Constantes de pKa ph, Apuntes de Bioquímica Médica

¡Descarga Constantes de pKa ph y más Apuntes en PDF de Bioquímica Médica solo en Docsity! *Values <0 for H2O and DMSO, and values >14 for water and >35 for DMSO were extrapolated using various methods. 0.79 SULFINIC & SULFONIC ACIDS PEROXIDES pKa (DMSO)(DMSO)pKapKa (DMSO) pKa's of Inorganic and Oxo-Acids 8.2 11.5 12.5 15.5 15.7 (11.1) (12.3) (1.6) (0.3)-14 (7.9) (12.9) (15) (1.8) (0.9) (32) (DMSO) cis-CO2H trans-CO2H R= 3.6, 10.3 3.77 -0.25 0.65 1.29 -8.0 11.6 -3.0, 1.99 1.9, 7.21 4.00 2.12, 7.21, 12.32 7.00 -1.7 15.7 -1.3 3.29 4.72 9.24 3.17 -0.98, 6.50 9.4 -2.6 -10 7.5 -9.00 9.23 INORGANIC ACIDS Chem 206 SubstrateSubstrate + + 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= 1.68 2.66 2.86 2.86 3.12 4.76 4.2 o-O2NC6H4 m-O2NC6H4 p-O2NC6H4 o-(CH3)3N+C6H4 p-OMeC6H4 p-ClC6H4 o-ClC6H4 m-ClC6H4 2.17 2.45 3.44 2.94 3.83 3.99 1.37 p-(CH3)3N+C6H4 3.43 4.47 4.25 3.02, 4.38 Substrate Substrate (13.7) (18.5) PROTONATED SPECIESCARBOXYLIC ACIDS (31.2) (27.9) (29.3) (23.5) (18.2) (29.4) 10.2 7.1 8.4 p-OMeC6H4OH p-O2NC6H4OH m-O2NC6H4OH 9.95 (18.0) 2-napthol (17.1) (10.8) (19.1) ALCOHOLS 16.5 17.0 c-hex3COH 24.0 OXIMES & HYDROXAMIC ACIDS 8.88 11.3 (20.1) pKa O OHR PhPh N OH N H Ph OH N+ O OH O+ H HMe N OH Ph O Me O OHX Me O+ Me N+ O OHPh OH OHPh Ph CH3 OH O+ H H Me S OH O O Ph S OH O S OH MeMe O+ H MePh For a comprehensive compilation of Bordwell pKa data see: http://www.chem.wisc.edu/areas/reich/pkatable/index.htm H2OH2OH2O CH3CO3H MeOOH CF3SO3H (CF3)2CHOH CF3CH2OH t-BuOH MeOH HOH H HO H CF3 CCl3 CHCl2 HOOH H2SO4 H2SO3 HSCN H3PO4 H2S H3O+ H2O HNO3 HNO2 HN3 NH4Cl H2CrO4 HCN CH3SO3H HClO4 HOCl HF HCl HBr B(OH)3 CH2NO2 CH2F CH2Cl CH2Br CH2I CH3 C6H5 i-PrOH C6H5OH (NH) H2O 9.3 (+5.55)N OHMe Me Me (+1.63) pKa Table.1 11/4/05 1:43 PM D.H. Ripin, D.A. Evans *Values <0 for H2O and DMSO, and values >14 for water and >35 for DMSO were extrapolated using various methods. 38 (12) (estimate) pKa's of Nitrogen Acids (DMSO) Chem 206 SubstrateSubstrate Substrate pKa Substrate DABCO (41) (36 THF)) (37) (30) (10.5)9.2 10.6 11.05 10.75 (30.6) (25.0)4.6 0.78 2-napthal-N+H3 4.16 (3.6) 8.12 5.96 + -9.3 5.21 (3.4) + DMAP 9.2 + 4.95 (0.90) 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) (44) (16.9) (26.5) (13.9) R= Ph (urea) NH2 OEt (23.5) (25.5) (23.3) (17.2) (26.9) (24.8) 15.1 (21.6) (17.9) Cl, H 0.72 (14.7)8.30 8.88 (13.7) (13.6) (21.6) (18.9) (17.2) (26.1) AMIDES & CARBAMATES PROTONATED NITROGEN AMINES (17.5) (16.1) 6.3 (9.7) 4.7 (7.9) -10 (12.9) IMIDES SULFONAMIDE HYRDAZONES,- IDES, & -INES HETEROCYCLES PROTONATED HETEROCYCLES R= Me (17.3) Ph (15.0) pKa (DMSO) (DMSO)pKa pKa (DMSO) GUANIDINIUM, N+ N+ N N H NH Me Me Me Me O2N NO2 NO2 NH3 NH HN H NHMe2N NH R R H H3N+ +NH3 NH3NH3 NHO O Bn O N+ H N+H2 H N HN N NH H2N N N N NH R NH2 O NH O N H Et Ph N H X NH O NH O O O O NH O N H Ph OH PhMe2N NMe2 N+H2 Me NNH2 O NHNH2Ph NSO2Ph NH2R 26(THF) For a comprehensive compilation of Bordwell pKa data see: http://www.chem.wisc.edu/areas/reich/pkatable/index.htm H2O DBU Et3N+H i-Pr2N+H2 i-Pr2NH EtN+H3 TMS2NH N+H4 NH3 PhNH2 Ph2NHPhN+H3 Ph2N+H2 H2NN+H3 HON+H3 H (PPTS) PhN+(Me)2H NCNH2 H CH3 CF3 Ac2NH (NH) PhSO2NHNH2 PhNHNHPh RSO2NH2 HN3 PhCN+H MeSO2NHPh HYDROXAMIC ACID & AMIDINES H2O H2O H2O ( )n n= 1 (24.1) n= 2 (26.4) X= O (24) X= S (13.3) O NH O (20.8) O NH O (15) N H O O (12.1) N H X= O (14.8) X= S (11.8) X (16.4) N H N (11.9) N N H N N H N (19.8) N X H X= O (24.4)X= S (27.0) (18.4)NMe NMe H N N i-Pr i-Pr Me Me H (24) + + R = Me Ph CF3 N S H N Me S H Me + (29.4) (16.5) pKa Table.2 11/4/05 1:43 PM (24.3) IMINES n (15.8) (17.9) (16.0) (17.8) (26.9) 7 6 5 4 3n= (7.7) (7.1) (11.8) (16.2) (12.2) (16.9) (16.7) (17.2) CH2COPh CH2SO2Ph CH2SPh CH2Bn CH2Ph CHMe2 CH2Me R= NITRO (20.2) (29.9) (16.9) (24.9)SPhX= PHOSPHINES (28.8) (26.2) (18.6) (16.4) (27.6) SiMe3 CO2Et PhX= PHOSPONATES & PHOSPHINE OXIDES (7.0) (6.2) (21.2) (22.4) 9.1 2.7 -14 (24.9) (20.0) (14.6) (19.4) (20.6) CONEt2 CO2Et COPh SO2Ph X= AMMONIUM (22.85) (27.9) (28.1) (30.7) (49) SELENIDES ETHERS (27.2) (31.0) (31.3) (27.5) (18.6) (DMSO) D. H. Ripin, D. A. Evans SubstrateSubstrate Substrate pKapKa (DMSO) (DMSO)pKa pKa's 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) 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 Org. Chem., 3rd Ed. J. March (1985) Unpublished results of W. P. Jencks THF: JACS 110, 5705 (1988) See cited website below for additional data ≈10 *Values <0 for H2O and DMSO, and values >14 for water and >35 for DMSO were extrapolated using various methods. (EtO)2P X O Ph2P O X O2N Ph Ph N Ph 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 For a comprehensive