The reaction of an aromatic heterocycle with a proton is called a protonation. One of articles about this theory is 《Iodo derivatives of pyrroles》. Authors are Treibs, Alfred; Kolm, Hans Georg.The article about the compound:Ethyl 3,5-Dimethyl-2-pyrrolecarboxylatecas:2199-44-2,SMILESS:O=C(C1=C(C)C=C(C)N1)OCC).Computed Properties of C9H13NO2. Through the article, more information about this compound (cas:2199-44-2) is conveyed.
Although iodo derivatives of pyrrole are quite stable to alkali, the iodine is rather easily replaced by H, Br, Cl, aryl azo, NO2, and CHR groups. Nitropyrroles are prepared almost exclusively by replacing other substituents by the NO2 group. To 6.7 g. pyrrole and 66 g. KI in 400 cc. 25% EtOH at 30° was added 28 g. AcOH, 10 g. AcONa, 38 cc. 10% H2O2, and 50 cc. H2O; the resulting exothermic reaction was kept 20 min. at 45° giving 2,3,4,5-tetraiodopyrrole, m. 162-4° (decomposition) (EtOH). 2,4-Dimethylpyrrole (I) (3 g.) in 100 cc. MeOH and 9 g. K2CO3 in 100 cc. H2O with 64 cc. M KI3 was shaken until colorless and diluted gradually with H2O to give 9.7 g. 3,5-diiodo derivative (II) of I, m. 83° (aqueous MeOH followed by petr. ether), stable for only 1-2 days. I in EtOH and AcOH with KI3 gave a dark oil yielding only 3-8% II. Formed similarly to II was 2,5-dimethyl-3,4-diiodopyrrole, m. 132°, decompose 135-45° (petr. ether containing Et2O followed by vacuum sublimation), very sensitive to light, especially in solution To 1.75 g. 1,2,5-trimethytpyrrole (III) in 125 cc. MeOH and 10 g. K2CO3 in 50 cc. H2O at -10° was added dropwise 16 cc. M KI3, the mixture kept colorless, filtered promptly from a brown precipitate, and evaporated in vacuo; the residue in petr. ether refiltered and evaporated gave 2.7 g. 3-iodo derivative (IV) of III, m. 71° (MeOH or sublimation), decompose within 30 min. in daylight, stable 1-2 days under extreme precautions. III (1 g.) and 10 g. K2CO3 in 180 cc. 60% MeOH treated in 1 portion with 4.6 g. iodine in 50 cc. MeOH gave 3.2 g. 4-iodo derivative of IV, pale yellow, m. 129° (dilute EtOH). Formed similarly to IV from 2,3,4-trimethylpyrrole (V) (using iodine in MeOH), was the 5-iodo derivative of V, m. 90° (petr. ether at -70°), giving a pos. Ehrlich reaction at 20°, decomposing readily in warm solution From 3-formyl derivative of I in alk. MeOH was formed 90.4% 3-formyl-5-iodo derivative of I, m. 157° (MeOH), also prepared in similar yield by treating 2.5 g. 3-formyl derivative of I in 20 cc. EtOH with 3 g. AcONa and 2.3 g. H2O2, acidifying with 2 g. AcOH at 40-50°, and adding 2.3 g. KI in H2O. By either of these methods, the 5-formyl derivative of I gave 84-6% 3-iodo-5-formyl derivative of I, m. 172° (EtOH). In alk. MeOH containing KI3 and in AcOHMeOH with KI and 3% H2O2 2-methyl-3-carbethoxypyrrole (VI) gave 90-94% 4,5-diiodo derivative of VI, pale pink, m. 191° (decomposition) (when rapidly heated). From 2 g. 3-methyl-2,4-dicarbethoxypyrrole (VII) in 30 cc. 50% EtOH at 80° with 8.9 cc. M KI3 (gradually added) was formed 2.8 g. 5-iodo derivative (VIII) of VII, m. 174° (EtOH), also prepared by Kleinspehn and Corwin’s method (C.A. 49, 285g); under these conditions a hitherto undescribed very insoluble dark green iodine adduct of VIII (not analyzed) was also formed. The 5-carbethoxy derivative of I in acid solution by the usual procedures