FI73669C - Foerfarande foer framstaellning av 5-alkyl-2-karboxipyrazin. - Google Patents
Foerfarande foer framstaellning av 5-alkyl-2-karboxipyrazin. Download PDFInfo
- Publication number
- FI73669C FI73669C FI821832A FI821832A FI73669C FI 73669 C FI73669 C FI 73669C FI 821832 A FI821832 A FI 821832A FI 821832 A FI821832 A FI 821832A FI 73669 C FI73669 C FI 73669C
- Authority
- FI
- Finland
- Prior art keywords
- alkyl
- carboxypyrazine
- preparation
- acid
- general formula
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 5
- 238000002360 preparation method Methods 0.000 title claims description 4
- 239000002253 acid Substances 0.000 claims description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 239000001301 oxygen Substances 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- OTVZGAXESBAAQQ-UHFFFAOYSA-N pyrazine-2,3-dicarbonitrile Chemical compound N#CC1=NC=CN=C1C#N OTVZGAXESBAAQQ-UHFFFAOYSA-N 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- DPZSNGJNFHWQDC-ARJAWSKDSA-N (z)-2,3-diaminobut-2-enedinitrile Chemical compound N#CC(/N)=C(/N)C#N DPZSNGJNFHWQDC-ARJAWSKDSA-N 0.000 description 2
- RHYUBLSWHDYKAO-UHFFFAOYSA-N 5-methylpyrazine-2,3-dicarbonitrile Chemical compound CC1=CN=C(C#N)C(C#N)=N1 RHYUBLSWHDYKAO-UHFFFAOYSA-N 0.000 description 2
- RBYJWCRKFLGNDB-UHFFFAOYSA-N 5-methylpyrazine-2-carboxylic acid Chemical compound CC1=CN=C(C(O)=O)C=N1 RBYJWCRKFLGNDB-UHFFFAOYSA-N 0.000 description 2
- AIJULSRZWUXGPQ-UHFFFAOYSA-N Methylglyoxal Chemical compound CC(=O)C=O AIJULSRZWUXGPQ-UHFFFAOYSA-N 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- NPHXBQJRDOVAAF-DAFODLJHSA-N (e)-2-aminobut-2-enedinitrile Chemical compound N#CC(/N)=C\C#N NPHXBQJRDOVAAF-DAFODLJHSA-N 0.000 description 1
- DJQOOSBJCLSSEY-UHFFFAOYSA-N Acipimox Chemical compound CC1=CN=C(C(O)=O)C=[N+]1[O-] DJQOOSBJCLSSEY-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229940015043 glyoxal Drugs 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three 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
- C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Saccharide Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
7 3 6 6 9
MENETELMÄ 5-ALKYYLI-2-KAR30KSIPYRATSIININ VALMISTAMISEKSI -FÖRFARANDE FÖR FRAMSTÄLLN I NG AV 5-ALKYL-2-KARBOX IPYRAZI N
Keksintö koskee menetelmää 5-a 1 kyy 1i-2-karbok sipyratsiinin valmistamiseksi, jolla on yleinen kaava
COOH
JOJ
R1 [Ί jossa R merkitsee C -C -a 1 kyy1iryhmää. v 1 1 Λ
Kaavan (I) mukaisia yhdisteitä on kuvattu ja suojattu GB-pa-tentilla 1 361 967 ja niillä on veren rasvaa ja sokeria vähentävä vaikutus. Keksinnön mukaisesti valmistetusta 5 - m e -tyyli-2-karboksipyratsiinista voidaan edelleen edullisesti valmistaa 2-karboksi-5-metyylipyratsiini-4-oksidia, joka . . sellaisenaan on suojattu mainitulla GB-patentiliä.
