Table 1.

Reaction of imine 1 with p-cresol.^a

entry	aqueous buffer (aqueous component)	yieldb (%)	3a:3bc
1	200 mM NaH2PO4, pH 5	55	1.3:1
2	200 mM NaH2PO4-Na2HPO4, pH 6.0	36 (20)	1.2:1
3	200 mM NaH2PO4-Na2HPO4, pH 7.0	44	2.0:1
4	200 mM NaH2PO4-Na2HPO4, pH 8.0	46	3.3:1
5d	200 mM NaH2PO4-Na2HPO4, pH 8.0	50	2.5:1
6e	200 mM NaH2PO4-Na2HPO4, pH 8.0	52	2.5:1
7f	200 mM NaH2PO4-Na2HPO4, pH 8.0	53	2.8:1
8	200 mM Na2HPO4, pH 9	44	3.9:1
9	PBS, pH 7.4g	41	2.3:1
10	100 mM Tris, pH 8.0g	41	3.2:1
11	25 mM HEPES, pH7.5g	50	2.8:1
12	10% CH3COOH, pH 2	24	0.8:1
13	H2O	36	2.7:1
14	200 mM Na2CO3, pH 10	49	2.1:1
15	200 mM Et3N, pH 10	29	2.1:1
16h	100 mM NaH2PO4, pH 5	23 (60) [143]	1.3:1
17h	100 mM NaH2PO4-Na2HPO4, pH 6	31 (48) [127]	1.5:1
18h	100 mM NaH2PO4-Na2HPO4, pH 7	39 (27) [93]	2.0:1
19h	100 mM Na2HPO4,pH 9	[76]	ndi
20j	100 mM NaH2PO4-Na2HPO4, pH 7	32 (45)	2.0:1

^aConditions: Imine 1 (95 mM) and p-cresol (25 mM) in 5% DMSO/indicated aqueous buffer (or aqueous component) at 23 °C for 24 h.

^bSum of 3a and 3b; yield of 3c is indicated in parenthesis; determined by ¹H NMR of the extracted mixture. For entries 1-15, yield of 3c was <10% except where noted. Percentage of modified ortho positions of the phenolic OH of p-cresol is indicated in bracket; complete conversion to 3c = 200% in bracket.

^cDetermined by ¹H NMR of the extracted mixture.

^dImine 1 (95 mM) and p-cresol (5 mM).

^eImine 1 (25 mM) and p-cresol (500 μM).

^fImine 1 (5 mM) and p-cresol (500 μM).

^gPBS = phosphate buffered saline. Tris = tris(hydroxymethyl)aminomethane. HEPES= 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid.

^hImine 1 (50 mM) and p-cresol (10 mM) in indicated buffer prepared with D₂O (no DMSO was added) at 37 °C for 24 h. Yield was determined by ¹H NMR of the reaction mixture.

ⁱNot determined.

^jImine 1 (50 mM) and p-cresol (10 mM) in the absence of DMSO at 37 °C.