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Just an idea I had: IOTL the Treaty of Madrid was the first official agreement between Spain and Portugal that recognized that the old borders defined by the Treaty of Tordesillas couldn't be kept.
According to the treaty, in exchange for giving the Colony of Sacramento (in OTL Uruguay) to the Spanish, Portugal would receive the Jesuitic Missions located on the eastern side of the Uruguay River (the Missiones Orientales). However, it caused a revolt of the local Guarany who lived in the missions, leading to the Guarani War that destroyed those populations.The treaty wasn't kept by both kingdoms (as they eventually refused to surrender the lands they should exchange) but the destruction of the missions made later conquests of the territory by the Portuguese much easier.

So, WI the Treaty of Madrid had not been signed? Maybe we could have it by making Ferdinand VI of Spain dieing earlier (his marriage to the Portuguese princess was very influential to the peace proposal) and Charles III assumes the throne. Could we see the territory of the Missiones Orientales integrating a kind of greater Paraguay? Or the anti-Jesuitic measures taken by the Spanish government (that would probably still happen ITTL) could still weaken the Guarany enough to make a Portuguese conquest likely? http://en.wikipedia.org/wiki/Treaty_of_Madrid_(1750)
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