’ Kaavan (I) mukaisia 5-'“lkyyli-2-karboksipyratsiineja, joissa R : 11M on edellä esitetty merkitys, voidaan keksinnön mukaan valmistaa siten, että kondensoidaan diaminomaleonitriiliä, jolla on kaava H2N cn (II)
H N "''''''''''‘CN
‘ j ‘ yleisen kaavan CHOCOR^ mukaisen yhdisteen kanssa, jossa R : 11 ä on edellä mainittu merkitys, polaarisissa liuottimes-sa lämpötilassa 35-85°C ja näin saatu yhdisti, jonka yleinen kaava on 7 3 6 6 9
CM
' fr::)
! W I
missä R, :ilä on edellä esitetty .merkitys, saatetaan reagoimaan hapon kanssa polaarisessa liuotti mess a lämpötilassa n. ICC,J C .
Sopivia liuottimia öiaminomaleonitriilin kondersoinnissa glyoksaalin tai -ketoa1dehydin kanssa ovat vesi, 1-60 C-atc-mia sisältävä alkoholi tai niiden seos. K o n d e n s a a t: 1 o r e a k t i o saa mieluimmin tapahtua hapon läsnäollessa.
Disyanopyratsiinin (III) reaktio hapon kanssa tuottaa vain y hde n y h d i s t e e n, j olla on k aav.a (I) . Sopiva happo on rikkihappo ja sopiva liuotin on vesi. Hapon väkevyys en edullisesti 30-50 %.
Disyanopyrats i. inier. ja happojen väliset reaktiot ovat sinänsä ennestään tunnettuja mm. japanilaisista patenttijulkaisuista 53-3767^, 53-12378 ja 54-154776. Kuitenkin mainitais- s a j ji 1 k a 1 suissa k u vatuilla r e aktio! LI a s a adaan lopputuotteena 2-sy ano-3-k a r bok s 1 am i ·! i oy a t. s i i ni tai 2-karbancyy1i-3-karboksioynatsiini, kun taas keksintömme mukainen voimakas hapan hydro iyy s i muuttaa alkyyl isubsti tuoidur. disyanopyratsiinin 5-alkyyli-2-karboksipyratniiniksi, jossa lähtöaineen molemmat syanoryhmät ovat hydrolysoi tuneet. Lisäksi keksin-"in ·> u k a. 1 n e n r e a k t.. o o r. y 1 i ä 11 ä v '·n s e i e k t i i vinen s i in.a , et t ä se antaa lopputuotteeksi pelkästään kaavan (I) mukaisen 5-a1k y y1i-2-k a r b o k s i p y r a t s i i n in; edes sen kanssa isomeeristä 5-a1kyy1i-3-karboksipyratsiinia ei reaktiossa synny.
ti 3 7 3 6 6 9
Esimerkki a) L70 g palorypälehappoaldehydiä (10 %:inen vesiliuos mas-sa/tilav.) lisättiin sekoittamalla tipoittain ja huoneenlämpötilassa 100 g:n diaminomaleonitriiliä suspensioon seoksessa, jossa oli 800 ml vettä, 900 ml etanolia ja 45 ml etikka-happoa. 20 minuutin kuluttua oli liukeneminen päättynyt; lämpötila nostettiin 80°C: seen ja sekoitusta jatkettiin vielä 30 minuutin ajan.
Sitten jäähdytettiin reaktioseos 0°C:seen ja tuote otettiin talteen suodattamalla. Pestiin vedellä neutraalisuuteen saakka ja kuivattiin, minkä jälkeen jälkeen saatiin 112 g raakaa 2,3-disyano-5-metyyiipyratsiinia, sp. 9?-110uC.
NKR (CDC1g) TMS:n suhteen: 2,88 (s, CH ) , 8,858 (s, aromaat tinen protoni).
b) 10 g raakaa 2,3-disyano-5-metyy1ipyratsiinia, joka oli saatu a):n mukaisesti, suspensoituna 100 ml aan rikkihappoa (50 tilav.-% vesiliuos) pidettiin 3 tuntia sekoittaen 100°C:n lämpötilassa. Sitten reaktioseos jäähdytettiin lisäämällä 100 g murskattua jäätä ja saatettiin pH-arvoon 1 lisäämällä 270 ml natriumhydroksidin vesiliuosta (20 % mas-sa/tilav. ) . Vesifaasi uutettiin metyy1ietyy1iketoni11 a; uutteet yhdistettiin ja pestiin neutraa1iseksi kyllästetyllä natriumkloridiliuoksella.
