NO742587L - - Google Patents
Info
- Publication number
- NO742587L NO742587L NO742587A NO742587A NO742587L NO 742587 L NO742587 L NO 742587L NO 742587 A NO742587 A NO 742587A NO 742587 A NO742587 A NO 742587A NO 742587 L NO742587 L NO 742587L
- Authority
- NO
- Norway
- Prior art keywords
- ethyl
- methyl
- reaction
- pyrrolidine
- methoxy
- Prior art date
Links
- 238000000034 method Methods 0.000 claims description 14
- UNRBEYYLYRXYCG-UHFFFAOYSA-N (1-ethylpyrrolidin-2-yl)methanamine Chemical compound CCN1CCCC1CN UNRBEYYLYRXYCG-UHFFFAOYSA-N 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- ZQSFLXDMGBSJKV-UHFFFAOYSA-N ethyl 2-methoxy-5-sulfamoylbenzoate Chemical compound CCOC(=O)C1=CC(S(N)(=O)=O)=CC=C1OC ZQSFLXDMGBSJKV-UHFFFAOYSA-N 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 12
- AUKXFNABVHIUAC-UHFFFAOYSA-N pyrrolidin-2-ylmethylamine Chemical compound NCC1CCCN1 AUKXFNABVHIUAC-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- BGRJTUBHPOOWDU-NSHDSACASA-N (S)-(-)-sulpiride Chemical compound CCN1CCC[C@H]1CNC(=O)C1=CC(S(N)(=O)=O)=CC=C1OC BGRJTUBHPOOWDU-NSHDSACASA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- FKCMADOPPWWGNZ-YUMQZZPRSA-N [(2r)-1-[(2s)-2-amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1B(O)O FKCMADOPPWWGNZ-YUMQZZPRSA-N 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 229960004940 sulpiride Drugs 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-O azanium;hydron;hydroxide Chemical compound [NH4+].O VHUUQVKOLVNVRT-UHFFFAOYSA-O 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- LZDKZFUFMNSQCJ-UHFFFAOYSA-N 1,2-diethoxyethane Chemical compound CCOCCOCC LZDKZFUFMNSQCJ-UHFFFAOYSA-N 0.000 description 1
- 208000004547 Hallucinations Diseases 0.000 description 1
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 239000012056 semi-solid material Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
- C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyrrole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Fremgangsmåte ved fremstilling Method of manufacture
av et benzamid- derivatof a benzamide deriv
Foreliggende oppfinnelse angår en ny meget økonomisk industriell fremgangsmåte for fremstilling av N-[(ethyl-l-pyrrolidinyl-2)-methyl ] -methoxy-2-sulf amoy1-5-benzamid , "sulpiride", en kjent neuro-*-lektiv ikke-sedativ anti-hallusinasjonsforbindelse. The present invention relates to a new very economical industrial process for the production of N-[(ethyl-1-pyrrolidinyl-2)-methyl]-methoxy-2-sulfamoyl-5-benzamide, "sulpiride", a known neuro-*-lective non-sedative anti-hallucination compound.
Sulpiride er en nylig fremkommet droge som har gitt utmerkede resultater på det psykiatrisk-medisinske felt, også ved administra-sjon sammen med forbindelser med psykosedativ virkning. Sulpiride is a recently developed drug that has produced excellent results in the psychiatric-medical field, also when administered together with compounds with psychosedative effects.
Denne forbindelse, skjønt den er innbefattet i den generelle formel av forbindelser krevet i fransk patent nr. 1.472.025, ble for første gang virkelig beskrevet og fremstilt (ved en forskjellig fremgangsmåte fra den som er beskrevet i fransk patent nr. l.Zf72.025) This compound, although included in the general formula of compounds claimed in French Patent No. 1,472,025, was for the first time actually described and prepared (by a different method from that described in French Patent No. 1.Zf72. 025)
i BSM6833 og 6834 M. in BSM6833 and 6834 M.
