CA1082194A - Aliphatic sulfamates - Google Patents
Aliphatic sulfamatesInfo
- Publication number
- CA1082194A CA1082194A CA239,484A CA239484A CA1082194A CA 1082194 A CA1082194 A CA 1082194A CA 239484 A CA239484 A CA 239484A CA 1082194 A CA1082194 A CA 1082194A
- Authority
- CA
- Canada
- Prior art keywords
- bis
- sulfamyl
- propanediol
- compound
- hydrogen
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired
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Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
Abstract of the Disclosure Aliphatic sulfamates are prepared by reacting an alkanediol with sulfamoyl chloride. The aliphatic sulfamates arc novel compounds and are useful in the control of fertility in male animals.
Description
108~ 4 Background of the~Invention The present invention relates to novel aliphatic sulfamates. The sulfamates may be represented by the formula:
Y~n CH2S2NRlR2 wherein n is an integer from 0-8 and X and Y are hydrogen; -provided that when n is 1, X and Y are hydrogen, lower alkyl having 1-3 carbon atoms, aryl such as phenyl or arylal~yl such as benzyl, phenethyl and the like; and Rl and R2 are -hydrogen, alkyl having 1-7 carbon atoms, aryl, arylalkyl such as benzyl, phenethyl, phenylpropyl and the like, cycloalkyl -~
such as cyclopentyl, cyclohexyl and the like, or Rl and R2 together with the N-atom to which they are attached form a saturated heterocyclic ring. Preferred among these compounds are those compounds wherein Rl and R2 are hydrogen.
j The novel aliphatic sulfamates of the present invention I
are prepared by reacting an alkanediol with a sulfamoyl halide in a suitable solvent in the presence of a strong base.
Suitable alkanediols which may be employed include 1,2~
ethanediol, 1,3-propanediol, 1,4-butanediol, 1,5-pentanediol, l,lQ-decanediol and the like. As the halide reactant, sulfamoyl --chloride and N,N-di or mono substituted sulfamoyl halides may be employed. Bases such as sodium hydride, sodium amide, sodium hydroxide, pyridine and tributyltin are examples of -suitable strong bases. Examples of solvents which may be ~ ;
employed include 1,2-dimethoxyethane, ether, tetrahydrofuran, - -diglyme and p-dioxane. The reaction with the sulfamoyl halide ~
. .
- -2- ~ ~
~ ~.
.. . . . .
108;~194 may be carried out at room temperature, but it is preferred to carry out the reaction at a temperature between 0-10C.
~ The sulfamate is obtained from the reaction mixture by techniques known to those skilled in the art.
The present invention also relates to an alternative process for the preparation of aliphatic primary sulfamates.
The sulfamates which can be prepared by said alternative process may be represented by- the formula:
:~ IH20SO2NH2 I' .
~CXY~n : :
wherein n, X and Y are as defined above. .
. The aliphati.c primary sulfamates of the present invention are prepared in accordance with said alternative process- by reacting an alkanediol with a substituted sulfamoyl :~
hali.de such as a substituted sulfamoyl chloride, for example, in a suitable solvent in the presence of a strong base. Suitable alkanediols which may be employed include 1,2-ethanediol, 1,3-propanediol, 1,4-butanediol, 1,5-pentanediol, l,10-decane-diol and the like. As the~halide reactant, a substituted sulfamoyl halide is employed wherein the substituent is a protecting group which can be readily removed under acid conditions. Suitable groups which. may be employed include groups such. as t-butyl, benzyl, ~-alkyl benzyl wherein the alkyl group has 1-3 carbon atoms, allyl and l-alkyl-allyl wherein the alkyl group has 1-3 carbon atoms. The substituent on the sulfamoyl halide reactant is removed by treating the compound obtained from the reaction mixture with a strong acid. Acids such as trich.loroacetic acid, trifluoroacetic acid, methanesulfonic ' ~ . . , ' ~ ' ~ :
1~8~1~4 acid, conc. sulfuric acid and conc. hydrochloric acid, for example, may be employed. The preparation of unsubstituted sulfamoyl halides involves steps ~hich are inherently hazardous.
The use of a substituted sulfamoyl halide in place of an unsubstituted sulfamoyl halide avoids the hazards associated with the preparation of sulfamoyl halides. Substituted sulfamoyl halides are prepared by reacting an appropriate amine such as, for example, t-butylamine or benzylamine, with a sulfuryl halide in a suitable solvent, such as acetonitrile, for example.
Bases such as sodium hydride, potassium t-butoxide, potassium hydride, tributyltin, sodium amide and sodium are examples of bases which may be employed for the initial reaction. Suitable solvents for the reaction include toluene, benzene, xylene, ether, tetrahydrofuran, diglyme, 1,2-dimethoxyethane and p-dioxane.
The reaction with the substituted sulfamoyl halide may be carried out at room temperature, but it is preferred to carry out the reaction at a temperature between room temperature and about 60C. The removal of the protecting group is preferably carried out at room temperature in an inert atmosphere such as nitrogen, for example. The product is obtained from the reaction mixture by techniques known to those skilled in the art.
The novel aliphatic sulfamates are useful in the control of fertility in male animals. The compounds are capable of interfering with sperm as they sojourn in the epidimdymis and thus result in what is known as functional sterility, i.e. the gametes remain morphologically normal and show motility but normal fertilization is not achieved.
Generally dosage levels of from about 5-200 mg./kg. are effective in inducing functional sterility. The preferred ., -:
`~ 108Z194 . :
dosage range is from about 1~-150 mg./kg, In addition to causing functional sterility of epididymal sperm, the novel sulfamates have antiandrogenic properties as manifested by -inhibition of the size of the ventral prostate.
The general procedure followed to determine the activity of compounds which inhibit male fertility by altering the functional capacity of epididymal sperm is as -' follows: ~, A two week dosing period (i.e., the approximate period required for sperm transport through the epididymis) enables separation of those drugs which affect epididymal sperm maturation and/or function from the antispermatogenic agents which have a longer delay in the onset of sterility.
Each individual test involves 5 male rats (250-300 g.) caged together in air conditioned animal quarters and maintained on laboratory chow and tap water ad libitum. The compound to be tested is dissolved or suspended in appropriate ~- vehicles (usually methylcellulose~ and administered dailyusually i.g.~ for 14 consecutive days. Control animals ' 20 receive the vehicle only. At the end of the 14th day of treatment each male is individually caged with a proestrus - -female. Vaginal smears are checked the following morning for evidence of positive mating, and those males failing to mate are recohabited with proestrus females the following night.
Males are sacrificed and autopsied the day after cohabitation for a gross examination of testes, epididymides, and accessory sex organs. Tissue samples of these organs are preserved for histological processing if observation yields a possible effect. Females Cregardless of sperm presence in the vaginal washingsl are autopsied 14 days after cohabitation to examine for pregnancy-. ~;~
.. .
~.
.
- ' ' . ' ,,' ': '' " ' " "' . . ' ' , .
lOBZ194 The inability of females to produce a viable embryo following a successful mating wïth treated males (two weeks of medication~ is used as a measure of functional infertility.
