US3917692A - Arylsulfonylcarbamoyl-1,3-dicarbonylalicyclic - Google Patents

Arylsulfonylcarbamoyl-1,3-dicarbonylalicyclic Download PDF

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US3917692A
US3917692A US478497A US47849774A US3917692A US 3917692 A US3917692 A US 3917692A US 478497 A US478497 A US 478497A US 47849774 A US47849774 A US 47849774A US 3917692 A US3917692 A US 3917692A
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cyclohexanedione
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compound
compounds
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US478497A
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Frederick A Grunwald
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Mead Johnson and Co LLC
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Mead Johnson and Co LLC
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Priority to AU81291/75A priority patent/AU8129175A/en
Priority to CA227,783A priority patent/CA1051924A/en
Priority to GB2445575A priority patent/GB1454737A/en
Priority to BE157097A priority patent/BE829953A/en
Priority to NL7506830A priority patent/NL7506830A/en
Priority to ZA00753689A priority patent/ZA753689B/en
Priority to LU72697A priority patent/LU72697A1/xx
Priority to DK261775A priority patent/DK261775A/en
Priority to FR7518300A priority patent/FR2274288A1/en
Priority to JP50069778A priority patent/JPS5829785B2/en
Priority to SE7506707A priority patent/SE7506707L/en
Priority to CH756575A priority patent/CH596158A5/xx
Priority to IE1312/75A priority patent/IE41477B1/en
Priority to DE19752526195 priority patent/DE2526195A1/en
Priority to YU1515/75A priority patent/YU40265B/en
Priority to US05/604,971 priority patent/US3998879A/en
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    • 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
    • A61K31/18—Sulfonamides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/50—Compounds containing any of the groups, X being a hetero atom, Y being any atom
    • C07C311/52—Y being a hetero atom
    • C07C311/53—X and Y not being nitrogen atoms, e.g. N-sulfonylcarbamic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/50—Compounds containing any of the groups, X being a hetero atom, Y being any atom
    • C07C311/51—Y being a hydrogen or a carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