I henhold til dette går den eneste hittil kjente fremgangsmåte for fremstilling av sulpiride ut på å omsette ethyl-2-methoxy-5-sulfamid-benzoat oppløst i diethylglycol ved 90°C med 2-amino-methyl-pyrrolidin, som også er oppløselig i glycol , under anvendelse av et overskudd av pyrrolidin-derivatet på 20% over den støkio-metriske mengde. Reaksjonsblandingen holdes ved 50 - 55°C i According to this, the only hitherto known method for the preparation of sulpiride consists in reacting ethyl-2-methoxy-5-sulfamide-benzoate dissolved in diethylglycol at 90°C with 2-amino-methyl-pyrrolidine, which is also soluble in glycol, using an excess of the pyrrolidine derivative of 20% over the stoichiometric amount. The reaction mixture is kept at 50 - 55°C i
64 timer. Ved utløpet av denne tid er reaksjonen avsluttet.64 hours. At the end of this time, the reaction is finished.
Det fraskilte rensede sulpiricte har et smeltepunkt på 179 - 180°C og fåes med utbytter på ca. 80%. The separated purified sulpiricte has a melting point of 179 - 180°C and is obtained with yields of approx. 80%.
Det har nu forbausende vist seg at det er mulig å forbedreIt has now surprisingly proven that it is possible to improve
den kjente fremgangsmåte sterkt ved fullstendig å forandre reaksjons-betingelsene på'en måte som ikke kunne forutsees av en fagmann. the known method greatly by completely changing the reaction conditions in a way that could not be foreseen by one skilled in the art.
Tvert imot alle forventninger har det vist seg at ved direkte å omsette ethyl-2-methoxy-5-sulfamid-benzoat med 2-amino-methyl-pyrrolidin i fravær av reaksjonsmidler og under bestemte kritiske betingelser, fåes en uforutsebar forbedring fra synspunktet industriell anvendelse av fremgangsmåten. Contrary to all expectations, it has been shown that by directly reacting ethyl-2-methoxy-5-sulfamide-benzoate with 2-amino-methyl-pyrrolidine in the absence of reactants and under certain critical conditions, an unpredictable improvement is obtained from the point of view of industrial application of the procedure.
Mere presist har det vist seg at ved å blande ethyl-2-methoxy-5-sulfamid-benzoat med 2-arnino-methylpyrrolidin i en blander i det støkiometriske forhold, eller med et svakt overskudd av pyrrolidin-derivatet, i en inert atmosfære (nitrogen) ved en temperatur mellom 80 og 90 C, fort rinnsvis ca. 85 C, er reaksjonen fullstendig i løpet av 8 timer. More precisely, it has been shown that by mixing ethyl-2-methoxy-5-sulfamide-benzoate with 2-arnino-methylpyrrolidine in a mixer in the stoichiometric ratio, or with a slight excess of the pyrrolidine derivative, in an inert atmosphere ( nitrogen) at a temperature between 80 and 90 C, rapidly running approx. 85 C, the reaction is complete within 8 hours.
Et meget rent produkt fåes med smeltepunkt 180 - 181°C med utbytter på 90 - 93% med hensyn på ethyl-2-methoxy-5-sulfamid-benzoatet . A very pure product is obtained with a melting point of 180 - 181°C with yields of 90 - 93% with respect to the ethyl-2-methoxy-5-sulfamide benzoate.
Større utbytter fåes ved å gjenvinne det uomsatte pyrrolidin-derivat og resirkulere det i prosessen, idet denne gjenvinning ikke byr på noen spesielle vanskeligheter. Greater yields are obtained by recovering the unreacted pyrrolidine derivative and recycling it in the process, as this recovery does not present any particular difficulties.
Den nye fremgangsmåte ifølge oppfinnelsen var fullstendig uforutsebar, idet det er en vanlig oppfatning at nærværet av et reaksjonsmiddel, et oppløsningsmiddel for reagensene, letter og på-skynder reaksjonen. The new method according to the invention was completely unpredictable, as it is a common belief that the presence of a reaction agent, a solvent for the reagents, facilitates and accelerates the reaction.