The number of males mating of those cohabited gives a gross indication of the drug's effect on libido. The size of the accessory sex organs provides an indication of the effect on androgen production. Microscopic analysis of epididymal sperm provides information on sperm quality ~motility and morphology~ and quantity.
lQ The following examples describe the invention in greater particularity and are intended to be a way of illustrating and not limiting the invention.
1,2-Bis-O-sulfamyl-1,2-ethanediol A 57~ oil dispersion of sodium hydride (8.45 g.; ~-a. 2~ mol.l is added to a solution of ethylene glycol ~3.1 g.; 0.05 mol.l in 1,2-dimethoxyethane (100 ml.). The resulting suspension is stirred at room temperature for two hours and then cooled to +4C. Sulfamoyl chloride (20.79 g.;
0.18 mol.l is dissolved in 1,2-dimethoxyethane (400 ml.l and added dropwise to the solution with stirring. The reaction mixture is stirred at +4C for an additional 24 hours. A
precipitate forms which is filtered off and the filtrate is concentrated. The residue is partitioned between heptane and methanol, and the methanol solution is concentrated to a syrup which crystallizes from ethyl acetate to yield 6.1 g. ~ ~ -(58%~ of 1,2-bis-O-sulfamyl-1,2-ethanediol, m.p. 96.5-99C.
When in the above procedure 1,5-pentanediol is employed in place of ethylene glycol, 1,5-bis-O-sulfamyl-1,5-pentanediol is obtained.
-.. . . .. .. , . . . . :
: , , .,, - . . . ,: . . .
10~32194 1,10-Bis-O-sulfamyl-l, la.-decaned;ol A 57% oil dispersion of sodium hydride (8.45 g.; 0.20 mol.l is added to a solution of l,10-decanediol (8.71 g.; 0.05 mol.~ in 1,2-dimethoxyethane ClOO ml.~. The resulting solution is stirred at room temperature for two hours and then cooled to +4C. Sulfamoyl chloride ~20.79 g.; 0.18 mol.~ is dissolved in 1,2-dimethoxyethane ~400 ml.) and added dropwise to the solution with stirring. The reaction mixture is stirred at +4C for an additional 48 hours. A precipitate forms which is filtered off and the filtrate is concentrated. The residue is partitioned between heptane and methanol and the methanol solution is concentrated to a syrup which crystallizes from ethyl acetate to yield 6.0 g. (36%~ of l,10-bis-O-sulfamyl-l,10-decanediol, m.p. 129-131C.
When în the above procedure 1,6-hexanediol is employed ` in place of l,10-decanediol, 1,6-bis-O-sulfamyl-1,6-hexanediol is obtained.
1,4-Bis-O-sulfamyl-1,4-butanediol A 57% oil dispersion of sodium hydride (8.45 g.;
a. 20 mol.l is added to a solution of 1.4-butanediol (4.5 g.;
~ 0.05 mol.~ in 1,2-dimethoxyethane (100 ml.~. The resulting ; solution is stirred at room temperature for two hours and then cooled to +4C. Sulfamoyl chloride (20.79 g.; 0.18 mol.~ is dissolved in 1,2-dimethoxyethane (400 ml.) and added dropwise to the solution with stirring. The reaction mixture is stirred at +4C for an additional 48 hours. A
precipitate forms which is filtered off and the filtrate is concentrated. The residue is partitioned between heptane and methanol and the methanol solution is concentrated to a ~82~9d~
syrup which crystallizes from ethyl alcohol to yield 5.5 g.
~47%~ of 1,4-bis-O-sulfamy1-1,4-butanediol, m.p. 126-129C.
When in the above procedure 1,7-heptanediol is employed in place of 1,4-butanediol, 1,7-bis-O-sulfamyl-1,7-heptanediol is obtained.
1,3-Bis-O-sulfamyl-1,3-propanediol A 57% oil dispersion of sodium hydride (25.4 g.;
a.60 mol.l is added to a solution of 1,3-propanediol (11.41 g.;
Q.15 mol.~ in 1,2-dimethoxyethane (100 ml.~. The resulting solution is stirred at room temperature for two hours and then cooled to ~4C. Sulfamoyl chloride (62.37 g.; 0.54 mol.~ is dissolved in 1,2-dimethoxyethane (400 ml.~ and added dropwise to the solution with stirring. The reaction mixture is stirred at +4C for an additional 24 hours. A precipitate ` forms which is filtered off and the filtrate is concentrated.
^ , The residue is partitioned between heptane and methanol and the methanol solution is concentrated to a syrup. The residue ~
is washed with heptane and chromatographed through SilicAR, - -CC-7 using 50% acetone-chloroform as the eluent. The fractions are collected and upon removal of the solvent 1,3-bis-O-sulfamyl-1,3-propanediol is obtained as a crystalline residue, m.p. 85-87.5C.
When in the above procedure 1,8-octanediol and 1,9-nonanediol are employed in place of 1,3-propanediol, 1,8-bis-O-sulfamyl-1,8-octanediol and l,9-bis-O-sulfamyl 1,9-nonanediol respectively are obtained.
Y~n CH2S2NRlR2 wherein n is an integer from 0-8 and X and Y are hydrogen; -provided that when n is 1, X and Y are hydrogen, lower alkyl having 1-3 carbon atoms, aryl such as phenyl or arylal~yl such as benzyl, phenethyl and the like; and Rl and R2 are -hydrogen, alkyl having 1-7 carbon atoms, aryl, arylalkyl such as benzyl, phenethyl, phenylpropyl and the like, cycloalkyl -~
such as cyclopentyl, cyclohexyl and the like, or Rl and R2 together with the N-atom to which they are attached form a saturated heterocyclic ring. Preferred among these compounds are those compounds wherein Rl and R2 are hydrogen.
j The novel aliphatic sulfamates of the present invention I
are prepared by reacting an alkanediol with a sulfamoyl halide in a suitable solvent in the presence of a strong base.
Suitable alkanediols which may be employed include 1,2~
ethanediol, 1,3-propanediol, 1,4-butanediol, 1,5-pentanediol, l,lQ-decanediol and the like. As the halide reactant, sulfamoyl --chloride and N,N-di or mono substituted sulfamoyl halides may be employed. Bases such as sodium hydride, sodium amide, sodium hydroxide, pyridine and tributyltin are examples of -suitable strong bases. Examples of solvents which may be ~ ;
employed include 1,2-dimethoxyethane, ether, tetrahydrofuran, - -diglyme and p-dioxane. The reaction with the sulfamoyl halide ~
. .
- -2- ~ ~
~ ~.
.. . . . .
108;~194 may be carried out at room temperature, but it is preferred to carry out the reaction at a temperature between 0-10C.
~ The sulfamate is obtained from the reaction mixture by techniques known to those skilled in the art.
The present invention also relates to an alternative process for the preparation of aliphatic primary sulfamates.
The sulfamates which can be prepared by said alternative process may be represented by- the formula:
:~ IH20SO2NH2 I' .
