FI63750C - PROCEDURE FOR FRAMSTATION OF AV 2-OXO-PYRROLIDINE-N-ALKYLAMIDER - Google Patents
PROCEDURE FOR FRAMSTATION OF AV 2-OXO-PYRROLIDINE-N-ALKYLAMIDER Download PDFInfo
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- FI63750C FI63750C FI770088A FI770088A FI63750C FI 63750 C FI63750 C FI 63750C FI 770088 A FI770088 A FI 770088A FI 770088 A FI770088 A FI 770088A FI 63750 C FI63750 C FI 63750C
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- 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
- C07D207/18—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 one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—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 one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
- C07D207/27—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
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- 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
- C07D207/30—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 two double bonds between ring members or between ring members and non-ring members
- C07D207/34—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 two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/36—Oxygen or sulfur atoms
- C07D207/40—2,5-Pyrrolidine-diones
- C07D207/404—2,5-Pyrrolidine-diones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. succinimide
Description
RTÄS^Tl rm #·« kuulutusjulkaisu , τ η c Λ ^ ( 1) UTLÄGGNINGSSKRIFT 6 3 750 ^ τ ^ (51) K».llc.3/lnt.a.3 C 07 D 207/27 SUOMI —FINLAND (21) IWttlhakemu· —P**n**i.6»«ii»nt 770088 (22) Hakamtapllvi — AiNeknlng^ag 12.01.77 ' ' (23) Alkupllvt — Glltlfhatadag 12.01.77 (41) Tulhit lulklMkH — Bllvlt offwtMg 15.07.77 fvmta. |. rrtlrt^htllltu. μι-M— PMant· och ragirtentyrelMn ' ' Am<Mcm utiigd oeh utLskrifun pubiic*r*d 29.0U. 83 . (32)(33)(31) Pyydetty «uoikwM —Begird prtorttet lU. 01.76RTÄS ^ Tl rm # · «advertisement publication, τ η c Λ ^ (1) UTLÄGGNINGSSKRIFT 6 3 750 ^ τ ^ (51) K» .llc.3 / lnt.a.3 C 07 D 207/27 FINLAND —FINLAND (21 ) IWttlhakemu · —P ** n ** i.6 »« ii »nt 770088 (22) Hakamtapllvi - AiNeknlng ^ ag 12.01.77 '' (23) Alkupllvt - Glltlfhatadag 12.01.77 (41) Tulhit lulklMkH - Bllvlt offwtMg 15.07 .77 fvmta. |. rrtlrt ^ htllltu. μι-M— PMant · och ragirtentyrelMn '' Am <Mcm utiigd oeh utLskrifun pubiic * r * d 29.0U. 83. (32) (33) (31) Requested «uoikwM —Begird prtorttet lU. 01.76
Jugoslavia-Jugoslavien(YU) P 78/76 (71) PLIVA, Pharmaceutical and Chemical Works, Ive Lole Ribara 89»Yugoslavia-Yugoslavia (YU) P 78/76 (71) PLIVA, Pharmaceutical and Chemical Works, Ive Lole Ribara 89 »
Zagreb, Jugoilavia-Jugoslav!en(YU), Karl 0. Helm, Nordkanal- strasse 28, D-2 Hamburg 1, Saksan Liittotasavalta-Förbundsrepubliken lyskland(DE) .(72) Zdravko Cmic, Zagreb, Slobodan Djokic, Zagreb, Branimir Gaäpert,Zagreb, Yugoslavia-Yugoslavia (YU), Karl 0. Helm, Nordkanal-Strasse 28, D-2 Hamburg 1, Federal Republic of Germany (DE) (72) Zdravko Cmic, Zagreb, Slobodan Djokic, Zagreb, Branimir Gaäpert,
Zagreb, Zlatko Vajtner, Zagreb, Jugoslavia-Jugoslavien(YU),Zagreb, Zlatko Vajtner, Zagreb, Yugoslavia-Yugoslavia (YU),