compilation of Brodwell pKa data see: http://www.chem.wisc.edu/areas/reich/pkatable/index.htm CH3 RNO2 Ph2PCH2SO2Ph Ph2PCH2PPh2 CN Cl CN Ph3P+CH2CN Ph3P+CH2COPh Ph3P+i-Pr Ph3P+CH3 Et3P+H MeP+H3 P+H4 PHOSPHONIUM CN Me3N+CH2X PhOCH2SO2Ph PhOCH2CN MeOCH2SO2Ph CH3OPh PhSeCH=CHCH2SePh PhSeCH2Ph (PhSe)2CH2 PhSeCHPh2 H2OH2O H2O pKa Table.5 11/4/05 1:45 PM N H N N H N N H N H N N N N H N H O N H N H N H N H N H O O S O S O O N H O O N H ON H O N H N N DMSO Acidities of Common Heterocycles Bordwell, ACR, 1988, 21, 456 Bordwell http://www.chem.wisc.edu/areas/reich/pkatable/index.htm 23.0 19.8 18.6 16.4 13.9 11.9 18.0 24.0 20.8 15.0 12.1 26.4 24.0 13.3 14.8 11.8 N S H N S H Me Me 29.4 16.5 N N Me Me H N N Me Me Me Me Me Me H+ + + 18.4 24 Pka Table.6.cdx 11/4/05 1:45 PM pKa Data Compiled by R. Williams page-1 pKa Values INDEX Inorganic 2 Phenazine 24 Phosphates 3 Pyridine 25 Carboxylic acids 4, 8 Pyrazine 26 Aliphatic 4, 8 Aromatic 7, 8 Quinoline 27 Phenols 9 Quinazoline 27 Alcohols and oxygen acids 10, 11 Quinoxaline 27 Amino Acids 12 Special Nitrogen Compounds 28 Peptides 13 Hydroxylamines 28 Nitrogen Compounds 14 Hydrazines 28 Aliphatic amines 15, 17, 19 Semicarbazones 28 Cyanoamines 16 Amidoximes 28 Anilines 17, 18, 20 Thiols 29 Nucleosides 21 Carbon Acids 30,31 Special Table Heterocycles 22 Indicators 31 Acridine 23 References 32-34 Benzoquinoline 24 Cinnoline 23 Hydantoin 24 Imidazole 24 For complex chelating agents, see also reference 77. Note. This document was compiled by W.P. Jencks and has been added to by F.H. Westheimer fluorophosphate 0.55, 4.8 56 Acetic acids, substituted Phosphonates (Ref. 2) H- 4.76* 20 X -H -H -NH3+ -NH3+ O2N- 1.68* 20 X(CH2)PO3H2 2.35 7.1 1.85 5.35 (CH3)3N+- 1.83* 20 X(CH2)2PO3H2 2.45 7.85 2.45 7.00 (CH3)2NH+- 1.95* 20 X(CH2)4PO3H2 2.55 7.55 CH3NH2+- 2.16* 20X(CH2)5PO3 H2 2.6 7.65 NH3+- 2.31* 20X(CH2)6PO2H2 2.6 7.9 CH3SO2- 2.36* 20X(CH2)10PO2H2 8.00 NC- 2.43* 20Phosphines in acetonitrile, see ref. 89. C6H5SO2- 2.44 20 HO2C 2.83* 20CARBOXYLIC ACIDS Aliphatic C6H5SO- 2.66 20 Compound pK Ref. F- 2.66 20 Acetoacetic 3.58 6 Cl- 2.86* 20 Acetopyruvic 2.61, 7.85 (enol) 6 Br- 2.86 20 Aconitic, trans- 2.80, 4.46 6 Cl2- 1.29 20 Betaine 1.84 6 F2- 1.24 20 Citric 3.09, 4.75, 5.41 6 Br3- 0.66 20 Crotonic 4.69 6 Cl3- 0.65 20 Dihydroxyfumaric 1.14 6 F3- 0.23 (-0.26) (2) 20Dethylenediamine- 2.00, 2.67 6 HONC4 3.01 20tetraacetic 6.16, 10.26 F3C- 3.07* 20Formic 3.77* 2 N3- 3.03 20Fumaric 3.03, 4.54 6 I- 3.12 20Glyceric 3.55 6 C6H5O- 3.12 20Glycollic 3.82 6 C2H5O2C- 3.35 20Glyoxylic 3.32 6 C6H5S- 3.52* 20Homogentistic 4.40 6 CH3O- 3.53 20α-keto-β-methyl valeric 2.3 6 NCS- 3.58 20Lactic 3.86 6 CH3CO- 3.58* 20Maleic 1.93, 6.58 6 Malic 3.40, 5.2 6 C2H5O- 3.60 20 Oxaloacetic (trans-enol) 2.56 6 n-C3H7O 3.65 20 +(cis-enol) 2.15, 4.06 6 n-C4H9O 3.66 20 Protocatechuic 4.48 6 sec.-C4H9O- 3.67 20 Pyruvic 2.50 6 HS- 3.67* 20 Tartaric + 2.99, 4.40 6 i-C3H7O- 3.69* 20 + or - 2.89, 4.40 6 CH3S- 3.72* 20meso 3.22, 4.85 6 i-C3H7S- 3.72* 20Vinylacetic 4.42 6 C6H5CH2S- 3.73* 20 C2H5S- 3.74* 20 n-C3H7S- 3.77* 20 n-C4H9S- 3.81* 20 HO- 3.83* 20 –O3S- 4.05 20 (C6H5)3CS- 4.30* 20 C6H5- 4.31* 20 CH2-CH- 4.35* 20 * Indicates thermodynamic values. Unsaturated acids (25°) Compound pK ref. Compound pK ref. trans-CH3-CH=CHCO2H 4.69* 20 H-CH2CH2CO2H 4.88* 2 cis-CH3-CH=CHCO2H 4.44* 2 H-CH=CHCO2H 4.25* 2 C6H5-CH2CH2CO2H 4.66* 2 C6H5CH2CH2CO2H 4.66* 2 trans-C6H5-CH=CHCO2H 4.44* 2 C6H5CH=CHCO2H** 4.44* 2 m-CH3OC6H4CH2CH2CO2H 4.65* 2 C6H5CH2CH2CO2H 4.66* 2 C6H5CH=CHCO2H** 4.44 2 m-CH3OC6H4CH=CHCO2H 4.38* 2 m-ClC6H4CH=CHCO2H** 4.29* 2 m-ClC6H4CH2CH2CO2H 4.58* 2 Unsaturated acids, Cis- and Trans- C C R2H R1 CO2H C C R2R1 H CO2H Cis-Acid Trans-Acid R1 R2 cis-acid trans-acid Ref. H- H- 4.25* 4.25* 2 CH3- H- 4.44* 4.69* 2 Cl- H- 3.32 3.65 2 C6H5- H- 3.88* 4.44* 2 ClC6H4 H- 3.91 4.41 2 6-BrC6H4 H- 4.02 4.41 2 CH3- CH3- 4.30 5.02 2 C6H5- H- 5.26*** 5.58*** 2 2,4,6-(CH3)3C6H2- H- 6.12*** 5.70*** 2 C6H5- CH3- 4.98*** 5.98*** 2 Dicarboxylic acids, unsaturated* Maleic 1.92, 6.23 2 Alicyclic Dicarboxylic acids Citraconic (Dimethylmaleic acid) 2.29, 6.15 2 cis-Caronic(1,1-dimethylcyclopropane-23- dicarboxylic acid 2.34*, 8.31* 2Acetylenedicarboxylic 1.73, 4.40 2 ∆1-tetrahydrophthalic 3.01, 5.34 2 1,2-trans-cyclopropanedicarboxylic 3.65*, 5.13* 2Bromomaleic 1.45, 4.62 2 trans-caronic 3.82*, 5.32* 2Bromofumaric 1.46, 3.57 2 1,2-cis-cyclopropane-dicarboxylic 3.33*, 6.47* 2 Chlorofumaric 1.78, 3.81 2 Fumaric 3.02, 4.38 2 Mesaconic (Dimethylfumaric acid) **trans3.09, 4.75 2 ***in 40% acetonePhthalic 2.95, 5.41 2 *thermodynamicItaconic (1-Propene-2-3-dicarboxylic acid) 3.85, 5.45 2 Chloromaleic 1.72, 3.86 2 