~CXY~n : :
wherein n, X and Y are as defined above. .
. The aliphati.c primary sulfamates of the present invention are prepared in accordance with said alternative process- by reacting an alkanediol with a substituted sulfamoyl :~
hali.de such as a substituted sulfamoyl chloride, for example, in a suitable solvent in the presence of a strong base. Suitable alkanediols which may be employed include 1,2-ethanediol, 1,3-propanediol, 1,4-butanediol, 1,5-pentanediol, l,10-decane-diol and the like. As the~halide reactant, a substituted sulfamoyl halide is employed wherein the substituent is a protecting group which can be readily removed under acid conditions. Suitable groups which. may be employed include groups such. as t-butyl, benzyl, ~-alkyl benzyl wherein the alkyl group has 1-3 carbon atoms, allyl and l-alkyl-allyl wherein the alkyl group has 1-3 carbon atoms. The substituent on the sulfamoyl halide reactant is removed by treating the compound obtained from the reaction mixture with a strong acid. Acids such as trich.loroacetic acid, trifluoroacetic acid, methanesulfonic ' ~ . . , ' ~ ' ~ :
1~8~1~4 acid, conc. sulfuric acid and conc. hydrochloric acid, for example, may be employed. The preparation of unsubstituted sulfamoyl halides involves steps ~hich are inherently hazardous.
The use of a substituted sulfamoyl halide in place of an unsubstituted sulfamoyl halide avoids the hazards associated with the preparation of sulfamoyl halides. Substituted sulfamoyl halides are prepared by reacting an appropriate amine such as, for example, t-butylamine or benzylamine, with a sulfuryl halide in a suitable solvent, such as acetonitrile, for example.
Bases such as sodium hydride, potassium t-butoxide, potassium hydride, tributyltin, sodium amide and sodium are examples of bases which may be employed for the initial reaction. Suitable solvents for the reaction include toluene, benzene, xylene, ether, tetrahydrofuran, diglyme, 1,2-dimethoxyethane and p-dioxane.
The reaction with the substituted sulfamoyl halide may be carried out at room temperature, but it is preferred to carry out the reaction at a temperature between room temperature and about 60C. The removal of the protecting group is preferably carried out at room temperature in an inert atmosphere such as nitrogen, for example. The product is obtained from the reaction mixture by techniques known to those skilled in the art.
The novel aliphatic sulfamates are useful in the control of fertility in male animals. The compounds are capable of interfering with sperm as they sojourn in the epidimdymis and thus result in what is known as functional sterility, i.e. the gametes remain morphologically normal and show motility but normal fertilization is not achieved.
Generally dosage levels of from about 5-200 mg./kg. are effective in inducing functional sterility. The preferred ., -:
`~ 108Z194 . :
dosage range is from about 1~-150 mg./kg, In addition to causing functional sterility of epididymal sperm, the novel sulfamates have antiandrogenic properties as manifested by -inhibition of the size of the ventral prostate.
The general procedure followed to determine the activity of compounds which inhibit male fertility by altering the functional capacity of epididymal sperm is as -' follows: ~, A two week dosing period (i.e., the approximate period required for sperm transport through the epididymis) enables separation of those drugs which affect epididymal sperm maturation and/or function from the antispermatogenic agents which have a longer delay in the onset of sterility.
Each individual test involves 5 male rats (250-300 g.) caged together in air conditioned animal quarters and maintained on laboratory chow and tap water ad libitum. The compound to be tested is dissolved or suspended in appropriate ~- vehicles (usually methylcellulose~ and administered dailyusually i.g.~ for 14 consecutive days. Control animals ' 20 receive the vehicle only. At the end of the 14th day of treatment each male is individually caged with a proestrus - -female. Vaginal smears are checked the following morning for evidence of positive mating, and those males failing to mate are recohabited with proestrus females the following night.
Males are sacrificed and autopsied the day after cohabitation for a gross examination of testes, epididymides, and accessory sex organs. Tissue samples of these organs are preserved for histological processing if observation yields a possible effect. Females Cregardless of sperm presence in the vaginal washingsl are autopsied 14 days after cohabitation to examine for pregnancy-. ~;~
.. .
~.
.
- ' ' . ' ,,' ': '' " ' " "' . . ' ' , .
lOBZ194 The inability of females to produce a viable embryo following a successful mating wïth treated males (two weeks of medication~ is used as a measure of functional infertility.
The number of males mating of those cohabited gives a gross indication of the drug's effect on libido. The size of the accessory sex organs provides an indication of the effect on androgen production. Microscopic analysis of epididymal sperm provides information on sperm quality ~motility and morphology~ and quantity.
lQ The following examples describe the invention in greater particularity and are intended to be a way of illustrating and not limiting the invention.
1,2-Bis-O-sulfamyl-1,2-ethanediol A 57~ oil dispersion of sodium hydride (8.45 g.; ~-a. 2~ mol.l is added to a solution of ethylene glycol ~3.1 g.; 0.05 mol.l in 1,2-dimethoxyethane (100 ml.). The resulting suspension is stirred at room temperature for two hours and then cooled to +4C. Sulfamoyl chloride (20.79 g.;
0.18 mol.l is dissolved in 1,2-dimethoxyethane (400 ml.l and added dropwise to the solution with stirring. The reaction mixture is stirred at +4C for an additional 24 hours. A
precipitate forms which is filtered off and the filtrate is concentrated. The residue is partitioned between heptane and methanol, and the methanol solution is concentrated to a syrup which crystallizes from ethyl acetate to yield 6.1 g. ~ ~ -(58%~ of 1,2-bis-O-sulfamyl-1,2-ethanediol, m.p. 96.5-99C.
When in the above procedure 1,5-pentanediol is employed in place of ethylene glycol, 1,5-bis-O-sulfamyl-1,5-pentanediol is obtained.
-.. . . .. .. , . . . . :
: , , .,, - . . . ,: . . .
10~32194 1,10-Bis-O-sulfamyl-l, la.-decaned;ol A 57% oil dispersion of sodium hydride (8.45 g.; 0.20 mol.l is added to a solution of l,10-decanediol (8.71 g.; 0.05 mol.~ in 1,2-dimethoxyethane ClOO ml.~. The resulting solution is stirred at room temperature for two hours and then cooled to +4C. Sulfamoyl chloride ~20.79 g.; 0.18 mol.~ is dissolved in 1,2-dimethoxyethane ~400 ml.) and added dropwise to the solution with stirring. The reaction mixture is stirred at +4C for an additional 48 hours. A precipitate forms which is filtered off and the filtrate is concentrated. The residue is partitioned between heptane and methanol and the methanol solution is concentrated to a syrup which crystallizes from ethyl acetate to yield 6.0 g. (36%~ of l,10-bis-O-sulfamyl-l,10-decanediol, m.p. 129-131C.
When în the above procedure 1,6-hexanediol is employed ` in place of l,10-decanediol, 1,6-bis-O-sulfamyl-1,6-hexanediol is obtained.