gave 98% 3-iodo-5-carbethoxy derivative (IX) of I, nacreous leaflets, m. 141°, also formed from the 3-carboxy analog of IX by iodination and decarboxylation. IX heated with alk. MeOH gave the 5-CO2Me analog of IX, m. 182°. Formed by the usual procedures from the 3-carbethoxy derivative of I or its 5-carboxy derivative was the 3-carbethoxy-5-iodo derivative (IXa) of I, m. 146°. IX stirred with KOH at 135-40° and acidified with HCl gave 3-iodo-5-carboxy derivative of I, m. 112° (decomposition), giving a pos. Ehrlich reaction; this could not be converted into the 3-iodo derivative of I by thermal decarboxylation. To 3.94 g. of the product formed by condensing VI with BzH (Fischer and Schubert, C.A. 21, 381) in 50 cc. MeOH and 3 g. K2CO3 in 10 cc. H2O was added gradually 20 cc. M KI3 and the mixture boiled briefly giving (HN.CHMe:CR.CI:C)2CHR’ (X) (R = CO2Et, R’ = Ph), m. 217-18° (decomposition) (when rapidly heated). Formed analogously was X (R = CO2Et, R’ = Me), m. 168° (decomposition) (MeOH). In either case X was identified by coupling with p-O2NC6H4N2OAc and subsequent fission giving p-O2C6H4N:NC:CI.CR:CHMe.NH (Xa) (R = CO2Et) (cf. C.A. 52, 13705g). The 4,5-diiodo derivative of VI refluxed with 0.5 g. NH4Cl and 15 cc. 80% EtOH with gradual addition of 0.3 g. Zn dust, filtered, and treated with 75 cc. H2O containing little NH4OH or HCl gave VI, m. 72°. This method failed to remove iodine from the 5-iodo derivative of VII, which however with Zn in warm glacial AcOH gave VII, m. 91°. Under similar conditions the 5-Br derivative of VII remained unchanged. The 4-iodo-5-nitro derivative (Xb) of VI (0.65 g.) refluxed 30 min. with 0.32 g. Natur-kupfer C and 15 cc. glacial AcOH, filtered hot, and treated with 10% HCl gave 90% 5-NO2 derivative of VI, m. 144°, giving deep yellow alk. solutions, yielding pale yellow needles on acidification, giving no Ehrlich reaction and extremely unreactive. The following could be reduced similarly by means of the same catalyst: IX, the 5-iodo derivative of VII, and the 4,5-iodo derivative of VI. None of the corresponding Br derivatives was affected by this catalyst. IX (0.3 g.) in 5 cc. Ac2O warmed gently with 0.8 g. KI did not react until small amounts of H2O were added to the hot solution followed by cold H2O, whereupon a mixture of IX and the 5-CO2Et derivative of I was formed. On long standing the amounts of IX increased, but in the presence of NaHSO3 the yield of 5-CO2Et derivative of I was quant. In the above reaction KBr could replace KI, but KCl or NH4Cl were inactive unless IX was prehydrolyzed with HCl. The 3-iodo-5-carboxy derivative of I warmed with dilute HCl, made alk. with NaOH, and extracted with Et2O gave I (picrate, m. 90°). IX in 10 cc. 70% Et2O treated with BF3, poured on ice, and neutralized with Na2CO3 gave mostly black products and little I. In the presence of Cu, BF3-Et2O reacted with IX at 50° giving 5-CO2Et derivative of I, m. 122°. IXa with equimolar amounts of Ph3P in dry Et2O after 2 hrs. gave unanalyzed yellow crystals (XI), m. 218° (N-free), the filtrate from which gave the 3-CO2Et derivative of I, m. 75°. IX gave a similar reaction with Ph3P but required 2 weeks to give XI; the filtrate gave the 5-CO2Et derivative of I. In 100-200 mg. of various iodo- and bromopyrroles, the % halogen could be determined by treating