Haihduttamalla liuotin pois tyhjössä saatiin kiinteä jäännös, joka kiteytettiin vedestä. Saatiin 6 g 5-metyyii-2-pyratsiini-karboksyy1ihappoa, sp. 163-167°C.
NMR (CDClg) TMS:n suhteen: 2,8& (s, CH3)t 8,9, 9.3& (kaksi s, aromaattisia protoneja), 10, 8 S (s, C00H ) .
Claims (2)
1. Menetelmä yleisen aavan (I) mukaisen 5-alkyyli-i-karbok-s ipyr a s :. ini n v a I m 1 s 1 sniseksi , COOK Γr\ 1 . W (n E Λ ^\· jossa P, on C1 -C -a Ikyy 1 i ryhmä, t u n n e t t u s i itä, et t a yhdiste, jonka yleinen k a a v a on . r r* V ί ( 111 ) ! w ; C N mif* ,'i ?, : 11 ä on mainittu merkitys, rwaete taan reagoi maan hapen, kuten rikkihapon kanssa polaariset; a liuottimessa noin 100 -C: n lämpötilassa.
2. Patenttivaatimuksen 1 mukainen menetelmä, t u n n e t t u siitä, että reaktio di s y a n o o y r a ts i i ni n (III', ja hapon v ä1i1--1' n n, o ''tietä r. n v e d e g s i , j o 11 o 1 n h a r e n v ä k e v y y s on 3 ° - 5 0 % . il
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8116263 | 1981-05-28 | ||
| GB8116263 | 1981-05-28 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI821832A0 FI821832A0 (fi) | 1982-05-24 |
| FI73669B FI73669B (fi) | 1987-07-31 |
| FI73669C true FI73669C (fi) | 1987-11-09 |
Family
ID=10522093
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI821832A FI73669C (fi) | 1981-05-28 | 1982-05-24 | Foerfarande foer framstaellning av 5-alkyl-2-karboxipyrazin. |
Country Status (20)
| Country | Link |
|---|---|
| JP (1) | JPS57200368A (fi) |
| AT (1) | AT387217B (fi) |
| AU (1) | AU8412682A (fi) |
| BE (1) | BE893317A (fi) |
| CA (1) | CA1237724A (fi) |
| CH (1) | CH649763A5 (fi) |
| CS (1) | CS226741B2 (fi) |
| DE (1) | DE3219407A1 (fi) |
| DK (1) | DK155325C (fi) |
| FI (1) | FI73669C (fi) |
| FR (1) | FR2506768B1 (fi) |
| GR (1) | GR76417B (fi) |
| HU (1) | HU187716B (fi) |
| IE (1) | IE52992B1 (fi) |
| IL (1) | IL65864A (fi) |
| IT (1) | IT1210478B (fi) |
| NL (1) | NL8202105A (fi) |
| SE (1) | SE462971B (fi) |
| YU (1) | YU42766B (fi) |
| ZA (1) | ZA823660B (fi) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1201417B (it) * | 1985-05-17 | 1989-02-02 | Montedison Spa | Procedimento per la preparazione di 2-carbossipirazine 4 ossido |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1361967A (en) * | 1972-04-28 | 1974-07-30 | Erba Carlo Spa | Pyrazine 4-oxide derivatives and process for their preparation |
| JPS565742B2 (fi) * | 1973-09-29 | 1981-02-06 | ||
| JPS5134175A (en) * | 1974-09-18 | 1976-03-23 | Sagami Chem Res | Pirajinjudotai no seizohoho |
| JPS52153980A (en) * | 1976-06-17 | 1977-12-21 | Nippon Soda Co Ltd | Synthesis of 2,3-dicyanopyrazine |
| JPS5488281A (en) * | 1977-12-20 | 1979-07-13 | Nitsupou Kagaku Kk | Manufacture of pyrazine monocarboxylic acid |
