1. Part 2 CHM1C3 Organic Acids and Bases

2. Content of Part 2 Definition of Bronsted acids and bases Definition of conjugate acids and bases K a pK a Typical pK a values Eplaining differences in acidity: Resonance Effects Eplaining differences in acidity: Inductive Effects

3. – Learning Objectives Part 2 – Organic Acids and Bases After completing PART 2 of this course you should have an understanding of, and be able to demonstrate, the following terms, ideas and methods. (i)You should be able to show the equilibrium between an organic acid in water with its conjugate base and the hydroxonium ion. (ii)You should know what K a equals with respect to this equilbrium. (iii)You should know the relationship between K a and pKa. (v)You should understand that the smaller the pK a or the more negative the pK a the stronger is the acid. (vi)By consideration of resonance structures of structurally related organic acids you should be able to make an assessment of which structure is likely to be the most acidic. (vii)By consideration of inductive effects in structurally related organic acids you should be able to make an assessment of which structure is likely to be the most acidic. CHM1C3 – Introduction to Chemical Reactivity of Organic Compounds–

5. Bronsted Acids and Bronsted Bases Bronsted Acid:A Bronsted acid (HA) is a compound which acts as a proton donor. Bronted Base: A Bronsted Base (B:) is a compound which acts as a proton acceptor. HA + B: A + BH Bronsted Acid Bronsted Base Conjugate Base Conjugate Acid proton acceptor proton donor proton acceptor proton donor

6. Examples of Bronsted Acids and Bronsted Bases AH + B: A + BH Bronsted Acid Bronsted Base Conjugate Base Conjugate Acid H 3 O + NH 3 : H 2 O: + NH 4 CH 3 CO 2 H + CH 3 O CH 3 CO 2 + CH 3 OH H 2 SO 4 + H 2 O: HSO 4 + H 3 O

7. Quantifying the Equilibrium: K a The dissociation of an acid, HA, in water may be represented as HA + H 2 O: A + H 3 O The water is acting as the base. Furthermore, the water is acting as the solvent and is in huge excess. The degree of ionisation is quantified by the equilibrium constant…

8. Values of K a [1]Very strong acid Almost complete ionization Large Small large number Approaches infinity [2]Very weak acid No perceptible ionization Small Large small number Approaches zero

9. The pK a Very weak acid low ionization Very strong acid high ionization = -Log 10 K a KaKa pKapKa % Dissociation @ 1 mM 1 x 10 3 -399.9 1 x 10 1 92 1 x 10 0 062 1 x 10 -1 127 1 x 10 -11 110.0003 HA + H 2 O: A + H 3 O p K a = -Log 10 HA A H 3 O

10. Some Heteroatom pK a Values i.e. atoms attached to acidic protons other than carbon AcidpKapKa HBr-8 HCl-7 H 2 SO 4 -3 HNO 3 -1.4 HF3.18 CF 3 CO 2 H0.23 CCl 3 CO 2 H0.66 NCCH 2 CO 2 H2.47 HCO 2 H3.75 AcidpKapKa PhCO 2 H4.20 CH 3 CO 2 H4.76 (CH 3 ) 3 CCO 2 H5.03 4-nitrophenol7.15 2-nitrophenol7.23 3-nitrophenol8.36 Phenol10.00 C2H5SHC2H5SH10.6 CF 3 CH 2 OH12.4 AcidpKapKa CH 3 OH15.5 C2H5OHC2H5OH15.9 STRONG ACID WEAK ACID

11. Resonance Effects and Acidity

12. Explaining the Differences in Acidity: Resonance Effects 4.76 15.5 pKapKa This resonance process imparts stability on the anionic structure (see Part 1 of the course) Thus, carboxylate anion is more stable than the alkoxide anion. Lone pairs of electrons adjacent to double bonds are able to delocalise through a process referred to as resonance.

14. pK a = 7.23 pK a = 8.36 Explaining the Differences in Acidity: Resonance Effects Stronger Acid Weaker Acid 3-Nitrophenol

15. Lone pair delocalised into  - system of the aromatic ring Lone pair delocalised into  - system of the nitro group 2-Nitrophenol

16. It is not possible for the lone pair to be positioned on the carbon atom adjacent to the nitrogen atom. Lone pair delocalised into  - system of the aromatic ring Therefore, there is one less resonance structure in this case, and this anion is subsequently less stable, and more difficult to form from its protonated form. 3-Nitrophenol

17. pK a = 20 pK a = 9 Stronger Acid Weaker Acid Explaining the Differences in Acidity: Resonance Effects

18. An Enolate Dr Cox’s Lecture Course two resonance structures three resonance structures Less stable anion More stable anion

19. Inductive Effects and Acidity

20. Same Hydroxonium Ion: Protonated water Nature of anion is different 0.23 3.75 4.20 4.76 5.03 pKapKa Explaining the Differences in Acidity: Inductive Effects

