Alkylation of the ambident indole ion in ionic liquids

Abstract

Alkylation of the ambident indole anion in ionic liquids has been investigated. The reaction rate is greater in ionic liquids than in organic solvents. The polarity of certain ionic liquids has been determined to be located between methanol and acetonitrile.Conversions of ambident anions in ionic liquids (IL) have been little investigated in organic synthesis [1][2][3][4][5][6][7][8][9][10][11], in spite of the great interest of chemists in these solvents during the past 20 years [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. Only a few conversions of ambident anions of heterocyclic compounds are reported in the literature [1][2][3][4][5]. The poor availability of information does not permit generalizations on rules for such reactions and the forecasting of their results.The ambident anion of indole (1) forms several products in alkylation reactions, viz. the N-substituted compound 1-alkylindole 3, the C-substituted compound 3-alkylindole 4, and the N,C-disubstituted compound 1,3-dialkylindole 5 [32][33][34]. The rate of the alkylation reaction and the distribution of isomers in the mixture of products 3-5 depend on various factors, the properties of the solvents used, the form and charge of the cation, the structure of the alkylating agent, etc. [32][33][34]. The overall effect of these factors is considered in reactions which are carried out in molecular liquids (organic solvents), and a difference in their influence has N H N N N R N R N R R MY M + _ _ M + 1A 1B 1 R-X 2a-c 3 4 5 + + Y a = OMe, b Y = Bu, c Y = Me; 1 a M = Na, b M = Li, c M = MgI;2−5 a R = n-C 4 H 9 , b R = PhCH 2 , c R = CH 2 =CHCH 2 ; 2a 1 X = Cl, a 2 X = Br, a 3

Room-Temperature Ionic Liquids: Solvents for Synthesis and Catalysis. 2

“…Pyrrole itself has been found to almost exclusively undergo C-alkylation under similar conditions in [C 4 C 1 im][SbF 6 ], with some dialkylation . In a study using a wider range of ionic liquids, it was shown that the selectivities found in alkylations with the halogenobutanes fell in the order found for polar protic solvents for [C 4 C 1 im]Br, but in the order found in polar aprotic solvents in [C 7 pyr]Br and [C 1 C 1 im][OTs] …”

“…319 In a study using a wider range of ionic liquids, it was shown that the selectivities found in alkylations with the halogenobutanes fell in the order found for polar protic solvents for [C 4 C 1 im]Br, but in the order found in polar aprotic solvents in [C 7 pyr]Br and [C 1 C 1 im][OTs]. 532 Base-promoted alkylation of 2-hydroxypyridine in the ionic liquids [C n C 1 im][OTs] (n = 1 or 4), [C 4 C 1 im]Br, and [C n pyr]Br (n = 4 or 7) with a range of bases {MX; M = K, Na, Li, or Ag; X = H, C 4 H 9 , OH, or OCH 3 } has been found to favor N-alkylation over O-alkylation in comparison to molecular solvents. 533 The selectivities and rates of these reactions in the [C n pyr]Br (n = 4 or 7) ionic liquids were found to be greater than for the imidazolium ionic liquids.…”

2- and 3-phenylsulfonylindoles – synthetic equivalents of unsubstituted indole in N-alkylation reactions

“…Although high selectivity for this reaction may be achieved by varying these factors, the problem of selective preparation of an indole N-alkylation product requires a specific solution in each concrete case [2, 6-8]. Special synthetic methods based on the use of phase-transfer catalysis [9][10][11], ionic liquids as the solvent [12,13], other special solvents [14,15], bases [16], and alkylating agents [17], as well as microwave irradiation have been proposed to resolve this problem. Furthermore, generation of the indolyl anion from an N-unsubstituted indole and indole derivatives lacking electron-withdrawing substituents requires the use of a stoichiometric amount of strong bases, which significantly limits the range of functional group tolerating the reaction conditions.…”