Preparation of Grignard Reagents and the Preparation of 2-methyl-3-heptanol from 2-methylpropanal and Grignard Reagents

II. Introduction

Organometallic compounds are substances with a carbon-metal bond (structure 1); these metals may be Li, Na, Mg, Cu, Hg, Pd, or any other transition metal (Gilbert, Martin 639). Organometallic compounds with M representing MgBr are organomagnesium compounds, or more commonly Grignard reagents.
Grignard reagents are unique due to their polarization. The carbon atom in the Grignard reagent is made electron-rich by the electropositive metal giving the carbon atom a partial negative charge (δ-), and the metal a partial positive charge (δ+). This unique charge distribution allows carbon to act as a nucleophile in chemical reactions. However, when carbon is bonded to a more electronegative atom, such as a halogen (structure 2) or to oxygen (structure 3), it acts as an electrophile in chemical reactions (Gilbert, Martin 639).

Figure 1. Structure of an organometallic reagent (structure 1), an alkyl halide (structure 2), and a carbonyl compound (structure 3). *
Due to the nucleophilic properties, organometallic compounds are commonly used in reactions to form new carbon-carbon bonds. Equation 1 is a general example of a reaction between an alkyl halide and an organometallic compound. Equation 2 is an example of a reaction of a carbonyl and an organometallic compound. In both reactions the nucleophilic carbon atom of the organometallic compound bonds to the electrophilic carbon of the other reagent (Gilbert, Martin 640).

Equation 1

Equation 2

Grignard reagents R-MgX or Ar-MgX are prepared through the reaction of an alkyl halide (R-X) or an aryl halide (Ar-X) with magnesium metal in an anhydrous ethereal solvent (equation 3). Grignard reagents are commonly represented by R-MgX or Ar-MgX; however the structure of the organometallic species in a solution is more complex (Gilbert, Martin 640). The alkyl halide to be used may be either alkyl or aryl chlorides, bromides, or iodides. Grignard reagents are formed most easily from alkyl iodides, bromides, and then chlorides; aryl halides are less reactive but follow the same trend. Magnesium, as seen in equation 3, is normally used in the form of turnings, or thin shavings. This form is used because the thin shavings increase the surface area which in turn increases its reactivity (Gilbert, Martin 641).
Equation 3 R-X or Ar-X + Mg° dry ethersolvent→ R-MgX or Ar-MgX

The ether solvent is essential in the preparation of a Grignard reagent because the basic oxygen atom will complex with the electropositive magnesium to help stabilize the organometallic product (Gilbert, Martin 641). Diethyl ether [(C2H5)2O] and tetrahydrofuran, THF [(CH2)4O], are among the most commonly used ethers. Diethyl ether is preferred because it is inexpensive, may be bought in anhydrous form, and its relatively low boiling point (36 ˚C) makes it easy to remove from the reaction mixture (Gilbert, Martin 641). In order to prevent exposure to atmospheric oxygen; it is important that the anhydrous ether be from a freshly opened container during the preparation of the Grignard reagent. Atmospheric oxygen promotes the formation of hydroperoxides which are explosive (Gilbert, Martin 641).
The preparation of the Grignard reagent must be carried out under anhydrous conditions and, if possible, in the absence of oxygen as noted above. It is exceedingly important to maintain completely dry conditions throughout, because water inhibits the initiation of the reaction and destroys the reagent as it forms (Gilbert, Martin 642). The acid-base reaction that occurs when the Grignard reagent comes in contact with water is shown in equation 4.
Equation 4

The Grignard reagent is a strong base and because of this the reagent removes a proton from water. The overall effect is the hydrolysis of the reagent, with the formation of a hydrocarbon (RH) and a magnesium salt. This is why it is critical to exclude water from the reaction mixture. Other weakly acidic compounds such as alcohols, carboxylic acids, and amines also destroy the Grignard reagent and inhibit the reaction (Gilbert, Martin 642).
In addition to the reaction with water, other side reactions may occur. These side reactions include the Grignard reagent with oxygen (equation 5), with carbon dioxide (equation 6), and a coupling reaction with the organic halide (equation 7).
Equation 5
Equation 6

