SE448875B - 2-AROYL (FORMYL) -SUBSTITUTED PYROL RELEASES AND PROCEDURES FOR PREPARING THEREOF - Google Patents
2-AROYL (FORMYL) -SUBSTITUTED PYROL RELEASES AND PROCEDURES FOR PREPARING THEREOFInfo
- Publication number
- SE448875B SE448875B SE8000734A SE8000734A SE448875B SE 448875 B SE448875 B SE 448875B SE 8000734 A SE8000734 A SE 8000734A SE 8000734 A SE8000734 A SE 8000734A SE 448875 B SE448875 B SE 448875B
- Authority
- SE
- Sweden
- Prior art keywords
- formula
- formyl
- aroyl
- alkyl group
- methyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 12
- -1 (FORMYL) -SUBSTITUTED PYROL Chemical class 0.000 title description 7
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 150000003233 pyrroles Chemical class 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 2
- 125000000218 acetic acid group Chemical class C(C)(=O)* 0.000 claims 1
- 239000000543 intermediate Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 13
- 238000001816 cooling Methods 0.000 description 9
- 239000005457 ice water Substances 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- WKUBFPPJDMDEFL-UHFFFAOYSA-N (4-methylphenyl)-(1-methylpyrrol-2-yl)methanone Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=CN1C WKUBFPPJDMDEFL-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- DIWYVXWWMORQBV-UHFFFAOYSA-N 1-methyl-5-(4-methylbenzoyl)pyrrole-2-carbaldehyde Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(C=O)N1C DIWYVXWWMORQBV-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 125000003435 aroyl group Chemical group 0.000 description 2
- DIKBFYAXUHHXCS-UHFFFAOYSA-N bromoform Chemical compound BrC(Br)Br DIKBFYAXUHHXCS-UHFFFAOYSA-N 0.000 description 2
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- 230000022244 formylation Effects 0.000 description 2
- 238000006170 formylation reaction Methods 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- KLLYGDXCCNXESW-UHFFFAOYSA-N (2-fluoroacetyl) 2-fluoroacetate Chemical compound FCC(=O)OC(=O)CF KLLYGDXCCNXESW-UHFFFAOYSA-N 0.000 description 1
- OXHNLMTVIGZXSG-UHFFFAOYSA-N 1-Methylpyrrole Chemical compound CN1C=CC=C1 OXHNLMTVIGZXSG-UHFFFAOYSA-N 0.000 description 1
- JIIXLYUMPKMWIQ-UHFFFAOYSA-N 2-methyl-5-(4-methylbenzoyl)-1H-pyrrole-3-carbaldehyde Chemical compound C1(=CC=C(C=C1)C(=O)C1=CC(=C(N1)C)C=O)C JIIXLYUMPKMWIQ-UHFFFAOYSA-N 0.000 description 1
- ANVJJTICAOERJQ-UHFFFAOYSA-N CC(C=C1)=CC=C1C1=CC(C=O)=CN1C Chemical compound CC(C=C1)=CC=C1C1=CC(C=O)=CN1C ANVJJTICAOERJQ-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229950005228 bromoform Drugs 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 150000002391 heterocyclic compounds Chemical group 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 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
- C07D207/30—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
- C07D207/32—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/333—Radicals substituted by oxygen or sulfur atoms
Description
sol 443 875 2 der basiska förhållanden (hänvisning till hänvisningsexempel 2, som beskrives härefter). sol 443 875 2 der basic conditions (reference to Reference Example 2, described below).
Vanligen är följande sätt kända såsom metoder för framställ- ning av dessa l-metyl-5-aroylpyrrol-Z-ättiksyror. 1) En metod, som omfattar en reaktion med en aroylklorid i när- varo av en Lewis-syra, såsom aluminíumklorid, etc. 34 153/70).Generally, the following methods are known as methods for preparing these 1-methyl-5-aroylpyrrole-Z-acetic acids. 1) A method which comprises a reaction with an aroyl chloride in the presence of a Lewis acid, such as aluminum chloride, etc. 34 153/70).
