1、D.H. Ripin, D.A. Evans *Values 14 for water and 35 for DMSO were extrapolated using various methods. 0.79 SULFINIC & SULFONIC ACIDS PEROXIDES H 2 O pKa (DMSO) (DMSO) pKa H 2 O H 2 O pKa (DMSO) pKas of Inorganic and Oxo-Acids 8.2 11.5 CH 3 CO 3 H MeOOH 12.5 15.54 15.7 (11.1) (12.3) (1.6) (0.3) CF 3 S
2、O 3 H -14 (7.9) (12.9) (15) (1.8) (0.9) (32) (DMSO) (CF 3 ) 2 CHOH CF 3 CH 2 OH t-BuOH MeOH HOH cis-CO 2 H trans-CO 2 H H R= 3.6, 10.3 HO 3.77 H -0.25 CF 3 0.65 CCl 3 1.29 CHCl 2 -8.0 11.6 HOOH -3.0, 1.99 H 2 SO 4 1.9, 7.21 H 2 SO 3 4.00 HSCN 2.12, 7.21, 12.32 H 3 PO 4 7.00 H 2 S -1.7 15.7 H 3 O + H
3、 2 O -1.3 HNO 3 3.29 HNO 2 4.72 HN 3 9.24 NH 4 Cl 3.17 -0.98, 6.50 9.4 -2.6 -10 7.5 -9.00 9.23 H 2 CrO 4 HCN CH 3 SO 3 H HClO 4 HOCl HF HCl HBr B(OH) 3 INORGANIC ACIDS Chem 206 Substrate Substrate + + 1.92, 6.23 -12.4 -7.8 -6.2 -3.8 -2.05 -2.2 -2.6 2.1 + -1.8 -6.5 X= CH 2 NO 2 CH 2 F CH 2 Cl CH 2 Br
4、 CH 2 I 1.68 2.66 2.86 2.86 3.12 CH 3 4.76 4.2 o-O 2 NC 6 H 4 m-O 2 NC 6 H 4 p-O 2 NC 6 H 4 o-(CH 3 ) 3 N + C 6 H 4 p-OMeC 6 H 4 p-ClC 6 H 4 o-ClC 6 H 4 m-ClC 6 H 4 2.17 2.45 3.44 2.94 3.83 3.99 1.37 p-(CH 3 ) 3 N + C 6 H 4 3.43 4.47 C 6 H 5 4.25 3.02, 4.38 Substrate Substrate (13.7) (18.5) PROTONAT
5、ED SPECIES CARBOXYLIC ACIDS (31.2) (27.9) (29.3) (23.5) (17.9) (29.4) i-PrOH C 6 H 5 OH 10.20 7.14 8.35 p-OMeC 6 H 4 OH p-O 2 NC 6 H 4 OH m-O 2 NC 6 H 4 OH 9.95 (18.0) 2-napthol (17.1) (10.8) (19.1) ALCOHOLS 16.5 17 c-hex 3 COH 24 OXIMES & HYDROXAMIC ACIDS 8.88 (NH) 11.3 (20.1) pKa H 2 O O OH R Ph P
6、h N OH N H Ph OH N + O OH O + H H Me N OH Ph O Me O OH X Me O + Me N + O OH Ph OH OH Ph Ph CH 3 OH O + H H Me S OH OO Ph S OH O S OH Me Me O + H Me PhD.H. Ripin, D.A. Evans *Values 14 for water and 35 for DMSO were extrapolated using various methods. 38 (12) (estimate) pKas of Nitrogen Acids H 2 O (
7、DMSO) Chem 206 Substrate Substrate Substrate pKa Substrate DABCO DBU Et 3 N + H i-Pr 2 N + H 2 i-Pr 2 NH EtN + H 3 TMS 2 NH N + H 4 NH 3 TMP (41) (36 THF) (37) (30) (10.5) 9.2 10.6 11.05 10.75 PhNH 2 Ph 2 NH (30.6) (25.0) PhN + H 3 Ph 2 N + H 2 4.6 0.78 2-napthal-N + H 3 4.16 (3.6) H 2 NN + H 3 HON
8、+ H 3 8.12 5.96 + -9.3 H (PPTS) 5.21 (3.4) + DMAP 9.2 + 4.95 (0.90) PhN + (Me) 2 H 5.20 (2.50) R= t-Bu Me 6.75 (4.46) + 6.95 N-Me morpholine 7.38 Morpholine 8.36 2.97, 8.82 (2.97, 8.93) (9.00) 6.90, 9.95 Quinuclidine 11.0 (9.80) Proton Sponge -9.0, 12.0 (-, 7.50) + + (20.5) 12 + (20.95) (18.6) (23.0
9、) (44) NCNH 2 (16.9) (26.5) 1,2,3 triazole (13.9) R= H CH 3 Ph CF 3 NH 2 (urea) OEt (23.5) (25.5) (23.3) (17.2) (26.9) (24.8) 15.1 (21.6) Ac 2 NH (17.9) Cl, H 0.72 (17.0) (24.1) (14.7) 8.30 (NH) 8.88 (13.7) (13.6) PhSO 2 NHNH 2 (21.6) (18.9) (17.2) PhNHNHPh (26.1) AMIDES & CARBAMATES PROTONATED NITR