with equal amounts of KI in 50-80 cc. 80% MeOH at 50-60°, acidifying with 2N H2SO4, and titrating with 0.1N Na2S2O3. Usually the results were satisfactory. However the iodo derivatives of VII and X reacted so slowly with hot methanolic KI solutions that the method could not be used. A technique for the qual. identification of iodine in pyrrole derivatives is described. To 0.5 g. 3,5-di-CO2Et derivative of I in 30 cc. MeOH at 0° 1 g. iodine in MeOH was added gradually and the mixture poured into 400 cc. ice-cold 1% aqueous KI giving the deep blue adduct C12H17NO4.I, m. 146° (after washing with H2O and drying rapidly over P2O5), which in hot EtOH gave the original pyrrole, m. 137°. Similarly, the 5-Bt derivative of VII gave the adduct C11H14BrNO4.I, m. 152-4°, decolorized at 60° by aqueous alcoholic KI, but giving the adduct on cooling. Similar (undescribed) iodine adducts were obtained with pyrrole, VII, and the 5-CO2H derivative of VII; the latter on heating in alk. solution gave VIII. IX (4 g.) was added gradually to 30 cc. concentrated HNO3 at 0°, kept 1 hr., the precipitate washed with H2O and triturated with little aqueous NaHCO3, and extracted with 2 g. KI; the residue gave 2.5 g. 3-nitro-5-carbethoxy derivative (XII) of I, m. 204° (CHCl3); the corresponding 5-CO2Me analog, m. 184°. XII (65%) was also formed by adding the 5-CO2Et derivative of I at 0° to HNO3 and after 10 hrs. pouring into ice H2O. From IXa and HNO3 at -10° was formed 55% 3-carbethoxy-5-nitro derivative of I, m. 149° (dilute EtOH), identical with the compound obtained by Fischer and Zerweck (C.A. 17, 106). From the 4,5-diiodo derivative of VI and HNO3 was formed 75% Xb, m. 181°, and from VIII was formed the 5-NO2 derivative of VII, pale yellow, m. 111° (ligroine). The 4,5-diiodo derivative of VI (0.5 g.) in 30 cc. glacial AcOH with 0.24 g. p-O2NC6H4N2OAc in 5 cc. AcOH gave Xa, orange red, m. 186-7° (decomposition) (EtOH), soluble in MeOH containing NaOH, reprecipitated with acid. Similarly the 4-iodo derivative of IV gave 1,2,5-trimethyl-3-iodo-4-(p-nitrophenylazo)pyrrole, brown needles, sintering 160°, m. 185° (decomposition), 2,3,4,5-Tetraiodopyrrole similarly gave 2,3,4-triiodo-5-(p-nitrophenylazo)pyrrole, red, m. 221° (decomposition), giving a violet solution in alk. MeOH, reprecipitated by HCl. No azo dye was isolated by similar treatment of the 3-formyl-5-iodo and 5-formyl-3-iodo derivatives of I, X, or the 5-NO2 derivative of VI. IXa (2.9 g.) in 25 cc. EtOH was boiled briefly with 0.5 cc. 30% HCHO and 1 cc. concentrated HCl added dropwise giving bis(2,4-dimethyl-3-carbethoxy-5-pyrryl)methene-HCl, red with blue surface luster, m. 224° (cf. Fischer and Zerweck, C.A. 17, 1465), which in boiling EtOH with NH4OH gave the corresponding free methene (XIII), yellow, m. 190°. IXa treated as above, but in cold MeOH, with HCHO and a drop of 2N HCl and after 15 hrs. made barely alk. with 2N NaOH and crystallized from MeOH gave a mixture which was fractionated from CHCl3 giving 18% less soluble bis(2,4-dimethyl-3-carbethoxy-5-pyrryl)methane (XIIIa), m. 224°, whose mother liquor gave 73% XIII. IXa (2.9 g.) in 25 cc. hot EtOH with 0.5 cc. 30% HCHO was heated with 5 g. Na2S2O3 in 15 cc. H2O and acidified with HCl to pH 3. The precipitate was triturated with hot EtOH containing little NaOH and filtered giving