CS209254B1 - Manufacturing process of 2-acetamino-p-nitroacetophenone - Google Patents
Manufacturing process of 2-acetamino-p-nitroacetophenone Download PDFInfo
- Publication number
- CS209254B1 CS209254B1 CS844266A CS844266A CS209254B1 CS 209254 B1 CS209254 B1 CS 209254B1 CS 844266 A CS844266 A CS 844266A CS 844266 A CS844266 A CS 844266A CS 209254 B1 CS209254 B1 CS 209254B1
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- nitroacetophenone
- methanol
- added
- toluene
- hydrochloric acid
- Prior art date
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- JZXFEEAAHUBNQT-UHFFFAOYSA-N n-[2-(4-nitrophenyl)-2-oxoethyl]acetamide Chemical compound CC(=O)NCC(=O)C1=CC=C([N+]([O-])=O)C=C1 JZXFEEAAHUBNQT-UHFFFAOYSA-N 0.000 title claims description 6
- 238000004519 manufacturing process Methods 0.000 title description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 33
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 8
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 claims description 7
- 150000003839 salts Chemical group 0.000 claims description 7
- MBUPVGIGAMCMBT-UHFFFAOYSA-N 2-bromo-1-(4-nitrophenyl)ethanone Chemical compound [O-][N+](=O)C1=CC=C(C(=O)CBr)C=C1 MBUPVGIGAMCMBT-UHFFFAOYSA-N 0.000 claims description 6
- 238000000354 decomposition reaction Methods 0.000 claims description 4
- 239000008346 aqueous phase Substances 0.000 claims description 3
- 235000010299 hexamethylene tetramine Nutrition 0.000 claims description 3
- 230000021736 acetylation Effects 0.000 claims description 2
- 238000006640 acetylation reaction Methods 0.000 claims description 2
- 238000002955 isolation Methods 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims 2
- 238000006243 chemical reaction Methods 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 1
- 230000002378 acidificating effect Effects 0.000 claims 1
- 150000008064 anhydrides Chemical class 0.000 claims 1
- 239000011541 reaction mixture Substances 0.000 claims 1
- 235000017557 sodium bicarbonate Nutrition 0.000 claims 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims 1
- 239000011780 sodium chloride Substances 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 4
- QGMHMZOHCYYHBA-UHFFFAOYSA-N 2-amino-1-(4-nitrophenyl)ethanone Chemical compound NCC(=O)C1=CC=C([N+]([O-])=O)C=C1 QGMHMZOHCYYHBA-UHFFFAOYSA-N 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 239000000725 suspension Substances 0.000 description 2
- 230000000397 acetylating effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000007031 hydroxymethylation reaction Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
ČeskoslovenskáSOCIALISTICKÁREPUBLIKA( 19 )Czechoslovak Socialist Republics (19)
POPIS VYNALEZU K AUTORSKÉMU OSVĚDČENÍ 209254 (11) (Bl)DESCRIPTION OF THE COPYRIGHT CERTIFICATE 209254 (11) (Bl)
(22) Přihlášeno 31 12 66(21) (PV 8442-66)(22) Registered 31 12 66 (21) (PV 8442-66)
ÚŘAD PRO VYNÁLEZYA OBJEVY (40) Zveřejněno (45) Vydáno 01 05 83 (51) Int. a.3 C 07 C 79/36 (75)OFFICE OFFICE AND DISCOVERY (40) Published (45) Released 01 05 83 (51) Int. a.3 C 07 C 79/36 (75)
Autor vynálezu NEDBAL JINDŘICH, ŠESTAJOVICE, KVTTA VRATISLAV RNDr. CSc.,Author of the invention NEDBAL JINDŘICH, ŠESTAJOVICE, KVTTA VRATISLAV RNDr. CSc.,
PRAHA a PAVIENSKÝ LADISLAV ing., HOSUVICE (54) Způsob výroby 2-acetamino-p-nitroacetofenonuPRAGUE and PAVIENSKY LADISLAV ing., HOSUVICE (54) Method of production of 2-acetamino-p-nitroacetophenone
Vynález se týká způsobu výroby 2-acetamino-p-nitroacetofenonu, důležitého meziproduktu synté-zy chloramfenikolu. 'Tato látka se dosud připravovala tak, že sepůsobením urotropinu na 2-brom-p-nitroacetofe-non v benzenu nebo toluenu získala kvartémí sůl,která se rozložila nadbytečným množstvím kyseli-ny solné a methanolu. Po oddělení toluenové nebobenzenové vrstvy se hydrochlorid 2-amino-p-nit-roacetofenon, vyloučený ve spodní vrstvě, oddělil.Tento postup má řadu nevýhod. V matečnýchlouzích, které se likvidují, se ztrácí 2-amino-p-nit-roacetofenon v množství až 3 %, poněvadž obsa-hují velké množství methanolu, ve kterém je aminvelmi dobře rozpustný. Dále dochází k manipulač-ním ztrátám při izolaci aminu.The present invention relates to a process for the preparation of 2-acetamino-p-nitroacetophenone, an important intermediate for the synthesis of chloramphenicol. This substance has so far been prepared by treating the urotropin to 2-bromo-p-nitroacetophenone in benzene or toluene to obtain a quaternary salt which is decomposed by excess amounts of hydrochloric acid and methanol. After separation of the toluene or benzene layer, the 2-amino-β-nitroacetophenone hydrochloride deposited in the lower layer is separated. This process has a number of disadvantages. Up to 3% of 2-amino-β-nitroacetophenone is lost in the mother liquors because they contain large amounts of methanol in which the amine is well soluble. Furthermore, there is a manipulation loss in the isolation of the amine.
