Butyl-1-Methylpyrrole

If an equivalent amount of TMEDA is added to the solution of 2-thienyllithium, benzylation gives the expected product in a yield of only 50 %, a contamination of about 15 % of PhCH2CH2Ph being present. If 0.05 mol of f-BuOK is added prior to benzylation (which now occurs at temperatures between —40 and 0 °C), the main impurity is probably stilbene. Phenyllithium TMEDA in THF-hexane reacts with PhCH2Br even at —40 °C, giving PhCH2CH2Ph as the predominant product. 

N-alkylpyrroles are metallated much less easily than furan and thiophene. This is reflected in the higher temperature, longer reaction time and excess of the pyrrole derivative necessary to obtain a satisfactory yield in the subsequent alkylation (compare the metallation conditions with those in the preceding experiments). If no excess of A-methylpyrrole were used, THF would seriously compete with this substrate for butyllithium in the end stage of the metallation. In other experiments in this chapter (14, 39, 40) TV-methylpyrrole is metallated under different conditions, which permit a more economic use of this compound. 

Comparison of the reaction conditions prescribed for the alkylation of 2-lithio-1-methylpyrrole with those applied in the reaction of 2-lithiothiophene with butyl bromide suggests that the former reacts more smoothly (compare Exp. 3). Since further experimental data is lacking, it cannot be said whether this difference in 

Similar poor results in alkylations may be general with organometallic derivatives having the metal linked to the azomethyne carbon atom. 

9 3-Bromo-2-Kthv]thiophene and 3-Bromo-2(l-Hydroxyethyl)Thiophene 

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A comparison of the relative basicities of pyrrole, furan and thiophene may be made by comparing the pK values of their 2,5-di-t-butyl derivatives, which were found to be -1.01, —10.01 and —10.16, respectively. In each case protonation was shown by NMR to occur at position 2. The base-strengthening effect of alkyl substitution is clearly apparent by comparison of pyrrole and its alkyl derivatives, e.g. A-methylpyrrole has a pKa. for a-protonation of -2.9 and 2,3,4,5-tetramethylpyrrole has a pK of 4-3.7. In general, protonation of a-alkylpyrroles occurs at the a -position whereas /3-alkylpyrroles are protonated at the adjacent a-position. As expected, electron-withdrawing groups are base-weakening thus A-phenylpyrrole is reported to have a p/sTa of -5.8. The IR spectrum of the hydrochloride of 2-formylpyrrole indicates that protonation occurs mainly at the carbonyl oxygen atom and only to a limited extent at C-5. 

When the same [NiI (NHC)2] complexes are employed as alkene dimerisation catalysts in ionic liquid (IL) solvent [l-butyl-3-methylimidazolium chloride, AICI3, A-methylpyrrole (0.45 0.55 0.1)] rather than toluene, the catalysts were found to be highly active, with no evidence of decomposition. Furthermore, product distributions for each of the catalyst systems studied was surprisingly similar, indicating a common active species may have been formed in each case. It was proposed that reductive elimination of the NHC-Ni did indeed occur, as outlined in Scheme 13.8, however, the IL solvent oxidatively adds to the Ni(0) thus formed to yield a new Ni-NHC complex, 15, stabilised by the IL solvent, and able to effectively catalyse the dimerisation process (Scheme 13.9) [25-27],... 

As indicated in Scheme 27, indoles may be alkylated by their acid-catalyzed reaction with alcohols. Similarly, r-butylation of pyrroles has been effected by the acid-catalyzed reaction with t- butyl acetate (B-77MI30502), and the diarylmethylation of 1-methylpyrrole from the acid-catalyzed reaction with the chromium trichloride complex of the diarylcarbinol has been described (78JA4124). The alkylation of indoles by alcohols in the presence of the aluminum alkoxide and Raney nickel appears to be efficient for the synthesis of 3-substituted indoles, but is less successful in the alkylation of 2-methylindole (79JHC501). The corresponding isopropylation of pyrrole produces 2,5-diisopropylpyrrole and 1-isopropylpyrrolidine, as the major products (79JHC501). 

Pyrrole reacts with di-<-butyl peroxide at 150° to give the pyrryl-pyrroline (68) iV-methylpyrrole under the same conditions undergoes a hydrogen abstraction from the methyl group.14 The carbon radical... 