Aliphatic Alicyclic Dicarboxylic acids Compound pK Ref Compound pK Ref 1,2-trans-Cyclopropane- cis-Ethyleneoxide- dicarboxylic 3.65, 5.13 2 dicarboxylic 1.94, 3.92 2 trans-Ethyleneoxide- 1,3-cis-Cyclobutane- dicarboxylic 1.93, 3.25 2 dicarboxylic 4.03, 5.31 2 1,3-trans -Cyclobutanedi- 1,2-cis-Cyclopentane- carboxylic 3.81, 5.28 2 dicarboxylic 4.37, 6.51 2 1,2-trans-Cyyclopentane- 1,3-cis-Cyclopentane dicarboxylic 3.89, 5.91 2 dicarboxylic 4.23, 5.53 2 1,3-trans-Cyclopentane- 1,2-cisCyclohexane- dicarboxylic 4.40, 5.45 2 dicarboxylic 4.34, 6.76 2 1,2-trans-Cyclohexane- 1,3 -cis-Cyclohexane- dicarboxylic 4.18, 5.93 2 dicarboxylic 4.10, 5.46 2 1,3-trans-Cyclohexane- 1,4-cis-Cyclohexane dicarboxylic 4.31, 5.73 2 di-carboxylic 4.44, 5.79 2 1,4-trans-Cyclohexane- dicarboxylic 4.18, 5.42 2 Dicarboxylic acids* oxalic 1.23, 4.19 2 Succinic 4.19, 5.48 2 Malonic 2.83, 5.69 2 O-O’-Dimethyl- 3.77, 5.94 2 Methyl- 3.05, 5.76 2 (high melting) Ethyl- 2.99, 5.83 2 O-O’-Dimethyl- 3.94, 6.20 2 n-propyl 3.00, 5.84 2 (low melting) i-propyl- 2.94, 5.88 2 O,O’-Diethyl- 3.63, 6.46 2 Dimethyl- 3.17, 6.06 2 (high melting) Methylethyl- 2.86, 6.41 2 O,O’-Diethyl- 3.51, 6.60 2 Diethyl- 2.21, 7.29 2 (low melting) Ethyl-n-propyl- 2.15, 7.43 2 Tetramethyl- 3.50, 7.28 2 Di-n-propyl- 2.07, 7.51 2 Glutaric 4.34, 5.42 2 Adipic 4.42, 5.41 2 B-Methyl 4.25, 6.22 2 Pimelic 4.48, 5.42 2 B-Ethyl 4.29, 6.33 2 Suberic 4.52, 5.40 2 B-n-Propyl 4.31, 6.39 2 Azelaic 4.55, 5.41 2 B,B-Dimethyl- 3.70, 6.29 2 DL-1:2-Dichlorosuccinic 1.68, 3.18 20 B,B-Methylethyl- 3.62, 6.70 2 meso-1:2-Dichlorosuccinic 1.74, 3.24 20 B,B-Diethyl- 3.62, 7.12 2 DL-1:2-Dibromosuccinic 1.48, ---- 20 B,B-Di-n-propyl 3.69, 7.31 2 meso-1:2-Dibromosuccinic 1.42, 2.97 20 D-Tartaric 3.03, 4.45 20 DL-1:2-Dimethylsuccinic 3.93, 6.00 20 DL-Tartaric 3.03, ---- 20 meso-1:2-Dimethylsuccinic 3.77, 5.36 20 meso-Tartaric 3.29, 4.92 20 *All are thermodynamic values Aliphatic HO- 6.33 2 Bicyclo[2.2.2]octane-1-carboxylic acids, 4- substituted Br- 6.08 2 Lysergic acid, etc. H- 6.75 2 ergometrine 6.8, -- 2 C2H5O2C- 6.31 2 Dihydroergometrine 7.4, -- 2 β-dihydrolysergol 8.2, -- 2NC- 5.90 2 PHENOLS Compound pK Ref. Compound pK Ref. Chromotropic acid 5.36, 15.6 6 Resorcinol --, 9.15 (30o) 50 o-Methoxyphenol --, 9.93 50 p-Methoxyphenol --, 10.16 50 o-Hydroxybenz- 3-Hydroxyanthran- aldehyde 7.95 50 ilic acid 10.09, 5.20 51 2-Amino-4,5 dimethyl- 2-Aminophenol phenol hydrochloride 10.4 5.28 51 hydrochloride 9.99, 4.86 51 4,5-dihydroxybenzene- 1,3 disulphonic acid 7.66 12.6e Kojic acid 9.40 77 Phenol o m p Phenol o m p H- 9.95* 9.94* O2N- 7.23* 8.35* 7.14* (CH3)3N+- 7.42 8 8 OCH- 6.79 8.00 7.66 CH3SO2- 9.33 7.83 NC- 8.61**7.95 CH3CO- 9.19 8.05 CH3O2C- 8.47* C2H5O2C- 8.50* n-C4H9O2C- 8.47* C3H5CH2O2C- 8.41* I- 9.17* Br- 8.42* 9.11* 9.34* Cl- 8.48* 9.02* 9.38* F- 8.81* 9.28* 9.95* CH3S- 9.53 9.53 HO- 9.48 9.44 9.96 HOCH2- 9.92* 9.83* 9.82* CH3- 10.28*10.08 10.19* C2H5- 10.2 9.9 10.0 CH3O- 9.93 9.65 10.20 H2N- 9.71 9.87 10.30 -O2C- 9.94* 9.39* -O3S- 9.29 9.03 --O3P- 10.2 9.9 --O3As 8.37 C6H5- 9.93 9.59 9.51 NO- 6.35** 2-Chloro-4-Nitro- 5.42 79 2-Nitro-4-Chloro- 6.46 79 * Thermodynamic **Reference 52 ALCOHOLS and other OXYGEN ACIDS Alcohols Compound pK Ref. Compound pK Ref. Choline 13.9 6 C3F7•CH(C2F5)•OH 10.48 65 Chloral hydrate 9.66, 11.0 61 (C3F7)2CH•OH 10.52 65 Trifluoroethanol 12.5 62 Carbonium ions CF3CH2OH 11.4, 12.43 63 CF3CH(OH)CH3 11.8 63 Triphenylmethanols in H2SO4 HC1O4 HNO3 ref CF3CH2(CH3)3OH 12.43 10 4,4,4-Trimethoxy .82. .82 .80 66 C3F7CH2OH 11.4** 63 4,4’-Dimethoxy -1.24 -1.14 -1.11 66 (C3F7)2CHOH 10.6** 63 4-Methoxy -3.40 -3.59 -3.41 66 HCCCH2OH 13.55 64 4-Methyl -5.41 -5.67 66 C(CH2OH))4 14.1 64 4-Trideuteriomethyl- 5.43 5.67 66 HOCH2CHOHCH2OH 4.4 64 3,3’,3”-Trimethyl- 6.35 -5.95 66 HOCH2CH2OH 14.77 64 Unsubstituted triphenyl- CH3CCH2OH 14.82 64 methanol- 6.63 -6.89 6.60 66 CH3OH 15.54 64 4,4;,4;-Trichloro- 7.74- 8.01 66 CH2=CHCH2OH 15.52 64 4-Nitro- 9.15- 9.76 66 H2O 15.74 64 CCl3CH2OH 11.8*** CH3CH2OH 16 64 CF3CH2OH 11.3*** Substituent effects for ionization of RCH2OH R CCl-3 12.24,11.80 64,65 CF3- 12.37 64 CHF2CH2- 12.74 64 Hydroxamic acids CHCl2- 12.89 64 Furo- 8.45 72 CHEC- 13.55 64 Glycine 7.40 72 H2Cl- 14.31 64 Hippuro- 8.80 72 CH3CCH2- 14.8 64 isoNicotin 7.85 72 HOCH2 15.1 64 p-Methylbenz- 8.90 72 H- 15.5 64 Nicotin- 8.30 72 CH2=CH- 15.5 64 Nicotin-methiodide 6.46 72 CH3-(extrap) (15.9) 64 m-Nitrobenz- 8.07 72 CF3C(CH3)2OH 11.6 64 Picolin 8.50 72 HOCH2CF2CH2OH 11 64 Pyrimidine-2-carbox- 7.88 72 Primary alcohols=R•CH2•OH and Salicyl- 7.43 72 Secondary alcohols in 50% alcohol Tropo- 9.09 72 C2F5 11.35 65 C4F9 11.35 65 C5F11 11.37 65 C7F15 11.35 65 