US3152167A - Process for preparing trisubstituted methyl chloroformates - Google Patents
Process for preparing trisubstituted methyl chloroformates Download PDFInfo
- Publication number
- US3152167A US3152167A US32562A US3256260A US3152167A US 3152167 A US3152167 A US 3152167A US 32562 A US32562 A US 32562A US 3256260 A US3256260 A US 3256260A US 3152167 A US3152167 A US 3152167A
- Authority
- US
- United States
- Prior art keywords
- alcoholate
- phosgene
- methyl
- ether
- solution
- 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 - Lifetime
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/12—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C68/00—Preparation of esters of carbonic or haloformic acids
- C07C68/02—Preparation of esters of carbonic or haloformic acids from phosgene or haloformates
Definitions
- R is an alkyl or alkyne substituent
- R is an alkyl group
- R is an alkyl group, with the provisos that R and R have a total of 3 to 4 carbon atoms and R has 1 to 2 carbon atoms.
- the compounds are active when adminstered orally, rectally or parenterally. They are only slightly soluble in Water, however, and for therapeutic use, in order to ensure proper absorption and favorable therapeutic effect, they are preferably incorporated in suitable pharmaceutical carriers. In clinical use of these compounds the recommended dosage is 50 to 800 mgs., preferably 100 iidgilhl Patented Get. 6, 1954 to 400 mg, of active drug 2 to 4 times per day. Thus in preparing tablets, capsules, elixirs, suppositories or other dosage forms with pharmaceutical carriers the formulation should preferably contain to 409 mg. of active drug per dosage unit.
- a principal object of this invention is to provide the foregoing compounds in a commercially feasible and tech nically simple manner in such yields and purity as materially to lower their cost of production.
- R is an alkyl or alkyne substituent, R is an alkyl group, and R is an alkyl group, with the provisos that R and R have a total of 3 to 4- carbon atoms and R has 1 to 2 carbon atoms, is placed in contact with an alkali metal, alkali metal hydride or alkali metal amide, in the presence of an inert organic solvent.
- the reaction is continued at a temperature and for a time suflicient for formation of the corresponding alkali metal alcoholate as a solute in the inert organic solvent.
- the resulting alkali metal alcoholate solution is added to a solution of phosgene in an organic solvent to provide a reaction mixture of the solutions and the reaction mixture is maintained at a temperature and for a time suitable for formation of the corresponding chloroformate of the alcohol, i.e., a chloroformate of the formula,
- a feature of the invention is the utilization of a solution of the sodium alcoholate in the alcoholate-phosgene reaction. This procedure is of course dependent on the alkali metal alcoholate being soluble in the inert organic solvent. The solubility of the alcoholate in such solvents is surprising and is a novel discovery.
- the alcoholate is provided as a solute in an inert organic solvent, it is possible to add the alcoholate to the phosgene, and this manner of contacting the reactants is significant. If the phosgene were added to the alcoholate, which would be necessary if the alcoholate were insoluble, side reactions substantially reducing the yield would occur.
- the alkali metal alcoholate is formed in the presence of an inert solvent.
- Suitable solvents are 3 organic solvents, for example, benzene, toluene, xylene, hexane, cyclohexane, and petroleum ether.
- hydrocarbon solvents boiling at about 80 C. or above are suitable.
- the preferred solvent is toluene since it is a good solvent for the alcoholate and has a boiling point well suited for the process of the invention.
- the alcoholate dissolved in an inert solvent as described above for preparation of the alcoholate, and phosgene contained in an organic solvent are admixed.
- the inert organic solvent in which the phosgene is dissolved can be selected from among those described above as suitable for preparation of the alcoholate.
- an ether is included in the reaction mixture of the alcoholate solution and phosgene solution, and, conveniently, the olvent for the phosgene can be an ether, or can include an ether. Suitable ethers are cyclic and aliphatic others.
- the amounts of the alcoholate and phosgene reactants used can be the stoichiometric amounts.
- the use of larger amounts of the alcoholate is merely wasteful.
- An excess of phosgene can be used. Suitable phosgene excess is from about 3 to about 20%.
- the amount of solvent in which the phosgene i dissolved is not critical and can be varied over wide limits.
- small amounts exert an appreciable effect on the overall yields, of the order of 20% higher than otherwise can be realized by not employing ethers. About 0.6 mole of ether per mol of phosgene gives good results. Smaller amounts can, however, be used.