Definitions

  • ABSTRACT A new class of arylsulfonylcarbamoyl-l,3- cyclohexanediones and arylsulfonylcarbamoyl-l,3- dicarbonylacyclic compounds are disclosed. These substances have hypoglycemic or hyperglycemic properties and are of value in controlling abnormal blood sugar levels.
  • the arylsulfonylcarbamoyl derivatives of 1,3-dicarbonylalicyclic and acyclic compounds are prepared by reacting an arylsulfonylisocyanate with a 1,3-dicarbonylalicyclic or acyclic reactant.
  • Typical embodiments are Z-(N-pchlorobenzenesulfonylc arbamoyl )-5 ,5 -dimethylcyclohexanel ,3-dione and 5-( l-ethylpropyl 2-( N-pchlorobenzenesulfonylcarbamoyl )-l ,3- cyclohexanedione.
  • This invention pertains to carbon compounds having drug and bio-affecting properties.
  • this invention relates to arylsulfonylcarbamoyl-l.3-dicarbonyl compounds effective in controlling blood sugar levels.
  • arylsulfonylcarbamoyl-l.3-dicarbonyl compounds effective in controlling blood sugar levels.
  • Both chronic hypoglycemic and hyperglycemic states are known but the most prevalent condition found with regard to abnormal levels of blood sugar is that caused by diabetes which produces increased blood glucose levels.
  • Various agents have been developed to lower blood sugar level for treatment of diabetes and among presently available antidiabetic agents there can be mentioned. by way of example.
  • This invention relates generally to sulfonylcarbamoyl derivatives of l.3-dicarbonylcompounds having blood sugar regulating properties. More particularly the invention pertains to arylsulfonylcarbamoyl-1.3- cyclohexanediones characterized by Formula I. arylsulfonylcarbamoyl-l.3-dicarbonylacyclic compounds of Formula II and pharmaceutically acceptable basic salts thereof.
  • R signifies a lower alkyl radical from 1 to carbon atoms inclusive or phenyl
  • R signifies hydrogen or a straight chain alkyl radical from 1 to 3 carbon atoms inclusive
  • R and R taken together form (CH R in Formulas I and II signifies hydrogen, halogen including chlorine, bromine. fluorine and iodine or lower alkyl from 1 to 4 carbon atoms inclusive.
  • R represents methyl, phenyl or benzyl.
  • lower alkyl comprehends both straight or branched chain hydrocarbon radicals such as methyl, ethyl. propyl. isopropyl. l-butyl. l-methylpropyl, 2- methylpropyl. tert.-butyl for those radicals containing 1 to 4 carbon atoms inclusive.
  • Lower alkyl radicals con- 2 taining 5 carbon atoms include pentyl and branched chain isomers thereof such as 3-methylbutyl. l-methylbutyl. l-ethylpropyl. 2.2-dimethylpropyl. and 1.1- dimethylpropyl.
  • pharmaceutically acceptable basic salts as used herein. reference is made to salts of the Formula I or II compounds with alkaline agents. Said pharmaceutically acceptable basic salts of the above compounds are provided by admixture of Formula I or II compounds with substantially one chemical equivalent of an alkaline agent, such as for example. alkali metal alkoxides. alkali metal hydroxides. alkaline earth metal hydroxides, alkali metal carbonates. alkaline earth metal carbonates, alkali metal bicarbonates and alkaline earth metal bicarbonates.
  • an alkaline agent such as for example. alkali metal alkoxides. alkali metal hydroxides. alkaline earth metal hydroxides, alkali metal carbonates. alkaline earth metal carbonates, alkali metal bicarbonates and alkaline earth metal bicarbonates.
  • a preferred method of a salt formation is to treat a compound of Formula I or II with substantially one chemical equivalent of sodium methoxide in methanol solution.
  • the desired sodium salt precipitates from methanolic solution upon the addition of anhydrous ether or the solvent is removed by distillation.
  • the arylsulfonylcarbamoyl-l.3-dicarbonyl compounds of the present invention characterized by For mulas l and II are prepared by a process which comprises reacting an alicyclic-l,3-dione or acyclic-1.3- dione selected from the group consisting of R O O 1 R l (H t H
  • reaction inert solvent refers to a solvent which functions as a diluent for the reaction and does not interact with the alicyclic or acyclic diketone or sulfonylisocyanate reactant.
  • Benzene is a preferred solvent for carrying out the process but other solvents such as toluene.
  • xylene, hexane, dioxane, tetrahydrofuran, 1,1-dichlorethane and the like are also satisfactory.
  • Cyclohexanedione intermediates of Formula III are known or they can be prepared by means of a Michael Condensation involving diethylmaloanate and the appropriate afi-unsaturated ketone according to the pro- 3 cedure of R. L. Frank and H. K. Hall. J. Am. Chem. Soc.. 72. 1645 (1950).
  • the process of the present invention for regulating blood sugar concentration in a mammal comprises administering to a mammal requiring blood sugar concentration regulation an effective amount of a compound characterized by Formula I or 11 ranging from 3 to 200 mg./kg. body weight of said mammal to exert a blood sugar regulating effect.
  • the compounds of the present invention are effective as hypoglycemic or hyperglycemic agents.
  • Oral administration of the compounds of the present invention is a particularly preferred form of administration but parenteral routes such as intramuscular. intravenous. intraperitoneal and subcutaneous administration may also be employed.
  • parenteral routes such as intramuscular. intravenous. intraperitoneal and subcutaneous administration may also be employed.
  • the compounds of the invention can be incorporated into pharmaceutical preparations such as tablets and capsules which contain the usual adjuvants and carriers such as talc. starch. lactose. magnesium stearate. and the like.
  • the compounds above provide a decrease in blood sugar for a period of more than eight hours after the animals were treated.
  • Compounds particularly preferred for long lasting hypoglycemic action are 5-isopropy1-(N-ptoluenesulfonylcarbamoyl)-1.3-cyclohexanedione and 2-( N-p-chlorobenzenesulfonylcarbamoyl )-5 .5-dimethylcyclohexane-1.3-dione whereafter 8 hours decreased blood sugar level values of 34 and 36 percent respectively were obtained.
  • Tolubutamide. by comparison. gave a 50 percent depression of the blood sugar level of rats one hour after dosing but 5 hours after dosing the blood sugar level had recovered to less than 20 percent below normal.
  • 5-( 1 -Ethy1propy1)-2-(N-pch1orobenzenesulfonylcarbamoyl)-1.3-cyclohexanedione is particularly preferred for its hyperglycemic activity.
  • Oral administration of 5-( l-ethylpropyl)-2-(N-p-chlorobenzenesulfonylcarbamoyl)-1.3-cyclohexanedione to rats at a 4 dose of mg./kg. provides a marked hyperglycemic effect with a 25 percent elevation of blood sugar at 6 hours increasing to 44 percent in 8 hours.
  • EXAMPLE 1 A mixture of 5,5-dimethyl-1,3-cyclohexanedione (7.0 g.. 0.05 mole) and p-toluenesulfonylisocyanate (9.86 g.. 0.05 mole) in ml. of benzene is stirred at 4060C. for a period of 6 hr. The mixture is then heated on a steam bath for 2 hr. and concentrated under reduced pressure providing a semi-solid residue which is taken up in a mixture of 45 ml. of acetone and 5 ml. of methanol. Addition of 10 ml. of water to the acetone-methanol solution provides a quantitative yield of product. m.p. 94108C.
  • EXAMPLE 7 Reaction of equimolar amounts of 5-isopropyl-l.3 cyclohexanedione with p-chlorobenzenesulfonylisocyanate in benzene according to the procedure of Example 1 affords Z-(N-p-CHLOROBEN- ZENESULFONYLCARBAMOYL)-5-1SOPROPYL- 1.3-CYCLOHEXANED1ONE. m.p. 100.5-101.5C. (resolidified and melting at 183.5C. with dec. )(corr.
  • EXAMPLE 10 Reaction of equimolar amounts of 5-( 1-ethylpropyl)- 1.3-cyclohexanedione with p-toluenesulfonylisocyanate in benzene according to the procedure of Example 1 affords 5-( l-ETHYLPROPYLLZ-(N-p- TOLUENESULFONYLCARBAMOYL)-1.3- CYCLOHEXANEDIONE. m.p. 11 1.5-112.5C. corr.
  • EXAMPLE 1 1 Reaction of equimolar amounts of 5-( l-ethylpropyl 1.3-eyclohexanedione with p-chlorobenzenesul fonylisocyanate in benzene according to the procedure of Example 1 affords 5-( l-ETHYLPROPYL)-2-(N-p- CHLOROBENZENESULFONYLCARBAMOYL l.3-CYCLOHEXANEDIONE. m.p. 12l-122C. (corr.).
  • EXAMPLE 12 Reaction of equiimolar equimolar of l-phenyl-l.3- butanedione with p-toluenesulfonylisocyanate in benzene according to the procedure of Example 1 affords l-PHENYL-2-(N-p-TOLUENESULFONYLCAR- BAMOYL)-1.3-BUTANED1ONE. m.p. l13.5l16.5 C. (corr.).
  • EXAMPLE 14 Reaction of equimolar amounts of 5-propyl-l .3- cyclohexanedione with p-toluenesulfonylisocyanate in benzene according to the procedure of Example 1 affords 5-PROPYL -2-( N-p-TOLUENESULFONY L CARBAMOYL)-1.3-CYCLOHEXANED1ONE. m.p. l32.5133.5C. (corr.).
  • EXAMPLE 15 Reaction of equimolar amounts of 5-isopropyl-l.3- cyclohexanedionc with benzenesulfonylisocyanate in benzene according to the procedure of Example 1 affords 5-ISOPROPYL-2-( N-benzenesulfonylcarbamoyl)-1.3-CYCLOHEXANEDIONE. m.p. ll2.5l 14C. (corr.).
  • EXAMPLE 16 Reaction of equimolar amounts of 5-sec.-butyl-l .3- cyclohexanedione with p-toluenesulfonylisocyanate in benzene according to the procedure of Example 1 affords 5-sec.-BUTYL-2-(N-p-TOLUENESULFONYL- CARBAMOYLH.3-CYCLOHEXANED1ONE. m.p. 9293C. (corr.).
  • R is hydrogen or alkyl from 1 to 3 carbon atoms inclusive
  • CH R is hydrogen. halogen or lower alkyl of 1 to 4 carbon atoms inclusive; and basic salts thereof.

