AbstractThe reaction between granular arrowroot starch and sodium monochloroacetate (SMCA) in isopropanol‐water mixtures has been studied in a systematic way using experimental design strategies. The effect of six factors, i.e. the theoretical degree of substitution (DSt), reaction time, weight fraction of water in the mixture, NaOH/SMCA ratio, temperature and weight fraction of starch on three responses, i.e. the degree of substitution (DS), the conversion of SMCA and the selectivity of SMCA towards carboxymethyl starch, has been determined in a systematic manner. Granular carboxymethyl arrowroot starch with a maximum DS of 1.4 could be prepared in a singlestep procedure. The results are compared with data obtained for potato starch. Similar trends for all responses were observed, suggesting close similarities between the chemical composition and the topochemistry of granular arrowroot‐ and potato‐starch.