Bylo zjištěno, že tyto nedostatky lze odstranitzpůsobem výroby 2-acetamino-p-nitroacetofeno-nu reakcí 2-brom-p-nitroacetofenonu s urotropi-nem na příslušnou kvartérní sůl, rozkladem tétosoli přebytečnou kyselinou solnou v přítomnostimethanolu a acetylací vzniklého 2-amino-p-nit-roacetofenonu podle tohoto vynálezu, jehož pod-stata spočívá v tom, že se rozklad kvartémí soli2-brom-p-nitroacetofenonu s urotropinem prová-dí v prostředí toluenu nebo benzenu pomocíteoretického množství methanolu a koncentrovanékyseliny solné, přidávané ve dvou stejných dáv- 209254 kách, přičemž první dávka kyseliny solné se přidás teoretickým množstvím methanolu a druhá sepřidá samostatně, načež se vodná fáze oddělí a v nípřítomný 2-amino-p-nitroacetofenon se o soběznámým způsobem acetyluje. Způsobem podlevynálezu se dosavadní postup zjednodušuje. Jakbylo zjištěno, základní podmínkou je co nejdoko-; nalejší vázání formaldehydu uvolňujícího se při! rozkladu urotropinové soli v množství 6 mol na ‘1 mol vznikajícího 2-amino-p-nitroacetofenonu veformě dimethylacetalu. Tento produkt vzniká vel-mi snadno, když se vytvoří příznivé podmínky, tj.když v prostředí není nadbytek kyseliny solné. Zadosud běžných podmínek bylo ve vodné fázi| přítomno značné množství volného formaldehydu, | který při následující acetylaci aminu působil nejeni hydroxymethylačně, nýbrž byl příčinou vznikuřady vedlejších produktů. Na základě těchto po-znatků byly podmínky pro rozklad urotropinovésoli upraveny tak, že do její suspenze v toluenunebo benzenu bylo přidáno vedle methanolu pouze i 1,5 molu kyseliny solné, tj. 50 % množství, kteréi odpovídá teorii, a dalších 50 % po rozrušeníi molekuly urotropinové soli (což se vizuálně projeví ,tím, že jemná suspenze této soli přejde na hruběkrystalickou formu), přidá-li se po kapkách 10—15 iminut po dávce první. Při této úpravě vznikádimethylacetal tak snadno, že se ukázal být zbyteč-It has been found that these drawbacks can be overcome by the process of producing 2-acetamino-p-nitroacetophenone by reacting 2-bromo-p-nitroacetophenone with urotrophin on the corresponding quaternary salt, decomposing this with excess hydrochloric acid in the presence of methanol and acetylating the resulting 2-amino-p -nitroacetophenone according to the invention, wherein the decomposition of the quaternary salt of 2-bromo-p-nitroacetophenone with urotropin is carried out in toluene or benzene using the theoretical amount of methanol and concentrated hydrochloric acid added in two equal portions. The first portion of hydrochloric acid is added with a theoretical amount of methanol and the second is added separately, whereupon the aqueous phase is separated and the 2-amino-p-nitroacetophenone present is acetylated in a conventional manner. The method of the invention simplifies the present process. As it was found, the basic condition is as far as possible; the more formaldehyde-releasing bonding! decomposition of urotropin salt in an amount of 6 moles per mol mole of 2-amino-p-nitroacetophenone formed in the form of dimethyl acetal. This product is very easily formed when favorable conditions are created, i.e. when there is no excess of hydrochloric acid in the environment. Previously common conditions were in the aqueous phase | a considerable amount of free formaldehyde is present which, in subsequent acetylation of the amine, did not only cause hydroxymethylation but was the cause of the byproducts. On the basis of these findings, the decomposition conditions of the urotropin salt were adjusted by adding only 1.5 moles of hydrochloric acid, i.e. 50% of the amount corresponding to the theory, to the suspension in toluene or benzene and another 50% after breaking up. urotropin salt molecules (which are visually manifested by the fine suspension of this salt being converted to a coarse-crystalline form) when 10-15 iminutes after the first dose are added dropwise. In this treatment, the dimethyl acetal was so easy that it
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS844266A CS209254B1 (en) | 1966-12-31 | 1966-12-31 | Manufacturing process of 2-acetamino-p-nitroacetophenone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS844266A CS209254B1 (en) | 1966-12-31 | 1966-12-31 | Manufacturing process of 2-acetamino-p-nitroacetophenone |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS209254B1 true CS209254B1 (en) | 1981-11-30 |
Family
ID=5434919
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS844266A CS209254B1 (en) | 1966-12-31 | 1966-12-31 | Manufacturing process of 2-acetamino-p-nitroacetophenone |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS209254B1 (en) |
-
1966
- 1966-12-31 CS CS844266A patent/CS209254B1/en unknown
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