Alfred Maasbol, Hamburg, Saksan Liittotasavalta-Förbundsrepubliken Tyskland(DE) (7*0 Berggren Oy Ab (5*0 Menetelmä 2-okso-pyrrolidiini-N-alkyyliamidien valmistamiseksi -Förfarande för framställning av 2-oxo-pyrrolidin-N-alkylamiderAlfred Maasbol, Hamburg, Federal Republic of Germany-Förbundsrepubliken Tyskland (DE) (7 * 0 Berggren Oy Ab (5 * 0 Process for the preparation of 2-oxo-pyrrolidine-N-alkylamides -Förfarande för framställning av 2-oxo-pyrrolidine-N-alkylamider
Tämä keksintö kohdistuu 2-okso-pyrrolidiini-N-alkyyliamidien valmistusmenetelmään, joilla on yleinen kaava IThis invention relates to a process for the preparation of 2-oxo-pyrrolidine-N-alkylamides of general formula I
(CH2)nCONH2 jossa n on kokonaisluku 1-4, pelkistämällä elektrolyyttisesti 2,5-diokso-pyrrolidiini-N-alkyyliamideja.(CH2) nCONH2 where n is an integer from 1 to 4, by electrolytic reduction of 2,5-dioxo-pyrrolidine-N-alkylamides.
On tunnettua, että yleisen kaavan I mukaisia yhdisteitä voidaan valmistaa saattamalla 2-okso-pyrrolidiini-natrium reagoimaan omega-halogeeni-alkyyliamidien kanssa (brittiläinen patentti n:o 1 039 113) sekä antamalla ammoniakin vaikuttaa 2-okso-l-pyrrolidino-alkaanihappojen estereihin tai happoklorideihin (brittiläinen patentti n:o 1 039 113) tai termisesti lyhentämällä niiden ammoniumsuolojen ketjuja (brittiläinen patentti nso 1 309 692). On myös selostettu, että nestemäisen ammoniakin vaikuttaessa gamma-butyrolaktoniin korkeammissa lämpötiloissa ja korkeissa paineissa muodostuu osittain myös 2-okso-pyr- 2 6375 0 rolidiini-N-gamma-butyyriamidia (US-patentti n:o 3 250 784).It is known that compounds of general formula I can be prepared by reacting sodium 2-oxo-pyrrolidine with omega-haloalkylamides (British Patent No. 1,039,113) and by allowing ammonia to act on esters of 2-oxo-1-pyrrolidinoalkanoic acids. or acid chlorides (British Patent No. 1,039,113) or by thermally shortening the chains of their ammonium salts (British Patent No. 1,309,692). It has also been reported that the action of liquid ammonia on gamma-butyrolactone at higher temperatures and high pressures also results in the partial formation of 2-oxo-pyrrolidine-N-gamma-butyramide (U.S. Patent No. 3,250,784).
Muutamilla yllä mainituista yhdisteistä on terapeuttinen vaikutus hoidettaessa liikuntasairauksia, hypertoniaa, hyperkineesiaa ja muistisairauksia. Parhaiten tunnettu näistä yhdisteistä on 2-okso-l-pyrrolidiini-asetamidi, joka tunnetaan yleisnimikkeellä "Pyracetam".Some of the above compounds have therapeutic activity in the treatment of exercise disorders, hypertension, hyperkinesia and memory disorders. The best known of these compounds is 2-oxo-1-pyrrolidine acetamide, commonly known as "Pyracetam".
On myös tunnettua, että 2,5-dioksipyrrolidiini kuten myös sen N-met-yylijohdannainen voidaan elektrolyyttistä tietä muuttaa 2-okso-pyr-rolidiiniksi tai sen N-metyylijohdannaiseksi /Ber. 3K3 (1900) 2224; Coll. Czech. Chem. Comm. 2^ (1930) 531; J. Am. Chem. Soc. 5_5 (1933) 295/.It is also known that 2,5-dioxypyrrolidine as well as its N-methyl derivative can be converted by electrolytic route to 2-oxo-pyrrolidine or its N-methyl derivative / Ber. 3K3 (1900) 2224; Coll. Czech. Chem. Comm. 2 ^ (1930) 531; J. Am. Chem. Soc. 5_5 (1933) 295 /.