Z) En metod, som använder en blandad syraanhydrid erhållen från en arylkarboxylsyra och fluoroättiksyraanhydrid (Japan Kokai No 418/71) 3) En metod, som använder en reaktionsprodukt av dimetylaroylamid och fosforoxiklorid (Japan Kokai No 418/71). 4) En metod, som använder en blandad syraanhydrid erhâllen från en arylkarboxylsyraanhydrid och en syra såsom metansulfonsyra, etc.Z) A method using a mixed acid anhydride obtained from an aryl carboxylic acid and fluoroacetic anhydride (Japan Kokai No 418/71) 3) A method using a reaction product of dimethylaroylamide and phosphorus oxychloride (Japan Kokai No 418/71). 4) A method using a mixed acid anhydride obtained from an aryl carboxylic anhydride and an acid such as methanesulfonic acid, etc.
(Japan Koaki No 126660/75).(Japan Koaki No. 126660/75).
S) En metod, som omfattar reaktion av syran med fosgen för fram- (Japan Kokai No ställning av S-klorokarbonylderivat och sedan reaktion av deriva- tet med en arylmetallförening (Japan Kokai No 55659/74).S) A method comprising reacting the acid with phosgene to produce S-chlorocarbonyl derivatives and then reacting the derivative with an aryl metal compound (Japan Kokai No. 55659/74).
Dessa metoder har emellertid nackdelar i att de ger lågt ut- byte av produkten och alstrar såsom biprodukter isomerer, som in- ncháller en aroylgrupp vid 4-ställningen och som mäste frânskiljas.However, these methods have disadvantages in that they give a low yield of the product and generate as by-products isomers which contain an aroyl group at the 4-position and which must be separated.
Man har nu funnit en ny formyleríngsmetod, genom vilken 2- aroyl-formyl-substituerat pyrrolderivat lätt kan framställas i högt utbyte genom att använda Z-aroylpyrrolderivat, vilket lätt kan erhållas från ett industriellt tíllängligt pyrrolderivat så- som utgångsmaterial, och också genom vilken, skilt från allmänna metoder, formylering av heterocykliska föreningar substituerade med en aroylgrupp kan fortgå. 2-aroylpyrrolderivatet, som användes såsom utgångsmaterialet i föreliggande uppfinning och som motsvaras av formeln.A new formylation method has now been found by which 2-aroyl-formyl-substituted pyrrole derivative can be easily prepared in high yield using Z-aroylpyrrole derivative, which can be easily obtained from an industrially elongated pyrrole derivative as starting material, and also by which, apart from general methods, formylation of heterocyclic compounds substituted with an aroyl group can proceed. The 2-aroylpyrrole derivative used as the starting material in the present invention and corresponding to the formula.
I //~\\f- c- i! 4:/ u , x o R 21 Z '“““'"“ (Il) vari R' betecknar väte och vari R betecknar en alkylgrupp och X betecknar en alkylgrupp, kan lätt framställas genom att bringa en addukt billdad genom reaktionen av forforoxiklorid med ett arylamidderivat, att reagera ned ett pyrrolderivat (hänvisning till hänvisníngsexempel l, som beskrives härefter). 1.1 'G1 10 15 20 25 30 35 3 448 svsf Exempel på 2-aroylpyrrolderivat, som motsvaras av formeln (II) omfattar 2-p-toluoylpyrrol, 2-p-toluoyl-1-metylpyrrol och liknande.I // ~ \\ f- c- i! Wherein R 'represents hydrogen and wherein R represents an alkyl group and X represents an alkyl group can be easily prepared by bringing an adduct formed by the reaction of phosphorus oxychloride with an arylamide derivative, to react down a pyrrole derivative (reference to Reference Example 1, which is described below) 1.1 'G1 10 15 15 25 25 35 35 448 svsf , 2-p-toluoyl-1-methylpyrrole and the like.
Addukten av_dimetylformamid (DMF) och fosforoxiklorid, som an- vändes såsom ett annat utgångsmaterial, är ett välkänt formylerings- medel, som kan erhållas genom att blott blanda båda ovanstående för- eningar.The adduct of dimethylformamide (DMF) and phosphorus oxychloride, which was used as another starting material, is a well known formylating agent which can be obtained by simply mixing both of the above compounds.
