Cobalt(I) Complex Nucleophile: Catalysis of Sn 2 Reactions with Alkyl Halides

1. Cobalt(I) Complex Nucleophile: Catalysis of Sn2 Reactions with Alkyl Halides Kinetics of Bimolecular Substitution Reactions

2. A Brief Introduction Half a century ago, it was a common belief that organocobalt compounds were reactive and thermodynamically unstable. In 1964, H. Barker, H. Weissbach and R.D. Smyth discovered a coenzyme of vitamin B12, 5-deoxyadenosyl (5,6-dimethylbenzimidazolyl)-cobinamide (I), which was not only naturally occurring but one of the most stable organometallic compounds to date.

3. Introduction (cont.) The stability of the compound was initially contributed to the electronic effects of the corrin ligand. Since then, chemists have been trying to find cobalt complexes other than corrin that are capable of forming stable organometallic derivatives. 5-deoxyadenosyl (5,6-dimethylbenzimidazolyl) -cobinamide (I

4. Introduction (cont.) Soon, it was discovered that bis (dimethyl-glyoximato) cobalt complexes display many reactions of the cobalt atom in the corrins. The planar compound with axial bases is also susceptible to various alkylation reaction at the axial position (Sn2 mechanism). B= pyridine R= Br, alkyl groups

5. Synthesize a cobalt(III) complex- bromo (pyridine) cobaloxime; reduce Co(III) to Co(I), which is now a “supernucleophile” Use Co(I) nucleophile in a series of Sn2 reactions involving alkyl halides Conduct kinetic studies on the rates of reactions and account for the rate constants as a function of the alkyl halide structures. Goal of Research

6. Methods of Experiment 1. Synthesis of Bromo (pyridine) Cobaloxamine CoII(H2O)6(NO3)2 + NaBr + DMG + pyridine  2. Reduction to Co(I)- sodium borohydride reduces the Co(III) species into the Co(I) nucleophile 3. Alkylation: The Co(I) species is a dark blue color. As alkyl halide is added to solution and reacts with Co(I), the disappearance of the dark blue color is reflective of the depletion of Co(I) and the progress of reaction. This colorimetric reaction may be monitor by UV-Vis spec and used to determine the kinetics of the reactions.

7. Alkyl Halides of Interest  Chlorobutane  Bromobutane Bromopentane  2-Bromopropane  2-Bromobutane 

8. Graphical Analysis of Results Co(I) + 2-bromopropane Co(I) + 2-bromobutane Time versus Absorbance graphs

9. Graphical Analysis (cont.) Co(I) + chlorobutane Co(I) + bromobutane Time versus Absorbance graphs

10. Calculating the Rate Constant • A third-degree polynomial regression was • calculated for all the graphs • The 1st derivative of the functions is • representative of the rates of reaction at • each point of the graph • For example, the regression for • bromopentane is: • A(t) = -9e-9t3 + 3e-6t2 – 0.001t • Its derivative function is: • dA(T)/dt = -27e-9t2 + 6e-6t - 0.001 Co(I) + bromopentane Time versus Absorbance graph

11. Calculating the Rate Constant (cont.) • Substituting each point in time into the first derivative permits • the calculation of R(t), • the slope of the tangent at each point, which represents the rate of reaction. • The ratio of the rate at time t and time t+Δ gives the relative rate of a reaction • and presents a consistent relationship between the rates: • R(t)/R(t+Δ) = e-kΔ = r • The rate constant of a reaction may be obtained from the mean • r over a range of time: • k = (ln rm)/Δ

12. Results: Rate Constants of Reactions Alkyl HalideRate Constant (k, mole/L/sec) Bromopentane 0.00004246 Bromobutane 0.00005352 Chlorobutane 0.0000009852 2-Bromopropane -0.004527783 2-Bromobutane -0.00067206

13. Discussion of Results • Results obey the following chart summarizing the reactivities of alkyl halides KChlorobutane=0.0000009852 vs. KBromobutane=0.00005352 kbr /kcl ~54.3 R-F R-Cl R-Br R-I ----------------------------- Increasing Reactivity

14. Discussion (cont.) • In an Sn2 reaction, the energy of the transition state of a crowded molecule is higher than that of a less crowded molecule. Hence, it is expected that the rates of reactions decrease as the molecules are more sterically hindered: K2-Bromopropane=-0.004527783 K2-Bromobutane= -0.00067206 3° R-X 2° R-X 1° R-X CH3-X ------------------------------------------ Increasing Rate of Sn2 Sec-alkylcobalt complexes are highly unstable and difficult to isolate

15. Discussion (cont.) Increasing the length of the alkyl chain by one carbon decreased the rate constant of the reaction only minimally KBromopentane = 0.00004246 KBromobutane = 0.00005352 KBromobutane/ KBromopentane = 1: 1.26

16. Conclusions • In an Sn2 mechanistic manner, Co(I) functions as a supernucleophile in a variety of alkylation reactions. • Lengthening of the alkyl chain of the alkyl halide does not significantly decrease the rate constant of alkylation by Co(I)- corroborates Sn2 mechanism. • Attaching alkyl groups at the α-carbon decreases the rate of reaction by increasing the molecule’s steric hindrance.

17. Literature Cited • R. Nast and H. Lewinsky, Z. Anorg. Allgem. Chem, 282, 210 (1955). • W. Hieber, O. Vohler, and G. Braun, Z. Naturforsch., 13b, 192 (1958). • J. Chatt and B.L. Shaw, J. Chem. Soc., 285 (1961). • H Barker, H. Weissbach and R.D. Smyth, Proc. Natl. Acad. Sci.U.S., 1093 (1958). • G.N.Schrauzer and J. Kohnle, Chem.Ber., 97, 3056 (1964). • G.N. Schrauzer, E. Deutsch, and R.J. Windgassen, J. Amer. Chem Soc, 90, 2441 (1968). • G.N. Schrauzer; E. Deutsch; Reactions of Cobalt (I) Supernucleophiles. The Alkylation of Vitamin B12s, Cobaloximes (I) and Related Compounds, December 1968; unpublished experiments with L.P. Lee and J.W. Sibert. • A Laboratory Manual for Advanced Inorganic Chemistry, Roth J.P., The Johns Hopkins University, Baltimore, Fall 2007. • Organic Chemistry, Fessenden, Ralph; Fessenden., Joan S.; Sixth Edition, Brooks/Cole Publishing Company, 1998.