1,4-Bis-O-sulfamyl-1,4-butanediol A 57% oil dispersion of sodium hydride (8.45 g.;
a. 20 mol.l is added to a solution of 1.4-butanediol (4.5 g.;
~ 0.05 mol.~ in 1,2-dimethoxyethane (100 ml.~. The resulting ; solution is stirred at room temperature for two hours and then cooled to +4C. Sulfamoyl chloride (20.79 g.; 0.18 mol.~ is dissolved in 1,2-dimethoxyethane (400 ml.) and added dropwise to the solution with stirring. The reaction mixture is stirred at +4C for an additional 48 hours. A
precipitate forms which is filtered off and the filtrate is concentrated. The residue is partitioned between heptane and methanol and the methanol solution is concentrated to a ~82~9d~
syrup which crystallizes from ethyl alcohol to yield 5.5 g.
~47%~ of 1,4-bis-O-sulfamy1-1,4-butanediol, m.p. 126-129C.
When in the above procedure 1,7-heptanediol is employed in place of 1,4-butanediol, 1,7-bis-O-sulfamyl-1,7-heptanediol is obtained.
1,3-Bis-O-sulfamyl-1,3-propanediol A 57% oil dispersion of sodium hydride (25.4 g.;
a.60 mol.l is added to a solution of 1,3-propanediol (11.41 g.;
Q.15 mol.~ in 1,2-dimethoxyethane (100 ml.~. The resulting solution is stirred at room temperature for two hours and then cooled to ~4C. Sulfamoyl chloride (62.37 g.; 0.54 mol.~ is dissolved in 1,2-dimethoxyethane (400 ml.~ and added dropwise to the solution with stirring. The reaction mixture is stirred at +4C for an additional 24 hours. A precipitate ` forms which is filtered off and the filtrate is concentrated.
^ , The residue is partitioned between heptane and methanol and the methanol solution is concentrated to a syrup. The residue ~
is washed with heptane and chromatographed through SilicAR, - -CC-7 using 50% acetone-chloroform as the eluent. The fractions are collected and upon removal of the solvent 1,3-bis-O-sulfamyl-1,3-propanediol is obtained as a crystalline residue, m.p. 85-87.5C.
When in the above procedure 1,8-octanediol and 1,9-nonanediol are employed in place of 1,3-propanediol, 1,8-bis-O-sulfamyl-1,8-octanediol and l,9-bis-O-sulfamyl 1,9-nonanediol respectively are obtained.
2-Methyl-2-propyl-1,3-bis-O-sulfamyl-1,3-propanediol To a solution of 10 g. ~0.076 mol.) of 2-methyl-.. . . -:
2-propyl-1,3-propanediol in 20Q ml. of dimethoxyethane is added 12.7 g. (0.3 mol.l of 57~ sodium hydride followed by an additîonal 400 ml. of dimethoxyethane. After stirring overnight the suspension is cooled to 4C and a solution of 31.2 g. (-0.27 mol.~ of sulfamoyl chloride in 600 ml. of dimethoxyethane is added dropwise. The resulting suspension is stirred overnight at room temperature. The mixture is then filtered, the filtrate is concentrated and the residue washed with heptane. The residue is then chromatographed through SilicAR, CC-7 and eluted with 25~ acetone-chloroform.
The solid obtained after removal of the solvent is crystallized from a mixture of ethyl acetate-hexane-methylene chloride to afford 2-methyl-2-propyl-1,3-bis-O-sulfamyl-1,3-propanediol, m.p. 92-94C.
When in the above procedure 2-ethyl-2-propyl-1,3-propanediol, 2,2-dimethyl-1,3-propanediol and 2-methyl-1,3-propanediol are employed instead of 2-methyl-2-propyl-1,3-propanediol, 2-ethyl-2-propyl-1,3-bis-O-sulfamyl-1,3-propanediol, 2,2-dimethyl-1,3-bis-O-sulfamyl-1,3-propanediol and 2-methyl-1,3-bis-O-sulfamyl-1,3-propanediol, respectively, are obtained.
2,2-Diphenyl-1,3-bis-O-sulfamyl-1,3-propanediol To a solution of 17.3 g. (0.076 mol.) of 2,2-diphenyl-1,3-propanediol in 200 ml. of dimethoxyethane is added 12.7 g. ~0.3 mol.l of 57% sodium hydride followed by an additional 400 ml. of dimethoxyethane. After stirring overnight the suspension is cooled to 4C. A solution of 31.2 g. (0.27 mol.l of sulfamoyl chloride in 600 ml. of dimethoxyethane is then added dropwise. The suspension is stirred overnight at room temperature. After filtering the 108~9~
mixture the filtrate is concentrated and the residue washed with heptane. Chromatography on SilicA~R, CC-7, followed by crystallization affords 2,2-diphenyl-1,3-bis-O-sulfamyl-1,3-propanediol.
When in the above procedure 2,2-dibenzyl-1,3-propanediol and 2,2-dicyclohexyl-1,3-propanediol are employed in place of 2,2-diphenyl-1,3-propanediol, 2,2-dibenzyl-1,3-bis-O-sulfamyl-1,3-propanediol and 2,2-dicyclohexyl-1,3-bis-O-sulfamyl-1,3-propanediol are obtained.
1,2-Bis-O-(N,N-dimethylsulfamyl~-l, `
2-ethanediol A 57~ oil dispersion of sodium hydride (8.45 g.;
0.20 mol.l is added to a solution of ethylene glycol (3.1 g.; 0.05 mol.~ in 1,2-dimethoxyethane (100 ml.). The resulting suspension is stirred at room temperature for two hours and then cooled to +4C. N,N-dimethylsulfamoyl chloride, 25.8 g. ~0.18 mol.l, is dissolved in 1,2-dimethoxy-, ethane ~400 ml.) and added dropwise to the solution with -~
stirring. The reaction mixture is stirred at +4C for an -additional 24 hours. A precipitate forms which is filtered off and the filtrate is concentrated. The residue is - partitioned between heptane and methanol, and the methanol solution is concentrated to a syrup which crystallizes from ethyl acetate to yield 1,2-bis-O-~N,N-dimethylsulfamyl)-l, :
2-ethanediol.
When in the above procedure N,N-diphenylsulfamoyl chloride and N-ethylsulfamoyl chloride are employed in place of sulfamoyl chloride, 1,2-bis-O-(N,N-diphenylsulfamyl)-1,2-ethanediol and 1,2-bis-O-(N-ethylsulfamyl)-1,2-ethanediol -~
are obtained.
"' ' ' '' `
--10-- , .
: :' -, 108Zl9~
When in the above procedure N-cyclohexylsulfamoyl chloride, N,N-cyclopentylsulfamoyl chloride, N,N-dibenzyl-sulfamoyl chloride and l-piperidylsulfonyl chloride are employed ïn place of sulfamoyl chloride, 1,2-bis-O-(N-cyclohexysulfamyl~-1,2-ethanediol, 1,2-bis-O-(N,N-dicyclopentyl-sulfamyl~-1,2-ethanediol, 1,2-bls-O-(N,N-dibenzylsulfamyl~-1,2-ethaned;ol and 1,2-bis-~1-piperidylsulfonyl)-1,2-ethanediol are obtained.