Other oxygen acids CHF2 12.00 65 Trimethylamine-n-oxide 4.6 18 CF2Cl 11.63 65 Dimethylglyoxime 12.84 77 CHF2CF2 11.34 65 (50% dioxane) CHF2 • (CF2)2 11.35 65 O-methyl ether 12.92 77 CF3 • CH2 12.7 65 Tropolone 12a 77 CF3 • (CH2)2 12.9 65 α-Bromotropolone 6.95a 77 CF3 • CHMe • OH 11.28 65 Acetald hydrate 13.48 91 C3F7 • CHMe • OH 11.38 65 Formald hydrate 13.29 91 C3F7CHEt • OH 11.37 65 C3F7CHPr • OH 11.37 65 C3F7 • CH(CF3) • OH 10.46 65 a50% dioxane ***50 aquaeous ethanol OTHER OXYGEN ACIDS Hydroxamic acids Aceto- 9.40 68 Compound pK Ref. n-Butyro- 9.48 68 Pyridine oxides n-Butyro- 9.00 68 4-Aminopyridine 1-oxide 3.69 67 p-Methoxybenzo- 9.19 68 4-Dimethylaminopyridine 1-oxide 3.88 67 N-Hydroxyphthalimide 7.00, 6.10 71, 72 Salicylo 7.32 68 4-Dimethylaminopyridine 1-oxide 3.88 67 Benzo- 8.88 68 p-Chlorobenzo- 9.59 68 4-Dimethylamino-1-methoxypyridinium perchlorate >11 67 α-Naphtho- ~7.7 68 Propiono- 9.46 68 2-Methylaminopyridine 1-oxide 2.61 67 2-Amino-1-methoxypyridinium perchlorate 12.4 67 Oximes 4-Hydroxypyridine 1-oxide 2.45 67 Benzophenone oxime 11.3 18 4-Methoxypyridine 1-oxide 2.05 67 Diethyl ketoxime 12.6 18 1-Methoxypyridi-4-one 2.57 67 Isonitrosoacetylacetone (INAA) 7.4 76 2-Hydroxypyridine 1-oxide -0.8 67 5-Methyl-1,2,3-cyclohexanetrione-1,3-dioxime 8.3 762-Ethoxypyridine 1-oxide 1.18 67 1-Methoxypyrid-2-one -1.3 Acetophenone oxime 11.48 18 4-Methylaminopyridine 1-oxide 3.85 67 Acetoxime 11.42 18 4-Amino-1-methoxypyridinium perchlorate >11 67 Isonitrosoacetone (INA) 8.3 76 Salicyclaldoxime (SA) 9.2 76 2-Aminopyridine 1-oxide 2.67 67 1,2,3-Cyclohexanetrionetrioxime 8.0 76 2-Dimethylaminopyridine 1-oxide 2.27 67 5-Methyl-1,2,3-cyclohexane-trionetrioxime 8.0 76 2-Methylamino-1-methoxypyridinium toluene- p-sulphonate >11 67 4-Benzyloxypyridine 1-oxide 1.99 67 Oxygen acids 1-Benzyloxypyrid-4-one 2.58 67 sulfinic acids 2-Methoxypyridine 1-oxide 1.23 67 p-Toluene- 1.99 73 1-Benzyloxypyrid-2-one -1.7 67 p-Chlorobenzene- 73 p-Nitrobenzene- 73 Pyridine 1-oxides p-Bromobenzene- 1.89 73 R pK Ref. m-Nitrobenzene- 1.88 73 4-CH3 1.29 47 Benzene- 1.84, 2.16 73 3-CH3 1.08 47 Peroxyacids3,4-(CH)4 1.01 47 Peroxymonosulfuric 9.4 693-COOC4H9 0.03 47 Acetic 8.2 704-NO2 -1.7 47 n-Butyric 8.2 703-NH2 1.47 47 Formic 7.1 70H 0.79 47 Propionic 8.1 703-COOH 0.09 47 peroxydiphosphoric 5.18, 7.8 854-COOH -0.48 47 peroxymonophosphoric 4.85 90 Peroxides ROOH (Ref. 70) H CH3 C2H5 iso-C3H7 tert-C4H9 iso-C4H9 11.6 11.5 11.8 12.1 12.8 12.8 Oximes ref. 93 Pyridine-2-aldoxime heptiodide 8.00 benzoquinoline mon- 6.25 Pyridine-4-aldoxime methiodide 8.50 3-pyridine-1,2-ethanedione-2-oxime methiodide 7.20 Pyridine-4-aldoxime pentiodide 8.50 Lysyllysine (LD) 2.85 7.53 9.92 92 NITROGEN COMPOUNDS Aliphatic Amines pK ref. Ammonia 9.21 1 n-Propyl- 10.53 1 Primary Amines Trimethylsilymethyl- 10.96 1 β-Alanine ester 9.13 1 CH3ONH2 4.60 12 Allylamine- 9.69 2 Allyl- 9.49 1 Benzyl 9.34 1 γ-Amino-n-butyric acid ester 9.71 1 n-Butyl- 10.59 1 sec-Butyl- 10.56 1 t-Butyl- 10.55 1 Cyclohexyl- 10.64 1 Cyclohexylmethyl- 10.49 1 β-difluoroethyl- 7.52 1 Ethanol- 9.50 1 Ethyl 10.63 1 Ethylenedi- 9.98, 7.52 1, 77 Glycine ester 7.75 1 Hydrazine 8.10 1 Hydroxyl- 5.97 1 Isopropyl- 10.63 1 Methoxy- 4.60 1 Methyl- 10.62 1 neo-Pentyl- 10.21 1 Phenylamyl- 10.49 2 δ-Phenylbutyl 10.40 2 β-Phenylethyl- 9.83 1 γ-Phenylpropyl- 10.20 1 Triethylenedi- 8.8* ? X XNH3 + XCH2NH3 + X(CH2)2NH3 + X(CH2)3NH3 + X(CH2)4NH3 + X(CH2)5NH3 + ref. H- 9.25* 10.64* 10.67* 10.58* 10.61* 10.63* 2 HF2C- 7.52 RO2C- 7.75 9.13 9.71 10.15* 10.37 2 HO- 5.96* 9.50* C6H5- 4.58* 9.37* 9.83* 10.20* 10.39* 10.49* 2 H2N- 8.12* 9.98* 10.65* 10.84* 11.05* 2 H2C=CH- 9.69 CH3- 10.64* 10.67* 10.58* 10.61* 10.63* 10.64* 2 X -H -NH3+ -CO2– -SO3– -PO3– 2 X-NH3+ 9.25* -.88 1 10.25 X(CH2)2NH3+ 10.64 9.77 5.75 10.8 X(CH2)2NH3+ 10.67 10.19 9.20 10.8 X(CH2)4NH3+ 10.61 9.31 10.77 10.65 10.9 X(CH2)5NH3+ 10.63 9.74 10.75 10.95 11.0 X(CH2)8NH3+ 10.65 10.10 X(CH2)10NH3+ 10.64 11.35 11.25 X(CH2)3NH3+ 10.58 8.59 10.43 10.05 Secondary amines Di-n-butyl- 11.25 1 Dimethyl- 10.64 1 Diisobutyl- 10.50 1 Di-n-propyl- 11.00 1 α-Ethylpyrroline 7.43 2 Diisopropyl- 11.05 1 α-Benzylpyrroline- 7.08 2 t-Butylcyclohexyl- 11.23 1 2-Methylpiperidine 10.99 2 α-Cyclohexylpyrroline 7.95 2 α-Cyclohexylpyrrolidine 10.80 2 α-(p-Tolyl)pyrroline 7.59 2 α-(p-Tolyl)pyrrolidine 10.01 2 α-Ethylpyrrolidine 10.43 2 N,O-dimethylhydroxylamine 4.75 12 α-Benzylpyrrolidine 10.36 2 Acetanilide +0.61 4 N-methylhydroxylamine 5.96 12 *thermodynamic value Diethyl- 10.98 1 Aliphatic Amines Methyl-β-diethylamino-ethyl-sulfide 1,2-Iminoethane 7.98 7 1,2-Dimethyl-∆2-pyrroline 11.94 2 cis-2,3-Iminobutane 8.72 7 