Nyt on havaittu, että yleisen kaavan I mukaisia yhdisteitä voidaan valmistaa yksinkertaisesti alla olevan reaktiokaavan mukaisesti: H+ 0=Kl,^=0 + Hal<CH2»nG™H2-^0=1\NXUoir5iÄ. ^Ν>=0It has now been found that the compounds of general formula I can be prepared simply according to the following reaction formula: H + O = K1, O = O + Hal <CH2 »nG ™ H2- ^ 0 = 1 \ NXUoir5iÄ. ^ Ν> = 0
I I II I I
Na (CH_) O0NH_ (CHJ CONHLNa (CH_) ONH_ (CHJ CONHL
z n z z n z (II) (III) (IV) (I) joissa n on kokonaisluku 1-4.z n z z n z (II) (III) (IV) (I) where n is an integer from 1 to 4.
Menetelmälle on tunnusomaista, että yleisen kaavan IV mukainen 2,5-diokso-pyrrolidiini-N-alkyyliamidi pelkistetään elektrolyyttisesti rikkihapossa käyttäen lyijykatodia diafragmakennossa 0-30°C:n lämpötilassa.The process is characterized in that the 2,5-dioxo-pyrrolidine-N-alkylamide of the general formula IV is electrolytically reduced in sulfuric acid using a lead cathode in a diaphragm cell at a temperature of 0-30 ° C.
Tämän keksinnön mukaan valmistetaan sukkinimidi-natrium tavanomaisella tavalla, esim. antamalla natriummetylaatin vaikuttaa sukkin-imidiin alhaisessa alkoholissa, esim. etanolissa, joka kondensoimal-la omega-halogeenialkyyliamidien kanssa etanolissa, dimetyyliform-amidissa, tolueenissa tai muussa sopivassa liuottimessa 80-150°C:ssa saatetaan sen jälkeen reagoimaan 2-okso-pyrrolidiini-N-alkyyliami-deiksi. Tämän jälkeen yhdisteet saatetaan alttiiksi elektrolyyttiselle pelkistykselle 0-30°C:ssa metallikatodilla (Pb) varustetussa elektrolyyttikennossa, jossa on diafragma happamassa väliaineessa ja vakio virtatiheydellä 5-8 A.According to the present invention, succinimide sodium is prepared in a conventional manner, e.g. by allowing sodium methylate to act on succinimide in a low alcohol, e.g. ethanol, which is condensed with omega-haloalkylamides in ethanol, dimethylformamide, toluene or other suitable solvent at 80-150 ° C: is then reacted to give 2-oxo-pyrrolidine-N-alkylamides. The compounds are then subjected to electrolytic reduction at 0-30 ° C in a metal cathode (Pb) electrolyte cell with a diaphragm in an acidic medium and a constant current density of 5-8 A.
3 637503,63750
Anodina voi toimia esim. platina tai lyijy. Reaktion kulkua voidaan seurata ohutlevykromatografiällä. Reaktion loputtua voidaan katalyytti^ käsitellä neutraloimalla 0-5°C:ssa, suodattamalla ja haihduttamalla suodate kuiviin alennetussa paineessa. Jäännös lietetään alhaiseen alkoholiin, esim. etanoliin, suodatetaan, saatu liuos haihdutetaan kuiviin alennetussa paineessa ja siten saatu tuote puhdistetaan sen jälkeen tunnetuilla menetelmillä (kiteytys tai pilarikro-matografia).The anode can be, for example, platinum or lead. The progress of the reaction can be monitored by thin layer chromatography. After completion of the reaction, the catalyst can be treated by neutralization at 0-5 ° C, filtration and evaporation of the filtrate to dryness under reduced pressure. The residue is slurried in a low alcohol, e.g. ethanol, filtered, the resulting solution is evaporated to dryness under reduced pressure and the product thus obtained is then purified by known methods (crystallization or column chromatography).