- the temperature for the alcoholate-phosgene reaction can be below C., for example in the range of 70 to C., and preferably is 40 to 50 C. While the temperatures outside the mentioned range can be used, this will usually be at the expense of significantly reduced effectiveness for the process.
- the time for the reaction can be 112 hours, and is preferably 1-2 hours, and the reaction mixture is preferably agitated during the reaction. Atmospheric pressure can be used.
- the final step wherein the cbloroformate is reacted with ammonia i a type reaction known heretofore for production of carbamates from chloroformates. It can be carried out by introducing ammonia gas or liquid into the solvent-chloroformate solution resulting from the previous step.
- the temperature can be 50 to 0 C., and is preferably to C. Temperatures outside the ranges mentioned can be used but at the expense of reduced effectiveness for the process. Stirring is desirable.
- Reaction times are commonly from 2-7 hours, and a stoichiometric amount or a slight excess of ammonia can be used.
- any one of the following compounds can be made by substitution of the corresponding alcohol for the diethylmethylcarbinol of the example:
- R is selected from the group consisting of alkyl and alkyne substituents, R is an alkyl group, and R is an alkyl group, R and R having a total of 3 to 4 carbon atoms and R haw'ng 1 to 2 carbon atoms, which comprises contacting an alcohol of the formulao 112 ⁇ OH wherein R R and R are as above, with an alkaline reagent selected from the group consisting of alkali metals, alkali metal hydrides, and alkali metal amides, in the presence of an inert organic solvent at a temperature between and the boiling point of said inert solvent, until the said alcohol is substantially transformed into the corresponding alkali metal alcoholate as a solute in said inert organic solvent, gradually adding the said alkali metal alcoholate solution to a solution of at least a stoichimetrical amount of phosgene in an inert solvent and maintaining the resultant reaction mixture below 0 C. to form said chloroformate ester.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
United States Patent "cc 3,152,167 PROCESS FOR PREPARlNG TRISUBSTITUTED METHYL CHLGROFUfiVIATES Meyer Sletzinger, North Plainfield, N.J., assignor to Merck & Co., Inc., Railway, N.J., a corporation of New Jersey No Drawing. Filed May 31, 1969, Ser. No. 32,562 9 Claims. (Cl. 269-463) This invention relates to compounds having muscle relaxing and tranquilizing action, and provides novel procedures useful in their preparation.
The active muscle relaxing and tranquilizing compounds are of the following structural formula:
wherein R is an alkyl or alkyne substituent, R is an alkyl group, and R is an alkyl group, with the provisos that R and R have a total of 3 to 4 carbon atoms and R has 1 to 2 carbon atoms.
Of particular interest as the muscle relaxing and tranquilizing compounds are the compounds described and claimed in copending application Serial No. 774,091, filed November 17, 1958, and now US. Patent 2,972,564. The compounds of the said copending application are of the above structural formula except the the Rs are of more limited meaning, R and R being alkyl substituents having a combined total of 4 carbon atoms, and R being an alkyl substituent having 1 to 2 carbon atoms.
Specific compounds embraced by Formula I are the following:
3-methyl-3-pentanol carbamate, 3-ethyl-3-pentanol carbamate, Z-methyl-Z-pentanol carbamate, 3-methyl-3-ol-pentyne-l carbamate, and 3-methyl-3-ol-butyne-l carbamate.
The following structural formulae for two of these compounds will facilitate understanding of the nomenclature employed.
zHa CH3 C2 5 OfiNHs (H) 3-methyl-3-pentano1 carbamate HCEC CH3 C2 Hs ONE:
(H) (III) 3-methy1-3-o1-pentyne-1 earbamate Compounds of Formula I above posesss muscle relaxing properties and selective tranquilizing effects on the central nervous system. They are effective as skeletal relaxants, and are useful in the management of anxiety and tension states with a minimal incidence of undesirable side elfects. These properties appear to be unique with the foregoing compounds, and are not found in even quite closely related carbamate compounds.
The compounds are active when adminstered orally, rectally or parenterally. They are only slightly soluble in Water, however, and for therapeutic use, in order to ensure proper absorption and favorable therapeutic effect, they are preferably incorporated in suitable pharmaceutical carriers. In clinical use of these compounds the recommended dosage is 50 to 800 mgs., preferably 100 iidgilhl Patented Get. 6, 1954 to 400 mg, of active drug 2 to 4 times per day. Thus in preparing tablets, capsules, elixirs, suppositories or other dosage forms with pharmaceutical carriers the formulation should preferably contain to 409 mg. of active drug per dosage unit.