Vid utförandet av föreliggande uppfinning är användningen av ett lösningsmedel lämplig. Exempel på lösningsmedlet omfattar l,2-dikloroetan, diklorometan, dietyleter och liknande och också utgångs-DMP kan verka såsom lösningsmedel, när det användes i en överskottsmängd.In the practice of the present invention, the use of a solvent is suitable. Examples of the solvent include 1,2-dichloroethane, dichloromethane, diethyl ether and the like and also starting DMP can act as a solvent when used in an excess amount.
Reaktíonen fortgår vid området från -20 ° till 80 OC, mera lämpligt vid -l0 °^v 40 OC vid betraktande av att förbättra pro- duktutbytet. Dessutom är det karakteristiskt för föreliggande upp- finning, att bildningsförhållnadet av Z-aroyl-5-formyl-substituerade pyrrolderívat ökar, när reaktionen utföres vid -10 0 rumstempera- lur.The reaction proceeds at the range of -20 ° to 80 ° C, more suitably at -10 ° C at 40 ° C when considering improving the product yield. In addition, it is characteristic of the present invention that the formation ratio of Z-aroyl-5-formyl-substituted pyrrole derivative increases when the reaction is carried out at room temperature.
Föreliggande uppfinning belyses ytterligare i detalj genom följande hänvisningsexempel och exempel.The present invention is further illustrated in detail by the following reference examples and examples.
Hänvisningsexempel l Till fosforoxiklorid (l0,7 g, 0,07 mol) sattes droppvis en lös- ning (25 ml) av N,N-dimetyl-p-tolylamid (l1,43 g, 0,07 mol) löst i 1,2-dikloroetan vid rumstemperatur och blandningen upphettades under âterflöde i 2 timmar. Efter kylning av blandningen till rums- temperatur tillsattes sakta droppvis en lösning av N-metylpyrrol (5,7 g, 0,07 mol löst i dikloroetan (15 ml) därtill och sedan upp- hettades reaktionsblandníngen till 50-60 OC följt av omröríng ö- ver natten. Till denna blandning, som rntur, sattes saktndroppvís en lösning av natríumacetat (48 g) igen kylts till rumstempe- löst i vutton (ISO ml) under is-vatten-kylning och blandningen upphettades till âterflöde i 30 min. Reaktionsblandningen hälldes i isvatten, extraherades med kloroform och torkades sedan. Efter borttagande av lösningsmedlet destillerades erhâllen lösning (kok- punkt 170-180 OC/135 Pa) och återstoden renades genom kolonnkroma~ tografi Csilikagel, 20 ß etylacetat-n-hexan) för att ge 2-p-toluoyl- 1-mctylpyrrol (8,98 g). Utbyte 64 %. 10 30 Un u: 40 H gig/län i šgååemg e 1 2 Till ett blandat lösningsmedel av acetonitríl (25 ml) och vat- ten (10 ml) sattes l-metyl-2-formyl-5-p-metylbensoylpyrrol (l,l35 g, 5 mmol), bromoform (l,54 g, 6,1 mmol) och etylmerkaptan (l,6l g,fi5mmol, 1,94 ml). Till denna blandning sattes droppvis en lösning av kali- umhydroxid (l,57 g, 28 mmol) löst i vatten (7,5 ml) och acetonitril (ZS mlJ under omröríng vid rumstemperatur. Efter det att tíllsatsen var över, umrördes rcaktionsblandningen över natten vid rumstempera- tur, följt av värme-omröring vid 80 OC i ett varmt vattenbad i 2 tim. Efter kylning till rumstemperatur, späddes blandningen med 50 ml vatten och tvättades med eter. När det vattenhaltíga skiktet, som togs ut, gjordes_surt med saltsyra, blev skiktet vitgrumligt och det fasta ämnet bildades. Detta fasta ämne extraherades med eter, torkades och koncentrerades för att ge 5-p-toluoyl-1-metylpyrrol~ 2-ättiksyra L0,90 g).Reference Example 1 To phosphorus oxychloride (10.7 g, 0.07 mol) was added dropwise a solution (25 ml) of N, N-dimethyl-p-tolylamide (11.43 g, 0.07 mol) dissolved in 1 ml. 2-Dichloroethane at room temperature and the mixture was heated under reflux for 2 hours. After cooling the mixture to room temperature, a solution of N-methylpyrrole (5.7 g, 0.07 