21. This resonance is the same for all the acids above. Thus, the R groups are influencing the stability of the carboxylate anion R affects CO 2 -

22. CF 3 is a strong electron withdrawing group (-I group) and is pulling electron density away from the carboxylate, i.e. reducing the charge on the carboxylate, and thus stabilising it, in a relative sense. R = CF 3 this is the strongest acid. CF 3 = -I Inductive Group Therefore, Is the most stable anion. R = CH 3 this is a weaker acid. CH 3 = +I Inductive Group Therefore, Is a less stable anion. CH 3 is an electron donating group (+I group) and is pushing extra electron density onto the carboxylate, i.e. increasing the charge on the carboxylate, and thus destabilising it, in a relative sense.

23. Some Carbon Atom pK a Values i.e. carbon atoms attached to acidic protons AcidpKapKa CH 3 C(O)CH 2 C(O)CH 3 9 CH 3 NO 2 10.2 CH 2 (C≡N) 2 11.2 Cyclopentadiene16.0 PhC(O)CH 3 19.0 CH 3 C(O)CH 3 20 PhC≡CH21 CH3C≡NCH3C≡N25 HC≡CH26 VERY WEAK ACID NOT REALLY AN ACID! AcidpKapKa (Ph) 3 CH31.5 PhCH 3 41 Ph-H43 CH 4 48 Cyclohexane51

24. – Summary Sheet Part 2 – Organic Acids and Bases A Bronsted acid is a compound which can donate a proton (H + ). Once the proton has been donated the resulting structure is referred to as the conjugate base. A Bronsted base is a compound which can accept proton. Once the proton has been accepted the resulting structure is referred to as the conjugate acid. Any acid/base reaction is, in principle, an equilibrium process. The equilibrium can be quantified by considering the degree of ionisation of an acid dissolved in water, where the water acts as the Bronsted base. This quantification is referred to as the pK a and is equal to the –log K a, where K a is equal to the equilibrium concentration of the conjugate base multiplied by the equilibrium concentration of the hydroxonium ion divided by the equilibrium concentration of the Bronsted acid. Consideration of inductive and resonance effects on the conjugate base between structurally related compounds allows a qualitative assessment of the order of acidity. The more delocalised the lone pair of electrons (formed from deprotonation of the acid) the more stable the conjugate base. If the conjugate base is stabilised, the easier it will be formed, and thus the stronger the Bronsted acid will be. CHM1C3 – Introduction to Chemical Reactivity of Organic Compounds–

25. http://classes.yale.edu/chem220a/studyaids/pKa.html http://www.chromatography.co.uk/TECHNIQS/Other/buffers.htm http://home.planet.nl/~skok/techniques/laboratory/pka_pkb.html http://www.wiu.edu/users/mftkv/Chem331/acidstrength.htm http://www.geocities.com/le_chatelier_uk/pka.htmlhttp://www.geocities.com/le_chatelier_uk/pka.html (interesting if you have audio!) http://www.chem.wisc.edu/areas/reich/pkatable/http://www.chem.wisc.edu/areas/reich/pkatable/ (pK a s in DMSO as solvent) http://www.agsci.ubc.ca/courses/fnh/410/protein/1_13.htmhttp://www.agsci.ubc.ca/courses/fnh/410/protein/1_13.htm (pK a s of aminoacids) http://classes.yale.edu/chem220a/studyaids/pKa.html http://www.chem.umd.edu/courses/chem231fribush/3-Chapter2-3.pdf www for further pKa information

26. Question 1: Acids and Bases Rationalise why acid A is a stronger acid than acid B. A, pK a = 11.2B, pK a = 25

27. Answer 1: Acids and Bases Rationalise why acid A is a stronger acid than acid B. A, pK a = 11.2B, pK a = 25 Most stable anion, as charge more delocalised over three resonance structures, compared to 2 in the conjugate base of B. Therefore, A is most acidic

28. Question 2: Acids and Bases A and B are two structurally related phenols. Identify the one which you think will be the most acidic. AB

29. Answer 2: Acids and Bases A and B are two structurally related benzoic acids. Identify the one which you think will be the most acidic. AB Two establish which is the strongest acid we need to consider the conjugate base resonance structures. We will be able to establish which has the most resonance structures, and is therfore the most stable conjugate base and therefore the most easiest to form. 4 Resonance Structures 5 Resonance Structures Most Acidic

30. Question 3: Acids and Bases A and B are two structurally related phenols. Identify the one which you think will be the most acidic. AB

31. Answer 3: Acids and Bases A and B are two structurally related phenols. Identify the one which you think will be the most acidic. AB Two establish which is the strongest acid we need to consider the conjugate base resonance structures. We will be able to establish which has the most resonance structures, and is therefore the most stable conjugate base, and thus the easiest to form. 4 Resonance Structures 5 Resonance Structures Most Acidic