A principal object of this invention is to provide the foregoing compounds in a commercially feasible and tech nically simple manner in such yields and purity as materially to lower their cost of production. Other objects will become apparent from the following description.
According to the invention, the muscle relaxing and tranquilizing compounds are made as follows: An alcohol of the formula,
wherein R is an alkyl or alkyne substituent, R is an alkyl group, and R is an alkyl group, with the provisos that R and R have a total of 3 to 4- carbon atoms and R has 1 to 2 carbon atoms, is placed in contact with an alkali metal, alkali metal hydride or alkali metal amide, in the presence of an inert organic solvent. The reaction is continued at a temperature and for a time suflicient for formation of the corresponding alkali metal alcoholate as a solute in the inert organic solvent. The resulting alkali metal alcoholate solution is added to a solution of phosgene in an organic solvent to provide a reaction mixture of the solutions and the reaction mixture is maintained at a temperature and for a time suitable for formation of the corresponding chloroformate of the alcohol, i.e., a chloroformate of the formula,
R1 R3 C R2 0001 wherein the Rs have the same meaning as above noted. Finally, the chloroformate is reacted with ammonia, to provide a compound according to Formula 1, above.
The step of forming the alcoholate solution is novel, as is also the step of reacting the alcoholate solution with the phosgene solution.
A feature of the invention is the utilization of a solution of the sodium alcoholate in the alcoholate-phosgene reaction. This procedure is of course dependent on the alkali metal alcoholate being soluble in the inert organic solvent. The solubility of the alcoholate in such solvents is surprising and is a novel discovery.
Since the alcoholate is provided as a solute in an inert organic solvent, it is possible to add the alcoholate to the phosgene, and this manner of contacting the reactants is significant. If the phosgene were added to the alcoholate, which would be necessary if the alcoholate were insoluble, side reactions substantially reducing the yield would occur.
In a preferred embodiment of the invention, in the reaction mixture obtained by adding the alcoholate solution to the phosgene solution, there is included an ether in an amount effective to provide improved yield of the chloroformate.
Going now to a more detailed discussion of the procedure according to the invention, among the reactants which can be employed in the formation of the alkali metal alcoholate are sodium metal, potassium metal, sodium amide, potassium amide, sodium hydride and potassium hydride. Other corresponding alkali metal and compounds can be used, if desired. The preferred material is alkali metal, particularly sodium.
A noted above, the alkali metal alcoholate is formed in the presence of an inert solvent. Suitable solvents are 3 organic solvents, for example, benzene, toluene, xylene, hexane, cyclohexane, and petroleum ether. In general, hydrocarbon solvents boiling at about 80 C. or above are suitable. The preferred solvent is toluene since it is a good solvent for the alcoholate and has a boiling point well suited for the process of the invention.
The amounts of the alkali metal material and alcohol used are preferably stoichiometric amounts, since the use of such amounts is more economical and provides an improved product in terms of purity. The amount of inert solvent should be an amount suflicient to dissolve the alcoholate produced. There is no upper limit. About 25 ml. of solvent per 50 grams of alcohol can be used, and preferably the amount of solvent is 40-60 ml. per 50 grams of alcohol. The temperature for the reaction can be 80 C. up to the boiling point of the solvent and the preferred temperature is the reflux temperature. Thus, if xylene is the solvent, the reflux temperature will be about 139 C. Atmospheric pressure is suitable. The time for the reaction should be until the reaction is complete, and this i indicated by the solution of all the alkali material. Up to about 18 hours for the reaction is reasonable but longer periods are uneconomical.
Preferred conditions for the alcoholate forming reaction are the use of toluene as the inert solvent, the use of sodium as the alkali material, and running the reaction at the reflux temperature of about 118 C. Under these conditions good time-yield results are obtained.
For the reaction of the alcoholate and phosgene, the alcoholate dissolved in an inert solvent as described above for preparation of the alcoholate, and phosgene contained in an organic solvent, are admixed. The inert organic solvent in which the phosgene is dissolved can be selected from among those described above as suitable for preparation of the alcoholate. esirably, an ether is included in the reaction mixture of the alcoholate solution and phosgene solution, and, conveniently, the olvent for the phosgene can be an ether, or can include an ether. Suitable ethers are cyclic and aliphatic others. For example, the ether can be tetrahydrofuran, dimethyl ether, diethyl ether, di-isopropyl ether, or dibutyl ether. The ether increases the yield of the chloroformate product. Maximum yields are obtained when the phosgene solution to which the alcoholate solution is added contains as solvent a combination of hydrocarbon solvent arid ether.
