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

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Cobalt(I) Complex Nucleophile: Catalysis of Sn2 Reactions with Alkyl Halides

Kinetics of Bimolecular Substitution Reactions

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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.

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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)5-deoxyadenosyl (5,6-dimethylbenzimidazolyl)-cobinamide (I-cobinamide (I

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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= pyridineR= Br, alkyl groups

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Goal of Research 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.

Time-resolved Spectroscopy of

alkylations Kinetic studies

Synthesis of Co(I) nucleophile

EXPERIMENT

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Methods of Experiment1. 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.

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Alkyl Halides of Interest

BrBrBrBrBr

Br

Br

Cl

Br

Br

Chlorobutane

Bromobutane

Bromopentane

2-Bromopropane

2-Bromobutane

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Graphical Analysis of Results

2-Bromopropane

y = 3E-08x3 - 1E-05x2 + 0.0007x + 0.9023

R2 = 0.9756

0.760.780.8

0.820.840.860.880.9

0.920.94

0 50 100 150 200 250 300

Time (seconds)

Abso

rban

ce (4

80nm

)

2-Bromobutane

y = -9E-09x3 + 1E-06x2 - 0.0009x + 1.4803

R2 = 0.9768

1.1

1.15

1.2

1.25

1.3

1.35

1.4

1.45

1.5

0 50 100 150 200 250 300

Time (seconds)

Abso

rban

ce (4

80nm

)

Time versus Absorbance graphs

Co(I) + 2-bromopropane Co(I) + 2-bromobutane

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Bromobutane

y = 4E-09x3 - 3E-06x2 + 3E-06x + 0.2585

R2 = 0.9908

0.1

0.15

0.2

0.25

-30 20 70 120 170 220 270

Time (seconds)

Abso

rban

ce (6

90nm

)

Chlorobutane

y = -9E-09x3 + 3E-06x2 - 0.0012x + 0.4258

R2 = 0.9933

0.13

0.18

0.23

0.28

0.33

0.38

0.43

-10 40 90 140 190 240 290

Time (seconds)

Abso

rban

ce (6

90nm

)

Graphical Analysis (cont.)

Co(I) + chlorobutane Co(I) + bromobutane

Time versus Absorbance graphs

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Calculating the Rate Constant

Bromopentane

y = -9E-09x3 + 3E-06x2 - 0.001x + 1.018

R2 = 0.9083

0.8

0.85

0.9

0.95

1

1.05

-30 20 70 120 170 220 270

Time (seconds)

Abso

rban

ce (4

80nm

)

•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

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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

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Results: Rate Constants of Reactions

Cl

Alkyl Halide Rate Constant (k, mole/L/sec)

Bromopentane 0.00004246

Bromobutane 0.00005352

Chlorobutane 0.0000009852

2-Bromopropane -0.004527783

2-Bromobutane -0.00067206

Br

Br

Br

Br

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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

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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

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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

Br Br

KBromobutane/ KBromopentane = 1: 1.26

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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.

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Literature Cited

1. R. Nast and H. Lewinsky, Z. Anorg. Allgem. Chem, 282, 210 (1955).2. W. Hieber, O. Vohler, and G. Braun, Z. Naturforsch., 13b, 192 (1958).3. J. Chatt and B.L. Shaw, J. Chem. Soc., 285 (1961). 4. H Barker, H. Weissbach and R.D. Smyth, Proc. Natl. Acad. Sci.U.S., 1093 (1958). 5. G.N.Schrauzer and J. Kohnle, Chem.Ber., 97, 3056 (1964).6. G.N. Schrauzer, E. Deutsch, and R.J. Windgassen, J. Amer. Chem Soc, 90, 2441

(1968).7. 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.

8. A Laboratory Manual for Advanced Inorganic Chemistry, Roth J.P., The Johns Hopkins University, Baltimore, Fall 2007.

9. Organic Chemistry, Fessenden, Ralph; Fessenden., Joan S.; Sixth Edition, Brooks/Cole Publishing Company, 1998.