mol dissolved in dichloroethane (15 ml) was slowly added dropwise thereto, and then the reaction mixture was heated to 50-60 ° C followed by stirring. To this mixture, as a solution, slowly added dropwise a solution of sodium acetate (48 g), cooled again to room temperature in vutton (ISO ml) under ice-water cooling, and the mixture was heated to reflux for 30 minutes. in ice water, extracted with chloroform and then dried After distilling off the solvent, the resulting solution was distilled (b.p. 170-180 ° C / 135 Pa) and the residue was purified by column chromatography on silica gel, 20 ß ethyl acetate-n-hexane) to give 2 -p-toluoyl-1-methylpyrrole (8.98 g). Yield 64%. To a mixed solvent of acetonitrile (25 ml) and water (10 ml) was added 1-methyl-2-formyl-5-p-methylbenzoylpyrrole (1, 135 g, 5 mmol), bromoform (1.54 g, 6.1 mmol) and ethyl mercaptan (1.61 g, fi5 mmol, 1.94 mL). To this mixture was added dropwise a solution of potassium hydroxide (1.5 g, 28 mmol) dissolved in water (7.5 ml) and acetonitrile (ZS ml) with stirring at room temperature. After the addition was over, the reaction mixture was stirred overnight at room temperature, followed by heat stirring at 80 DEG C. in a hot water bath for 2 hours. After cooling to room temperature, the mixture was diluted with 50 ml of water and washed with ether. When the aqueous layer removed was acidified with hydrochloric acid, the layer became whitish and the solid formed, this solid was extracted with ether, dried and concentrated to give 5-p-toluoyl-1-methylpyrrole-2-acetic acid L0.90 g).
Utbyte 70 %. smp. 155 ~ iso °c SMR (CDC15)2 62,37 (SH, s), 3,69 (ZH, s), 3,89 (SH, S), e,oø (in, d, J=4H;), 6,62 (in, d,J=4Hz), 7,1s (za, d, J=8Hz}, 7,66 (ZH, d, J = 8Hz).Yield 70%. m.p. 155-iso ° c SMR (CDCl 3) 2 62.37 (SH, s), 3.69 (ZH, s), 3.89 (SH, S), e, oø (in, d, J = 4H;) , 6.62 (in, d, J = 4Hz), 7.1s (za, d, J = 8Hz}, 7.66 (ZH, d, J = 8Hz).
IR (KBr): 3425, 2940, 2900, 1700, 1600 cm-1 Exemgel 1 Till dimetylformamid (O,365 g, 5 mmol) sattes sakta droppvis fosforoxíklorid (1 ml) under is-Vattenkylning. Efter fullbordan av tillsatsen omrördes blandningen vid rumstemperatur i 15 min följt av kylning igen med is-vatten, och en lösning (25 ml) av Z-p-toluoyl- l-metylpyrrol (U,995, 5 mmol) löst i 1,2-dikloroetan sattes dropp- ris därtill. Efter det att tíllsatsen var över, fick blandningen sta vid rumstemperatur över natten. Reaktionsblandníngen hälldes i 10-procentig vattenhaltigt natriumkarbonat och upphettades till rumstemperatur i 15 min och ytterligare till 60 OC i 10 min. Er- hàllen blandning kyldes igen till rumstemperatur, extraherades med kloroform, torkades och koncentrerades. Återstoden (l,22 g) rena- des genom silikagelkolonnkromatografi för att ge 5~p-toloyl-2-for- myl-l-metylpyrrol (0,78 g).IR (KBr): 3425, 2940, 2900, 1700, 1600 cm-1 Example 1 To dimethylformamide (0.5 g, 5 mmol) was slowly added dropwise phosphorus oxychloride (1 ml) under ice-water cooling. After completion of the addition, the mixture was stirred at room temperature for 15 minutes followed by cooling again with ice-water, and a solution (25 ml) of Zp-toluoyl-1-methylpyrrole (U, 995, 5 mmol) dissolved in 1,2-dichloroethane dripping rice was added to it. After the addition was over, the mixture was allowed to stand at room temperature overnight. The reaction mixture was poured into 10% aqueous sodium carbonate and heated to room temperature for 15 minutes and further to 60 ° C for 10 minutes. The resulting mixture was cooled again to room temperature, extracted with chloroform, dried and concentrated. The residue (1.22 g) was purified by silica gel column chromatography to give 5-p-toloyl-2-formyl-1-methylpyrrole (0.78 g).