Tällä tavoin vältetään parhaiten muutoin oletettavissa olevaa amidien · hydrolyysiä ja ketjun pilkkoutumista. Menetelmän etuna ovat helposti saatavat ja halvat raaka-aineet sekä yksinkertaisuus.In this way, the otherwise assumed hydrolysis of amides and chain cleavage are best avoided. The method has the advantage of readily available and cheap raw materials as well as simplicity.
Keksintöä selostetaan alla lähemmin esimerkkien avulla.The invention is described in more detail below by means of examples.
2.5- diokso-pyrrolidiini-N-alkyyliamidien valmistus Esimerkki 1 2.5- diokso-pyrrolidiini-N-asetamidiPreparation of 2,5-dioxo-pyrrolidine-N-alkylamides Example 1 2,5-dioxo-pyrrolidine-N-acetamide
Liuosta, jossa oli 18,78 g (0,155 moolia) sukkinimidi-natriumia ja 14,50 g (0,155 moolia) klooriasetamidia 500 mlrssa etanolia, keitettiin palautusjäähdyttäen 5 tuntia. Natriumkloridin erottuneet kiteet poistettiin suodattamalla ja 48 tunnin jälkeen emäliuoksesta kiteytettiin 9,4 g tuotetta, jonka sulamispiste oli 140-143°C.A solution of 18.78 g (0.155 mol) of succinimide sodium and 14.50 g (0.155 mol) of chloroacetamide in 500 ml of ethanol was refluxed for 5 hours. The separated crystals of sodium chloride were removed by filtration, and after 48 hours, 9.4 g of product with a melting point of 140-143 ° C was crystallized from the mother liquor.
Tuotteen suodattamisen jälkeen haihdutettiin etanoli alennetussa paineessa kuiviin ja raakatuote puhdistettiin tavanomaisilla menetelmillä. Saatiin jälleen 10,4 g tuotetta, jonka sulamispiste oli 140-143°C, niin että tuotteen saantoa oli 19,8 g (81,8 %).After filtration of the product, the ethanol was evaporated to dryness under reduced pressure and the crude product was purified by conventional methods. Again, 10.4 g of product with a melting point of 140-143 ° C was obtained, so that the yield of the product was 19.8 g (81.8%).
Analyysia varten kiteytettiin tuote etanolista, sp. oli 144-146°C.For analysis, the product was crystallized from ethanol, m.p. was 144-146 ° C.
Analyysi yhdisteelle c6hqN2°3 (molekyylipaino 156,14)Analysis for c6hqN2 ° 3 (molecular weight 156.14)
Laskettu: C 46,15; H 5,16; N 17,94 %Calculated: C 46.15; H 5.16; N 17.94%
Saatu : C 46,30; H 5,02; N 17,77 % IR-kirjo (KBr) , 63750 4 cm -CO-N-CO- 1780 (sh) * 1710 (s) -CONH2 1630-1690 br (vs) -NH2 3455 (s) 3410 (m) 3310 (s) 3170 (s) NMR-kirjo (CD3SOCD3) δ mult. integr.Found: C, 46.30; H 5.02; N 17.77% IR spectrum (KBr), 63750 4 cm -CO-N-CO- 1780 (sh) * 1710 (s) -CONH2 1630-1690 br (vs) -NH2 3455 (s) 3410 (m) 3310 (s) 3170 (s) NMR spectrum (CD3SOCD3) δ mult. integr.