Muligheten for å arbeide under de nye betingelser med den støkiometriske mengde 2-amino-methyl-pyrrolidin var også uforutsebar. Den spesifikke, kritiske anvendelse av ethyl-2-methoxy-5-sulfamid-benzoat var også fullstendig uforutsebar i lys av det forhold at hverken methylester, som notorisk er mere ^reaktiv enn ethylester , eller den tilsvarende propylester gjør det mulig å.utføre den nye fremgangsmåte, av forskjellige grunner. The possibility of working under the new conditions with the stoichiometric amount of 2-amino-methyl-pyrrolidine was also unpredictable. The specific, critical use of ethyl-2-methoxy-5-sulfamide-benzoate was also completely unpredictable in light of the fact that neither methyl ester, which is notoriously more reactive than ethyl ester, nor the corresponding propyl ester make it possible to carry it out new procedure, for various reasons.
Blanderen som anvendes ved den nye fremgangsmåte, er en Z-blander som aldri tidligere har vært anvendt i den kjemiske industri som en reaktor for utførelse av en reaksjon. The mixer used in the new method is a Z-mixer which has never before been used in the chemical industry as a reactor for carrying out a reaction.
Anvendelsene som er forutsett ved dens konstruksjon, står i forbindelse med knusning og blanding av faste og halvfaste materialer. Anvendelse av denne type blander må også betraktes som oppfinnerisk, idet det ikke er antydet ved noen presedens i teknikkens stand og ved at det har muliggjort løsningen av et ellers uløselig teknisk problem. Forholdet er at fremgangsmåten ifølge foreliggende oppfinnelse ikke kan utføres ved noe av de tidligere kjente kjemiske apparater forsynt med normale systemer for omrøring, og alle forsøk som har vært gjort i denne retning, førte fagfolkene til den konklu-sjon at det ikke var mulig direkte å omsette ethyl-2-methoxy-5-sulf-amid-benzoat med 2-amino-methyl-pyrrolidin i fravær av et passende opp-løsningsmiddel-reaksjonsmiddel. The applications foreseen by its construction are related to the crushing and mixing of solid and semi-solid materials. The use of this type of mixer must also be regarded as inventive, as it is not indicated by any precedent in the state of the art and by the fact that it has enabled the solution of an otherwise insoluble technical problem. The situation is that the method according to the present invention cannot be carried out with any of the previously known chemical devices equipped with normal systems for stirring, and all attempts that have been made in this direction led the experts to the conclusion that it was not possible directly to react ethyl-2-methoxy-5-sulfamide-benzoate with 2-amino-methyl-pyrrolidine in the absence of a suitable solvent-reagent.
Hovedfordelene ved den nye fremgangsmåte ifølge oppfinnelsen i forhold til teknikkens stand består i det vesentlige i: sparing av reaksjonsoppløsningsmiddel og eliminering av den relative gjenvinn-ingssyklus, store besparelser av 2-amino-methyl-pyrrolidin, et meget dyrt reagens: betraktelig økning i utbytter av meget rent produkt, eksoterm reaksjon slik at reaksjonsmassen spontant holdes ved den kritiske temperatur på 80 - 85°C inntil slutten av reaksjonen, uten ytterligere tilførsel av varme; nedsettelse av reaksjonstiden fra 64 til ca. 8 timer; anvendelse av et meget enkelt apparat. The main advantages of the new method according to the invention in relation to the state of the art essentially consist in: saving of reaction solvent and elimination of the relative recovery cycle, large savings of 2-amino-methyl-pyrrolidine, a very expensive reagent: considerable increase in yields of very pure product, exothermic reaction so that the reaction mass is spontaneously maintained at the critical temperature of 80 - 85°C until the end of the reaction, without further input of heat; reduction of the reaction time from 64 to approx. 8 hours; application of a very simple device.