| JPS5488280A (en) * | 1977-12-20 | 1979-07-13 | Nitsupou Kagaku Kk | Manufacture of dicyanopyradines |
-
1982
- 1982-05-21 NL NL8202105A patent/NL8202105A/nl active Search and Examination
- 1982-05-24 AT AT0203682A patent/AT387217B/de not_active IP Right Cessation
- 1982-05-24 FI FI821832A patent/FI73669C/fi not_active IP Right Cessation
- 1982-05-24 IL IL65864A patent/IL65864A/xx not_active IP Right Cessation
- 1982-05-24 DE DE19823219407 patent/DE3219407A1/de active Granted
- 1982-05-25 CA CA000403636A patent/CA1237724A/en not_active Expired
- 1982-05-25 AU AU84126/82A patent/AU8412682A/en not_active Abandoned
- 1982-05-25 FR FR8209038A patent/FR2506768B1/fr not_active Expired
- 1982-05-25 CS CS823842A patent/CS226741B2/cs unknown
- 1982-05-25 GR GR68246A patent/GR76417B/el unknown
- 1982-05-26 IE IE1261/82A patent/IE52992B1/en not_active IP Right Cessation
- 1982-05-26 SE SE8203273A patent/SE462971B/sv not_active IP Right Cessation
- 1982-05-26 ZA ZA823660A patent/ZA823660B/xx unknown
- 1982-05-26 JP JP57088153A patent/JPS57200368A/ja active Granted
- 1982-05-27 HU HU821712A patent/HU187716B/hu unknown
- 1982-05-27 YU YU1131/82A patent/YU42766B/xx unknown
- 1982-05-27 DK DK239482A patent/DK155325C/da not_active IP Right Cessation
- 1982-05-27 IT IT8221517A patent/IT1210478B/it active Protection Beyond IP Right Term
- 1982-05-27 CH CH3285/82A patent/CH649763A5/de not_active IP Right Cessation
- 1982-05-27 BE BE0/208187A patent/BE893317A/fr not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| SE462971B (sv) | 1990-09-24 |
| YU113182A (en) | 1985-03-20 |
| FR2506768B1 (fr) | 1985-06-21 |
| FI821832A0 (fi) | 1982-05-24 |
| BE893317A (fr) | 1982-11-29 |
| CS226741B2 (en) | 1984-04-16 |
| DK155325C (da) | 1989-09-18 |
| AU8412682A (en) | 1982-12-02 |
| FR2506768A1 (fr) | 1982-12-03 |
| CH649763A5 (de) | 1985-06-14 |
| DK239482A (da) | 1982-11-29 |
| IE821261L (en) | 1982-11-28 |
| JPH0456034B2 (fi) | 1992-09-07 |
| HU187716B (en) | 1986-02-28 |
| NL8202105A (nl) | 1982-12-16 |
| FI73669B (fi) | 1987-07-31 |
| DE3219407A1 (de) | 1983-01-05 |
| DE3219407C2 (fi) | 1990-09-06 |
| IT1210478B (it) | 1989-09-14 |
| IL65864A0 (en) | 1982-08-31 |
| ATA203682A (de) | 1988-05-15 |
| IE52992B1 (en) | 1988-04-27 |
| CA1237724A (en) | 1988-06-07 |
| ZA823660B (en) | 1983-03-30 |
| AT387217B (de) | 1988-12-27 |
| IL65864A (en) | 1985-08-30 |
| JPS57200368A (en) | 1982-12-08 |
| IT8221517A0 (it) | 1982-05-27 |
| DK155325B (da) | 1989-03-28 |
| GR76417B (fi) | 1984-08-10 |
| SE8203273L (sv) | 1982-11-29 |
| YU42766B (en) | 1988-12-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MA | Patent expired |
Owner name: FARMITALIA CARLO ERBA S.P.A |