1-methyl-2-n-butyl-∆2-pyrroline 11.90 1,2-Imino-2-methylpropane 8.61 7 1-Ethyl-2-methyl-∆2-pyrroline 11.92 2 1,2-Iminobutane 8.29 7 1-n-Butyl-2-methyl-∆2-pyrroline 11.90 2trans-2,3-Iminobutane 8.69 7 1,2-Dimethyl-∆2-tetrahydropyridine 11.57 2Secondary Amines N-Ethyl derivative of: 1,2-Imino-ethane 7.93 7 Allylmethyl- 10.11 1 Benzylethyl- 9.68 1 Trans-2,3-Iminobutane 9.47 7Morpholine 8.36 1 Trimethylhydroxylamine 3.65 12N-Benzoylpiperazine 7.78 1 Dimethylethyl- 9.99 1Di-sec-butyl- 11.01 1 Triethyl- 10.65 1N-Methylmethoxyamine 4.75 1 Dimethyl-n-butyl- 10.02 1Pyrolidine 11.27 1 Dimethyl-isopropyl- 10.30 11-Tosylpiperazine 7.39 Dimethyl-t-butyl- 10.52 1Benzylmethyl- 9.58 1 Tri-n-butyl- 10.89 1Piperidine 11.22 1 Diallylmethyl- 8.79 1N-Carbethoxypiperazin 8.28 1 1-n-Propylpiperidine 10.48 2Dietrimethylsilylmethyl- 11.40 1 10.1 10.1 5Diallyl- 9.29 1 9.8 -- 5N-Methylhydroxyl- 5.96 1 1,2-Dimethylpyrrolidine 10.26 2Trimethyleneimine 11.29 1 1-Methyl-2-n-butylpyrrolidin 10.24 2Cis-2,6-dimethyl-piperidine 10.92 3 1-Ethyl-2-methylpyrrolidine 10.64 2 1-n-Butyl-2-methylpyrrolidine 10.43 2 1-Ethyl-2-methylpyrrolidine 10.70 2 1,2-Iminobutane 8.18 7Tertiary amines cis-2,3-Iminobutane 8.56 7Trimethyl- 9.76 1 N-dimethylhydroxylamine 5.20 12Dimethyldiethyl- 10.29 1 Allyldimethyl 8.78 1Dimethyl-n-propyl- 9.99 1 1,2-Dimethylpiperidine 10.26 2Dimethyl-isobutyl- 9.91 1 1-Ethyl-2-methyl-∆2-tetrahydropyridine 11.57 2 Dimethyl-sec-butyl- 10.40 1 Tri-n-propyl- 10.65 1 Triallyl- 8.31 1 N-Allylpiperidine 9.69 2 1-Diethylamino-hexane-thiol-(6) Cyanoamines 2-Amino-2-cyanopropane 5.3 9 N-piperidine-CH2CN 4.55 8 β-Isopropylaminopropionitrile 8.0 9 Et2NCN -2.0 8 β-Diethylaminopropionitrile 7.6 9 Et2N(CH2)2CN 7.65 8 Et2NCH2CN 4.55 8 Et2N(CH2)4CN 10.08 8 Et2N(CH2)3CN 9.29 8 Et2NC(CH3)2CN 9.13 8 Et2N(CH2)5CN 10.46 8 EtN(CH2CN)2 -0.6 8 HN(CH2CN)2 0.2 8 EtN(CH2CH2CN)2 4.55 8 HN(CH2CH2CN)2 5.26 8 H2NCH2CN 5.34 8 N(CH2CH2CN)3 1.1 8 N-Amphetamine-(CH2)2-CN 7.23 8 N-piperidine-C(CH3)2CN 9.22 8 N-Norcodeine-(CH2)2CN 5.68 8 N-Methamphetamine-(CH2)2CN 6.95 8 Dimethylcyanimide 1.2 9 Methyl cyanamide 1.2 9 Diethylcyanimide 1.2 9 Ethyl cyanamide 1.2 9 Aminoacetonitrile 5.3 9 Cyanamide 1.1 9 Diethylaminoacetonitrile 4.5 9 Dimethylaminoacetonitrile 4.2 9 β-Aminopropionitrile 7.7 9 CF3CH2NHCH3 6.05 10 β-Dimethylaminopropionitrile 7.0 9 Phenylethylaminesβ,β"-Dicyanodiethylamine 5.2 9 2-phenylethylamine 9.78 11For complex chelating agents of aliphatic amines, see also ref. 77. N-methyl-2-(3,4-dihydroxyphenyl)- ethylamine 8.78 11 N-methyl-2-phenyl 10.31 11Fluoro-substituted amines Epinephrine 8.55 11CF3CH2NH2 5.7 10 Arterenol 8.55 11CF3CH2N(CH3)2 4.75 10 R2 R1 CHCH2NHR4 R3 ref. 11 R1 R2 R3 R4 pK H H H H 9.78 H H OH H 8.90 H OH OH H 8.81 OH H OH H 8.67 H OH H H 9.22 OH OH H H 8.93 OH OH OH H 8.58 H H H CH3 10.31 H H OH CH3 9.31 H OH OH CH2 8.62 OH H OH CH3 8.89 H OH H CH3 9.36 OH OH H CH3 8.78 OH OH OH CH3 8.55 Ring amines and imines (in 80% methyl cellosolve) (ref. 2) Pentamethylene 9.99 Cyclotridecyl 9.63 Hexamethylene 10.00 Cyclotetradecyl 9.54 Heptamethylene 9.77 Cyclopentadecyl 9.54 Octamethylene 9.39 Cycloheptadecyl 9.57 Nonamethylene 9.14 Cyclooctadecyl 9.54 Decamethylene 9.04 Undecamethylene 9.14 Amines other Dodecamethylene 9.31 Dimeoone 5.23 18 Tridecamethylene 9.35 Phthalimide 8.30 18 Tetradecamethylene 9.35 Nitrourea 4.57 18 Hexadecamethylene 9.29 Nitrourethane 3.28 18 Heptadecamethylene 9.27 Diphenylthiocarbazone 4.5 6 Cyclohexyl 9.82 β,β,β"-Triaminotriethylamine Cycloheptyl 9.99 8.42, 9.44, 10.13 87 Cyclooctyl Cyclononyl 9.95 Anilines Ref. 2 Cyclodecyl 9.85 Monosubstituted Cycloundecyl 9.71 Substituent o m p Cyclododecyl 9.62 H- 4.62* 4.64* 4.58* AMINES ref. 77 Secondary amines N-Butylaminoacetic acid 2.29, 10.07 Primary amines N,N'-Diethylethylenediamine 7.70, 10.46 2-aminoethylsulphonic acid 9.08 2,2'-dihydroxydiethylamine 9.00 Aminomalonic acid 3.32, 9.83 N,N'-di-n-propylethylenediamine 8.14, 10.97 N-n-butylethylenediamine 7.53, 10.30 Ethylenediamine-N,N'-diacetic acid 6.42, 9.46 2,3-diaminobutane, meso 6.92, 9.97 Iminodipropionic acid 4.11, 9.61 2,3-diaminobutane, racemic 6.91, 10.00 Piperazine 5.68, 9.82 2,2'-diaminodiethyl sulfide 8.84, 9.64 β-carboxymethylaminopropionic acid 1,3-diamino-2,2-dimethylpropane 8.18, 10.22 3.61, 9.46 N,N'-Di-(2-aminoethyl)-ethylenediamine 3.32, 6.67, 9.20, 9.92 N,N'-Dimethylethylenediamine 7.40, 10.16 N-ethylaminoacetic acid 2.30, 10.10 1,2-diamino-2-methylpropane 6.79, 10.00 Iminodiacetic acid 2.98, 9.89 1,3-Diaminopropan-2-ol 8.23, 9.68 N-isopropylaminoacetic acid 2.36, 10.06 N,N'-Diglycyethylenediamine 7.63, 8.35 N-n-propylaminoacetic acid 2.28, 10.03 Ethylenediamine-N,N-diacetic