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Abstract

A new class of arylsulfonylcarbamoyl-1,3-cyclohexanediones and arylsulfonylcarbamoyl-1,3-dicarbonylacyclic compounds are disclosed. These substances have hypoglycemic or hyperglycemic properties and are of value in controlling abnormal blood sugar levels. The arylsulfonylcarbamoyl derivatives of 1,3dicarbonylalicyclic and acyclic compounds are prepared by reacting an arylsulfonylisocyanate with a 1,3-dicarbonylalicyclic or acyclic reactant. Typical embodiments are 2-(N-pchlorobenzenesulfonylcarbamoyl)-5,5-dimethylcyclohexane-1,3-dione and 5-(1-ethylpropyl)-2-(N-p-chlorobenzenesulfonylcarbamoyl) -1,3cyclohexanedione.

Description

United States Patent [191 Grunwald ARYLSULFONYLC ARBAMOYL- 1 ,3-
DICARBONYLALICYCLIC [75] Inventor: Frederick A. Grunwald, Evansville,
Ind.
[22] Filed: June 12, 1974 [21] Appl. No.: 478,497
[52] US. Cl 260/556 AR; 260/556 AC;
260/556 A; 424/321 [51] Int. Cl. C07C 143/78; A61K 31/18 [58] Field of Search 260/556 AR, 556 AC [56] References Cited UNITED STATES PATENTS 3,298,917 1/1967 Bicking 260/556 AC X 3,578,658 5/1971 Dietrich 260/556 AR FOREIGN PATENTS OR APPLICATIONS 620,778 3/1949 7 United Kingdom 260/556 AC 1,012,623 2/1962 United Kingdom 260/556 AR Primary ExaminerAllen E. Curtis Attorney, Agent, or Firm-R. H. Uloth; R. E.
Camahan [57] ABSTRACT A new class of arylsulfonylcarbamoyl-l,3- cyclohexanediones and arylsulfonylcarbamoyl-l,3- dicarbonylacyclic compounds are disclosed. These substances have hypoglycemic or hyperglycemic properties and are of value in controlling abnormal blood sugar levels. The arylsulfonylcarbamoyl derivatives of 1,3-dicarbonylalicyclic and acyclic compounds are prepared by reacting an arylsulfonylisocyanate with a 1,3-dicarbonylalicyclic or acyclic reactant. Typical embodiments are Z-(N-pchlorobenzenesulfonylc arbamoyl )-5 ,5 -dimethylcyclohexanel ,3-dione and 5-( l-ethylpropyl 2-( N-pchlorobenzenesulfonylcarbamoyl )-l ,3- cyclohexanedione.
12 Claims, No Drawings ARYLSULFONYLCARBAMOYL-1,3-DICAR- BONYLALICYCLIC BACKGROUND OF THE INVENTION This invention pertains to carbon compounds having drug and bio-affecting properties. In particular. this invention relates to arylsulfonylcarbamoyl-l.3-dicarbonyl compounds effective in controlling blood sugar levels. Both chronic hypoglycemic and hyperglycemic states are known but the most prevalent condition found with regard to abnormal levels of blood sugar is that caused by diabetes which produces increased blood glucose levels. Various agents have been developed to lower blood sugar level for treatment of diabetes and among presently available antidiabetic agents there can be mentioned. by way of example. those of the sulfonylurea type such as tolubutamide. S. I-lunig, et al. Chem. Ber. 95. 926 1962) reported preparation of 2-(N-p-toluenesulfonylcarbamoyl)-cyclohexanone, a compound formally related to the compounds of the present invention. but discloses no biological properties therefor.
SUMMARY OF THE INVENTION This invention relates generally to sulfonylcarbamoyl derivatives of l.3-dicarbonylcompounds having blood sugar regulating properties. More particularly the invention pertains to arylsulfonylcarbamoyl-1.3- cyclohexanediones characterized by Formula I. arylsulfonylcarbamoyl-l.3-dicarbonylacyclic compounds of Formula II and pharmaceutically acceptable basic salts thereof.
CNHSO R Formula I ll R;C fi
CNHSO R CH,,C II
Formula II In Formula I above, R signifies a lower alkyl radical from 1 to carbon atoms inclusive or phenyl; R signifies hydrogen or a straight chain alkyl radical from 1 to 3 carbon atoms inclusive; and R and R taken together form (CH R in Formulas I and II signifies hydrogen, halogen including chlorine, bromine. fluorine and iodine or lower alkyl from 1 to 4 carbon atoms inclusive. In Formula II, R represents methyl, phenyl or benzyl.
It is to be understood that as used in this disclosure. the term lower alkyl" comprehends both straight or branched chain hydrocarbon radicals such as methyl, ethyl. propyl. isopropyl. l-butyl. l-methylpropyl, 2- methylpropyl. tert.-butyl for those radicals containing 1 to 4 carbon atoms inclusive. Lower alkyl radicals con- 2 taining 5 carbon atoms include pentyl and branched chain isomers thereof such as 3-methylbutyl. l-methylbutyl. l-ethylpropyl. 2.2-dimethylpropyl. and 1.1- dimethylpropyl.
By the term pharmaceutically acceptable basic salts" as used herein. reference is made to salts of the Formula I or II compounds with alkaline agents. Said pharmaceutically acceptable basic salts of the above compounds are provided by admixture of Formula I or II compounds with substantially one chemical equivalent of an alkaline agent, such as for example. alkali metal alkoxides. alkali metal hydroxides. alkaline earth metal hydroxides, alkali metal carbonates. alkaline earth metal carbonates, alkali metal bicarbonates and alkaline earth metal bicarbonates.
