide acétique et 11 ml d'eau, jusqu'à saturation complète. La température interne monte spontanément à 135 C. On refroidit le mélange, on l'alcalinise par addition progressive d'une solution d'hydroxyle de sodium 6 N et on recueille le précipité, on le lave à l'eau et on le sèche. On extrait ce précipité avec de l'acétonitrile chaud, puis avec de l'acétate d'éthyle et on évapore les solutions organiques réunies.
A partir du résidu, on obtient 10, 1 g de dibenzo [a, d] [1, 4] cyclohep- tadiène-5-carboxamide.
c) On chauffe à reflux pendant 1 heure une suspension agitée de 0,9 g de 5-cyano-dibenzo [a, d] [1, 4] cyclo heptadiène dans un mélange d'un ml chacun d'acide sulfurique, d'acide acétique et d'eau. On refroidit le mélange, on le dilue avec de l'eau, on recueille le précipité, on le lave avec une solution diluée d'hydroxyde de sodium, puis avec de l'eau, et on le sèche.
Après recris tallisation, on obtient 0, 4 g de dibenzo- [a, d] [l, 4] cyclo heptadiène-5-carboxamide.
d) On chauffe à reflux, pendant 15 à 30 heures, une solution de 2,0 g de 5-cyano-dibenzo [ad] [1, 4] cyclo- heptadiène, 6,0g d'hydroxyde de potassium et 100 ml d'éthanol anhydre. La couleur du mélange, qui est verte au début, vire graduellement au jaune, ce qui indique la conversion du nitrile.
La majeure partie du solvant est évaporée sous vide, on ajoute de l'eau, et on filtre le précipité, obtenant ainsi 2,0g d'amide brut. p. f. 174 1810. Après lavage avec de l'éther suivi de recristallisation dans le méthanol, on obtient 1,5 g de dibenzo [a, d] [1, 4] cycloheptadiène-5-carboxamide, p. f. 191-193
Exemple 2
De la mme manière que décrit dans l'exemple 1, on fait réagir 27,4g (0,12 mole) de 5-chloro-dibenzo [a, e] [1, 3,5] cycloheptatriène avec 32,4 g (0,24 mole) de cyanure d'argent dans 500 ml de benzène anhydre, en chauffant à reflux pendant 7 heures.
On a ainsi obtenu 20,6 g de 5-cyano-dibenzo [ae] [1, 3,5] cycloheptatriène, p. f. 99-100o C (après recristallisation dans de l'hexane).
On chauffe à reflux, pendant 10 à 24 heures, une solution de 1, 0 g de 5-cyano-dibenzo [a, e] [1, 2,3] cyclo heptatriène, 3,0g d'hydroxyde de potasse et 100ml d'éthanol anhydre. L'éthanol est évaporé sous vide et on ajoute de l'eau. Le précipité est filtré, dissous dans du chloroforme, et la solution est lavée à l'eau, séchée et évaporée. Le résidu est recristallisé dans de l'éthanol et fournit 0,6 g de dibenzo [a, e] [l, 3,5] cycloheptatriène 5-carboxamide, p. f. 217-219 .
Une liste d'autres composés intermédiaires et produits finals est donnée dans le tableau ci-après.
EMI2.1
Process for the preparation of alicyclic carboxamides
The present invention relates to a process for the preparation of alicyclic carboxamides of formula
EMI1.1
where Z represents ethylene-CH2CHg- or vinylidene-CH = CH-, R1 and R2 each represent hydrogen, halogen (preferably chlorine) or lower alkyl group (preferably methyl) .
These compounds are capable, at low oral or parenteral doses, of protecting against convulsions caused by the administration of pentylenetetrazole or by electroshock. These effects, together with very low toxicity, indicate that the compounds of the above formula are useful as anti-convulsant agents.