acid 5.58, 11.05 Furfurylamine 8.89 Tertiary amines 2-(2-hydroxypropylamino)-ethylamine 6.94, 9.86 4-(2-aminoethyl)morpholine 4.84, 9.45 Di-(2-hydroxyethyl)aminoacetic acid 8.08 2-(3-hydroxypropylamino)ethylamine Hexamethylenetetramine 5.13 6.78, 9.76 Methyliminodiacetic acid 2.81, 10.18 N-Methylaminoacetic acid 2.24, 10.01 Diethylaminoacetic acid 2.04, 10.47 Methyl-α-amino-β-mercaptoproionate 6.56, 8.99 Dimethylaminoacetic acid 2.08, 9.80 N-2-hydroxyethyliminodiacetic acid 2.2, 8.73 N-n-propylethylenediamine 7.54, 10.34 Triethylenediamine 4.18, 8.19 1,2,3-triaminopropane 3.72, 7.95, 9.59 Tris-(hydroxymethyl)-aminomethane 8.10 Ref. 1 2-amino-2'-hydroxydiethyl sulfide 9.04 Diallylmethyl 8.79 N-(carbamoylmethyl)-iminodiacetic acid 2.30, 6.60 Benzyldimethyl 8.93 N-Allylpiperidine 9.68 2,2'-diaminodiethylamine 3.58, 8.86, 9.65 N-Allylmorpholine 7.05 2,3-diamino-2,3-dimethylbutane 6.56, 10.13 Propargyldimethyl 7.05 3,3'-diaminodi-n-propylamine 8.02,9.70, 10.7 Propargylethyldimethyl 8.88 1,2-Di-(2-aminoethylthio)ethane 8.43, 9.32 N-Methylmorpholine 7.41 1,2-diaminopropane 7.13, 10.00 N-Methylpyrrolidine 10.46 N,N-diethylethylenediamine 7.07, 10.02 N,N-Dimethylhydroxylamine 5.20 N,N-dimethylethylenediamine 6.63, 9.53 Allyldimethyl 8.73 N-Ethylethylenediamine 7.63, 10.56 Benzyldiethyl 9.48 N-(2-hydroxyethyl)-ethylenediamine N-Ethylpiperidine 10.40 6.83, 9.82 N-Ethylmorpholine 7.70 N-isopropylethylenediamine 7.70, 10.62 Propargymethyldimethyl 8.33 2-Methoxyethylamine 9.20 N-Methylpiperidine 10.08 Mercaptoethylamine 8.27, 10.53 N-Methyltrimethyleneimine 10.40 N-Methylethylenediamine 7.56, 10.40 Triethanolamine 7.77 2-Methylthioethylamine 9.18 N,N-Dimethylmethoxyamine 3.65 2-thienylmethylamine 8.92 Triaminotriethylamine 8.56, 9.59, 10.29 Ref. 5 Methyl-[β-diethylamino-ethyl]sulfide 9.8 N-Dimethyl-cysteamine 7.95, 10.7 N-Diethyl-cysteamine 7.8, 10.75 N-Dipropyl-cysteamine 8.00, 10.8 N-β-Mercaptoethyl-piperidine 7.95, 11.05 N-β-Mercaptoethyl-morpholine 6.65, 9.8 1-Diethylamino-propan- (3) 8.0, 10.5 1-Diethylamino-butan- (4) 10.1 1-Diethylamino-hexan- (6) 10.1 ANILINES (Ref. 88) m-Substituted anilines m-C2H5 4.70 m-CH(CH3)2 4.67 -C(CH3)3 4.66 3,5-(CH3)2 4.74 3,5-[C(CH3)3]2 4.97 m-COCH3 3.56 m-CN 2.76 3-Cl,5-OCH3 3.10 3-OCH3.5-NO2 2.11 3,5-(OCH3)2 3.82 3,5-Br2 2.34 NAPHTHALAMINES (reference 88) substituted naphthalamines 2-naphthalamine X 4.16 2-naphthalamine X 1-NH2,3-X NO2 2.07 2-NH2,4-X NO2 2.43 CN 2.26 CN 2.66 Cl 2.66 Cl 3.38 Br 2.67 Br 3.40 I 2.82 I 3.41 COOCH3 3.12 COOCH3 3.38 OCH3 3.26 OCH3 4.05 OH 3.30 1-NH2,6-X NO2 2.89 CH3 3.96 Cl 3.48 Cl 2.71 OCH3 3.90 2-NH2,5-X NO2 3.01 OH 3.97 OH 4.07 2-NH2,7-X NO2 3.10 1-NH2,5-X NO2 2.73 Cl 3.71 OH 3.96 OCH3 4.19 Cl 3.34 OH 4.25 NH2 4.21 NH2 4.66 1-NH2,7-X NO2 2.55 2-NH2,6-X NO2 2.62 Cl 3.48 OCH3 4.64 OCH3 4.07 2-NH2,8-X NO2 2.73 OH 4.20 1-NH2,4-X NO2 0.54 1-NH2,2-X NO2 -1.74 Br 3.21 1-X,2-NH2 NO2 -0.85 2-NH2,3-X NO2 1.48 1-NH2,8-X NO2 2.79, Anilines (in 50% ethanol) 5'-IMP 8.9, 1.54, 6.04 6 Unhindered pK ref. 5-Methylcytosine 4.6, 12.4 6 Aniline 4.19 40 5-Methylcytosine deoxyriboside 5'-phosphate 4.4 6p-Aminodiphenyl 3.81 40 2-Naphthylamine 3.77 40 3-Methyluracil 9.75 37 3-Phenanthrylamine 3.59 40 3-Methylxanthine 8.5 (8.1), 11.3 38 m-Aminodiphenyl 3.82 40 Adenosine 3.63 62-Aminofluorene 4.21 40 " 3.3, 12.5 352-Phenanthrylamine 3.60 40 5'-AMP 3.3, 6.1 362-Anthrylamine 3.40 40 3.74, 6.2-6.4 6Hindered Barbituric acid 3.9, 12.5 37o-Aminodiphenyl 3.03 40 Cytidine 4.11 6 peri " 4.22, 12.5 35 1-Naphthylamine 3.40 40 2'-CMP 4.3-4.4, 6.19* 6 9-Phenanthrylamine 3.19 40 5'-CMP 4.5, 6.3 6 3-Aminopyrene 2.91 40 CTP 4.6, 6.4 6 1-Phenanthrylamine 3.23 40 2,6-Diaminopurine 5.09, 10.77 6 1-Anthrylamine 3.22 40 Isoguanine 4.51, 8.99 6 Guanosine (deoxy) 1.6-2.2, 9.16-9.5 6 meso GMP (2' + 3') 2.3, 9.36, 0.7, 5.9 69-Anthrylamine 2.7 40 5'-GMP (deoxy) 2.9, 9.7, 6.4 6o-Aminophenols GTP 3.3, 9.3, 6.5 63-Hydroxyanthranilic acid 10.09, 5.20 51 Inosine 1.2, 8.9 62-Aminophenol hydrochloride " 8.75, 12.5 69.99, 4.86 51 5-Methylcytosine deoxyribosideIndicators p-Aminoazobenzene 2.82, 2.76 60 4.5, 13.0 6 4-Chloro-2-nitroaniline -1.02, -1.03 60 1-Methyluracil 9.95 37 4,6-Dichloro-2-nitroaniline -3.61, -3.32 60 1-Methylxanthine 7.7, 12.05 38 6-Bromo-2,4-dinitroaniline -6.64, -6.71 7-Methylxanthine 8.5 (8.3) 38 2-Amino-4,5-dimethylphenol hydrochloride 10.40, 5.28 51 9-Methylxanthine 6.3 38 Purine 2.52, 8.90 37 N,N-Dimethyl-2,4-dinitroaniline -1.00, -- 60 Thymidine 9.8 6p-Nitrodiphenylamine 5'-TMP 10.0, 1.6, 6.5 6-2.4 to -2.9, -2.50 60 Uracil deoxyriboside 9.3 64-Methyl-2, dinitroaniline -3.96, -4.44 60 5'-UMP 9.5, 6.4 6 Heterocyclics UTP 9.5, 6.6 6 Nucleosides, etc. Uridine 