1,2-Bis--O--sulfamyl-1,2-ethanediol Ethylene glycol ~21.7 ml., 0.385 mol.) is added dropwise during 15 mins. to a suspension of sodium hydride C37 g. 50% m.o., 0.77 mol.~ in toluene (450 ml.) at room temperature. The suspension is stirred for 15 mins., then i warmed slowly to 45-50C and stirred at that temperature for , 2.5 hrs. The reaction mixture is then cooled to 20C and a solution of t- butyl-sulfamoyl chloride ~132 g., 0.77 mol.) in toluene ~131 ml.~ is added dropwise at 20-35C during 1.25 hrs. Heavy foaming occurs during the addition, and cooling is required to maintain the temperature at 20-35C. -The resulting tan colored viscous suspension is stirred for 2.5 hrs. at 20C, then for 1.5 hrs. at 45-50C and then for 16 hrs. without further heating. The gelatinous solid which forms is collected by filtration, washed with toluene, and extracted twice with hot chloroform (600 ml., 300 ml.).
The solids which remain are then suspended in water (500 ml.) and extracted with chloroform until no solid remains. The chloroform extracts are combined and evaporated. The resulting solid is crystallized from chloroform/heptane to afford 72.26 g. ~56.4%~ of 1,2-b -O-~N-t-buty-lsulfamyl~-l, 2-... . .
' , , 1082~94 ethanediol, m.p. 119-121~ The crystalline compound (llQ g., 0.33 mol.l is added to CF3CO2H C330 ml ) with stirring at 25 under N2. The resulting clear solution is stirred at room temperature for 20 hrs. The solid is ; collected by filtration, w-ashed wïth CHC13 (2 x 50 ml.l and ; dried _ vacuo at 50-55 to afford the crude product C61.1 g. 84~T The crude material (61.1 g.~ is dissolved in acetone C185 ml.~ at reflux temperature and treated with charcoal C1.2 g.). The charcoal suspension is refluxed for 5 mins. and then filtered through Supercel.
The colorless filtrate is treated with CHC13 (185 ml.), cooled and stirred at 0-5 for 1 hr. The solid which settles out is collected by filtration and dried in vacuo --at 50-55 to afford 54.0 g. (75.5~1 of 1,2-bls-O-sulfamyl-1,2-ethanediol, m.p. 98.5-101.
l,10-Bis-O-sulfamyl-l,10-decanediol -~
l,10-Bis-O-sulfamyl-l,10-decanediol is prepared in the s-ame manner as 1,2-bis-O-sulfamyl-1,2-ethanediol in Example 8 except that l,10-decanediol (67 g., 0.385 mol.) ~-is employed as the alkanediol.
When in the above procedure 1,6-hexanediol is employed in place of l,10-decanediol, 1,6-bis-O-sulfamyl-1,6-hexanediol is obtained.
EXAMPLE lQ
1,4-Bis-O-sulfamyl-1,4-butanediol ..... ...... .
1,4-Bis-O-sulfamyl-1,4-butanediol is prepared in the same manner as 1,2-bis-O-sulfamyl-1,2-ethanediol in Example 8 except that 1,4-butanediol (34.6 g., 0.385 mol.) ~ 30 is employed as the alkanediol.
.
- . :.:, .... . .
,, . ,:- ,: :: , - . '."' ' ,~ , . .
- , , ~ , : :
.. . .. . . . ..
When in the above procedure 1,7-heptanediol is employed in place of 1,4-butanediol, 1.7-bls-O-sulfamyl-1,7-heptanediol is obtained.
1 7 3-sis-o-sulfamyl-l~3-propanediol 1,3-Bis-O-sulfamyl-1,3-propanediol is prepared in the same manner as 1,2-bis-O-sulfamyl-1,2-ethanediol in Example 8 except that 1,3-propanediol (29.~ g., 0.385 mol.) is employed as the alkanediol.
When in the above procedure 1,8-octanediol and l,9-nonanediol are employed in place of 1,3-propanediol, 1,8-bis-O-sulfamyl-1,8-octanediol and l,9-bis-O-sulfamyl-l,9-nonanediol, respectively, are o~tained.
2-Methyl-2-propyl-1,3-bis-O-sulfamyl-1,3-propanediol 2-Methyl-2-propyl-1,3-bis-O-sulfamyl-1,3-propanediol is prepared in the same manner as 1,2-b -O-sulfamyl-1,2-ethanediol in Example 8 except that 2-methyl-2-propyl-1,3-propanediol (50.8 g., 0.385 mol.) is employed as the alkanediol.
When in the above procedure 2-ethyl-2-propyl-1,3-propanediol, 2,2-dimethyl-1,3-propanediol and 2-methyl-1,3-~ propanediol are employed instead of 2-methyl-2-propyl-1,3-- propanediol, 2-ethyl-2-propyl-1,3-b -O-sulfamyl-1,3-- propanediol, 2,2-dimethyl-1,3-bis-O-sulfamyl-1,3-propanediol and 2-methyl-1,3-bis-O-sulfamyl-1,3-propanediol, respectively, are obtained.
2,2-Diphenyl-1,3-bis-0-sulfamyl-1,3-propanediol 2,2-Diphenyl-1,3-bis-O-sulfamyl-1,3-propanediol is prepared in an identical manner as the sulfamate reported ': ' ; :. -in Example 8 except for the use of 2,2-diphenyl-1,3-propanediol (87.7 g., 0.385 mol.) as the alkanediol.
When in the above procedure 2,2--dibenzyl-1,3-propanediol and 2,2-dicyclohexyl-1,3-propanediol are employed in place of 2,2-diphenyl--1,3-propanediol, 2,2-dibenzyl-1,3-bis--O-sulfamyl-1,3-propanediol and 2,2-dïcyclohexyl-1,3-bis-o-sulfamyl-1,3-propanediol are obtained.
Preparation of t-butyl-sulfamoyl chloride t-Butylamine (65.7 g., 0.90 mol.~ is added during 1 hr. at 20-30C to a stirred solution of sulfuryl chloride (240 ml., 3 mol.~ in acetonitrile ~450 ml.~. A vigorous evolution of hydrogen chloride takes place and the amine hydrochloride settles out of solution. The mixture is refluxed for 24 hrs. and additional sulfuryl chloride ::
(240 ml.) is added. After stirring and refluxing the mixture ~ -for 40 hrs., a more complete solution forms. The solution is concentrated in vacuo to a viscous oil which is distilled under reduced pressure. A main fraction is collected at 89--94C, 0.3-0.5 mm., 100.1 g., 64.896 yield. On standing, transparent, needle-like crystals of t-butyl-sulfamoyl chloride form, m.p. 23-3~C.
'~
- .
" . . . . . . . .
'' : ', '' , , ~ , .
