Table 1

¹H and ¹³C NMR data for rofecoxib (5a), 5-hydroxyrofecoxib (6), and ¹⁸O-labeled rofecoxib analogs (5b–d)^1-a

Compound Position	¹H NMR Signals		¹³C NMR Signals^1-b		Δδ^1-c ^1-d
Compound Position	5a	6	5a	6	5b	5c	5d	6
2	—^1-e	—	172.5	169.7	0.047	0.012	0.032	∼0^1-f
3	—	—	126.8	129.1	0.008	∼0	0.009	∼0
4	—	—	155.9	154.8	0.011	0.009	∼0	∼0
5	5.40, s, 2H	6.70, d, 1H, J = 8.7	70.8	97.3	0.029	0.024	∼0	0.010
1"	—	—	135.6	135.7
2"	7.60, d, 2H, J = 8.5	7.60, d, 2H, J= 8.4	128.6	129.4
3"	7.93, d, 2H, J = 8.5	7.93, d, 2H, J = 8.4	127.3	127.1
4"	—	—	141.9	141.5
Me	3.23, s, 3H	3.23, s, 3H	43.1	43.1
1′	—	—	129.7	129.1
2′	7.34, m, 2H	7.32, m, 2H	129.0	129.0
3′	7.42, m, 2H	7.42, m, 2H	128.7	128.7
4′	7.42, m, 1H	7.42, m, 1H	128.9	129.1
OH	—	8.05, d, 1H, J = 8.7	—	—

↵1-a ¹H and ¹³C NMR signals are reported as δ (ppm) with reference to trimethylsilane. Coupling constants (J) are expressed in Hz.
↵1-b ¹³C signal assignments were deduced from two-dimensional ¹H-¹³C correlation experiments (HSQC and HMBC).
↵1-c The ¹⁸O isotope effect on¹³C chemical shift is reported as Δδ (upfield in ppm).
↵1-d For labeled compounds with an isotopic enrichment of >70% (5b, 5c, and6), unlabeled reference was added (1:1 ratio) to obtain Δδ.
↵1-e No signal detected.
↵1-f No measurable isotope shift was observed.