The compounds of the above formula are prepared as a result of the following reactions: A chloro-dibenzocycloheptene is reacted (described by Van der Stelt,
Harms and Nauta, J. Med. Pharm. Chem. 4,335 [1961] and by G. Berti, Gazz. Chim. Ital. 87, 293 [1957]) with a heavy metal cyanide, preferably silver cyanide, advantageously in an inert anhydrous solvent, for example an aromatic hydrocarbon, preferably benzene, or acetonitrile, hot. and preferably at the reflux temperature of the mixture, for several hours, to obtain an intermediate 5-cyano-di benzoeycloheptene.
Then, the nitrile group is directly converted into a carboxamide group by treating the intermediate compound with a hydrolyzing agent. An alkaline hydrolyzing agent, such as an alkali metal hydroxide, for example sodium or potassium hydroxide, can be used in a suitable solvent, preferably a lower alkanol, at the reflux temperature of the mixture and allowed to act. hydrolyzing agent for 10 to 30 hours. The desired 5-carboxamides are thus obtained in good yield by evaporation of the solvent and can be purified by crystallization.
It is also possible to cause gaseous boron trifluoride or sulfuric acid to act on a mixture of the corresponding 5-cyano compound and aqueous acetic acid, under hot conditions. The 5-carboxamides can also be obtained, in a small amount, by direct action of hot aqueous sulfuric acid on the corresponding 5-cyano compounds.
Example 1
5-Chlorodibenzo [a, d] [1, 4] cycloheptadiene can be prepared by the action of thionyl chloride on 5-hydroxydibenzo [a, d] [1, 4] cycloheptadiene in benzene as described by Mychajlyszyn and Protiva in
Coll. Czech. Chem. Common. 24, 2955 (1959) or, more conveniently, by saturating a benzene solution of carbinol with hydrogen chloride gas, according to the method of van der Stelt, Harms and Nauta, J. Med. Pharm. Chem., 4, 335 (1961).
To a stirred suspension of 56.5 g (0.42 mole) of silver cyanide in 350 ml of anhydrous acetonitrile, 70.0 g (0.31 mole) of the above 5-chloro compound is added and the mixture is added. heat the mixture under reflux for 12 hours.
The insoluble material is separated from the hot mixture by filtration and washed with fresh acetonitrile. The solvent is removed from the combined filtrates by evaporation in vacuo and the residue is recrystallized from an etherhexane or carbon tetrachloride-hexane mixture. There was thus obtained 55.7 g of 5-cyano-dibenzo [a, d] [1, 4] cycloheptadiene, p. f. 92-93 "C.
Analysis confirmed the crude formula CI6Ht3N.
a) 26.2 g of 5-cyano-dibenzo [a, d] [1, 4] cycloheptadiene are heated at reflux for 5.5 hours with 160 ml of aqueous sulfuric acid at 57%, with rapid stirring. The mixture is cooled, diluted with water and the precipitate collected. The latter is stirred with an excess of sodium hydroxide solution, the insoluble material is filtered off and recrystallized from acetonitrile, thus obtaining 4.0 g of dibenzo [a, d] [1 , 4] cycloheptadiene-5-carboxamide, p. f. 193 194 C.
Analysis confirmed the molecular formula C16Hl5NO.
b) A flow of boron trifluoride is passed over the surface of a stirred suspension of 11.0 g (0.05 mol) of 5-cyano-dibenzo [a, d] [1, 4] cycloheptadiene in 60 ml of acetic acid and 11 ml of water, until completely saturated. The internal temperature spontaneously rises to 135 ° C. The mixture is cooled, basified by the gradual addition of a 6 N sodium hydroxyl solution and the precipitate is collected, washed with water and dried. This precipitate is extracted with hot acetonitrile, then with ethyl acetate and the combined organic solutions are evaporated.
From the residue, 10.1 g of dibenzo [a, d] [1, 4] cycloheptadiene-5-carboxamide are obtained.
c) A stirred suspension of 0.9 g of 5-cyano-dibenzo [a, d] [1, 4] cyclo heptadiene in a mixture of one ml each of sulfuric acid, d 'is refluxed for 1 hour. acetic acid and water. The mixture is cooled, diluted with water, the precipitate is collected, washed with dilute sodium hydroxide solution, then with water, and dried.