Utbyte 68 % smp. x1~»s1 °t NHR (C0C15): 63,50 (BH, sl, 4,33 (SH, s), 6,77 (lH, d,J=3,6Hz), 7,03 (lH, d, J ,0H:), 7,42 (ZH, d, J = 7, 3 Hz), ?,é0 (zu, d, J ,s Hz), 9,98 (ia, S). ll ll \l UI u? 10 15 25 bl U| S 87 lR (KBr): 5025, 2950, 2830, 1640, lolü, l360,'lZ7áä4š%95, ššš, 745 cm_l.Yield 68% m.p. x1 ~ »s1 ° t NHR (COC15): 63.50 (BH, sl, 4.33 (SH, s), 6.77 (1H, d, J = 3.6Hz), 7.03 (1H, d , J, 0H :), 7.42 (ZH, d, J = 7, 3 Hz),?, É0 (zu, d, J, s Hz), 9.98 (ia, S). Ll ll \ l UI u? 10 15 25 bl U | S 87 lR (KBr): 5025, 2950, 2830, 1640, lolü, l360, 'lZ7áä4š% 95, ššš, 745 cm_l.
Exemgel 2 _ Till en lösning av fosforoxiklorid (1,0 g) löst i dímetyl~ formamid (9 ml) sattes droppvis on eterlösníng (3 ml) av 2~p-to- luoyl-l-metylpyrrol (0,995 g, S mmol) under is-Vattenkylning. Ef~ ter fullbordan av tillsatsen omrördes blandningen ytterligare i S min under ísvnttcnkylning och sedan togs is-vuttenbadct bort fràn systemet. Reaktionsblandnignen fick stå vid rumstemperatur i 19 tim följt av kylning igen med is-vatten. Till detta sattes 15 ml vatten och och blandningen omrördes i 15 min. Ett mättat vattenhaltígt natriumkarbonat sattes därtill och blandningen ex- traherades med kloroform. Återstoden torkades, koncentrerades . och renades genom kolonnkromatografi (silikagel-etylacetat; n- hexan = 1:9 volym/volym) för att ge 5-p-toluoy1-3-formyl-l-metyl- pyrrol (0,80 J. Utbyte 70 %.Example 2 To a solution of phosphorus oxychloride (1.0 g) dissolved in dimethylformamide (9 ml) was added dropwise ethereal solution (3 ml) of 2-p-toluoyl-1-methylpyrrole (0.995 g, 5 mmol) under ice-Water cooling. After completion of the addition, the mixture was stirred for a further 5 minutes under ice-cooling and then the ice-wet bath was removed from the system. The reaction mixture was allowed to stand at room temperature for 19 hours followed by cooling again with ice-water. To this was added 15 ml of water and the mixture was stirred for 15 minutes. A saturated aqueous sodium carbonate was added thereto, and the mixture was extracted with chloroform. The residue was dried, concentrated. and purified by column chromatography (silica gel-ethyl acetate; n-hexane = 1: 9 v / v) to give 5-p-toluyl-3-formyl-1-methyl-pyrrole (0.80 J. Yield 70%.
NMR (CDCl5): 2,50 (SH, 5), 4,15 (SH, S), 7,32 (lH, d, J = l,7Hz), 7,45 (ZH, d, J = 6,7H:), 7,67 (IH, d, J = 1,7H:), 7,92 (lH, d, J=6,7 Hz), 10,0 (lH, S).NMR (CDCl 3): 2.50 (SH, 5), 4.15 (SH, S), 7.32 (1H, d, J = 1.7Hz), 7.45 (ZH, d, J = 6, 7H, 7.67 (1H, d, J = 1.7H), 7.92 (1H, d, J = 6.7 Hz), 10.0 (1H, S).
Ch (70 JÜlÉÉ 5.Ch (70 JULY 5.