A preferred method of a salt formation is to treat a compound of Formula I or II with substantially one chemical equivalent of sodium methoxide in methanol solution. The desired sodium salt precipitates from methanolic solution upon the addition of anhydrous ether or the solvent is removed by distillation.
The arylsulfonylcarbamoyl-l.3-dicarbonyl compounds of the present invention characterized by For mulas l and II are prepared by a process which comprises reacting an alicyclic-l,3-dione or acyclic-1.3- dione selected from the group consisting of R O O 1 R l (H t H |ci 2 0 o an) (IV) with a sulfonylisocyanate of Formula V wherein R R R and R are as stated above in a suit able reaction inert solvent. The term reaction inert solvent as used herein refers to a solvent which functions as a diluent for the reaction and does not interact with the alicyclic or acyclic diketone or sulfonylisocyanate reactant. Benzene is a preferred solvent for carrying out the process but other solvents such as toluene. xylene, hexane, dioxane, tetrahydrofuran, 1,1-dichlorethane and the like are also satisfactory.
In carrying out the process of this invention for the preparation of compounds of the present invention. approximately equimolar quantities of the reactants are dissolved or suspended in the reaction inert solvent and the mixture maintained at a temperature of 0l50C. for a period of time ranging from 1 to 24 hours. The time period required for complete reaction is generally inversely proportional to the temperature at which the reaction is conducted, i.e.. the higher the temperature, the shorter the reaction period.
Cyclohexanedione intermediates of Formula III are known or they can be prepared by means of a Michael Condensation involving diethylmaloanate and the appropriate afi-unsaturated ketone according to the pro- 3 cedure of R. L. Frank and H. K. Hall. J. Am. Chem. Soc.. 72. 1645 (1950).
The process of the present invention for regulating blood sugar concentration in a mammal comprises administering to a mammal requiring blood sugar concentration regulation an effective amount of a compound characterized by Formula I or 11 ranging from 3 to 200 mg./kg. body weight of said mammal to exert a blood sugar regulating effect. In the instant process. the compounds of the present invention are effective as hypoglycemic or hyperglycemic agents.
Oral administration of the compounds of the present invention is a particularly preferred form of administration but parenteral routes such as intramuscular. intravenous. intraperitoneal and subcutaneous administration may also be employed. The compounds of the invention can be incorporated into pharmaceutical preparations such as tablets and capsules which contain the usual adjuvants and carriers such as talc. starch. lactose. magnesium stearate. and the like.
Conventional biological tests are employed to demonstrate blood sugar regulating properties of the compounds of the present invention characterized by For mulas 1 and 11. For instance. the compounds of the invention administered orally to laboratory mammals such as guinea pig. rat. rabbit. and mouse provide a decrease or an increase in blood glucose concentration as determined by standard glucose assay described by W. S. Hoffman. J. Biol. Chem.. 120. 51 (1937).
Significant hypoglycemic or hyperglycemic effects are obtained after an induction period of 1 to 2 hours when the compounds of the present invention are ad ministered at a dose of 100 mg/kg. body weight. These effects are generally welLmaintained for more than 8 hours post-drug administration.
Compounds of the present invention preferred for their hypoglycemic activity are:
5.5-Dimethyl-2-(N-p-toluenesulfonylcarbamoyl)-1.3-
cyclohexanedione.
-Ethyl-2-(N-p-toluenesulfonylcarbamoyl)-1.3-
cyclohexanedione.
5-lsopropyl-2-(N-p-toluenesulfonylcarbamoyl)-1.3-
cyclohexanedione.
5-tert.-Butyl-2-(N-p-toluenesulfonylcarbamoyl)-1 .3-
cyclohexanedione.
2-( N-p-Chlorobenzenesulfonylcarbamoyl )-5 .S-dirnethylcyclohexane-l .3-dione.
At a dose of 100 mg./kg. body weight, the compounds above provide a decrease in blood sugar for a period of more than eight hours after the animals were treated. Compounds particularly preferred for long lasting hypoglycemic action are 5-isopropy1-(N-ptoluenesulfonylcarbamoyl)-1.3-cyclohexanedione and 2-( N-p-chlorobenzenesulfonylcarbamoyl )-5 .5-dimethylcyclohexane-1.3-dione whereafter 8 hours decreased blood sugar level values of 34 and 36 percent respectively were obtained. Tolubutamide. by comparison. gave a 50 percent depression of the blood sugar level of rats one hour after dosing but 5 hours after dosing the blood sugar level had recovered to less than 20 percent below normal.