9.25 6 Adenine 4.15, 9.80 6 " 9.17, 12.5 35 2'-AMP 3.81, 6.17 6 Xanthosine 0, 5.5, 13.0 6 3'-AMP 3.74, 5.92 6 Orotic acid 2.8, 9.45, 13 6 ADP 3.95, 6.3 36 Pyrimidine 1.30 37 ATP 4.00 (4.1), 6.5 36 Thymine 0, 9.9, 713.0 6 Barbital 7.85, 12.7 37 Uracil .5, 9.5, 13.0 6 Cytosine 4.45, 12.2 6 UMP (2' + 3') 9.43, 1.02, 5.88 6 Cytosine (deoxy) 4.25 6 UDP 9.4, 6.5 6 3' CMP 4.16-4.31, 6.04 6 Uric acid 5.4, 10.3 6 CDP 4.44 6 Xanthine 0.8, 7.44, 11.12 6 CDP, (deoxy) 4.8, 6.6 6 " 7.2 38 Guanine 3.3, 9.2, 12.3 6 Guanosine 2.2, 9.5 6 " 1.6, 9.16, 12.5 35 5'-GMP 2.4, 9.4, 6.1 6 GDP 2.9, 9.6, 6.3 6 Hypoxanthine 1.98, 8.94, 12.10 6 2-Methylimidazole 7.75 43 Histidine methylester 5.2 (NH2 7.1) 43 N-Acetylhistidine 7.05 43 2-Methyl-4-hydroxy-aminobenz- 6.65 43 4-Hydroxymethyl- 6.45 43 2-Methyl-4-hydroxy-6-nitro-benzimidazole 3.9 432-Methylbenz- 6.1 43 Histamine 6.0 43 4-Hydroxy-6-Nitrobenz- 3.05 43 4-Hydroxy-6-aminobenz- 5.9 43 b2-Hydroxymethylnaphth(1,2)- 4-Hydroxybenz- 5.3 (OH 9.5)43 4.44, 12.23 86 4-Methoxybenz- 5.1 43 b2-Hydroxymethylnaphth(2,3)- 4-Bromo- 3.7 43 4.50, 12.23 86 6-Nitrobenz- 3.05, 10.6 43 4-Hydroxy- 4.80, 8.68 44 4-Nitro- 1.5, 9.1 43 1-Amino- 7.62 40 isoQuinolines 4-Amino- 6.28 40 1-Hydroxy- -1.2 44 6-Amino- 7.17 40 5-Hydroxy 5.40, 8.45 44 8-Amino- 6.06 40 3-Amino- 5.05 40 7-Hydroxy- 5.70 40 5-Amino- 5.59 40 1-Methoxy- 3.05 44 Amino- 6.20 40 4-NO2 1.35 88 6-Hydroxy- 5.85, 9.15 44 4-Br 3.31 88 8-Hydroxy- 5.66, 8.40 44 1-Hydroxy- --, 1.44 39 2-Methylisoquinolone -1.8 44 5-Methyl-1-phenazone --, 4.9 39 Isoquinoline 5.46, 5.14 44, 19 m-Phenanthroline 3.11a 19 Phenazine --, 1.23 39 1-Amino- ca. 7.3, 7.29a 19 2-Hydroxy- 7.5, 2.6 39 2,2'-Dipyridyl 4.23 19 10-Methyl-2-phenazone --, 3.0 2-Hydroxy- 8.79, 4.82 44 6-Aminophenanthridine 6.88 40 7-Hydroxy- 4.38, 8.68 44 9-Aminophenanthridine 7.31 40 9-Methoxy- --, 2.38 44 o-Phenanthroline 4.27a , 5.2 19 2-Amino-9-methyl- 5.66a 19 p-Phenanthroline 3.12a 19 2,7-Diamino-9-methyl- 6.26a 19 1,10-Diamino-3,8-Dimethyl- 8.78a , 6.31a 6-Amino- 6.88 40 Phenazine 1.23 19 Phenanthridine --, 4.65 44 1-Amino- 2.6a 19 6-Hydroxy- 8.43, 5.35 44 2-Amino- 4.75, 3.46a 199-Hydroxy (phenanthridone) <-1.5 44 1,3-Diamino- 5.64a 199-Amino- 7.31, 6.75a 19 2,3-Diamino- 4.74 19 2,7,9-Triamino- 8.06a 19 2,7-Diamino- 4.63, 3.9a 19Phthalazine 3.47 19 Pteroylglutamic acid 8.26 771-Amino- 6.60 19 1-Hydroxy- 11.00, -2 39 PyridinesPicolimic acid 5.52 4 2-Amino- 6.86 415,5-dimethyl-2-thio- 8.71 42 4-Amino- 9.17 415,5-Diphenyl-2-thio- 7.69 42 2-Methyl- 5.94b 451-Methyl-5,5-pentamethyl-ene-2-thio- 2-Vinyl- 4.98 459.25 42 2-Chloro- 0.49 454-Methyl- 7.45 43 2,4,6-Trihydroxy- 4,6, 9.0, 13 39Imidazole 6.95 43 1-Methyl-4-pyridone 3.334-(2',4'-Dihydroxyphenyl)- 6.45 43 2-(N-Methylacetamido)- 2.01 46Carbobenzoxy-L-histidyl-L-tyrosine ethyl ester 6.25 43 2-Benzamido- 3.33 2-(N-Methylbenzamido)- 1.446-Aminobenz- 6.0 (NH2 3.0) 3-(N-Methylacetamod)- 3.52 46Benzimidazole 5.4 43 3-(N-Methylbenzamido)- 3.66 46 4-(N-Methylacetamido)- 4.62 46 4-(N-Methylbenzamido)- 4.68 46 (CH3)2CH- 5.83b 5.72b 6.02b 4-Benzamido- 5.32 46 CH3CO 3.18b 3-NO2 0.81 88 H2N- 6.68b 5.80b 8.96b 3-COO– 4.77 47 CONH247 3.40 3.612,3-Me2 6.60 48 NC-47 1.45 2,5-Me2 6.47 48 3,4-Me2 6.52 48 2,4,6-Me3 7.48 48 4-OEt 6.67 48 3-Cl 2.84 48 3-CO2Et 3.35 48 3-COOH 3.13 88 2-Amyl- 6.00b 45 2-Hexyl- 5.95b 45 2-Benzyl- 5.13 45 2-Bromo- 0.71 45 2,4-Dihydroxy 6.50, 13, 1.37 39 1-Methyl-2-pyridone 0.32 39 2-Acetamido- 4.09 46 1-Methylpyrid-2-one acetylimine 7.12 46 3-Acetamido- 4.46 46 3-Benzamido- 3.80 46 1-Methylpyrid-4-one acetylimine 11.03 46 1-Methylpyrid-4-one benzylimine 9.89 46 4-COO– 4.90 47 2,4-Me2 6.72 48 2,6-Me2 6.77 48 3,5-Me2 6.14 48 2-Me,5-Et 6.51 48 3-F 3.10 48 3-Br 2.84 48 4-CO2Et 3.45 48 Pyridine N-oxides (see oxygen acids) Substituted Pyridines Pyridine 2- 3- 4- H- 5.17b Cl- 0.72b 2.84b I- 1.82b 3.25b CH3CH2- 5.97b 5.70b 6.02b (CH3)3C- 5.76b 5.82b 5.99b HO- 0.75 4.86 3.27 11.62 8.72 11.09 SO3-47 2.9 CH3O- 3.28 4.88 6.62 F- -0.44b 2.97b Br- 0.90b 2.84b CH3- 5.97b 5.68b 6.02b Ortho-Substituted Pyridines (in 50% ethanol) Pyridazine 2.33 19 Substituent pK ref. 3-Hydroxy- 10.46, -1.8 39 H- 4.38 2 3,6-Dihydroxy- 5,67, -2.2, 13 39 2-C2H5- 4.93 2 4-Methoxy- 3.70 39 3-Amino- 5.19 192-(CH3) 4.68 2 4-Hydroxy- 8.68, 1.07 392,6-[(CH3)2CH]2 3.58 2 3-Methoxy- 2.52 392-(CH3)3C- 4.68 2 3,6-Dimethoxy- 1.61 392-C2H5-6-(CH3)3C- 4.36 2 2,6-[(CH3)3C]2– 3.58 2 For complex chelating agents, see also ref. 77 2-CH3- 5.05 2 b thermodynamic at 25°. 