Methyl hydrazine Methyl isobutyl ketone Methyl isobutyrate Methyl, mercaptan Methyl methacrylate 1 -Methylnaphthalene 2-Methyl-2-propanethiol, see t-Butyl mercaptan Methyl-n-Propyl ketone 1 -Methylpyrrole Methyl salicylate a-Methyl styrene m.-p-Methyl styrene Methyl sulphate, see Dimethyl sulphate... 

Table 3 Total energies of cationic tr-complexes formed from pyrrole, N-methylpyrrole, and N-(tert-butyl)pyrrole on addition of trimethylsilyl cation at a- ( j and -positions ( ) as well as values characterizing preferable site of electrophilic attack... 

Coupling of the (erf-butyl ether of 5-bromouracil (125) with N-methylpyrrol-2-yl(trimethyl)stannane gave the expected product (126) in low yield (Scheme 27). Modest yields of coupling products (127) were also obtained in reactions with 2-thienyl- and 2-selenylstannanes and unprotected iodouracil. With the pyridylstannane only the 3-isomer showed some reactivity. Silylation of 5-bromouracil is recommended before the coupling reaction. Silyl-protected uracil (128) reacts with formation of a number of biheteroaryl derivatives (129) including pyridylstannanes, except for the 4-isomer (90JHC2165). 

K.23) 1//-Pyrrole, 2-methyl-l-(2-methylbutyl)-, 2-methyl-l-(2-methylbutyl)pyrrole, J-(sec-butyl)-2-methylpyrrole [78368-65-7]... 

Ethyl 2-methyl-4-(D-ara6mo-tetrahydroxybutyl)pyrrole-3-carbothiolate (18) yields a tetra-O-acetyl derivative, and, on oxidation with periodic acid, affords ethyl 4-formyl-2-methylpyrrole-3-carbothiolate (22). Lactone (27) gives a tri-O-acetyl derivative and, on alkaline hydrolysis, consumes one equivalent of base and furnishes 2-methyl-4-(D-arofemo-tetrahydroxy-butyl)pyrrole-3-carboxylic acid (19) in almost quantitative yield. This acid can, in turn, be transformed into a tetra-O-acetyl derivative, and, when oxidized with sodium metaperiodate, it gives 4-formyl-2-methyl-pyrrole-3-carboxylic acid (23). Attempts to determine the size of the lactone ring in compound (27) by oxidation with sodium metaperiodate were unsuccessful three moles of metaperiodate were consumed per mole, as if, during the oxidation, hydrolysis of the lactone had occurred. 

Amino-2-ethoxycarbonyl-4-methylpyrrole and methyl isocyanate gave the ureide, which was cyclized by potassium carbonate in methanol to give an excellent yield of 3,7-dimethylpyrrolo[3,2-rf]pyrimidine-2,4-dione (see 14).332 3-Amino-2-tert-butoxycarbonyl-4-ethoxycarbonyl-5-methylpyr-role and butyl isocyanate, in boiling acetonitrile, produced 3-butyl-7-tert-butoxycarbonyl-5-methylpyrrolo[3,4-d]pyrimidine-2,4-dione (see 13) in excellent yield.347... 

Reactions of Pyrroles. Pyrroles are efficiently alkylated at the nitrogen atom by alkyl halides in the presence of potassium hydroxide and 18-crown-6. In a study of the metallation of a series of A7-alkyl-pyrroles by butyl-lithium it was found that the ratio of 2,4- to 2,5-dilithio-compounds increases with increasing bulk of the alkyl group.Nitration of 1-methylpyrrole yields a mixture of 2,3-, 2,4-, 2,5-, and 3,4-dinitro-compounds, while 1,2-dimethylpyrrole gives the three possible mononitro- as well as 3,4-, 3,5-, and 4,5-dinitro-derivatives. ° ... 

Di-tert-butylsilylene (43) (generated by photolysis of hexa-rert-butylcyclotrisilane) reacts with N-methylpyrrole (44) possibly via an intermediate [2+1] cycloadduct 45 to furnish 3,3-di-ferf-butyl-2-methyl-2-aza-3-silabicyclo[2.2.0]hex-5-ene (46) <970M3080>. On heating, 46 undergoes electrocyclic rearrangement to afford the 1 -aza-2-silacyclohexa-3,5-diene 47. 

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