Immobilized Triazine-Type Dehydrocondensing Reagents for Carboxamide Formation: ROMP-Trz-Cl and ROMP(OH)-Trz-Cl

Abstract

The advance in combinatorial chemistry has resulted in the development of solid-supported reagents that can be applied to automated synthesis of a target molecule. As a result, many useful reagents that are well established in the field of solution-phase chemistry have been applied to immobilized reagents. [1][2][3][4][5][6][7][8][9] There have been some recent reports on the preparation of immobilized reagents for dehydrocondensation.10-18) However, since most of these reagents are immobilized by connecting dehydrocondensing reagents to insoluble carriers such as polystyrene and silica gel, they would be prepared by inefficient chemical transformation on the insoluble carrier under heterogeneous conditions. In addition, the weight proportion of the solid carrier relative to the amount of solidsupported reagent is generally high, which inevitably results in the generation of large amounts of waste; this is a serious problem common to solid-supported reagents. To resolve this issue, we developed a new immobilized triazine-type dehydrocondensing reagent by polymerizing the dehydrocondensing reagent itself.19) This polymer reagent is based on the condensing agent, 4,6-dimethoxy-1,3,5-triazinyl-2-methylmorpholinium chloride (DMT-MM) [20][21][22][23][24][25][26] and is a crosslinked polymer prepared by co-polymerizing tetra(ethylene glycol) bis(4-chloro-6-methoxy-1,3,5-triazin-2-yl) ether and tris(2-aminoethyl)amine, which is easily substituted onto the triazine ring under weakly basic conditions.In this work, we developed another application for polymer-type triazine condensing reagents: immobilization by well-established ROMP (ring opening metathesis polymerization) method, in which the reaction proceeds rapidly and with high yield under mild neutral conditions. The dramatically expanded ROMP methodology, based on the work of Grubbs et al. in the 1990s, has been developed as an effective method for acquiring high-loading polymer reagents by polymerizing the reagent unit as a monomer.27-31) Barrett et al. actively developed ROMP-gel supported reagents using this methodology, and reported many excellent immobilized reagents. 4,9,[32][33][34] These reagents have several advantages in addition to high-loading, e.g., high tolerance of the methathesis catalysts for diverse functionalities, and readily available monomers from inexpensive precursors. Recently, ROMP supported coupling reagents carrying fluoroformamidinium or 2-bromopyridinium were also reported.11) In this case, however, preparation of the monomers, which requires operation of 3-4 steps, seems not to be very easy.Our monomer 1a was readily prepared by reacting cyanuric chloride consecutively with 5-norbornene-2-methanol and MeOH (Chart 1). A CH 2 Cl 2 solution of the resulting monomer and cross-linker 2 35) in a mixing ratio of p : q, as shown in Table 1, was allowed to react in the presence of 0.1 mol% Grubbs' catalyst 3 to produce four kinds of polymer with cross-linking percentages of 10, 30, 50 and 100%. The polymer reagents exhibited condensation activ...

An Unconventional Reaction of 2,2‐Diazido Acylacetates with Amines

“…13 C NMR (151 MHz, CDCl 3 ): δ = 171.2, 143.2, 140.9, 128.7, 128.6, 128.5, 127.4, 126.3, 126.3, 48.7, 38.7, 31.8, 21.7 ppm. The analytical data are in agreement with previously reported data …”

AIBN-initiated metal free amidation of aldehydes using N-chloroamines

“…31 Yellow solid; 1 H NMR (CDCl 3 , 300 MHz): δ 7.71-7.69 (m, 2H), 7.41-7.15 (m, 8H), 6.74 (bs, 1H), 3.68-3.61 (m, 2H), 2.88(t, J = 7.0 Hz, 2H); 13 4-Chloro-N-phenethylbenzamide (3t). 30 Yellow solid; 1 H NMR (CDCl 3 , 300 MHz): δ 7.69-7.60 (m, 2H), 7.47-7.21 (7H, m), 6.12 (bs, 1H), 3.74-3.67 (m, 2H), 2.93 (t, J = 6.9 Hz, 2H); 13 N-Benzyl-2-bromobenzamide (3y). 35 Yellow solid; 1 H NMR (CDCl 3 , 300 MHz):…”

Amide bond formation: beyond the myth of coupling reagents

“…Hioki used another strategy to obtain polymeric triazine-type reagents. 169 Using a norbornene-derivatised triazine, they synthesised via ROMP an immobilised monomethoxychlorotriazine, which was tested on anilines and primary amines. Yields were good (nine examples, 80-98%), but no secondary amine was tested while the reagent was not compared to other classical amide bond formation methods.…”