5-( 1 -Ethy1propy1)-2-(N-pch1orobenzenesulfonylcarbamoyl)-1.3-cyclohexanedione is particularly preferred for its hyperglycemic activity. Oral administration of 5-( l-ethylpropyl)-2-(N-p-chlorobenzenesulfonylcarbamoyl)-1.3-cyclohexanedione to rats at a 4 dose of mg./kg. provides a marked hyperglycemic effect with a 25 percent elevation of blood sugar at 6 hours increasing to 44 percent in 8 hours.
The following examples are given by way of illustration and are not to be construed as limitations of this invention. variations of which are possible without departing from the scope and spirit thereof.
EXAMPLE 1 A mixture of 5,5-dimethyl-1,3-cyclohexanedione (7.0 g.. 0.05 mole) and p-toluenesulfonylisocyanate (9.86 g.. 0.05 mole) in ml. of benzene is stirred at 4060C. for a period of 6 hr. The mixture is then heated on a steam bath for 2 hr. and concentrated under reduced pressure providing a semi-solid residue which is taken up in a mixture of 45 ml. of acetone and 5 ml. of methanol. Addition of 10 ml. of water to the acetone-methanol solution provides a quantitative yield of product. m.p. 94108C. Crystallization of the crude product from acetone-water affords 9.6 g. (56% yield) of 5.5-D1METHYL-2-(N-p-TOLUENESUL- FONYLCARBAMOYL)-1.3-CYCLOHEXANED- IONE. m.p. 127.5-129.5C.
Analysis. Calcd. for C H NO S (percent): C. 56.96; H. 5.68; S. 9.50. Found (percent): C. 57.23; H, 5.94; S. 9.61.
EXAMPLE 2 Reaction of equimolar amounts of 5-methyl-1,3- cyclohexanedione with p-toluenesulfonylisocyanate in benzene according to the procedure of Example 1 affords 5-MET1-1YL2-(N-p-TOLUENESULFONYL- CARBAMOYL 1 .3-CYCLOHEXANEDIONE. m.p.
121.5-122.5C. (corr.).
Analysis. Calcd. for C -,H NO S (percent): C. 55.71; H. 5.30; N. 4.33; S. 9.92. Found (percent): C. 55.80: H. 5.38; N. 4.52; S. 10.14.
EXAMPLE 3 Reaction of S-ethyl-1.3-cyclohexanedione with ptoluenesulfonylisocyanate in benzene according to the procedure of Example 1 affords S-ETHYL-Z-(N-p- TOLUENESULFONYLCARBAMOYL)-1.3- CYCLOHEXANEDIONE. m.p. 8687C. (corr.).
Analysis. Calcd. for C H NO S (percent): C. 56.96; H. 5.68; N. 4.15; S. 9.50. Found (percent): C, 57.11; H. 5.74; N. 4.09; S. 9.79.
EXAMPLE 4 Reaction of S-isopropyl-1.3-cyclohexanedione with p-toluenesulfonylisocyanate in benzene according to the procedure of Example 1 affords 5-ISOPROPYL-2- (N-p-TOLUENESULFONYLCARBAMOYL)-1.3- CYCLOHEXANEDIONE. m.p. 106.5-107.5C. (corr.).
Analysis. Calcd. for C H NQ S (percent): C. 58.10; H. 6.01; N. 3.99. Found (percent): C. 58.24; H. 5.71; N. 4.01.
EXAMPLE 5 Reaction of 5-tert.-buty1-l,3-cyclohexanedione with p-toluenesulfonylisocyanate in benzene according tothe procedure of Example 1 affords 5-tert.-BUTYL-2- (N-p-TOLUENESULFONYLCARBAMOYL)-1.3- CYCLOHEXANEDIONE. m.p. 161.5163C. (corr.).
Analysis. Calcd. for C ,.H- NO S (percent): C. 59.16;.
H. 6.34; N. 3.83; S. 8.78 Found (percent): C. 59.43; H. 6.27; N. 3.79; S. 8.71.
EXAMPLE 6 Reaction of equimolar amounts of spiro[5.5]undecane-2.4-dione with p-toluenesulfonylisocyanate in benzcne according to the procedure of Example 1 affords 3-[N-(p-TOLUENESULFONYL)CARBAMOYL]- SP1RO-[5.5 UNDECANE-ZADIONE. m.p. 150.5-152C. (corr.).
Analysis. Calcd. for C .,H -,NO,-.S (percent): C. 60.46:
H. 6.14; N. 3.71; S. 8.50. Found (percent): C. 60.75; H. 6.26; N. 3.69; S. 3.57.
EXAMPLE 7 EXAMPLE 8 Reaction of equimolar amounts of 5-isopropyl-l.3 cyclohexanedione with p-chlorobenzenesulfonylisocyanate in benzene according to the procedure of Example 1 affords Z-(N-p-CHLOROBEN- ZENESULFONYLCARBAMOYL)-5-1SOPROPYL- 1.3-CYCLOHEXANED1ONE. m.p. 100.5-101.5C. (resolidified and melting at 183.5C. with dec. )(corr.
Analysis. Calcd. for C H ClNO-S (percent): C. 51.68; H. 4.88; N. 3.77; S. 8.62: Cl. 9.54. Found (percent): C. 51.90: H. 5.03; N. 3.92; S. 8.871Cl. 9.84.
EXAMPLE 9 Reaction of equimolar amounts of 5.5- dimethyl-l.3-cyclohexanedione with benzenesulfonylisocyanate in benzene according to the procedure of Example 1 affords 5.5-D1METHY L-2-(N-BEN- ZENESULFONYLCARBAMOYL)-1.3-CYCLOHEX ANEDIONE. m.p. 10l103 C. (corr.).
Analysis. Calcd. for C, -,H, NO,-.S (percent): C. 55.71; H. 5.30; N. 4.23; S. 9.91. Found (percent): C. 55.81 H. 5.40; N. 4.37; S. 9.82.
EXAMPLE 10 Reaction of equimolar amounts of 5-( 1-ethylpropyl)- 1.3-cyclohexanedione with p-toluenesulfonylisocyanate in benzene according to the procedure of Example 1 affords 5-( l-ETHYLPROPYLLZ-(N-p- TOLUENESULFONYLCARBAMOYL)-1.3- CYCLOHEXANEDIONE. m.p. 11 1.5-112.5C. corr.
Analysis. Calcd. for C,.,H- -,NO -,S (percent): C. 60.13; H. 6.64; N. 3.69; S. 8.45; Found (percent): C. 60.10; H. 6.61; N. 3.67: S. 8.57.
EXAMPLE 1 1 Reaction of equimolar amounts of 5-( l-ethylpropyl 1.3-eyclohexanedione with p-chlorobenzenesul fonylisocyanate in benzene according to the procedure of Example 1 affords 5-( l-ETHYLPROPYL)-2-(N-p- CHLOROBENZENESULFONYLCARBAMOYL l.3-CYCLOHEXANEDIONE. m.p. 12l-122C. (corr.).
