How do signalling molecules find their receptors at large distances?
Yes, any individual ligand may have the wrong orientation to interact effectively with an individual receptor, but so what?  There are typically thousands of each type of receptor on a single cell1 and there will be many molecules of a given ligand present as well.  

For your synapse example, I suggest looking up:


How many neurotransmitter molecules will be present in a synapse
How many receptors will present in a synapse
How many of those receptors need to be bound to get a signal


I think that will help you make sense of this phenomenon and I encourage you to post a detailed answer to your own question!

You might also want to look into molecular dynamics simulations ...

1: Milo, R., &amp; Phillips, R. (2015). Cell biology by the numbers. Garland Science.