Till dimutylformamid (3,54 g, Jo mmol) sattes droppvis fos- foroxiklorid (6,99 g, 0,046 mmol) under is-Vattenkylning. Efter att reaktionsblandningen stelnat, tillsattes 1,3-dikloroetan oçh man upp- löste den vid rumstemperatur. Lösningen kyldes igen med is-vat- ten och till detta sattes långsamt droppvis en lösning av 2ïp~to- luoyl~l-metylpyrrol (7,22 g, 56 mmol) löst i dikloroetan (50 ml).To dimutylformamide (3.54 g, Jo mmol) was added dropwise phosphorus oxychloride (6.99 g, 0.046 mmol) under ice-water cooling. After the reaction mixture solidified, 1,3-dichloroethane was added and it was dissolved at room temperature. The solution was cooled again with ice-water and to this was slowly added dropwise a solution of 2β-toluoyl-1-methylpyrrole (7.22 g, 56 mmol) dissolved in dichloroethane (50 ml).
Is-vattenbadet togs bort från systemet och blandningen fick stå vid rumstemperatur i 20 timmar. Reaktionsblandningen upphettades till 100 OC under âterflöde i 1 timma, kyldes till rumstemperatur och hydrolyserades genom att tillsätta en lösning av natriumace- tat-3HlO (75 g) löst i vatten (100 ml). Det organiska skiktet ex- traherades med metylenkloríd, torkades och koncentrerades för att ge den atcrstucndc lösningen (l2,84 g). Denna renades genom ko- lonnkromatografi (silikagel-l0 $ etylacetat-n-hexan] för att ge 4,26 g S-p-toluoyl-2-formyl-l-metylpyrrol (utbyte 52 %) och 3,34 g 5-p-toluoyl-3-formyl-metylpyrrol (utbyte 41 %).The ice-water bath was removed from the system and the mixture was allowed to stand at room temperature for 20 hours. The reaction mixture was heated to 100 ° C under reflux for 1 hour, cooled to room temperature and hydrolyzed by adding a solution of sodium acetate-3H 10 (75 g) dissolved in water (100 ml). The organic layer was extracted with methylene chloride, dried and concentrated to give the concentrated solution (12.84 g). This was purified by column chromatography (silica gel-10% ethyl acetate-n-hexane] to give 4.26 g of Sp-toluoyl-2-formyl-1-methylpyrrole (yield 52%) and 3.34 g of 5-p-toluoyl -3-formyl-methylpyrrole (yield 41%).
Claims (8)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP54009227A JPS5846513B2 (en) | 1979-01-31 | 1979-01-31 | 2↓-Aroylformyl-substituted pyrrole derivative and method for producing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SE8000734L SE8000734L (en) | 1980-08-01 |
| SE448875B true SE448875B (en) | 1987-03-23 |
Family
ID=11714519
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE8000734A SE448875B (en) | 1979-01-31 | 1980-01-30 | 2-AROYL (FORMYL) -SUBSTITUTED PYROL RELEASES AND PROCEDURES FOR PREPARING THEREOF |
Country Status (4)
| Country | Link |
|---|---|
| JP (1) | JPS5846513B2 (en) |
| CH (1) | CH641778A5 (en) |
| IT (1) | IT1143954B (en) |
| SE (1) | SE448875B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5332736A (en) * | 1993-11-01 | 1994-07-26 | Ortho Pharmaceutical Corporation | Anti-convulsant aroyl aminoacylpyrroles |
-
1979
- 1979-01-31 JP JP54009227A patent/JPS5846513B2/en not_active Expired
-
1980
- 1980-01-25 IT IT47713/80A patent/IT1143954B/en active
- 1980-01-29 CH CH70980A patent/CH641778A5/en not_active IP Right Cessation
- 1980-01-30 SE SE8000734A patent/SE448875B/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| JPS55102561A (en) | 1980-08-05 |
| JPS5846513B2 (en) | 1983-10-17 |
| SE8000734L (en) | 1980-08-01 |
| IT8047713A0 (en) | 1980-01-25 |
| IT1143954B (en) | 1986-10-29 |
| CH641778A5 (en) | 1984-03-15 |
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