Den nye fremgangsmåte ifølge oppfinnelsen .illustreres og for-klares bedre i detalj i eksemplet. The new method according to the invention is illustrated and explained in better detail in the example.
EksempelExample
20 kg N-ethyl-2-amino-methyl-pyrrolidin (156 mol) og 40 kg ethyl-2-methoxy-5-sulfamoyl-benzoat (154 mol) helles i en Z-blander, og temperaturen på blandingen bringes til 85°C. Til å begynne med dannes en oppløsning fra hvilken krystaller begynner å utskilles, og massen overføres efter hvert til et krystallinsk pulver. Reaksjonen er eksoterm, og temperaturen holdes spontant ved 80 - 85°C uten ytterligere tilførsel av varme. Reaksjonen er avsluttet i løpet av ca. 20 kg of N-ethyl-2-amino-methyl-pyrrolidine (156 mol) and 40 kg of ethyl-2-methoxy-5-sulfamoyl-benzoate (154 mol) are poured into a Z-mixer, and the temperature of the mixture is brought to 85° C. To begin with, a solution is formed from which crystals begin to separate, and the mass is gradually transferred to a crystalline powder. The reaction is exothermic, and the temperature is maintained spontaneously at 80 - 85°C without additional input of heat. The reaction is completed within approx.
8 timer. Det erholdte pulver oppløses ved 6o - 70° C i l6o liter8 hours. The powder obtained is dissolved at 6o - 70° C in 160 litres
1 N saltsyre (oppløsnings-pH ca. 4~5).1 N hydrochloric acid (solution pH approx. 4~5).
Der avkjøles, sentrifugeres og vaskes med 40 liter 50%--ig ethylalkohol. Hydrokloridet erholdt fra krystallisasjonen oppløses i 1000 - 1200 liter vann ved 30°C, og den erholdte oppløsning avfarves og filtreres. Ved å tilsette ammoniumhydrat opptil pH 10 fåes et bunnfall som sentrifugeres, vaskes med 200- 300liter vann og tørres. There it is cooled, centrifuged and washed with 40 liters of 50% ethyl alcohol. The hydrochloride obtained from the crystallization is dissolved in 1000 - 1200 liters of water at 30°C, and the resulting solution is decoloured and filtered. By adding ammonium hydrate up to pH 10, a precipitate is obtained which is centrifuged, washed with 200-300 liters of water and dried.
Det erholdte produkt har en renhet over 99%, smelter ved 180 - 181°C og veier 47 - 48 kg, svarende til et utbytte på 90 - 93%. The product obtained has a purity of over 99%, melts at 180 - 181°C and weighs 47 - 48 kg, corresponding to a yield of 90 - 93%.
Morlutene fra krystallisasjonen av hydrokloridet kan i sin tur bringes til pH 10 med ammoniumhydrat, og bunnfallet som fåes, kan sentrifugeres og vaskes og tilsettes til det rå produkt av en senere sats. The mother liquors from the crystallization of the hydrochloride can in turn be brought to pH 10 with ammonium hydrate, and the resulting precipitate can be centrifuged and washed and added to the crude product of a later batch.
Det uomsatte N-ethyl-2-amino-methyl-pyrrolidin kan gjenvinnes fra alkoholen som dannes og avdestilleres i løpet av reaksjonen. The unreacted N-ethyl-2-amino-methyl-pyrrolidine can be recovered from the alcohol that is formed and distilled off during the reaction.