-CO-CH2CH2-CO- 2,63 s 4 -NCH2- 3,90 s 2 -CONH2 7,27 d 2-CO-CH2CH2-CO- 2.63 s 4 -NCH2- 3.90 s 2 -CONH2 7.27 d 2
Esimerkki 2 2,5-diokso-pyrrolidiini-N-3-propioniamidiExample 2 2,5-Dioxo-pyrrolidine-N-3-propionamide
Analogisesti esimerkissä 1 selostetun menetelmän kanssa saatiin 4,84 g:sta (0,04 moolia) sukkinimidi-natriumia ja 6,07g:sta(0,04 moolia) 8-bromipropioniamidia 120 ml:ssa dimetyyliformamidia 118-120°C:ssa 1,14 g reagoimatonta sukkinimidiä ja 2,96 g (61,3 %) tuotetta, jonka sp. oli 110-111°C. Analyysia varten näyte uudelleenkiteytet-tiin bentseenin ja etanolin seoksesta, sp. 112-113°C.In analogy to the procedure described in Example 1, 4.84 g (0.04 mol) of succinimide sodium and 6.07 g (0.04 mol) of 8-bromopropionamide in 120 ml of dimethylformamide were obtained at 118-120 ° C. , 14 g of unreacted succinimide and 2.96 g (61.3%) of product, m.p. was 110-111 ° C. For analysis, the sample was recrystallized from a mixture of benzene and ethanol, m.p. 112-113 ° C.
Analyysi yhdisteelle C7H10N2O3 (sp. 170,17)Analysis for C7H10N2O3 (m.p. 170.17)
Laskettu: C 49,40; H 5,92; N 16,46 %Calculated: C 49.40; H 5.92; N 16.46%
Saatu : C 49,67; H 5,64; N 16,19 % IR-kirjo (KBr) , cm -CO-N-CO- 1770 (s) ! 1685 (vs) -CONH2 1660 (vs) 1630 (sh) -NH2 3395 (s) 3320 (sh) 3260 (sh) 3210 (s) 5 63750 NMR-kirjo (CD3SOCD3) δ mult. integr.Found: C, 49.67; H 5.64; N 16.19% IR spectrum (KBr), cm -CO-N-CO-1770 (s)! 1685 (vs) -CONH2 1660 (vs) 1630 (sh) -NH2 3395 (s) 3320 (sh) 3260 (sh) 3210 (s) δ 63750 NMR spectrum (CD3SOCD3) δ mult. integr.
-CH2C0- 2,28 t 2 -CO-CH2CH2-CO- 2,62 s 4 -NCH2- 3,56 t 2 -C0NH2 7,01 d 2-CH 2 CO- 2.28 t 2 -CO-CH 2 CH 2 -CO- 2.62 s 4 -NCH 2 - 3.56 t 2 -COCN 2 7.01 d 2
Esimerkki 3 2.5- diokso-pyrrolidiini-N-B-propioniamidiExample 3 2,5-Dioxo-pyrrolidine-N-β-propionamide
Analogisesti esimerkissä 2 selostetun menetelmän kanssa, lukuunottamatta, että reaktiolämpötila oli 150°C ja reaktioaika 3 tuntia, saatiin 1,18 g reagoimatonta sukkinimidiä ja 2,6 g (54,5 %) tuotetta, jonka sp. oli 109-111°C.In analogy to the procedure described in Example 2, except that the reaction temperature was 150 ° C and the reaction time was 3 hours, 1.18 g of unreacted succinimide and 2.6 g (54.5%) of product were obtained, m.p. was 109-111 ° C.
Esimerkki 4 2.5- diokso-pyrrolidiini-N-gamma-butyramidiExample 4 2,5-Dioxo-pyrrolidine-N-gamma-butyramide
Analogisesti esimerkissä 1 selostetun menetelmän kanssa saatiin 2,42 g:sta (0,02 moolia) sukkinimidi-natriumia, 2,43 g:sta (0,02 moolia) gamma-klooributyramidia ja 0,2 g:sta natriumjodidia 30 ml:ssa dimetyyliformamidia 118-120°C:ssa 0,6 g reagoimatonta sukkinimidiä ja 0,92 g (35,8 %) tuotetta, jonka sulamispiste oli 79-81°C.In analogy to the procedure described in Example 1, 2.42 g (0.02 moles) of succinimide sodium, 2.43 g (0.02 moles) of gamma-chlorobutyramide and 0.2 g of sodium iodide in 30 ml were obtained. dimethylformamide at 118-120 ° C 0.6 g of unreacted succinimide and 0.92 g (35.8%) of product with a melting point of 79-81 ° C.