2-(CH3)2CH- 4.82 2 2,6-(CH3)2 5.77 2 2,6-[(CH3)3C]2 3.58 2 2-CH3-6-(CH3)3C 5.52 2 2-(CH3)2CH-6-(CH3)3C- 5.13 2 pKNH 35° pKOH Benzimidazole 6.00 5.58 5.36 2-Methyl 6.96 6.29 6.18 --- 2-Ethyl 6.90 6.27 6.14 -- 2-Hydroxymethyl --- 5.40 --- 11.55 ref. 86 1-Methyl-2-hydroxymethyl --- 5.55 --- 11.45 2,4-Dihydroxy-(Uracil) 9.38, 12 39 4,6-Dihydroxy- 5.4 39 2,4,6-Trihydroxy-(Barbituric acid) Other (ref. 95) 3.9, 12.5 39 Thiazolidine 6.31 2-Methoxy- <1 39 Methyl thiazolidine-4-carboxylate 4.00 4-Methoxy- 2.5 39 Thiazolidine-4-COOH 1.51, 6.21 1-Methyl-2-pyrimidone 2.50 39 3-Methyl-4-pyrimidone 1.84 39 (ref. 96) 4-Amino- 5.71 19 2-Methyl-∆2-oxazoline 5.5 2-Amino-4-methyl- 4.15 19 2,4-Diamino- 7.26 194-Carbamoyl-2-phenyl-∆2-oxazoline 2.9 4-Methyl- 1.98 192-Phenyl-∆2-oxazoline 4.4 4-Hydroxy- 8.59, 1.85 39 4,5-Dihydroxy- 7.48, 1.99, 11.61 39Heterocyclics 2,4,5-Trihydroxy-(isoBarbituric acid)Pyrazines pK ref. 8.11, 11.48 39Pyrazine 1.1, 0.6 49, 39 4-Hydroxy-5-methoxy- 8.60 1.75 39 2,5-Dimethyl- 2.1 49 2,3,5,6-Tetramethyl- 2.8 49 1-Methyl-4-pyrimidone 1.8 392-Methoxy- --, 0.75 39 2-Methyl- 1.5 49 Miscellaneous2,6-Dimethyl- 2.5 49 4-Hydroxy-2-methylpyridazinium chloride 1.74 44 2-Hydroxy- 8.23, 0.1 39 1-Methyl-2-pyrazine -0.04 39 8-Hydroxy-6-methyl-1,6-naphthyridinium chloride 4.34 44 2-Amino- 3.14 19 Pyrimidine 1.30 19 2-Hydroxyphenazine 2.6 442-Amino- 3.54 19 4-Hydroxypteridine -0.17 445-Amino- 2.83 19 3-Methyl-4-pteridone -0.47 442-Amino-4,6-dimethyl- 4.85 19 5-Hydroxypyrimidine 1.87, 6.78 442,4,6-Triamino- 6.84 19 8-Hydroxy-1,6-Naphthyridine 4.08 442-Hydroxy- 9.17, 2.24 39 1-Hydroxyphenazine 1.44 44 p-Nitrobenzenethiol 5.1 58 o-Mercapto-phenylacetic acid Thioglycolic acid 3.67, 10.31 23 4.28, 7.67 59 Mercaptoethanol 9.5 23 Ethyl mercaptan 10.50 81 Cysteine 1.8, 8.3, 10.8 23 I-Thio-D-sorbitol 9.35 91 Cysteinylcysteine 2-mercaptoethanesulfonate 7.53 (9.1) 81 2.65, 7.27, 9.35, 10.85 23 o-aminothiophenol 6.59 81 Thiophenol 8.20a , 7.8, 6.52 59, 81, 82 Β-Mercaptopropionic acid 10.27 81 X= -H -S– -SH Methyl cysteine 6.5 (7.5) 81X(CH2)2SH 12.0 13.96 10.75 X(CH2)4SH 12.4 13.25 11.50 p-Cl-thiophenol 7.50 81 X(CH2)3SH 13.24 11.14 Mercaptans, RSHX(CH2)5SH 13.27 11.82 R CH3CCH2- 7.86 32 C6H5CH2- 9.43 82 HOCH2CH(OH)CH2- 9.51 82 CH2=CHCH2- 9.96 82 n-C4H9- 10.66 82 t-C5H11- 11.21 82 C2H5OCOCH2- 7.95 82 C2H5OCH2CH2- 9.38 82 HOCH2CH(OH)CH2- 9.66 82 n-C3H7- a10.65 82 t-C4H9- 11.05 82 CARBON ACIDS Dicyanomethane 12 2 Acetonitrile c. 25 24 Acetone ~20 24 Benzoylacetone (anol) 8.23 24 Acetylacetone 8.95 24 Dimethylsulfone 14 24 Diacetylacetone 6 24 Nitroethane 8.6 18 Hydrocyanic acid 9.21 25 2-nitropropane 7.74 18 1-nitropropane 9 18 Tricyanomethane strong 24 Saccharin 1.6 18 Trinitromethane strong 24 Tri-methylsulfonyl-methane strong 24 Nitromethane strong 25 Bis-( -Diketones):[(RCO)(R'CO)CH]2CHR (in 50% dioxane) (ref. 28) R R' R" pK pK CH3 CH3 (CH2)5CH3 11.33 12.52 CH3 CH3 C6H5 11.10 12.49 CH3 CH3 2-ClC6H4 11.04 12.73 CH3 CH3 2-C5H4N 9.80 12.46 CH3 CH3 2-CH3OC6H4 11.47 12.44 CH3 CH3 3,4-CH2O2C6H3 11.39 12.60 CH3 CH3 3-C5H4N 10.29 12.63 CH3 CH3 4-CH3OC6H4 11.62 12.61 CH3 CH3 4-(CH3)2NC6H4 11.50 12.45 CH3 CH3OCH2 C6H5 11.54 12.27 CH3 CH3OCH2 2-C5H4N 10.95 12.49 CH3 CH3OCH2 4-(CH3)2NC6H4 12.13 12.31 CH3 CH3OCH2 4-CH3OC6H4 11.74 12.49 CH3OCH2COCH2COCH3 9.66 (CH3CO)2CH(CH2)3CH3 12.07 Bis-( -Diketones) (RCO)-(R'CO)CH-Y-CH(COR)(COR') (in 50% dioxane) (ref. 26) R R' Y pK pK CH3 CH3 9.43 13.54 CH3 CH3 (CH2)4 11.99 12.48 CH3 CH3 (CH2)10 12.01 12.07 CH3 CH3 1,4-(CH3)2C6H4 11.27 12.15 Bis-( -Diketones) RCOCH2CO-Y-COCH2COR (in 75% dioxane) (ref. 26) R Y pK pK C6H5 (CH2)4 12.47 13.09 C6H5 (CH2)5 12.72 13.46 C6H5 (CH2)6 12.60 13.46 C6H5 (CH2)7 13.1 (est.) C6H5 (CH2)3 12.58 13.69 CH3 (CH2)5 12.29 13.00 CH3=CH(CH3)2 (CH2)5 12.95 13.60 CH3NO2 10.29 74 CO2Et O 10.96 74 CH3CHClNO2 7 74 CH3COCH2 NO2 5.1 74 CH(NO2)3 strong 74 CH3 O O 7.82 74 CH3COCHCl2 15 74 CH3COCHC2H5CO2C2H5 12.7 74 CH3COCHCH3COCH3 11 74 CH3COCH2COC6H5 9.4 74 Dinitromethane 4 2 C6H5COCH2COCF3 6.82 74 Potassium cyanide 9.21 2 CH3COCH2CHO 5.92 74 CH(CN)3 strong 74 CH3 COCH2 CO2CH3 10 74 CH2(CO2C2H5)2 13.3 74 CH3SO2CH2SO2CH3 14 74 CH3CO2H ~ 24 74 CH3SO2CH(COCH3)2 4.3 74 OEt O O 10.5 74 C2H5NO2 8.6 74 C2H5O2CCH2 NO2 5.82 74 CH2(NO2)2 3.57 74 O CH3 O 10.1 74 CH3COCH2Cl c. 16.5 74 CH3COCH2CO2C2H5 10.68 74 CH3COCH2COCH3 9 74 CH3COCHBrCOCH3 7 74 CH2(CHO)2 5 74CH3COCH2COCF3 4.7 74 C6H5COCH2NC5H5 10.51 74 CH(COCH3)3 5.85 74 IndicatorsCH3SO2CH3 c. 23 74 Tropeoline OO 2.0 28CH(SO2CH3)3 strong 74 Bromocresol green 4.9 28 CH2(CN)2 11.81 74 Thymol blue (1) 1.65 28 C2H5O2CCH2CN 9 74 Methyl orange 3.45 28 CH3CO2C2H5 ~ 24.5 74 Methyl yellow 3.25 28 CHC2H5(CO2C2H5)2 15 74 Neutral red 7.4 28 CH3CONH2 ~ 25 74 Bromophenol blue 4.1 28 S O O CF3 6.10 74 Bromothymol blue 7.3 28 Thymol blue (2) 9.2 28 Methyl red (1) 2.3 28 Methyl red (2) 5.0 28