Dynamic Nuclear Polarization MAS NMR is introduced to characterize model methylcellulose ether compounds at natural isotopic abundance. In particular an approach is provided to determine the position of the methyl ether group within the repeating unit. Specifically, natural abundance 13C-13C correlation experiments are used to characterize model 3-O-methylcellulose and 2,3-O-dimethylcellulose, and identify changes in chemical shifts with respect to native cellulose. We also probe the use of through space connectivity to the closest carbons to the CH3 to identify the substitution site on the cellulose ether. To this end, a series of methylcellulose ethers was prepared by a multistep synthesis approach. Key intermediates in these reactions were 2,6-O-diprotected thexyldimethylsilyl (TDMS) cellulose and 6-O-monoprotected TDMS cellulose methylated under homogeneous conditions. The products had degrees of substitution of 0.99 (3-O-methylcellulose) and 2.03 (2,3-O-dimethylcellulose) with exclusively regioselective substitution. The approaches developed here will allow characterization of the substitution patterns in cellulose ethers.