It is important to understand the efficiency and selectivity of biological processes on a molecular basis. One key aspect to the success of these processes is the proximity effect. We use 1,4-naphthoquinone derivatives as a model to examine the proximity effect. The reactivity of 1,4-naphthoquinones, particularly at the 2- and/or 3-positions, toward a thiolate nucleophile, is also critical in biological events. For instance, the modification of thiol group of cysteine in tyrosine phosphatase results in their anti-tumor activity. We study the reactivity of 1,4-naphthoquinone derivatives at the 2- and/or 3-positions toward a thiolate anion to compare intra- and intermolecular reactions and examine the reactivity difference due to the proximity effect. An intramolecular reaction of 2-ethylamino-3-bromo-1,4-naphthoquinone with dithiolate anion replaces both bromine and ethylamino groups but an intermolecular reaction with two thiolate anions fails to replace ethylamino group, which speaks to the effectiveness of an intramolecular process. Furthermore, we found a negative correlation between the distance in reacting groups to the percent yield of the intramolecularly cyclized product from reacting 2-bromo-3-methoxy-1,4-naphthoquinone with alkanedithiols where two thiols are separated with carbon chains of different lengths. The greater the distance between the reacting thiolates, the lower the product yield, due to the proximity effect. In the reaction with 1,4-butanedithiol we found four products, the intramolecularly cyclized product and its hydroquinone along with a macrocyclic ring that is made of two 1,4-naphthoquinones and two 1,4-butanedithiols. The elucidation of the structure of the fourth product is in progress.