XIIIa and from the mother liquor bis(2,4-dimethyl-3-carbethoxy-5-pyrryl) sulfide, C18H24N2O4S, m. 198-200° (slowly heated), 212° (rapid heating) (CHCl3-petr. ether followed by CCl4). IXa in EtOH with BzH and little HCl refluxed 30 min. and made alk. with dilute NH4OH gave 30% ms-phenylbis(2,4-dimethyl-3-carbethoxy-5-pyrryl)methene (XIV), orange-red, m. 158° (MeOH); HCl salt, m. 204°. Very similarly, IXa and 1,4-C6H4(CHO)2 in EtOH with a trace of concentrated HCl refluxed 10 min. gave a dark crystalline deposit which was triturated with 20% EtOH and warm H2O and treated with NH4OH giving p-phenylenebis [ms-bis(2,4-dimethyl-3-carbethoxy-5-pyrryl)methene], pale orange, turning black at 272° (CHCl3 and xylene), turning dark red on exposure to direct sunlight, which when treated with Zn and HCl in EtOH at 40° gave a colorless compound, m. 267° (putatively the corresponding methane, but not analyzed). By the usual procedure, IXa and p-Me2NC6H4CHO yielded ms-(p-dimethylaminophenyl)bis(2,4-dimethyl-3-carbethoxy-5-pyrryl)-methen-HCl, coarse dark crystals, m. 224-5° (even when the alcoholic solution was made alk. with NH4OH), which in 80% MeOH containing a little HCl treated with an excess 2N NaOH and heated gave the free methene, C27H33N3O4, red rodlets with green luster, m. 183°. XIIIa (70 mg.) in 20 cc. MeOH treated gradually with 68 mg. ICl in 2 cc. MeOH gave XIII. XIV was similarly formed from the corresponding methane. Tetrakis(2,4-dimethyl-3-carbethoxy-5-pyrryl)ethane and tris(2,4-dimethyl-3-carbethoxy-5-pyrryl)methane oxidized with ICl both gave XIII. IX (3 g.) in 20 cc. AcOH was boiled 20 min., treated with a mild stream of air, and distilled; any loss of AcOH was compensated for by AcOH addition H2O added to the distillate gave a dark precipitate which treated with C and fractionated from dilute EtOH gave principally the 5-CO2Et derivative of I, m. 122°, very small amounts of 3-Ac-5-CO2Et derivative of I, m. 142°, and after high vacuum sublimation at 120° [MeC:C(CO2Et).NH.CMe:C]2 (XV), m. 186°, showing a pale yellow-green fluorescence in EtOH, colorless in ligroine, giving no Ehrlich test, and forming no azo dye with p-O2NC6H4N2OAc in acid unless previously heated with alk. MeOH, after which both reactions were pos. An attempt to form a bipyrrole derivative analogous to XV by the deiodination of IXa gave an orangered compound, m. 254° (ligroine, CCl4, or CHCl3-Et2O), containing about 63% C, 6.6 H, and 8.0 N; the mother liquor gave 3-CO2Et derivative (XVI) of II, m. 76°. IXa in glacial AcOH with N Br in AcOH with addition of dilute Na2S2O3 gave the corresponding 5-Br analog (XVII) of IXa, m. 96° (decomposition) (when rapidly heated), m. 102° (decomposition), also formed by treating IXa in AcOH with concentrated aqueous HBr and crystallizing from dilute AcOH. When in this reaction excess Na2SO3 was added, XVI was obtained. IXa (200 mg.) in 4 cc. AcOH, 0.5 cc. concentrated HCl, a little H2O, and small amounts of Br followed by (but avoiding an excess of) Na2S2O3 gave the 5-Cl analog of IXa, m. 140° (decomposition) (aqueous MeOH or dilute AcOH), also formed from XVII. The 5-CO2Et derivative of I in AcOH with excess concentrated HCl and equivalent amounts of Br gave 5-CO2Et-3-Cl derivative of I, m. 182-3° (EtOH); 32 references.
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