The amounts of the alcoholate and phosgene reactants used can be the stoichiometric amounts. The use of larger amounts of the alcoholate is merely wasteful. An excess of phosgene, however, can be used. Suitable phosgene excess is from about 3 to about 20%. The amount of solvent in which the phosgene i dissolved is not critical and can be varied over wide limits. As regards the amountof ether, small amounts exert an appreciable effect on the overall yields, of the order of 20% higher than otherwise can be realized by not employing ethers. About 0.6 mole of ether per mol of phosgene gives good results. Smaller amounts can, however, be used.
The temperature for the alcoholate-phosgene reaction can be below C., for example in the range of 70 to C., and preferably is 40 to 50 C. While the temperatures outside the mentioned range can be used, this will usually be at the expense of significantly reduced effectiveness for the process. The time for the reaction can be 112 hours, and is preferably 1-2 hours, and the reaction mixture is preferably agitated during the reaction. Atmospheric pressure can be used.
The final step, wherein the cbloroformate is reacted with ammonia i a type reaction known heretofore for production of carbamates from chloroformates. It can be carried out by introducing ammonia gas or liquid into the solvent-chloroformate solution resulting from the previous step. The temperature can be 50 to 0 C., and is preferably to C. Temperatures outside the ranges mentioned can be used but at the expense of reduced effectiveness for the process. Stirring is desirable.
Reaction times are commonly from 2-7 hours, and a stoichiometric amount or a slight excess of ammonia can be used.
The following examples illustrate the practice of this mvention and are not to be construed as limitations of the invention. The temperatures given are in degrees centigrade.
EXAMPLE Preparation of 3-Methyl-3-Pentan0l Carbamate (1) PREPARATION OF SODIUM SALT OF 3-METHYL-3- PENTANOL A 500 ml. round bottom flask, equipped with stirrer, thermometer, addition funnel and a condenser, which was connected to a potassium hydroxide drying tube, was flushed thoroughly with dry nitrogen. Clean sodium (11.5 g., 0.5 mole) was added to the flask followed by addition of the toluene (50 ml.). The mixture was heated to 102 at which temperature the stirring and rapid addition of the diethylmethylcarbinol (52.5 g., 515 mole) was started. The mixture was then stirred rapidly at reflux (107l09) for 20 hours until the sodium had reacted. The clear, very pale yellow solution was then cooled, under a slow stream of nitrogen to 25. An amorphous precipitate settled out which redissolved on addition of 30 ml. of toluene. An additional ml. of toluene was then added and this solution was used directly in the following phosgene reaction.
(2) PREPARATION OF 3-METHYL3-PENTANOL To a 1 liter flask, equipped with a stirrer, thermometer, subsurface gas inlet tube and calcium sulfate drying tube, was charged 350 ml. of anhydrous ether. The ether was cooled to 30 by a Dry Ice-methanol bath and phosgene gas was passed into the ether until 51 grams (0.515 mole) were dissolved. The gas inlet tube was replaced by an addition fuel containing the toluene solution of the salt of 3-methyl-3-pentanol prepared as in the preceding section of this example. 225 ml. of the sodium alcoholate solution was then added over a period of 30 minutes while maintaining the temperature at 45i2. The thick mixture was then aged at 25:3 for 1 hour. During the addition and aging period the mixture was stirred as rapidly as possible without causing excessive splattering on the upper part of the flask.
(3) PREPARATION OF 3-METHYL8-PENTANOL The addition funnel used in the preparation of 3-methyl- 3-pentanol chloroformate in the preceding section of this example was replaced by an above the surface gas inlet tube and the calcium sulfate drying tube was replaced by a tube leading to the bottom of a combustion tube containing 6 mm. of mercury. Ammonia gas from a tank was then passed into the flask with good agitation at the rate of about .5 gram/min. for 1 hour. The temperature was maintained at 25i3 during the addition by periodic cooling with a Dry Ice-methanol bath. At the end of 1 hour the reaction mixture was strongly alkaline to alkacid paper. A total of 31 grams of ammonia was used as determined by loss of Weight of the tank. The mixture was stirred for 30 minutes at 25 and allowed to warm to room temperature overnight without stirring.
