N,N′‐Dimethylated Benzyloxytriazinedione: A Stable Solid Reagent for Acid‐Catalyzed O‐Benzylation

Abstract

N,N′‐Dimethylated 6‐(benzyloxy)‐1,3,5‐triazine‐2,4(1H,3H)‐dione (DMBOT) has been developed as a triazinedione‐based, stable solid reagent for acid‐catalyzed O‐benzylation. The conceptual basis of the design was to fix the core triazinedione skeleton, and the two methyl groups in positions 1 and 3 were introduced to acheive this. The coproduct of DMBOT can be easily removed by simple washing. Various acid‐ and base‐labile alcohols were O‐benzylated by using DMBOT in the presence of an acid catalyst. In particular, 2,6‐di‐tert‐butylpyridinium trifluoromethanesulfonate, which is a mild, stable, and nonhygroscopic acid catalyst, can be used with DMBOT for this reaction. Compared to other reported methods, DMBOT gave better results for several challenging O‐benzylation reactions under nonbasic conditions.

Development of Triazine-Based Benzylating Reagents Possessing <i>t</i>-Butyl Group on the Triazine Core: Thermally Controllable Reagents for the Initiation of Reaction

“…The benzylation of simple primary alcohols, 1b and 1c, proceeded in high yields (entries 1, 2). Bulky secondary and tertiary alcohols, 1a and 1d-f, were converted into their corresponding benzyl ethers in >80% yields which are comparable to those using DPT-BM (X-a) (entries 3,5,7,9). When the reaction temperature was increased to 60°C, the reactions completed within 1 h without a decrease of the yields (entries 4, 6, 8, 10).…”

“…1,2) Recently, we have developed several alkylating reagents based on the characteristics of 1,3,5-triazine. 2,4,6-Tris(benzyloxy)-1,3,5-triazine (TriBOT), 3,4) 2,4,6-tris(p-methoxybenzyloxy)-1,3,5-triazine (TriBOT-PM), 5) 6-(benzyloxy)-1,3,5-triazine-2,4(1H,3H)-dione (MonoBOT), 6,7) 2,4,6-tris(t-butoxy)-1,3,5-triazine (TriAT-tBu), 8) 2,4,6-tris(allyloxy)-1,3,5-triazine (TriAT-allyl), 9) and N,N′-dimethylated 6-(benzyloxy)-1,3,5-triazine-2,4(1H,3H)dione (DMBOT) 10) achieve the alkylation of various alcohols in good to excellent yields in the presence of a catalytic amount of an acid. 4-(4,6-Diphenoxy-1,3,5-triazin-2-yl)-4-benzylmorpholinium triflate (DPT-BM (X-a)) 11,12) converts acidor alkali-labile alcohols into corresponding benzyl ethers because of the nearly neutral conditions ( Fig.…”

Preparation of Alkyl Ethers with Diallyltriazinedione‐Type Alkylating Agents (ATTACKs‐R) Under Acid Catalysis

“…Following the procedure for DMBOT, acid‐catalyzed O ‐alkylation with ATTACKs‐R (1.2 equiv.) was conducted in 1,4‐dioxane, at room temperature, in the presence of molecular sieves 5 Å (Table ).…”

“…Methyl (2 R )‐3‐(Benzyloxy)‐2‐methylpropionate (7c‐Bn): Following GP‐2, 3 (17.1 mg, 50 µmol) was added to a mixture of 6c (55.2 µL, 0.500 mmol), ATTACK‐Bn (179.6 mg, 0.600 mmol), and molecular sieves 5 Å (62.5 mg) in 1,4‐dioxane (2.5 mL) at room temperature. After 5 h, the reaction mixture was diluted with Et 2 O (50 mL) and filtered.…”

“…Kinetic studies indicated the high reactivity of MonoBOT compared to that of TriBOT. Subsequently, further exploration of the core structure led to N , N′ ‐dimethylated benzyloxytriazinedione (DMBOT, R 1 = Me) as a next‐generation reagent for acid‐catalyzed O ‐benzylation . N , N′ ‐Dibenzylated analog 2 (R 1 = Bn), which can also be employed for acid‐catalyzed O ‐benzylation,, is accessible through rearrangement of the benzyl groups in TriBOT…”