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But without a significant redesign to reduce drag the Spitfire was not going to come up to snuff as a long range escort fighter. But I think it is important to restate the obvious. .
The design modifications necessary to turn the Spitfire into a successful long range escort fighter would inherently make it an altogether different aircraft in my humble opinion.
I think you are overstating the long range cruise speed of the Mustang.They miss two important factors.
1. The fighters, at least in areas where enemy fighters are likely to be encountered, need to cruise much faster than 220mph and more likely than not, faster than 260mph.
P-51s routinely cruised at a bit over 300mph.
It could take a Spitfire V (with under 85 gallons of fuel on board) over two minutes to accelerate from 200-220mph to full speed (350-360mph?) by which time the attackers are long gone.
Granted the MK IX had more power but adding 300-400lbs of tanks and fuel is NOT going to help acceleration.
2. Take-off and initial climb out was done on internal fuel as was combat (mostly) so radius is governed by internal fuel remaining over Germany (target) after 15 minutes combat. Spitfires were figured to have around a 24 Imp gallon "fuel allowance" which covered take-off and about a 20minute reserve to find their own (or any) airfield upon return. At about 18lbs boost a two stage Merlin was using about 3 IMP gallons a minute so 5 minutes is 18 imp and figure between 2 and 2.5 IMP gallons a minute for military power so 12 gallons for 10 minutes ? (Americans figured 5 minutes WER and 15 minutes at either military or max continuous).
So it is whatever internal tankage they can scheme minus about 54 gallons for the trip back. MK XIII with larger lower tank, wing leading edge and 35 gallons in rear fuselage has 157 IMP gallon without drop tanks or around 100-105 IMP gallons for trip back after dropping tanks and fighting for 15 minutes.
Not dividing total fuel in half. Exiting German airspace and crossing France/Low Countries at 220mph is asking to get bounced by a plane/s doing well over 300mph.
MK Vs were recommended to fly at 300mph at 20,000ft using 2400rpm and +1 1/2 lbs and using 46imp gallons an hour or 2200rpm/1 3/4 lbs for 263mph. I doubt the MK IX is going to be very different.
Every minute at combat settings is 3-4 minutes even at medium cruise speeds.