Building scientific arguments is a central ability for all scientists regardless of their specific domain. In organic chemistry, building arguments is a necessary skill to estimate reaction processes in consideration of the reactivities of reaction centres or the chemical and physical properties. Moreover, building arguments for multiple reaction pathways might help students overcome the tendency toward one-reason decision-making and offer them an authentic perspective on organic processes. Reasoning about multiple alternative organic reaction pathways requires students to build arguments and then judge and weigh the plausibility of these pathways. However, students often struggle to build strong arguments and use scientific principles appropriately to justify their claims. In the present study, the argumentation patterns of 29 chemistry majors students were analysed using a simplified version of Toulmin's argumentation model (claim–evidence–reasoning). The students solved various tasks related to alternative reaction pathways of a substitution reaction. They supported their claims with evidence and justified the evidence through reasoning. We investigated (a) the extent to which the students use evidence and reasoning in their argumentation (referred to as their argumentation approach), (b) how students with different argumentation approaches rationalised changes in their initial claims, and (c) how students used reasoning to justify their arguments. The results indicate that students need further support to appropriately use evidence and reasoning and to apply conceptual knowledge to build well-grounded arguments.