Ind. Eng. Chem. Res. 2008, 47, 8043–8047
8043
Organocatalysts for the Reaction of Dimethyl Carbonate with 2,4-Diaminotoluene† Raquel Jua´rez,‡ Ana Padilla,§ Avelino Corma,‡ and Hermenegildo Garcı´a*,‡ Instituto de Tecnologı´a Quı´mica CSIC-UPV, UniVersidad Polite´cnica de Valencia, AVda. de los Naranjos, 46022 Valencia, Spain, and Centro Tecnolo´gico de Repsol YPF, Crta. De Extremadura, Km 18, 28931 Madrid, Spain
Four nitrogen-containing organic compounds [1,5,7-triazabicyclo(4,4,0)dec-5-ene, 4-(N,N-dimethylamino)pyridine, N-methylimidazole, and L-proline] have been tested as organocatalysts for the reaction of dimethyl carbonate with an aromatic diamine, 2,4-diaminotoluene (DAT). Although, generally, N-methylation was the predominant process, variable proportions of N-carbamoylation were also observed. Reaction kinetics indicates that N-methylation and N-carbamoylation are independent and parallel processes. DAT conversion increases as the temperature increased over the range of 105-125 °C. Besides the nature of the organocatalyst, the ratio between N-methylation/N-carbamoylation was influenced by the DAT-to-DMC ratio: higher DAT proportions increased the DAT conversion and favored N-carbamoylation. 4-(N,N-dimethylamine)pyridine was determined to be the most active organocatalyst of the series and, under certain conditions, can lead to selective N-methylation with high conversion. Introduction There is much current interest in developing organocatalysts to promote organic transformations under metal-free conditions.1–4 The use of transition metals as catalysts is generally undesirable, from the environmental point of view. One of the reactions that has considerable synthetic utility is the selective N-methylation of amines.5 Aliphatic amines are more reactive than the aromatic amines, which are generally reluctant to undergo N-methylation.5 Thus, N-methylation of aromatic amines is still challenging, from the catalytic point of view. Besides the avoidance of metals as catalysts, some methylating agents are also not tolerable, from the green chemistry perspective, because of their toxicity or/and the presence of heavy heteroatoms. Thus, typical methylating agents as methyl halides and dimethyl sulfate are known to be highly mutagenic compounds and their use should be restricted.6,7 In addition, stoichiometric amounts of halides or sulfates are formed when using these conventional methylating reactants. For these reasons, dimethyl carbonate (DMC) has emerged as a suitable alternative green methylating agent with lower negative environmental impact, with carbon dioxide and alcohol being the reaction byproducts in the methylation.8 However, the use of DMC must be combined with adequate catalysts, because the reactivity of DMC at moderate temperatures can be significantly lower than that of methyl iodide or dimethyl sulfate. Thus, while the latter two reagents do not require catalysts to effect methylations of amines, in the case of DMC, no reaction occurs at moderate temperatures in the absence of a catalyst. Another problem that is associated with the use of DMC is its dual behavior as a methylating agent and as a carbamoylating reagent, which can lead to low selectivity toward the desired N-methyl derivatives.9–11 In this respect, catalysis also can be a way to achieve selectivity when using DMC. * To whom correspondence should be addressed. Tel.: +34963877807. Fax: +34963877809. E-mail:
[email protected]. † In memory of Dr. Juan Antonio Delgado Oyagu¨e. ‡ Instituto de Tecnologı´a Quı´mica CSIC-UPV, Universidad Polite´cnica de Valencia. § Centro Tecnolo´gico de Repsol YPF.
The present article describes the use of nucleophilic tertiary amines as suitable organocatalysts for the N-methylation of aromatic amines using DMC. Results and Discussion In a series of experiments, the N-methylation of 2,4diaminotoluene (DAT), using DMC as a methylating agent and solvent, was tested in the presence of four nitrogen-containing organic nucleophiles. The names and structures of the amines used as organocatalysts are shown in Scheme 1. Among the four organocatalysts, there is one that is a strong nucleophile with a guanidine substructure, namely, TABD.12,13 Our study also includes DMAP and N-Mim, which are two of the favorite organocatalysts to promote nucleophilic substitutions.3,14–18 We also tested the activity of L-Pro, because there are numerous reports describing the use of this aminoacid as a catalyst for nucleophilic additions and substitutions, particularly for the enantioselective version of them.19–21 DAT was selected as an aromatic amine, because it contains two amine groups, offering possibility to discuss regioselectivity and polyalkylation in addition to N-carbamoylation. Blank controls showed no reaction of DAT and DMC in the absence of catalyst, under the conditions used in the present work. The reaction parameters that have been considered, besides the nature of the organocatalysts, are the substrate-to-DMC ratio (1:10 and 1:30; see Tables 1 and 2, respectively), and the reaction temperature. The reaction mixtures contain a distribution of N-mono (ortho- and para-), N-di (para-, para-) and minor amounts of N,N,N-trimethylated (mostly para-, para-, ortho-) derivatives of DAT, together with variable proportions of 4-(N-carbamoyl)-4-(N-methyl) DAT arising from simultaneous N-methylation and N-carbamoylation (product 6). Scheme 2 shows the structure of the products that have been characterized. For the purpose of comparing the activity of different organocatalysts, we have classified the products as those compounds arising exclusively from N-methylation and distinguish them from those that contain a N-carbamoyl group (see Scheme 2). For the product that corresponds simultaneously to methylation and carbamoylation (compound 6), its yield in
10.1021/ie800126t CCC: $40.75 2008 American Chemical Society Published on Web 05/06/2008
8044 Ind. Eng. Chem. Res., Vol. 47, No. 21, 2008 Scheme 1. Structure and Name of the Organocatalysts Used in This Work
Table 1. Reaction of DAT (0.395 mmol) with DMC (11.8 mmol, 30 equiv), in the Presence of Different Organocatalysts (10% Molar Ratio, with Respect to DAT)a entry 1 2 3 4 5 6
selectivity (%) temperature, time, conversion T (°C) t (h) (%) N-methylation N-carbamoylation 105 105 115 115 125 125
4 20 2 8 2 5
Catalyst ) TABD