2-propyl-1,3-propanediol in 20Q ml. of dimethoxyethane is added 12.7 g. (0.3 mol.l of 57~ sodium hydride followed by an additîonal 400 ml. of dimethoxyethane. After stirring overnight the suspension is cooled to 4C and a solution of 31.2 g. (-0.27 mol.~ of sulfamoyl chloride in 600 ml. of dimethoxyethane is added dropwise. The resulting suspension is stirred overnight at room temperature. The mixture is then filtered, the filtrate is concentrated and the residue washed with heptane. The residue is then chromatographed through SilicAR, CC-7 and eluted with 25~ acetone-chloroform.
The solid obtained after removal of the solvent is crystallized from a mixture of ethyl acetate-hexane-methylene chloride to afford 2-methyl-2-propyl-1,3-bis-O-sulfamyl-1,3-propanediol, m.p. 92-94C.
When in the above procedure 2-ethyl-2-propyl-1,3-propanediol, 2,2-dimethyl-1,3-propanediol and 2-methyl-1,3-propanediol are employed instead of 2-methyl-2-propyl-1,3-propanediol, 2-ethyl-2-propyl-1,3-bis-O-sulfamyl-1,3-propanediol, 2,2-dimethyl-1,3-bis-O-sulfamyl-1,3-propanediol and 2-methyl-1,3-bis-O-sulfamyl-1,3-propanediol, respectively, are obtained.
2,2-Diphenyl-1,3-bis-O-sulfamyl-1,3-propanediol To a solution of 17.3 g. (0.076 mol.) of 2,2-diphenyl-1,3-propanediol in 200 ml. of dimethoxyethane is added 12.7 g. ~0.3 mol.l of 57% sodium hydride followed by an additional 400 ml. of dimethoxyethane. After stirring overnight the suspension is cooled to 4C. A solution of 31.2 g. (0.27 mol.l of sulfamoyl chloride in 600 ml. of dimethoxyethane is then added dropwise. The suspension is stirred overnight at room temperature. After filtering the 108~9~
mixture the filtrate is concentrated and the residue washed with heptane. Chromatography on SilicA~R, CC-7, followed by crystallization affords 2,2-diphenyl-1,3-bis-O-sulfamyl-1,3-propanediol.
When in the above procedure 2,2-dibenzyl-1,3-propanediol and 2,2-dicyclohexyl-1,3-propanediol are employed in place of 2,2-diphenyl-1,3-propanediol, 2,2-dibenzyl-1,3-bis-O-sulfamyl-1,3-propanediol and 2,2-dicyclohexyl-1,3-bis-O-sulfamyl-1,3-propanediol are obtained.
1,2-Bis-O-(N,N-dimethylsulfamyl~-l, `
2-ethanediol A 57~ oil dispersion of sodium hydride (8.45 g.;
0.20 mol.l is added to a solution of ethylene glycol (3.1 g.; 0.05 mol.~ in 1,2-dimethoxyethane (100 ml.). The resulting suspension is stirred at room temperature for two hours and then cooled to +4C. N,N-dimethylsulfamoyl chloride, 25.8 g. ~0.18 mol.l, is dissolved in 1,2-dimethoxy-, ethane ~400 ml.) and added dropwise to the solution with -~
stirring. The reaction mixture is stirred at +4C for an -additional 24 hours. A precipitate forms which is filtered off and the filtrate is concentrated. The residue is - partitioned between heptane and methanol, and the methanol solution is concentrated to a syrup which crystallizes from ethyl acetate to yield 1,2-bis-O-~N,N-dimethylsulfamyl)-l, :
2-ethanediol.
When in the above procedure N,N-diphenylsulfamoyl chloride and N-ethylsulfamoyl chloride are employed in place of sulfamoyl chloride, 1,2-bis-O-(N,N-diphenylsulfamyl)-1,2-ethanediol and 1,2-bis-O-(N-ethylsulfamyl)-1,2-ethanediol -~
are obtained.
"' ' ' '' `
--10-- , .
: :' -, 108Zl9~
When in the above procedure N-cyclohexylsulfamoyl chloride, N,N-cyclopentylsulfamoyl chloride, N,N-dibenzyl-sulfamoyl chloride and l-piperidylsulfonyl chloride are employed ïn place of sulfamoyl chloride, 1,2-bis-O-(N-cyclohexysulfamyl~-1,2-ethanediol, 1,2-bis-O-(N,N-dicyclopentyl-sulfamyl~-1,2-ethanediol, 1,2-bls-O-(N,N-dibenzylsulfamyl~-1,2-ethaned;ol and 1,2-bis-~1-piperidylsulfonyl)-1,2-ethanediol are obtained.
1,2-Bis--O--sulfamyl-1,2-ethanediol Ethylene glycol ~21.7 ml., 0.385 mol.) is added dropwise during 15 mins. to a suspension of sodium hydride C37 g. 50% m.o., 0.77 mol.~ in toluene (450 ml.) at room temperature. The suspension is stirred for 15 mins., then i warmed slowly to 45-50C and stirred at that temperature for , 2.5 hrs. The reaction mixture is then cooled to 20C and a solution of t- butyl-sulfamoyl chloride ~132 g., 0.77 mol.) in toluene ~131 ml.~ is added dropwise at 20-35C during 1.25 hrs. Heavy foaming occurs during the addition, and cooling is required to maintain the temperature at 20-35C. -The resulting tan colored viscous suspension is stirred for 2.5 hrs. at 20C, then for 1.5 hrs. at 45-50C and then for 16 hrs. without further heating. The gelatinous solid which forms is collected by filtration, washed with toluene, and extracted twice with hot chloroform (600 ml., 300 ml.).
The solids which remain are then suspended in water (500 ml.) and extracted with chloroform until no solid remains. The chloroform extracts are combined and evaporated. The resulting solid is crystallized from chloroform/heptane to afford 72.26 g. ~56.4%~ of 1,2-b -O-~N-t-buty-lsulfamyl~-l, 2-... . .
' , , 1082~94 ethanediol, m.p. 119-121~ The crystalline compound (llQ g., 0.33 mol.l is added to CF3CO2H C330 ml ) with stirring at 25 under N2. The resulting clear solution is stirred at room temperature for 20 hrs. The solid is ; collected by filtration, w-ashed wïth CHC13 (2 x 50 ml.l and ; dried _ vacuo at 50-55 to afford the crude product C61.1 g. 84~T The crude material (61.1 g.~ is dissolved in acetone C185 ml.~ at reflux temperature and treated with charcoal C1.2 g.). The charcoal suspension is refluxed for 5 mins. and then filtered through Supercel.
The colorless filtrate is treated with CHC13 (185 ml.), cooled and stirred at 0-5 for 1 hr. The solid which settles out is collected by filtration and dried in vacuo --at 50-55 to afford 54.0 g. (75.5~1 of 1,2-bls-O-sulfamyl-1,2-ethanediol, m.p. 98.5-101.
l,10-Bis-O-sulfamyl-l,10-decanediol -~
l,10-Bis-O-sulfamyl-l,10-decanediol is prepared in the s-ame manner as 1,2-bis-O-sulfamyl-1,2-ethanediol in Example 8 except that l,10-decanediol (67 g., 0.385 mol.) ~-is employed as the alkanediol.