Analysis. Calcd. for C H CINO S (percent): C. 54.05; H. 5.55; N. 3.50; S. 8.87. Found (percent): C. 53.97: H. 5.58; N. 3.52; S. 9.1.0.
EXAMPLE 12 Reaction of equiimolar equimolar of l-phenyl-l.3- butanedione with p-toluenesulfonylisocyanate in benzene according to the procedure of Example 1 affords l-PHENYL-2-(N-p-TOLUENESULFONYLCAR- BAMOYL)-1.3-BUTANED1ONE. m.p. l13.5l16.5 C. (corr.).
Analysis. Calcd. for C ,.H ;NO -.S (percent): C. 60.15; H. 4.77: S. 8.92. Found (percent): C. 59.86: H. 4.81; S. 8.99.
EXAMPLE 13 Reaction of equimolar amounts of 2.4-pentanedione with p-toluenesulfonylisocyanate in benzene according to the procedure of Example 1 affords 3(N-p- TOLUEN ESULFONYLCARBAMOY L )-2.4-PEN- TANEDIONE. m.p. 137139.5 C. (corr.).
Analysis. Calcd. for C,;,H -,NO-,S (percent): C. 52.51; H. 5.08: 5. 10.78. Found (percent): C. 52.65; H. 5.16; S. 10.79.
EXAMPLE 14 Reaction of equimolar amounts of 5-propyl-l .3- cyclohexanedione with p-toluenesulfonylisocyanate in benzene according to the procedure of Example 1 affords 5-PROPYL -2-( N-p-TOLUENESULFONY L CARBAMOYL)-1.3-CYCLOHEXANED1ONE. m.p. l32.5133.5C. (corr.).
Analysis. Calcd. for C,;H NO -.S (percent): C. 58. 10: H. 6.01; N. 3.99: S. 9.12. Found (percent): C. 58.38: H. 6.11; N. 4.06; S. 9.04.
EXAMPLE 15 Reaction of equimolar amounts of 5-isopropyl-l.3- cyclohexanedionc with benzenesulfonylisocyanate in benzene according to the procedure of Example 1 affords 5-ISOPROPYL-2-( N-benzenesulfonylcarbamoyl)-1.3-CYCLOHEXANEDIONE. m.p. ll2.5l 14C. (corr.).
Analysis. Calcd. for C,..H .,NO -.S (percent): C. 56.95: H. 5.68; N. 4.15; S. 9.50. Found (percent): C. 57.03; H. 5.78; N. 4.11; S. 9.72.
EXAMPLE 16 Reaction of equimolar amounts of 5-sec.-butyl-l .3- cyclohexanedione with p-toluenesulfonylisocyanate in benzene according to the procedure of Example 1 affords 5-sec.-BUTYL-2-(N-p-TOLUENESULFONYL- CARBAMOYLH.3-CYCLOHEXANED1ONE. m.p. 9293C. (corr.).
Analysis. Calcd. for C.,.H ,;NO,-.S (percent): C. 59. 16; H. 6.34: S. 8.77. Found (percent): C. 59.39; H. 6.55; S. 8.95.
EXAMPLE 17 Reaction of equimolar amounts of 5-sec.-buty1-l .3- cyclohexanedione with p-chlorobcnzenesulfonylisoeyanate in benzene according to the procedure of 7 Example 1 affords 5-sec.-BUTYL-2-( N-p- CHLOROBENZENESU LFONYLCARBAMOYL)- -fords 7 1.3-CYCLOHEXANED1ONE. m.p. (corr.).
Analysis. Calcd. for C H .,ClNO,-,S (percent): C. 52.92; H. 5.22; S. 8.31: Cl. 9.19. Found (percent): C. 52.82; H. 5.16; S. 8.45; Cl. 9.04.
EXAMPLE 18 Reaction of equimolar amounts of -isobutyl-l.3-
,cyclohexanedione with p-toluenesulfonylisocyanate in EXAMPLE 19 Reaction of equimolar amounts of 5-phenyl-1.3- cyclohexanedione with p-toluenesulfonylisocyanate in benzene according to the procedure of Example 1 af- 5-PHENYL-2-[N-p-TOLUENESULFONYL- CARBAMOYL]-1.3-CYCLOHEXANED1ONE. m.p.
l63.5166C. (corr.).
Analysis. Calcd. for C .,H ,NO,-,S (percent): C. 62.32; H. 4.97; S. 8.32. Found (percent): C. 62.15: H. 5.1 1'.S.
EXAMPLE 20 BAMOYL)-2.4-PENTANED1ONE. m.p.
Analysis. Calcd. for- C H NO S (percent): C. 61.1 1; H. 5.13; N. 3.76. Found (percent): C. 60.94; H. 5.03;
What is claimed is; l. A compound having the formula wherein R is lower alkyl from 1 to 5 carbon atoms inclusive or phenyl;
R is hydrogen or alkyl from 1 to 3 carbon atoms inclusive;
R and R taken together form (CH R is hydrogen. halogen or lower alkyl of 1 to 4 carbon atoms inclusive; and basic salts thereof.
2. The compound of the group defined in claim 1 which is 5.5-dimethy1-2(N-p-toluenesulfonylcarbamoyl 1.3-cyclohexanedione.
3. The compound of the group defined in claim 1 which is 5-methyl-2-(N-ptoluenesulfonylcarbamoyl)- 1.3-cyclohexanedione.
4. The compound of the group defined in claim 1 which is 5-ethyl-2-(N-p-toluenesulfonylcarbamoyl)- 1.3-cyclohexanedione.
5. The compound of the group defined in claim 1 which is 5-isopropyl-2-(N-p-toluenesulfonylcarbamo vl)-1.3-cyclohexanedione.
6. The compound of the group defined in claim 1 which is 5-tert.-butyl-2-(N-p-toluenesulfonylcarbamoyl 1 .3-cyclohexanedione.
7. The compound of the group defined in claim 1 which is 3-[N-(p-toluenesulfonyl)carbamoyl]spiro[5.- 5 ]undecane2.4-dione.
8. The compound of the group defined in claim '1 which is 2-(N-p chl0robenzenesulfonylcarbamoyl)- 5.S-dimethylcyclohexane-1.3-dione.
9. The compound of the group defined in claim 1 which is 2-(N-p-chlorobenzenesulfonylcarbamoyl)-5- isopropyl-1.3-cyclohexanedione.
10. The compound of the group defined in claim 1 which i is 5.5-dimethyl-2-(N-benzenesulfonylcarbamoyl 1 .3-cyclohexanedione.
11. The compound of the group defined in claim 1 which is 5-( 1-ethylpropyl)-2-(N-p-toluenesulfonylcarbamoyl)--1.3-cyclohexanedione.
12. The compound of the group defined in claim 1 which is 5-( 1-ethylpropy1)-2-(N-p-chlorobenzenesulfonylcarbamoyl)-1.3-cyclohexanedione.