To the thick slurry (volume-600 ml.) was added with stirring 25 ml. of water. The salts became considerably more dense and filtered rapidly from the organic solvents. The cake was washed with 50 ml. of benzene. The cake was then removed from the funnel and slurried with 100 ml. of benzene. The slurry was filtered and cake was Washed with an additional 50 ml. of benzene. The main filtrate and benzene washes were combined and washed with 2 x 50 ml. of water. The second wash was still alkaline. The organic solution was dried over sodium sulfate, filtered and concentrated to a thick syrup at 20 mm. and an internal temperature not exceeding 60 C. The residue crystallized on cooling and weighed 62 grams. The product was dissolved in 120 ml. of Skellysolve B brand hexane and cooled overnight at 0. The carbamate was filtered and washed by displacement with 2 x 25 ml. of cold (0) Skellysolve B. The desired carbamate was air dried at room temperature, wt. 52.0 g., 71.8%, MP. 5657. Amide N as NH =1-l.39, theory=1l.73.
In the foregoing example, instead of using metallic sodium, sodium hydride or sodium amide can be used. Further, by the procedure of the example instead of 3-methyl-3-pentanol carbamate, any one of the following compounds can be made by substitution of the corresponding alcohol for the diethylmethylcarbinol of the example:
3-ethyl-3-pentanol carbamate 2-methyl-2-pentanol carbamate 3-methyl-3-ol-pentyne-1 carbamate 3-methyl-3-ol-butyne-l carbamate While the invention has been described in detail with reference to particular embodiments thereof, it is intended that all such modifications and alterations of the disclosed embodiments as are within the scope of the appended claims be secured by these Letters Patent.
What is claimed is:
1. The process for preparing chloroformate compounds having the structural formula:
wherein R is selected from the group consisting of alkyl and alkyne substituents, R is an alkyl group, and R is an alkyl group, R and R having a total of 3 to 4 carbon atoms and R haw'ng 1 to 2 carbon atoms, which comprises contacting an alcohol of the formulao 112 \OH wherein R R and R are as above, with an alkaline reagent selected from the group consisting of alkali metals, alkali metal hydrides, and alkali metal amides, in the presence of an inert organic solvent at a temperature between and the boiling point of said inert solvent, until the said alcohol is substantially transformed into the corresponding alkali metal alcoholate as a solute in said inert organic solvent, gradually adding the said alkali metal alcoholate solution to a solution of at least a stoichimetrical amount of phosgene in an inert solvent and maintaining the resultant reaction mixture below 0 C. to form said chloroformate ester.
2. The process of claim 1 wherein there is included in said alcoholate phosgene reaction mixture an ether selected from the group consisting of di lower alkyl ether and tetrahydrofuran, the usage of said ether being approximately 0.6 mole per mole of phosgene.
3. The process of claim 1, wherein said alkali metal material is sodium.
4. The process of claim 1, wherein the inert organic solvent in the presence of which the alcoholate is formed is toluene.
5. The process for preparing 3-methyl-3-pentanol chloroformate in accordance with the process of claim 1, the alcohol starting material being 3-methyl-3-pentanol.
6. The process of preparing 3-ethyl-3-pentanol chloroformate according to the process of claim 1 in which the starting alcohol is 3-ethyl-3-pentanol.
7. The process for preparing 2-methyl-2-pentanol chloroformate according to the process of claim 1, wherein the starting alcohol is 2-methyl-2-pentanol.
8. The process for preparing 3-methyl-3-o1-pentyne-1- chloroformate according to the process of claim 1, in which the starting alcohol is 3-methyl-3-ol-pentyne.
9. The process of preparing 3-methyl-3-ol-butyne-1- chloroformate according to the process of claim 1, the starting alcohol being 3-methyl-3-ol-butyne.
References Cited in the file of this patent UNITED STATES PATENTS 2,337,172 Wojcik Dec. 21, 1943 2,430,017 Honk Nov. 4, 1947 2,816,910 Junkmann et a1 Dec. 17, 1957 FOREIGN PATENTS 1,042,601 Germany Nov. 6, 1958 OTHER REFERENCES Saunders et al.: J. Am. Chem. Soc., vol. 73, pp. 3796- 3797 (1951). Wagner and Zook: Synthetic Organic Chemistry, pp. 483-484 (1953).
