Kenneth K. Laali

Fluorodediazoniation in ionic liquid solvents: new life for the Balz–Schiemann reaction

Abstract Drawbacks associated with the classic Balz–Schiemann reaction are eliminated in a series of examples by conducting fluorodediazoniation in ionic liquid solvents, thus opening up a new horizon for a much in demand process.

Ethylammonium nitrate (EAN)/Tf2O and EAN/TFAA: ionic liquid based systems for aromatic nitration.

Acting as in situ sources of triflyl nitrate (TfONO(2)) and trifluoroacetyl nitrate (CF(3)COONO(2)), the EAN/Tf(2)O and EAN/TFAA systems, generated via metathesis in the readily available ethylammonium nitrate (EAN) ionic liquid as solvent, are powerful electrophilic nitrating reagents for a wide variety of aromatic and heteroaromatic compounds. Comparative nitration experiments indicate that EAN/Tf(2)O is superior to EAN/TFAA for nitration of strongly deactivated systems. Both systems exhibit low substrate selectivity (K(T)/K(B) = 5-10) in between values reported for covalent nitrates and preformed nitronium salts.

Facile benzylation of aromatics in ionic liquid solvents promoted by TfOH, Sc(OTf)3, and Yb(OTf)3·xH2O; New life for a classic transformation

Benzylation of aromatics with PhCH2Cl and PhCH2OH is conveniently performed in [BMIM][OTf] or [BMIM][PF6] ionic liquids (ILs), by using TfOH, Sc(OTf)3 and Yb(OTf)3·xH2O as catalysts. With PhCH2Cl, high conversions were achieved by using 20% Sc(OTf)3 or Yb(OTf)3 hydrate under mild conditions (65–80 °C). Triflic acid is superior to Yb(OTf)3 as promoter for benzylation with PhCH2OH in the IL solvent, since in most cases little or no dibenzyl ether (DBE) was formed as side product. The scope of arene benzylation with benzyl alcohol in the TfOH-catalyzed and Yb(OTf)3-catalyzed reactions was examined in [BMIM][PF6] solvent. Whereas conversions are typically quantitative at 65–70 °C, minor amounts of DBE were produced, along with the corresponding ArCH2Ph (with minor amounts of dibenzylated derivatives being detected in benzylation of mesitylene and biphenyl). Substrate selectivity (KT/KB) and regioselectivity (isomer distribution) measured for benzylation in IL solvents employing TfOH or Yb(OTf)3 as catalyst are similar to those reported previously in molecular solvents employing Nafion-H, AlCl3, TiCl4 or “clayzic”. The observed high yields and chemoselectivities (absence of DBE), coupled to easy isolation of the benzylated products and recycling/reuse of the IL, provide a new life for this classical transformation.

Triflic acid-promoted transacylation and deacylation reactions in ionic liquid solvents

A convenient process for transacylation by sterically crowded aromatic ketones (namely acetylmesitylene 1, acetyldurene 2, acetylprehnitene 3, acetylpentamethylbenzene 4 and diacetyldurene 5) to activated aromatic compounds such as anisole has been developed using triflic acid (TfOH) as catalyst and employing various room temperature imidazolium ionic liquids as “eco-friendly” solvents under relatively mild conditions (at 70 °C). The yields have been optimized based on the arene to TfOH molar ratios and the reaction temperature. Deacetylation to transacylation product ratios depend on the reaction conditions and increase on raising temperature. In the absence of an activated arene receptor, hindered ketones are efficiently deacetylated by TfOH in the ionic liquid solvents. The simple process employed avoids the use of large excess of AlCl3 or TFA, and chlorinated or nitrated solvents which were previously utilized to effect this transformation.

Chlorination of Aromatics with Trichloroisocyanuric Acid (TCICA) in Brønsted-Acidic Imidazolium Ionic Liquid [BMIM(SO3H)][OTf]: an Economical, Green Protocol for the Synthesis of Chloroarenes*

A survey study on electrophilic chlorination of aromatics with trichloroisocyanuric acid (TCICA) in Bronsted-acidic imidazolium ionic liquid [BMIM(SO3H)][OTf] is reported. The reactions are performed under very mild conditions (at ~50°C) and give good to excellent yields, depending on the substrates. Chemoselectivity for mono- v. dichlorination can be tuned by changing the arene-to-TCICA ratio and the reaction time. The survey study and competitive experiments suggest that triprotonated/protosolvated TCICA is a selective/moderately reactive transfer-chlorination electrophile. Density functional theory was used as guide to obtain further insight into the nature of the chlorination electrophile and the transfer-chlorination step.