When in the above procedure 1,6-hexanediol is employed in place of l,10-decanediol, 1,6-bis-O-sulfamyl-1,6-hexanediol is obtained.
EXAMPLE lQ
1,4-Bis-O-sulfamyl-1,4-butanediol ..... ...... .
1,4-Bis-O-sulfamyl-1,4-butanediol is prepared in the same manner as 1,2-bis-O-sulfamyl-1,2-ethanediol in Example 8 except that 1,4-butanediol (34.6 g., 0.385 mol.) ~ 30 is employed as the alkanediol.
.
- . :.:, .... . .
,, . ,:- ,: :: , - . '."' ' ,~ , . .
- , , ~ , : :
.. . .. . . . ..
When in the above procedure 1,7-heptanediol is employed in place of 1,4-butanediol, 1.7-bls-O-sulfamyl-1,7-heptanediol is obtained.
1 7 3-sis-o-sulfamyl-l~3-propanediol 1,3-Bis-O-sulfamyl-1,3-propanediol is prepared in the same manner as 1,2-bis-O-sulfamyl-1,2-ethanediol in Example 8 except that 1,3-propanediol (29.~ g., 0.385 mol.) is employed as the alkanediol.
When in the above procedure 1,8-octanediol and l,9-nonanediol are employed in place of 1,3-propanediol, 1,8-bis-O-sulfamyl-1,8-octanediol and l,9-bis-O-sulfamyl-l,9-nonanediol, respectively, are o~tained.
2-Methyl-2-propyl-1,3-bis-O-sulfamyl-1,3-propanediol 2-Methyl-2-propyl-1,3-bis-O-sulfamyl-1,3-propanediol is prepared in the same manner as 1,2-b -O-sulfamyl-1,2-ethanediol in Example 8 except that 2-methyl-2-propyl-1,3-propanediol (50.8 g., 0.385 mol.) is employed as the alkanediol.
When in the above procedure 2-ethyl-2-propyl-1,3-propanediol, 2,2-dimethyl-1,3-propanediol and 2-methyl-1,3-~ propanediol are employed instead of 2-methyl-2-propyl-1,3-- propanediol, 2-ethyl-2-propyl-1,3-b -O-sulfamyl-1,3-- propanediol, 2,2-dimethyl-1,3-bis-O-sulfamyl-1,3-propanediol and 2-methyl-1,3-bis-O-sulfamyl-1,3-propanediol, respectively, are obtained.
2,2-Diphenyl-1,3-bis-0-sulfamyl-1,3-propanediol 2,2-Diphenyl-1,3-bis-O-sulfamyl-1,3-propanediol is prepared in an identical manner as the sulfamate reported ': ' ; :. -in Example 8 except for the use of 2,2-diphenyl-1,3-propanediol (87.7 g., 0.385 mol.) as the alkanediol.
When in the above procedure 2,2--dibenzyl-1,3-propanediol and 2,2-dicyclohexyl-1,3-propanediol are employed in place of 2,2-diphenyl--1,3-propanediol, 2,2-dibenzyl-1,3-bis--O-sulfamyl-1,3-propanediol and 2,2-dïcyclohexyl-1,3-bis-o-sulfamyl-1,3-propanediol are obtained.
Preparation of t-butyl-sulfamoyl chloride t-Butylamine (65.7 g., 0.90 mol.~ is added during 1 hr. at 20-30C to a stirred solution of sulfuryl chloride (240 ml., 3 mol.~ in acetonitrile ~450 ml.~. A vigorous evolution of hydrogen chloride takes place and the amine hydrochloride settles out of solution. The mixture is refluxed for 24 hrs. and additional sulfuryl chloride ::
(240 ml.) is added. After stirring and refluxing the mixture ~ -for 40 hrs., a more complete solution forms. The solution is concentrated in vacuo to a viscous oil which is distilled under reduced pressure. A main fraction is collected at 89--94C, 0.3-0.5 mm., 100.1 g., 64.896 yield. On standing, transparent, needle-like crystals of t-butyl-sulfamoyl chloride form, m.p. 23-3~C.
'~
- .
" . . . . . . . .
'' : ', '' , , ~ , .
Claims (20)
1. A process for preparing a compound of the formula:
I
wherein n is an integer from 0 to 8 and X and Y are hydrogen;
provided that when n is 1, X and Y are hydrogen, lower alkyl, of 1 to 3 carbon atoms, phenyl, benzyl or phenethyl; R1 and R2 are hydrogen, alkyl of 1 to 7 carbon atoms, benzyl, phenethyl or cycloalkyl having 5 to 6 carbon atoms or R1 and R2 together with the N-atoms to which they are attached form a saturated heterocyclic ring: characterized by a) reacting a compound of the formula:
II
with a compound of the formula (Halide)-SO2NR1R2 in a suitable solvent in the presence of a strong base or b) alternatively reacting an alkanediol of the formula II
with a substituted sulfamoyl halide of the formula :
RNHSO2 (halide) in the presence of a strong base and a suitable solvent, and treating the resulting intermediate compound with acid, wherein n, X and Y are as defined above, and R is a protecting group capable of being removed by acid, in order to prepare a compound of the formula I '
I
wherein n is an integer from 0 to 8 and X and Y are hydrogen;
provided that when n is 1, X and Y are hydrogen, lower alkyl, of 1 to 3 carbon atoms, phenyl, benzyl or phenethyl; R1 and R2 are hydrogen, alkyl of 1 to 7 carbon atoms, benzyl, phenethyl or cycloalkyl having 5 to 6 carbon atoms or R1 and R2 together with the N-atoms to which they are attached form a saturated heterocyclic ring: characterized by a) reacting a compound of the formula:
II
with a compound of the formula (Halide)-SO2NR1R2 in a suitable solvent in the presence of a strong base or b) alternatively reacting an alkanediol of the formula II
with a substituted sulfamoyl halide of the formula :
RNHSO2 (halide) in the presence of a strong base and a suitable solvent, and treating the resulting intermediate compound with acid, wherein n, X and Y are as defined above, and R is a protecting group capable of being removed by acid, in order to prepare a compound of the formula I '
2. A process for preparing 1,2-bis-0-sulfamyl-1, 2-ethanediol, comprising reacting sulfamoyl chloride with ethylene glycol.
3. A process for preparing 1,3-bis-0-sulfamyl-1,3-propanediol, comprising reacting sulfamoyl chloride with 1,3-propanediol.
4. A process for preparing 1,4-bis-0-sulfamyl-1,4-butanediol, comprising reacting sulfamoyl chloride with 1,4-butanediol.
5. A process for preparing 1,10-bis-0-sulfamyl-1,10-decanediol, comprising reacting sulfamoyl chloride with 1,10-decanediol.
6. A process for preparing 2-methyl-2-propyl-1,3-bis-0-sulfamyl-1,3-propanediol, comprising reacting sulfamoyl chloride with 2-methyl-2-propyl-1,3-propanediol.