Claims (1)
1. THE PROCESS FOR PREPARING CHLOROFORMATE COMPOUNDS HAVING THE STRUCTURAL FORMULA:
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US32562A US3152167A (en) | 1960-05-31 | 1960-05-31 | Process for preparing trisubstituted methyl chloroformates |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US32562A US3152167A (en) | 1960-05-31 | 1960-05-31 | Process for preparing trisubstituted methyl chloroformates |
Publications (1)
Publication Number | Publication Date |
---|---|
US3152167A true US3152167A (en) | 1964-10-06 |
Family
ID=21865587
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US32562A Expired - Lifetime US3152167A (en) | 1960-05-31 | 1960-05-31 | Process for preparing trisubstituted methyl chloroformates |
Country Status (1)
Country | Link |
---|---|
US (1) | US3152167A (en) |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2337172A (en) * | 1941-05-21 | 1943-12-21 | Hooker Electrochemical Co | Halogenated alkyl carbonates and process for producing the same |
US2430017A (en) * | 1945-03-08 | 1947-11-04 | Rohm & Haas | Mildewproofing textiles |
US2816910A (en) * | 1952-04-10 | 1957-12-17 | Schering Ag | Esters of carbamic acid and a method of making same |
DE1042601B (en) * | 1955-12-05 | 1958-11-06 | Solvay Werke Gmbh | Process for the production of mixed carbonic acid esters of highly chlorinated phenols |
-
1960
- 1960-05-31 US US32562A patent/US3152167A/en not_active Expired - Lifetime
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2337172A (en) * | 1941-05-21 | 1943-12-21 | Hooker Electrochemical Co | Halogenated alkyl carbonates and process for producing the same |
US2430017A (en) * | 1945-03-08 | 1947-11-04 | Rohm & Haas | Mildewproofing textiles |
US2816910A (en) * | 1952-04-10 | 1957-12-17 | Schering Ag | Esters of carbamic acid and a method of making same |
DE1042601B (en) * | 1955-12-05 | 1958-11-06 | Solvay Werke Gmbh | Process for the production of mixed carbonic acid esters of highly chlorinated phenols |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US5599994A (en) | Amino acid-derived diaminopropanols | |
US2789978A (en) | Dimethylaminopropyl-dipyridothiazane | |
JP2013177407A (en) | Exo- and diastereo-selective synthesis of himbacine analog | |
CA1086315A (en) | Morphanthridine derivatives | |
FR2565981A1 (en) | Novel thieno[2,3-b]pyrrole derivatives, process for their preparation and the pharmaceutical compositions which contain them | |
US3152167A (en) | Process for preparing trisubstituted methyl chloroformates | |
Ellzey Jr et al. | Interaction of Phenyl Isocyanate and Related Compounds with Sodium Borohydride1 | |
CA1055960A (en) | N,n'-disubstituted naphthaleneacetamidines | |
Isidor et al. | Synthesis of 2-methylene-4-thiazolidinones | |
US2580832A (en) | Preparation of nitrilotrispropion-amide | |
US2523275A (en) | Substituted glycinamides | |
US2870164A (en) | Process for making d, l-methysticin and d, l-dihydromethysticin | |
CA1110639A (en) | Process for producing optically active bases | |
US2842555A (en) | Method of preparing quaternary salts of amino carbinols | |
US3639468A (en) | Process for preparing amphoteric surface active agents | |
US3133964A (en) | Benzamides | |
US3055937A (en) | Substituted glycineamides | |
US4197410A (en) | N-[(N-Nitrosoalkylamino)methyl]carbamic acid esters for generating diazoalkanes | |
US3332994A (en) | Alkoxycyanamides and their preparation | |
US3651137A (en) | Selective conversion of nalpha nepsilon-diacetyllysine esters to nalpha -diacetyllysine | |
JP2810465B2 (en) | Method for producing N-methyl-4-t-butylbenzylamine | |
US4474987A (en) | Process for preparing N,N-disubstituted p-phenylenediamine derivatives | |
US2973385A (en) | Dialkylaminoalkyl chlorocarbanilates and process | |
US3264344A (en) | Arylamides of beta, beta-dimethyl-alpha, gamma-dihydroxy butyric acid and their alkanoyl ester derivatives | |
US3959379A (en) | Preparation of primary amines |