Triflic acid-catalyzed adamantylation of aromatics in [BMIM][OTf] ionic liquid; synthetic scope and mechanistic insight

A mild and efficient process has been developed for the one-pot adamantylation of aromatic substrates employing 1-AdaOH, 1-AdaCl, 1-AdaBr, and 1-Br-3,5,7-trimethyladamantane as adamantylating agents, with triflic acid (TfOH) as promoter and n-butylmethylimidazolium triflate [BMIM][OTf] room temperature ionic liquid (IL) as solvent. The influence of reaction temperature, reaction time and the amount of TfOH was gauged in model reactions employing 1-AdaOH, 1-AdaCl and 1-AdaBr with toluene as the substrate. Under optimal conditions, the reactions exhibit high para selectivity with little or no adamantane side-product being formed. The synthetic scope of this transformation was tested for representative alkylbenzenes and haloalkylbenzenes. Comparative reactions carried out in 1,2-dichloroethane (DCE) produce increased amounts of the meta isomer and substantial amounts of adamantane. Substrate selectivities (K(T)/K(B)) were measured in competitive experiments in [BMIM][OTf] and in DCE as solvents. Isomerization tests were performed to shed light on the origin of the meta isomer. A DFT study was also conducted to compare relative stabilities of the isomeric products, to gauge the relative stabilities of the intermediate isomeric benzenium ions of adamantylation and their charge distribution modes, and to explore the intramolecular process for isomerization in the benzenium ion.

A theoretical (DFT, GIAO-NMR, NICS) study of the carbocations and oxidation dications from azulenes, homoazulene, benzazulenes, benzohomoazulenes, and the isomeric azulenoazulenes.

Protonation of parent azulene (1), homoazulene (8), representative isomeric benzazulenes (9, 9A, and 9B), and benzohomoazulenes (10, 10A, and 10B) as well as the mono- and diprotonation of isomeric azulenoazulenes (11-16) were studied by DFT at the B3LYP/6-31G(d) level. The most likely carbocations were identified based on relative protonation energies. For comparison, complete experimental 13C NMR data were obtained for parent azulenium ion 1H+ and guaiazulenium ion 2H+ in TFA. The oxidation dications derived from benzazulenes (9, 9A, and 9B), benzohomoazulenes (10, 10A, and 10B) and azulenoazulenes (11, 16) were also investigated. For azulenoazulene dications the singlet and triplet states are both minima, but except for 11(2+) and 13(2+), the triplet states are higher in energy. Structural/geometrical changes in the carbocations were examined. GIAO-NMR, NPA charges (and changes in charges), and NICS (and delta NICS) were employed to compute the NMR chemical shifts (delta delta 13C values) in order to derive charge delocalization maps and to gauge relative aromaticitylantiaromaticity in the energetically most favored carbocations and oxidation dications. The emerging trends are discussed and compared. Creation of tropylium or homotropylium entities in the carbocations (monoprotonated) and carbodications (diprotonated) is identified as an important driving force governing the protonation outcomes. Consideration of the AM1-derived delta delta Hf values (and the DFT-derived delta delta G values) suggests that the two-electron oxidation of azulenoazulenes should be experimentally feasible. Given their antiaromatic (paratropic) character, azulenoazulene dications represent interesting targets for NMR study. GIAO-derived charge delocalization mapping allows the most likely sites for nucleophilic attack on the dications to be identified.

Electrophilic chemistry of propargylic alcohols in imidazolium ionic liquids: Propargylation of arenes and synthesis of propargylic ethers catalyzed by metallic triflates [Bi(OTf)3, Sc(OTf)3, Yb(OTf)3], TfOH, or B(C6F5)3