7. The process of Claim 1, step b) wherein the-substituted sulfamoyl halide is t-butylsulfamoyl chloride.
3. The process of Claim 1, step b) wherein the acid is trifluoroacetic acid.
9. The process of Claim 1, step b) wherein the base is sodium hydride.
10. The process of Claim 1, step b) wherein n is 0.
11. The process of Claim 1, step b) wherein n is 1 and X and Y are hydrogen.
12. The process of Claim 1, step b) wherein n is 2 and X and Y are hydrogen.
13. The process of Claim 1, step b) wherein n is ? and X and Y are hydrogen.
14. The process of Claim 1, step b) wherein n is 1, X is methyl and Y is ethyl.
- 15. A compound of the formula I
wherein n is an integer from 0 to 8 and X and Y are hydrogen;
provided that when n is 1, X and Y are hydrogen, lower alkyl of 1 to 3 carbon atoms, phenyl, benzyl or phenethyl, R1 and R2 are hydrogen, alkyl of 1 to 7 carbon atoms, phenyl, aryl, benzyl, phenethyl, or cycloalkyl of 5 to 6 carbon atoms or R1 and R2 together with the N-atom to which they are attached form a saturated heterocyclic ring;
whenever prepared according to the process claimed in claim 1, or by the obvious chemical equivalent thereof.
- 15. A compound of the formula I
wherein n is an integer from 0 to 8 and X and Y are hydrogen;
provided that when n is 1, X and Y are hydrogen, lower alkyl of 1 to 3 carbon atoms, phenyl, benzyl or phenethyl, R1 and R2 are hydrogen, alkyl of 1 to 7 carbon atoms, phenyl, aryl, benzyl, phenethyl, or cycloalkyl of 5 to 6 carbon atoms or R1 and R2 together with the N-atom to which they are attached form a saturated heterocyclic ring;
whenever prepared according to the process claimed in claim 1, or by the obvious chemical equivalent thereof.
18
16. The compound 1,2-bis-0-sulfamyl-1,2-ethanediol whenever prepared according to the process claimed in claim 2, or by the obvious chemical equivalent thereof.
17. The compound 1,3-bis-0-sulfamyl-1,3-pro-panediol whenever prepared according to the process claimed in claim 3, or by the obvious chemical equivalent thereof.
18. The compound 1,4-bis-0-sulfamyl-1,4-butanediol whenever prepared according to the process claimed in claim 4, or by the obvious chemical equivalent thereof.
19. The compound 1,10-bis-0-sulfamyl-1,10-decanediol whenever prepared according to the process claimed in claim 5 , or by the obvious chemical equivalent thereof.
20. The compound 2-methyl-2-propyl-1,3-bis-0-sulfamyl-1,3-propanediol whenever prepared accordins to the process claimed in claim 6, or by the obvious chemical equivalent thereof.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/537,613 US3997585A (en) | 1974-12-30 | 1974-12-30 | Aliphatic sulfamates |
| US537,613 | 1974-12-30 | ||
| US05/618,998 US4061663A (en) | 1975-10-02 | 1975-10-02 | Process for preparation of aliphatic primary sulfamates |
| US618,998 | 1975-10-02 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1082194A true CA1082194A (en) | 1980-07-22 |
Family
ID=27065556
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA239,484A Expired CA1082194A (en) | 1974-12-30 | 1975-11-12 | Aliphatic sulfamates |
Country Status (11)
| Country | Link |
|---|---|
| JP (1) | JPS5198217A (en) |
| AT (1) | AT357998B (en) |
| CA (1) | CA1082194A (en) |
| CH (1) | CH617184A5 (en) |
| DE (1) | DE2559210A1 (en) |
| DK (1) | DK579975A (en) |
| FR (1) | FR2296410A1 (en) |
| GB (1) | GB1524727A (en) |
| NL (1) | NL7514794A (en) |
| NO (1) | NO141607C (en) |
| SE (1) | SE7514459L (en) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5194446A (en) * | 1989-06-12 | 1993-03-16 | A. H. Robins Company, Incorporated | Compounds having one or more aminosulfaonyloxy radicals useful as pharmaceuticals |
| US5273993A (en) * | 1989-06-12 | 1993-12-28 | A. H. Robins Company, Incorporated | Compounds having one or more aminosulfonyloxy radicals useful as pharmaceuticals |
| PT94305B (en) * | 1989-06-12 | 1997-02-28 | Robins Co Inc A H | METHOD FOR PREPARING COMPOUNDS HAVING ONE OR MORE USED AMINOSULFONYLOXIDE RADIATIONS AS PHARMACEUTICAL PRODUCTS |
| US6476011B1 (en) | 1991-08-28 | 2002-11-05 | Sterix Limited | Methods for introducing an estrogenic compound |
| US6011024A (en) | 1991-08-28 | 2000-01-04 | Imperial College Of Science Technology & Medicine | Steroid sulphatase inhibitors |
| US6903084B2 (en) | 1991-08-29 | 2005-06-07 | Sterix Limited | Steroid sulphatase inhibitors |
| KR970027051A (en) * | 1995-11-02 | 1997-06-24 | 조규향 | Novel Sulfamate Compounds Containing Carbamoyl Groups |
| ES2154840T3 (en) * | 1995-11-02 | 2001-04-16 | Sk Corp | NEW SULFAMATE COMPOUND CONTAINING A CARBAMOIL GROUP REPLACED IN N AND METHOD TO PREPARE IT. |
| US7335650B2 (en) | 2000-01-14 | 2008-02-26 | Sterix Limited | Composition |
-
1975
- 1975-11-12 CA CA239,484A patent/CA1082194A/en not_active Expired
- 1975-11-27 GB GB48763/75A patent/GB1524727A/en not_active Expired
- 1975-11-27 NO NO754009A patent/NO141607C/en unknown
- 1975-12-04 CH CH1580475A patent/CH617184A5/en not_active IP Right Cessation
- 1975-12-16 FR FR7538528A patent/FR2296410A1/en active Granted
- 1975-12-18 NL NL7514794A patent/NL7514794A/en unknown
- 1975-12-19 SE SE7514459A patent/SE7514459L/en unknown
- 1975-12-19 DK DK579975A patent/DK579975A/en unknown
- 1975-12-23 JP JP50152961A patent/JPS5198217A/ja active Pending
- 1975-12-29 AT AT986175A patent/AT357998B/en not_active IP Right Cessation
- 1975-12-30 DE DE19752559210 patent/DE2559210A1/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| CH617184A5 (en) | 1980-05-14 |
| NO141607B (en) | 1980-01-02 |
| AT357998B (en) | 1980-08-11 |
| NL7514794A (en) | 1976-07-02 |
| JPS5198217A (en) | 1976-08-30 |
| DK579975A (en) | 1976-07-01 |
| NO141607C (en) | 1980-04-09 |
| GB1524727A (en) | 1978-09-13 |
| NO754009L (en) | 1976-07-01 |
| DE2559210A1 (en) | 1976-07-01 |
| SE7514459L (en) | 1976-07-01 |
| ATA986175A (en) | 1980-01-15 |
| FR2296410B1 (en) | 1979-09-21 |
| FR2296410A1 (en) | 1976-07-30 |
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