Claims (2)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH1050873A CH605738A5 (en) | 1973-07-18 | 1973-07-18 | Substd N-(2-pyrrolidinylmethyl)-benzamide |
Publications (1)
Publication Number | Publication Date |
---|---|
NO742587L true NO742587L (en) | 1975-02-17 |
Family
ID=4363963
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO742587A NO742587L (en) | 1973-07-18 | 1974-07-16 |
Country Status (10)
Country | Link |
---|---|
JP (1) | JPS5052053A (en) |
CA (1) | CA965425A (en) |
CH (1) | CH605738A5 (en) |
DK (1) | DK385274A (en) |
ES (1) | ES428341A1 (en) |
FI (1) | FI217174A (en) |
NL (1) | NL7409749A (en) |
NO (1) | NO742587L (en) |
SE (1) | SE399884B (en) |
YU (1) | YU196674A (en) |
-
1973
- 1973-07-18 CH CH1050873A patent/CH605738A5/en not_active IP Right Cessation
- 1973-10-26 CA CA184,323A patent/CA965425A/en not_active Expired
- 1973-12-06 JP JP48136694A patent/JPS5052053A/ja active Pending
-
1974
- 1974-07-15 YU YU01966/74A patent/YU196674A/en unknown
- 1974-07-16 FI FI2171/74A patent/FI217174A/fi unknown
- 1974-07-16 NO NO742587A patent/NO742587L/no unknown
- 1974-07-17 SE SE7409313A patent/SE399884B/en unknown
- 1974-07-17 DK DK385274A patent/DK385274A/da unknown
- 1974-07-17 ES ES428341A patent/ES428341A1/en not_active Expired
- 1974-07-18 NL NL7409749A patent/NL7409749A/en unknown
Also Published As
Publication number | Publication date |
---|---|
FI217174A (en) | 1975-01-19 |
ES428341A1 (en) | 1976-07-16 |
SE399884B (en) | 1978-03-06 |
NL7409749A (en) | 1975-01-21 |
YU196674A (en) | 1982-02-28 |
CH605738A5 (en) | 1978-10-13 |
CA965425A (en) | 1975-04-01 |
DK385274A (en) | 1975-03-03 |
SE7409313L (en) | 1975-01-20 |
JPS5052053A (en) | 1975-05-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2023071293A1 (en) | Method for preparing molnupiravir | |
NO742587L (en) | ||
CN115636790A (en) | Synthetic refining process of naphazoline hydrochloride | |
US5476948A (en) | Preparation of 5-acetoacetylamino-2-benzimidazolone | |
US7217840B2 (en) | Method for preparing 1,3,5-triaminobenzene and hydrolyzing it into high-purity phloroglucinal | |
CN111004184A (en) | Synthesis process of 4, 6-dichloropyrimidine | |
JPH02200661A (en) | Preparation of alkanesulfonamide | |
US3059029A (en) | Process for alkyl and aralkyl biguanides | |
CN111303045A (en) | Production process of 2-ethoxy-4, 6-difluoropyrimidine | |
CN110698381A (en) | Method for synthesizing N- (benzyloxycarbonyl) succinimide by one-pot two-phase method | |
CN110183355B (en) | Refining method of high-purity o-chloro mandelonitrile | |
US3346634A (en) | Process for the preparation of nu-substituted amides of diphenylacetic acid | |
CN117756625B (en) | Preparation method of o-ethoxybenzoyl chloride | |
JPS63425B2 (en) | ||
CN109535025B (en) | Preparation method of Evonib intermediate 3, 3-difluorocyclobutylamine hydrochloride | |
EP0151835B1 (en) | Process for producing pentachloronitrobenzene from hexachlorobenzene | |
US6452046B2 (en) | Process for producing 2,3,5,6-tetrachloro-1,4-benzenedicarboxylic acid | |
CN1130623A (en) | Synthesis of dL-phenylglycine by halogenating-ammoniation of phenylacetic acid | |
JPS5811938B2 (en) | Nitroanthraquinone 1- Nitroanthraquinone | |
JPH0243734B2 (en) | ||
JPH01275590A (en) | Production of alkyldihalogenophosphane | |
CN115772098A (en) | Preparation method of p-phenylene diisocyanate | |
KR920009575B1 (en) | Process for the preparation of p-substituted 6-bromo-2-cyano benzeneamine | |
CN116178128A (en) | Preparation method and application of 3-chloro-2, 4, 5-trifluoro-benzoic acid | |
US2766282A (en) | Preparation of guanidino substituted fatty acids |