Metallic triflates M(OTf)(3) (M = Bi, Sc, Yb), immobilized in imidazolium ionic liquids [BMIM][BF(4)], [BMIM][PF(6)] and [BMIM][OTf] are efficient systems for one-pot reactions of propargylic alcohols 1,3-diphenyl-2-propyn-1-ol Ia, 1-methyl-3-phenyl-2-propyn-1-ol Ib, and 2-pentyn-1-ol Ic, with a wide range of arenes bearing activating substituents, under mild conditions. The [BMIM][PF(6)]/B(C(6)F(5))(3) and [BMIM][PF(6)]/TfOH systems were superior in propargylation with Ib and Ic, while reaction of 3-phenyl-2-propyn-1-ol Id with activated aromatics resulted in the formation of diaryl-propanones instead. Propargylation of anisole with Ib under M(OTf)(3) catalysis is highly para selective, but with TfOH or B(C(6)F(5))(3) as catalyst the ortho isomer was also formed. Steric influence of the propargylic moiety on substrate selectivity is reflected in the lack of ortho propargylation for phenol and ethylbenzene by using propargylic alcohol Ia, and notable formation of the ortho isomer employing alcohol Ib. In the later case para selectivity could be increased by running the reaction at r. t. for 10 h. The Bi(OTf)(3)-catalyzed reaction of 1,3-dimethoxybenzene with Ia led to minor formation of dipropargylated derivative, along with the monopropargyl product. Propargylation of the less reactive arenes (mesitylene, ethylbenzene, toluene), using Sc(OTf)(3) as catalyst, led increasingly to the formation of dipropargylic ethers and propargyl ketones, with no ring propargylation product with toluene. Concomitant formation of dipropargylic ether was also observed in Yb(OTf)(3)-catalyzed propargylation of β-naphthol, whereas propargylation of 2-nitro and 4-nitro-aniline led to N-propargylation. The recycling/reuse of the IL was demonstrated in representative cases with no appreciable decrease in the conversions over 3 cycles. It was also shown that recycled IL could be used to propargylate a different aromatic compound. The efficacy of IL/M(OTf)(3) and IL/TfOH systems for cross-breeding two propargylic alcohols or a propargylic alcohol with a non-propargylic alcohol and/or self-coupling, to form a wide variety of functionalized ethers is also demonstrated.

Iodination of Organic Compounds with Elemental Iodine in the Presence of Hydrogen Peroxide in Ionic Liquid Media

Iodo-transformations using the reagent system I2/H2O2 were studied in the water miscible ionic liquid (IL) 1-butyl-3-methyl imidazolium tetrafluoroborate (bmimBF4) and in water immiscible IL, 1-butyl-3-methyl imidazolium hexafluorophosphate (bmimPF6). Two different forms of H2O2 as mediators of iodination were investigated, namely 30% aq. H2O2 and urea-H2O2 (UHP) in solid form. The role of the oxidant during the course of a reaction could be distinguished based on the amount of reagent required for the most efficient transformation. Two types of iodo-functionalizations through an electrophilic process were observed depending on the structure of the substrates. Whereas ring iodination took place in the case of dimethoxy- and trimethoxy-benzenes, with arylalkyl ketones the alkyl group α to the carbonyl was regioselectively iodinated. The results were further evaluated in comparison with iodination using the reagent system I2/H2O2 in water as medium, and under solvent-free reaction conditions, in terms of efficiency, selectivity, mechanism, and the ‘green’ aspects. The reusability/recycling of water immiscible bmimPF6 was investigated for 1,3,5-trimethoxy benzene (1b), which required a 1/0.5/0.6 molar ratio of substrat/I2/oxidant, and for 1,2,3-trimethoxy benzene (1f), which required a 1/1/1 ratio for complete iodine introduction. In addition, the efficiency of iodination was tested by varying the substrates, and employing the recycled hydrophobic IL bmimPF6.

Electrospray mass spectrometric and DFT study of substituent effects in Ag(+) complexation to polycyclic aromatic hydrocarbons (PAHs).

Complexation of Ag(i) cation to a series of substituted anthracenes (AN), phenanthrenes (PH), pyrenes (PY) and cyclopenta[a]phenanthrenes (CPaPH) was studied in competitive experiments by allowing PAHs to react in pairs with AgOTf. The resulting complexes were examined by electrospray mass spectrometry (ES-MS) to determine relative abundances of the corresponding monomeric and dimeric complexes. Based on this data a sequence of complexation ability rankings was derived for each group. Among the substituents examined, a -COMe group when placed at the meso position in AN and PH, or at the C-1 in PY is most effective in Ag(+) complexation, whereas an -NO(2) group is least efficient. Methyl groups at the meso positions are better than in the terminal rings. For the CPaPH series, bay region substitution (methyl and alkoxy) have limited effect as does carbonyl substitution in the annelated CP ring. In the PY series, a -COPh or a -CH(Me)OH group at C-1 is as efficient as -COMe. Based on extensive potential energy searches, four types of complexation modes were identified by B3LYP/LANL2DZ calculations involving Ag(+) complexation to -NO(2) oxygens, to -COMe or to -OH and a peri-carbon, to just one ring carbon, or by bridging two ring carbons. Among these modes, the first two are most favorable. The energetic preferences were rationalized with charge decomposition analysis (CDA). Effect of Ag(+) complexation on relative aromaticity in various rings was examined by NICS (nucleus independent chemical shift) in two representative cases. Structures and energies of the acetyl pyrene-Ag(+)-pyrene hetero-dimer and acetyl pyrene-Ag(+)-acetyl pyrene homo-dimer complexes were determined with the same model. These complexes have sandwich structures.