After recrystallization, 0.4 g of dibenzo- [a, d] [1,4] cycloheptadiene-5-carboxamide is obtained.
d) A solution of 2.0 g of 5-cyano-dibenzo [ad] [1, 4] cycloheptadiene, 6.0 g of potassium hydroxide and 100 ml of d) is refluxed for 15 to 30 hours. anhydrous ethanol. The color of the mixture, which is green at first, gradually turns yellow, indicating the conversion of nitrile.
Most of the solvent is evaporated in vacuo, water is added, and the precipitate is filtered, thus obtaining 2.0 g of crude amide. p. f. 174 1810. After washing with ether followed by recrystallization from methanol, 1.5 g of dibenzo [a, d] [1, 4] cycloheptadiene-5-carboxamide are obtained, p. f. 191-193
Example 2
In the same manner as described in Example 1, 27.4 g (0.12 mol) of 5-chloro-dibenzo [a, e] [1, 3.5] cycloheptatriene are reacted with 32.4 g (0 , 24 moles) of silver cyanide in 500 ml of anhydrous benzene, heating under reflux for 7 hours.
There was thus obtained 20.6 g of 5-cyano-dibenzo [ae] [1, 3,5] cycloheptatriene, p. f. 99-100o C (after recrystallization from hexane).
A solution of 1.0 g of 5-cyano-dibenzo [a, e] [1, 2,3] cyclo heptatriene, 3.0 g of potassium hydroxide and 100 ml of d is refluxed for 10 to 24 hours. anhydrous ethanol. The ethanol is evaporated off in vacuo and water is added. The precipitate is filtered off, dissolved in chloroform, and the solution is washed with water, dried and evaporated. The residue is recrystallized from ethanol and gives 0.6 g of dibenzo [a, e] [1,3,5] cycloheptatriene 5-carboxamide, p. f. 217-219.
A list of other intermediates and end products is given in the table below.
EMI2.1
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US176783A US3242212A (en) | 1962-03-01 | 1962-03-01 | 5-carboxamidodibenzo [a, d] [1, 4] cycloheptadiene |
| US23227362A | 1962-10-22 | 1962-10-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH433240A true CH433240A (en) | 1967-04-15 |
Family
ID=26872590
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH263263A CH433240A (en) | 1962-03-01 | 1963-03-01 | Process for the preparation of alicyclic carboxamides |
| CH132167A CH459995A (en) | 1962-03-01 | 1963-03-01 | Process for the preparation of alicyclic carboxamides |
| CH132067A CH459994A (en) | 1962-03-01 | 1963-03-01 | Process for the preparation of alicyclic carboxamides |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH132167A CH459995A (en) | 1962-03-01 | 1963-03-01 | Process for the preparation of alicyclic carboxamides |
| CH132067A CH459994A (en) | 1962-03-01 | 1963-03-01 | Process for the preparation of alicyclic carboxamides |
Country Status (4)
| Country | Link |
|---|---|
| CH (3) | CH433240A (en) |
| DE (1) | DE1443367C3 (en) |
| FR (1) | FR2706M (en) |
| GB (1) | GB1010572A (en) |
-
1963
- 1963-03-01 CH CH263263A patent/CH433240A/en unknown
- 1963-03-01 CH CH132167A patent/CH459995A/en unknown
- 1963-03-01 DE DE1443367A patent/DE1443367C3/en not_active Expired
- 1963-03-01 CH CH132067A patent/CH459994A/en unknown
- 1963-03-01 GB GB8401/63A patent/GB1010572A/en not_active Expired
- 1963-05-20 FR FR935425A patent/FR2706M/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| DE1443367C3 (en) | 1975-01-09 |
| CH459995A (en) | 1968-07-31 |
| DE1443367A1 (en) | 1968-10-31 |
| GB1010572A (en) | 1965-11-17 |
| DE1443367B2 (en) | 1974-05-30 |
| FR2706M (en) | 1964-08-03 |
| CH459994A (en) | 1968-07-31 |
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