Analyysiä varten näyte uudelleenkiteytettiin bentseenin, etanolin ja eetterin seoksesta, sp. 82-84°C.For analysis, the sample was recrystallized from a mixture of benzene, ethanol and ether, m.p. 82-84 ° C.
Analyysi yhdisteelle c8Hi2N2°3 (molekyylipaino 184,19)Analysis for c 8 H 12 N 2 O 3 (molecular weight 184.19)
Laskettu: C 52,16; H 6,57; N 15,21 %Calculated: C 52.16; H 6.57; N 15.21%
Saatu : C 52,30; H 6,51; N 15,39 % IR-kirjo (KBr) cm -CO-N-CO- 1770 (sh) I 1680 (vs) -CONH2 1660 (sh) 1630 (sh) -NH2 3415 (vs) 3350 (sh) 3290 (m) 3170 (vs) 63750 6 NMR-kirjo (CD3SOCD3) δ mult. integr.Found: C, 52.30; H 6.51; N 15.39% IR spectrum (KBr) cm -CO-N-CO- 1770 (sh) I 1680 (vs) -CONH2 1660 (sh) 1630 (sh) -NH2 3415 (vs) 3350 (sh) 3290 ( m) 3170 (vs) 63750 δ NMR spectrum (CD 3 SOCD 3) δ mult. integr.
-CH2CH2CO- 1,5-2,2 m 4 -CO-CH2CH2-CO- 2,60 s 4 -NCH2- 3,36 t 2 -C0NH2 6,88 d 2-CH2CH2CO- 1.5-2.2 m 4 -CO-CH2CH2-CO- 2.60 s 4 -NCH2- 3.36 t 2 -COCN2 6.88 d 2
Esimerkki 5 2.5- diokso-pyrrolidiini-N-gamma-butyramidi Täysin analogisesti esimerkissä 4 selostetun menetelmän kanssa, paitsi että reaktio suoritettiin 100 ml:ssa kuivaa tolueenia, saatiin 0,8 g reagoimatonta sukkinimidiä ja 0,667 g (32,6 %) tuotetta, sp. 80-82°C.Example 5 2,5-Dioxo-pyrrolidine-N-gamma-butyramide In complete analogy to the procedure described in Example 4, except that the reaction was carried out in 100 ml of dry toluene, 0.8 g of unreacted succinimide and 0.667 g (32.6%) of product were obtained, mp. 80-82 ° C.
2-okso-pyrrolidiini-N-alkyyliamidien valmistus pelkistämällä elektro- lyyttisesti vastaavia 2,5-diokso-pyrrolidiini-N-alkyyliamideja_Preparation of 2-oxo-pyrrolidine-N-alkylamides by electrolytic reduction of the corresponding 2,5-dioxo-pyrrolidine-N-alkylamides
Esimerkki 6 2-okso-pyrrolidiini-N-asetamidi 80 ml:an 50 %:sta rikkihappoa liuotettiin 0-5°C:ssa 1 g (0,0064 moolia) 2.5- dioksopyrrolidiini-N-asetamidia ja pelkistettiin elektrolyyttisesti noin 100 ml:n vetoisessa kennossa vakiovirralla 8 A lyijyka- 2 todilla, jonka pinta-ala oli 50 cm ja lyijyanodilla (anolyytti oli 10 %:nen rikkihappo) lämpötilassa 0-5°C. Katolyytti ja anolyytti 011 erotettu toisistaan synteettisellä diafragmalla. Katolyytin sekoittaminen suoritettiin magneettisella sekoittimella. Reaktion kulkua seurattiin ohutlevykromatografiällä (kloroformi:metanoli = 9:1). Tuote erotettiin reaktioliuoksesta neutraloimalla natriumhydroksidi-liuoksella 0-5°C:ssa pH-arvoon 7 ja suodattamalla muodostunut nat-riumsulfaatti.Haihduttamalla suodate alennetussa paineessa kuiviin saatiin raakatuotetta, joka puhdistettiin tavanomaisilla menetelmillä (uutto, kiteytys ja sentapainen). Saatiin 0,66 g (72,6 %) tuotetta, jonka sp. oli 149-151°C. Fysikaaliset vakiot ja kirjo vastasi tunnetuilla menetelmillä valmistettua autenttista näytettä.Example 6 2-Oxo-pyrrolidine-N-acetamide In 80 ml of 50% sulfuric acid was dissolved