10、OGEN AMINES PhSO 2 NH 2 MeSO 2 NH 2 CF 3 SO 2 NH 2 (17.5) (16.1) 6.3 (9.7) HN 3 4.7 (7.9) PhCN + H -10 MeSO 2 NHPh (12.9) IMIDES SULFONAMIDE HYRDAZONES,- IDES, & -INES HYDROXAMIC ACID AMIDINES HETEROCYCLES PROTONATED HETEROCYCLES R= Me (17.3) Ph (15.0) pKa (DMSO) H 2 OH 2 O (DMSO) pKa pKa (DMSO) H 2
11、 O GUANIDINIUM, N + N + N N H NH Me Me Me Me O 2 N NO 2 NO 2 NH 3 NH HN H NH Me 2 N NH R R H H 3 N + + NH 3 NH 3 NH 3 NH O O Bn O N + H N + H 2 H N HN N NH H 2 NN N N NH RN H 2 O NH O N H Et Ph N H O NH O NH O OO O NH O N H Ph OH Ph Me 2 NN M e 2 N + H 2 Me NNH 2 O NHNH 2 Ph NSO 2 Ph NH 2 R 26(THF)D
12、.H. Ripin, D.A. Evans 19-20 9 13 11 24.5 36 H 2 *Values 14 for water and 35 for DMSO were extrapolated using various methods. HCCH H 2 O (DMSO) Substrate Substrate Substrate pKa Substrate AMIDES HYDROCARBONS pKa (DMSO) H 2 OH 2 O (DMSO) pKa pKa (DMSO) H 2 O CH 4 CH 2 =CHCH 3 PhH CH 2 =CH 2 PhCH 3 Ph
13、 2 CH 2 Ph 3 CH (56) (44) (43) (32.2) (30.6) (Me) 3 CH 53 (Me) 2 CH 2 51 50 48 43 46 41 33.5 31.5 43 24 PhCCH 23 (28.8) XC 6 H 4 CH 3 X= p-CN p-NO 2 p-COPh (30.8) (20.4) (26.9) (26.1) (18.0) (20.1) 15 20 X= H Ph SPh COCH 3 SO 2 Ph (26.5) (19.8) (18.7) (13.3) (15.1) (27.1) (28.3) (27.7) (26.3) X= H C
14、H 3 COCH 3 COPh CO 2 Et CN OMe NPh 2 (22.85) N + Me 3 NO 2 SPh OPh SO 2 Ph SePh (24.7) (24.4) (17.7) (12.7) (13.3) (22.7) (10.2) (21.6) (20.3) (14.6) (7.7) (16.9) (21.1) (11.4) (18.6) X= H OMe NMe 2 Br CN (24.7) (25.7) (27.5) (23.8) (22.0) n= 8 7 6 5 4 (27.4) (27.7) (26.4) (25.8) (25.1) (29.0) (28.1
15、) (25.5) (32.4) (30.3) (23.6) (20.0) (14.2) (15.7) (20.9) (26.6) (25.9) (24.9) (17.2) (25.7) (18.2) F Ph KETONES ESTERS n 30.2 (THF) pKas of CH bonds in Hydrocarbons and Carbonyl Compounds Me Me Me Me Me O X O Et Et S i-Pr i-Pr O O Me t-Bu Ph X Ph i-Pr O O LiO O Ph Me O X O O O O O Me Me t-BuO O Me
16、t-BuO O Ph EtO O N + Me 3 O EtO Me O O OMe MeO O O MeO S N + Me 3 O Et 2 N Ph O Me 2 N Me 2 N O SPh N O CN Me 2 NM e S O Me Me 2 N O Chem 206D.H. Ripin, D.A. Evans 11 (10.3) (17.0) 7 10-11 PhSH BuSH *Values 14 for water and 35 for DMSO were extrapolated using various methods. (16.3) (18.2) Me 3 S +
17、=O SULFONIUM (20.7) (14.4) (33) (24.5) (30.7) (27.6) i-Pr Me R= SULFIMIDES & SULFOXIMINES X= H Ph SPh (29.0) (29.0) (24.5) (18.2) (27.2) (33) SOPh Ph H X= (35.1) SULFOXIDES (26.3) PhSCH=CHCH 2 SPh (22.9) (23.6) (24.0) (24.3) t-Bu i-Pr Et Me R= RSCH 2 CN (19.1) (20.8) (30.7) CN CO 2 Me Ph X= (30.5) (
18、31.3) (PrS) 3 CH (22.8) (PhS) 3 CH (26.7) PhSCHPh 2 (23.0) (PhS) 2 CHPh (23.4) MeSCH 2 SO 2 Ph (24.9) (11.0) (20.3) (30.8) (11.8) (16.9) (18.7) (20.8) (30.8) POPh 2 SO 2 CF 3 SO 2 Ph SPh NO 2 COPh COCH 3 CN Ph X= PhSCH 2 X SULFIDES (30.0) (30.2) (25.2) (26.7) (30.1) (28.2) H 2 O (DMSO) Substrate Sub