Claims (12)

1. A COMPOUND HAVING THE FORMULA
2. The compound of the group defined in claim 1 which is 5,5-dimethyl-2-(N-p-toluenesulfonylcarbamoyl)-1,3-cyclohexanedione.
3. The compound of the group defined in claim 1 which is 5-methyl-2-(N-p-toluenesulfonylcarbamoyl)-1,3-cyclohexanedione.
4. The compound of the group defined in claim 1 which is 5-ethyl-2-(N-p-toluenesulfonylcarbamoyl)-1,3-cyclohexanedione.
5. The compound of the group defined in claim 1 which is 5-isopropyl-2-(N-p-toluenesulfonylcarbamoyl)-1,3-cyclohexanedione.
6. The compound of the group defined in claim 1 which is 5-tert.-butyl-2-(N-p-toluenesulfonylcarbamoyl)-1,3-cyclohexanedione.
7. The compound of the group defined in claim 1 which is 3-(N-(p-toluenesulfonyl)carbamoyl)spiro(5.5)undecane-2,4-dione.
8. The compound of the group defined in claim 1 which is 2-(N-p-chlorobenzenesulfonylcarbamoyl)-5,5-dimethylcyclohexane-1,3-dione.
9. The compound of the group defined in claim 1 which is 2-(N-p-chlorobenzenesulfonylcarbamoyl)-5-isopropyl-1,3-cyclohexanedione.
10. The compound of the group defined in claim 1 which is 5,5-dimethyl-2-(N-Benzenesulfonylcarbamoyl)-1,3-cyclohexanedione.
11. The compound of the group defined in claim 1 which is 5-(1-ethylpropyl)-2-(N-p-toluenesulfonylcarbamoyl)-1,3-cyclohexanedione.
12. The compound of the group defined in claim 1 which is 5-(1-ethylpropyl)-2-(N-p-chlorobenzenesulfonylcarbamoyl)-1,3 -cyclohexanedione.
US478497A 1974-06-12 1974-06-12 Arylsulfonylcarbamoyl-1,3-dicarbonylalicyclic Expired - Lifetime US3917692A (en)