at 0-5 ° C 1 g (0.0064 mol) of 2,5-dioxopyrrolidine-N-acetamide and electrolytically reduced to about 100 ml: in a n-cell with a constant current of 8 A with a lead cathode 2 having a surface area of 50 cm and a lead anode (the anolyte was 10% sulfuric acid) at a temperature of 0-5 ° C. Catholite and anolyte 011 separated by a synthetic diaphragm. Stirring of the catholyte was performed with a magnetic stirrer. The progress of the reaction was monitored by thin layer chromatography (chloroform: methanol = 9: 1). The product was separated from the reaction solution by neutralizing with sodium hydroxide solution at 0-5 ° C to pH 7 and filtering the sodium sulfate formed. Evaporation of the filtrate to dryness under reduced pressure gave a crude product which was purified by conventional methods (extraction, crystallization and the like). 0.66 g (72.6%) of product was obtained, m.p. was 149-151 ° C. Physical Constants and spectrum corresponded to an authentic sample prepared by known methods.
Esimerkki 7 2-okso-pyrrolidiini-N-asetamidi Täysin analogisesti esimerkissä 6 selostetun menetelmän kanssa, paitsi että reaktio suoritettiin vakiovirralla 5 A ja 30°C:ssa, saatiin 0,44 g (48,4 %) tuotetta, sp. 148-150°C.Example 7 2-Oxo-pyrrolidine-N-acetamide In complete analogy to the procedure described in Example 6, except that the reaction was carried out at a constant current of 5 A and 30 ° C, 0.44 g (48.4%) of product was obtained, m.p. 148-150 ° C.
7 . · w A 637507. · W A 63750
Esimerkki 8 2-okso-pyrrolidiini-N-g-propioniamldiExample 8 2-Oxo-pyrrolidine-N-g-propionamide
Analogisesti esimerkissä 6 selostetun menetelmän kanssa, paitsi että reaktio suoritettiin 0-5°C:ssa, saatiin 0,5 g:sta (0,00294 moolia) 2,5-ndiokso-pyrrolidiini-N-g-propionamidia 0,31 g (67,5 %) tuotetta, jonka sp. oli 135-137°C. Fysikaaliset vakiot ja kirjo vastasivat tunnetuilla menetelmillä valmistettua autenttista näytettä.In analogy to the procedure described in Example 6, except that the reaction was carried out at 0-5 ° C, 0.51 g (0.00294 mol) of 2,5-n-dioxo-pyrrolidine-Ng-propionamide gave 0.31 g (67, 5%) product with m.p. was 135-137 ° C. The physical constants and spectrum corresponded to an authentic sample prepared by known methods.
Esimerkki 9 2-okso-pyrrolidiini-N-gamma-butyramidiExample 9 2-Oxo-pyrrolidine-N-gamma-butyramide
Analogisesti esimerkissä 6 selostetun menetelmän kanssa saatiin 0,5 g:sta (0,00272 moolia) 2,5-diokso-pyrrolidiini-N-gamma-butyramidia, 0,29 g (62,8 %) tuotetta, jonka sp. oli 95-97°C. Fysikaaliset vakiot ja kirjo vastasivat tunnetuilla menetelmillä valmistettua autenttista näytettä.In analogy to the procedure described in Example 6, 0.5 g (0.00272 mol) of 2,5-dioxo-pyrrolidine-N-gamma-butyramide, 0.29 g (62.8%) of product, m.p. was 95-97 ° C. The physical constants and spectrum corresponded to an authentic sample prepared by known methods.