19、strate Substrate pKa Substrate HETERO-AROMATICS NITRILES pKa (DMSO) H 2 OH 2 O (DMSO) pKa pKa (DMSO) H 2 O X= H CH 3 Ph COPh CONR 2 CO 2 Et CN OPh N + Me 3 SPh SO 2 Ph (31.3) (32.5) (21.9) (10.2) (17.1) (13.1) (11.1) (28.1) (20.6) (20.8) (12.0) SULFONES X= H CH 3 t-Bu Ph CH=CH 2 CH=CHPh CCH COPh CCP
20、h COMe OPh N + Me 3 CN NO 2 SMe SPh SO 2 Ph PPh 2 (29.0) (31.0) (31.2) (23.4) (22.5) (20.2) (22.1) (17.8) (11.4) (12.5) (27.9) (19.4) (12.0) (7.1) (23.5) (20.5) (12.2) (20.2) (22.3) (PhSO 2 ) 2 CH 2 Me (31.1) (18.8) (21.8) (32.8) (14.3) (26.6) pKas of CH bonds at Nitrile, Heteroaromatic, and Sulfur
21、Substituted Carbon NC X N Ph Ph N N Ph Ph N + O Ph Ph S O - S OO Ph X S O Ph S CHPh 2 O O O Me Me S S S H S S Ph SX O S O X S O CHPh 2 Ph X Me S NTs Ph S R Ph Me NTs O S ON M e Me Ph Ph S Me N + Me 2 O S ON T s CH 2 Cl Ph Ph S + CH 2 Ph Me Me CF 3 S Me O O S OO i-Pr CF 3 Et S Et O O CF 3 S O O Chem
22、206(24.3) IMINES n (15.8) (17.9) (16.0) (17.8) (26.9) 7 6 5 4 3 n= (7.7) (7.1) (11.8) (16.2) (12.2) (16.9) (16.7) (17.2) CH 2 COPh CH 2 SO 2 Ph CH 2 SPh CH 2 Bn CH 2 Ph CHMe 2 CH 2 Me CH 3 R= RNO 2 NITRO (20.3) (29.9) Ph 2 PCH 2 SO 2 Ph Ph 2 PCH 2 PPh 2 (16.9) CN (24.9) SPh X= PHOSPHINES (28.8) (26.
23、2) (18.6) (16.4) (27.6) SiMe 3 Cl CO 2 Et CN Ph X= PHOSPONATES & PHOSPHINE OXIDES (7.0) (6.2) (21.2) (22.4) Ph 3 P + CH 2 CN Ph 3 P + CH 2 COPh Ph 3 P + i-Pr Ph 3 P + CH 3 9.1 Et 3 P + H 2.7 MeP + H 3 -14 P + H 4 PHOSPHONIUM (24.9) (20.6) (14.6) (19.4) (20.6) CONEt 2 CO 2 Et COPh SO 2 Ph CN X= Me 3
24、N + CH 2 X AMMONIUM (21.1) (27.9) PhOCH 2 SO 2 Ph (28.1) PhOCH 2 CN (30.7) MeOCH 2 SO 2 Ph (49) CH 3 OPh SELENIDES ETHERS (27.2) PhSeCH=CHCH 2 SePh (31.0) PhSeCH 2 Ph (31.3) (PhSe) 2 CH 2 (27.5) PhSeCHPh 2 (18.6) H 2 O (DMSO) D. H. Ripin, D. A. Evans Substrate Substrate Substrate pKa pKa (DMSO) H 2
25、OH 2 O (DMSO) pKa pKas of CH bonds at Heteroatom Substituted Carbon & References REFERENCES DMSO: JACS 97, 7007 (1975) JACS 97, 7160 (1975) JACS 97, 442 (1975) JACS 105, 6188 (1983) JOC 41, 1883 (1976) JOC 41, 1885 (1976) JOC 41, 2786 (1976) JOC 41, 2508 (1976) JOC 42, 1817 (1977) JOC 42, 321 (1977)
26、 JOC 42, 326 (1977) JOC 43, 3113 (1978) JOC 43, 3095 (1978) JOC 43, 1764 (1978) JOC 45, 3325 (1980) JOC 45, 3305 (1980) JOC 45, 3884 (1980) JOC 46, 4327 (1981) JOC 46, 632 (1981) JOC 47, 3224 (1982) JOC 47, 2504 (1982) Acc. Chem. Res. 21, 456 (1988) Unpublished results of F. Bordwell Water: Advanced
27、 Org. Chem., 3rd Ed.J. March (1985) Unpublished results of W. P. Jencks THF: JACS 110, 5705 (1988) 10 *Values 14 for water and 35 for DMSO were extrapolated using various methods. (EtO) 2 PX O Ph 2 P O X O 2 N Ph Ph NP h PhSe Ph O O Ph MeO Chem 206 Oxime ethers are 10 pka units less acidic than their ketone counterparts Streitwieser, JOC 1991, 56, 1989
