Quantum Mechanics/Molecular Mechanics (QM/MM) can describe chemical reactions in molecular dynamics (MD) simulations at a much lower cost than MD. Still, it is prohibitively expensive for many systems of interest because such systems usually require long simulations for sufficient statistical sampling. Additional MM degrees of freedom are often slow and numerous but secondary in interest. Coarse-graining (CG) is well-known to be able to speed up sampling through both reduction in simulation cost and the ability to accelerate the dynamics. Therefore, embedding a QM system in a CG environment can be a promising way of expediting sampling without compromising the information about the QM subsystem. Sinitskiy and Voth first proposed the theory of Quantum Mechanics/Coarse-grained Molecular Mechanics (QM/CG-MM) with a bottom-up CG mapping. Mironenko and Voth subsequently introduced the DFT-QM/CG-MM formalism to couple a Density Functional Theory (DFT) treated QM system and to an apolar environment. Here, we present a more complete theory that addresses MM environments with significant polarity by explicitly accounting for the electrostatic coupling. We demonstrate our QM/CG-MM method with a chloride-methyl chloride S2 reaction system in acetone, which is sensitive to solvent polarity. The method accurately recapitulates the potential of mean force for the substitution reaction, and the reaction barrier from the best model agrees with the atomistic simulations within sampling error. These models also have generalizability. In two other reactive systems that they have not been trained on, the QM/CG-MM model still achieves the same level of agreement with the atomistic QM/MM models. Finally, we show that in these examples the speed-up in the sampling is proportional to the acceleration of the rotational dynamics of the solvent in the CG system.