Priority Applications (17)

Application Number Priority Date Filing Date Title
US478497A US3917692A (en) 1974-06-12 1974-06-12 Arylsulfonylcarbamoyl-1,3-dicarbonylalicyclic
AU81291/75A AU8129175A (en) 1974-06-12 1975-05-16 Sulfonylcarbamoyl derivatives
CA227,783A CA1051924A (en) 1974-06-12 1975-05-26 Arylsulfonylcarbamoyl-1,3-dicarbonylalicyclic and arylsulfonylcarbamoyl-1,3-dicarbony-lacyclic compounds
GB2445575A GB1454737A (en) 1974-06-12 1975-06-06 Sulphonylcarbamoyl derivatives
BE157097A BE829953A (en) 1974-06-12 1975-06-06 ARYLSULFONYLCARBAMOYL-1,3-DICARBONYL COMPOUNDS
ZA00753689A ZA753689B (en) 1974-06-12 1975-06-09 Sulfonylcarbamoyl derivatives
NL7506830A NL7506830A (en) 1974-06-12 1975-06-09 ARYLSULFONYLCARBAMOYL-1,3-DICARBONYL COMPOUNDS.
DK261775A DK261775A (en) 1974-06-12 1975-06-10 SULPHONYL CARBAMOYL DERIVATIVES AND THEIR PREPARATION
LU72697A LU72697A1 (en) 1974-06-12 1975-06-10
JP50069778A JPS5829785B2 (en) 1974-06-12 1975-06-11 Sulfonyl carbamoyl sulfonate
SE7506707A SE7506707L (en) 1974-06-12 1975-06-11 SULPHONYLCARBAMOYL DERIVATIVE.
CH756575A CH596158A5 (en) 1974-06-12 1975-06-11
IE1312/75A IE41477B1 (en) 1974-06-12 1975-06-11 Sulfonylcarbamoyl derivatives
FR7518300A FR2274288A1 (en) 1974-06-12 1975-06-11 NEW ARYLSULFONYLCARBAMOYL-1,3-DICARBONYL COMPOUNDS, THEIR PREPARATION PROCESS AND THE MEDICINAL PRODUCT CONTAINING THEM
DE19752526195 DE2526195A1 (en) 1974-06-12 1975-06-12 SULFONYL CARBAMOYL DERIVATIVES, THE PROCESS FOR THEIR MANUFACTURING AND MEDICINAL PRODUCTS CONTAINING THEM
YU1515/75A YU40265B (en) 1974-06-12 1975-06-12 Process for obtaining arysulfonylcarbomoyl-1,3-dicarbonyl compounds
US05/604,971 US3998879A (en) 1974-06-12 1975-08-15 Arylsulfonylcarbamoyl-1,3-dicarbonylacyclic compounds

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FR (1) FR2274288A1 (en)
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IE (1) IE41477B1 (en)
LU (1) LU72697A1 (en)
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4347380A (en) * 1979-04-20 1982-08-31 Stauffer Chemical Company N-Acylsulfonamide herbicidal antidotes
US5135941A (en) * 1989-12-18 1992-08-04 G. D. Searle & Co. LTB4 synthesis inhibitors

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS54156826A (en) * 1978-05-23 1979-12-11 Sumitomo Electric Ind Ltd Metod of making glass fiber for light transmission
AR037097A1 (en) 2001-10-05 2004-10-20 Novartis Ag ACILSULFONAMID COMPOUNDS, PHARMACEUTICAL COMPOSITIONS AND THE USE OF SUCH COMPOUNDS FOR THE PREPARATION OF A MEDICINAL PRODUCT
WO2004113091A1 (en) * 2003-06-24 2004-12-29 Idemitsu Kosan Co., Ltd. Heat-sensitive recording material and benzenesulfonamide derivative

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3298917A (en) * 1964-09-15 1967-01-17 Merck & Co Inc Antidiabetic nu-acylaliphaticsulfonamides
US3578658A (en) * 1966-08-25 1971-05-11 Geigy Chem Corp N'-substituted n-arylsulfonyl ureas

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3298917A (en) * 1964-09-15 1967-01-17 Merck & Co Inc Antidiabetic nu-acylaliphaticsulfonamides
US3578658A (en) * 1966-08-25 1971-05-11 Geigy Chem Corp N'-substituted n-arylsulfonyl ureas

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4347380A (en) * 1979-04-20 1982-08-31 Stauffer Chemical Company N-Acylsulfonamide herbicidal antidotes
US5135941A (en) * 1989-12-18 1992-08-04 G. D. Searle & Co. LTB4 synthesis inhibitors

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FR2274288A1 (en) 1976-01-09
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JPS5829785B2 (en) 1983-06-24
BE829953A (en) 1975-12-08
YU40265B (en) 1985-12-31
IE41477B1 (en) 1980-01-16
ZA753689B (en) 1976-05-26
SE7506707L (en) 1975-12-15
YU151575A (en) 1982-06-30
DK261775A (en) 1975-12-13
JPS5111734A (en) 1976-01-30
IE41477L (en) 1975-12-12
LU72697A1 (en) 1976-04-13
DE2526195A1 (en) 1976-01-02
AU8129175A (en) 1976-11-25
NL7506830A (en) 1975-12-16
GB1454737A (en) 1976-11-03
FR2274288B1 (en) 1978-11-10

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