Claims (5)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| YU7876 | 1976-01-14 | ||
| YU78/76A YU39341B (en) | 1976-01-14 | 1976-01-14 | Process for obtaining n-alkylamide-2-oxopyrrolidines |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI770088A FI770088A (en) | 1977-07-15 |
| FI63750B FI63750B (en) | 1983-04-29 |
| FI63750C true FI63750C (en) | 1983-08-10 |
Family
ID=25548234
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI770088A FI63750C (en) | 1976-01-14 | 1977-01-12 | PROCEDURE FOR FRAMSTATION OF AV 2-OXO-PYRROLIDINE-N-ALKYLAMIDER |
Country Status (10)
| Country | Link |
|---|---|
| JP (1) | JPS52116463A (en) |
| AT (1) | AT355013B (en) |
| CH (1) | CH624671A5 (en) |
| CS (1) | CS208719B2 (en) |
| FI (1) | FI63750C (en) |
| HU (1) | HU172999B (en) |
| PL (1) | PL103074B1 (en) |
| SE (1) | SE416730B (en) |
| SU (1) | SU893131A3 (en) |
| YU (1) | YU39341B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5933068A (en) * | 1982-08-17 | 1984-02-22 | Nitsukuu Kogyo Kk | Vacuum impregnation method |
| JPS59150655A (en) * | 1983-04-14 | 1984-08-28 | Taiho Kogyo Co Ltd | Method and device for impregnation to die cast parts |
| JPS59152030A (en) * | 1983-02-15 | 1984-08-30 | Taiho Kogyo Co Ltd | Method and device for impregnation of die casting parts |
| JPS62218028A (en) * | 1986-03-20 | 1987-09-25 | Toyota Motor Corp | Impregnation treatment method |
| RU2629117C1 (en) * | 2016-06-14 | 2017-08-24 | Сизов Владимир Владимирович | Method of producing 4-substituted 2-[2-oxo-1-pyrrolidinyl] acetamide |
-
1976
- 1976-01-14 YU YU78/76A patent/YU39341B/en unknown
- 1976-12-29 CH CH1643376A patent/CH624671A5/en not_active IP Right Cessation
- 1976-12-30 AT AT980876A patent/AT355013B/en not_active IP Right Cessation
-
1977
- 1977-01-04 CS CS7761A patent/CS208719B2/en unknown
- 1977-01-10 SE SE7700172A patent/SE416730B/en not_active IP Right Cessation
- 1977-01-11 HU HU77PI00000559A patent/HU172999B/en unknown
- 1977-01-12 FI FI770088A patent/FI63750C/en not_active IP Right Cessation
- 1977-01-12 SU SU772439826A patent/SU893131A3/en active
- 1977-01-12 PL PL1977195267A patent/PL103074B1/en unknown
- 1977-01-14 JP JP255077A patent/JPS52116463A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| PL195267A1 (en) | 1978-03-13 |
| PL103074B1 (en) | 1979-05-31 |
| JPS52116463A (en) | 1977-09-29 |
| SU893131A3 (en) | 1981-12-23 |
| JPS5744667B2 (en) | 1982-09-22 |
| YU7876A (en) | 1982-02-28 |
| FI770088A (en) | 1977-07-15 |
| ATA980876A (en) | 1979-07-15 |
| SE7700172L (en) | 1977-07-15 |
| CS208719B2 (en) | 1981-09-15 |
| CH624671A5 (en) | 1981-08-14 |
| FI63750B (en) | 1983-04-29 |
| AT355013B (en) | 1980-02-11 |
| SE416730B (en) | 1981-02-02 |
| YU39341B (en) | 1984-10-31 |
| HU172999B (en) | 1979-01-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: PLIVA, PHARMACEUTICAL AND Owner name: HELM, KARL O. |