Equation 7 It is possible to minimize these reactions by taking certain precautions when carrying out the reaction. The reactions with oxygen and carbon dioxide may be avoided by carrying out the reaction under an inert atmosphere (such as nitrogen or helium gas). However, when using diethyl ether as the solvent, an inert gas is not essential since ether’s very high vapor pressure excludes most of air from the reaction vessel (Gilbert, Martin 643).
The coupling reaction (equation 7) is an example of a Wurtz reaction. It is not possible to eliminate this coupling reaction completely, but it may be minimized by using dilute solutions to avoid localized high concentrations of the halide (Gilbert, Martin 643). This is done by using efficient stirring and slowly adding the halide to the magnesium and ether mixture. Normally the rate of addition of halide and the rate of reflux should be adjusted so that they are equal. Alkyl iodides are more prone to coupling reactions than are bromides or chlorides, therefore the iodides are less preferable for preparing Grignard reagents even though they are more reactive. If water has been carefully excluded, the most important side reaction to minimize is the coupling process, even though it is not as significant of a problem as the reaction with water (Gilbert, Martin 643).
During the formation of Grignard reagents, control is critical because it is an exothermic reaction and multiple side reactions are possible. An induction period may be needed to initiate the reaction prior to adding a large quantity of the alkyl halide. Even after an induction period, it is necessary to add the alkyl halide drop-wise. This helps keep the concentration of the alkyl halide low, which enables better regulation of the rate and better control of the evolution of heat (Gilbert, Martin 642). If the reaction appears to be getting out of control, it should be immediately cooled in an ice bath.
The formation of a tertiary alcohol from two moles of phenylmagnesium bromide (a Grignard reagent) and one mole of methyl benzoate, an ester, is a substitution reaction. The initially formed product is unstable and decomposes to a ketone. The ketone is more reactive than an ester so it immediately reacts with more Grignard reagent (Gilbert, Martin 649). This process is demonstrated by reaction 1. The primary impurity from this reaction is biphenyl, formed by the reaction of phenylmagnesium bromide with unreacted bromobenzene. The most effective way to reduce this side reaction is to add the bromobenzene slowly to the reaction mixture so it will react with the magnesium and not be present in high concentration to react with previously formed Grignard reagent. The biphenyl is easily separated by the use of cyclohexane since it is more soluble in hydrocarbon solvents than the triphenylmethanol (Gilbert, Martin 650).
Organic molecules may contain a variety of bonds, all of which will be vibrating at different frequencies. This information is used to identify specific bonds in organic molecules. For a particular covalent bond in a molecule, only a particular set of vibrational frequencies is possible. For example, if a bond is vibrating at a frequency ν1 and its next available frequency is ν2, if radiation is applied to the compound containing this bond, some of the radiation will be absorbed and the bond will vibrate at a higher frequency, ν2. The frequency for a particular bond is more or less independent of other bonds in the compound; therefore, determination of the frequencies in the infrared region gives information about the types of bonds which are present. An infrared spectrometer analyzes a compound by passing infrared radiation, over a range of different frequencies, through a sample and measuresthe absorptions made by each type of bond in the compound. This produces a spectrum, normally a ‘plot’ of percent transmittance against wavenumber. No two organic compounds have the same infrared spectrum, therefore individual, pure compounds can be identified by examination of their spectra. In the region, 7 - 11 microns (1430-910 cm-1) there are many absorption bands, this region is known as the fingerprint region and any unknown pure compound can be identified by comparing it to published spectrum. The region, 2.5 - 7 microns (4000-1430 cm-1) is simpler, and has less absorption bands. This region is used to aid the determination of structures because particular groups can be more easily identified. Stretching frequencies are more commonly used in spectroscopy, because important groups can be identified. Bending frequencies are also useful for identification but they are used less often because they tend to be more numerous and complicated.
In the finger print region different functional groups can be identified, for example the stretching mode of the alkane carbon-hydrogen bonds peak in the region of 2850-2970 cm-1 and bromine-carbon bonds peak between 500-700 cm-1.
When the IR spectra of a sample is identical to the known spectra of the pure compound, the sample can be identified as the pure compound. The observation of extra bands in a sample indicates that contaminates are present. The following IR spectra are of pure bromobenzene (Figure 2), pure methyl benzoate (Figure 3) and, pure triphenylmethanol (Figure 4).
In Figure 2 the peak between 500-700 cm-1 indicates the presence of the carbon-bromine bond, the peak between 3010-3100 cm-1 indicates the presence of carbon-hydrogen bonds in an aromatic ring and the peak between 1500-1600 cm-1 indicates the presence of carbon-carbon double bonds in an aromatic ring. In Figure 3 the peak between 1675-1760 cm-1 indicates the presence of a carbon-oxygen double bond (of an ester), the peak between 1500-1600 cm-1 is the carbon-carbon double bond in an aromatic ring, and the peak between 1050-1300 cm-1 is the carbon-oxygen bond. Finally, in Figure 4 the broad peak between 3200-3400 cm-1 indicates the presence of an oxygen-hydrogen bond (an alcohol), the peak between 1000-1100 cm-1 indicates the presence of a carbon-oxygen bond, and the peak between 1340-1470 cm-1 is the carbon-hydrogen bond of the alkene.

Figure 4
Figure 4
Figure 3
Figure 3
Figure 2
Figure 2

Main Reaction Mechanism

III. Results and Discussion

Table 1: Experimental, Theoretical, Percent Yields and Experimental and Known melting point ranges of triphenylmethanol | Experimental Yield (g) | Theoretical Yield (g) | Percent Yield | Experimental Melting Point Range (°C) | Literature Melting Point Range (°C) | 7.472 | 9.178 | 81.41% | 153.0-158.1 | 164 |

Figure 5
Figure 5
Figure 6
Figure 6
Table 1 shows the mass of the recovered triphenylmethanol to be 7.472g. The theoretical yield was found to be 9.178g and the percent yield was 81.41%. The limiting reagent was the methyl benzoate. Table 1 also shows the experimental melting point range to be 153.0-158.1 °C and the literature value is 164°C. The experimental value is wide and lower than the literature value which suggests impurities are present in the sample. Figure 5 shows the IR spectrum of the methyl benzoate used during the reaction, when compared to the spectrum of the pure methyl benzoate, Figure 3, it is identical. The IR spectrum of the recovered triphenylmethanol, Figure 6, is identical to the spectrum of pure triphenylmethanol, Figure 4.

In Figure 5 the carbon-oxygen double bond peak between 1675-1760 cm-1 confirms the reactant is an ester. This peak is not seen in Figure 6, however a broad peak between 3200-3400 cm-1 indicates that an oxygen-hydrogen bond has formed therefore confirming the formation of an alcohol. Both compounds have similar peaks carbon-oxygen peaks between 1050-1300 cm-1. They also have similar carbon-hydrogen bending peaks, between 1400-1450 cm-1 and similar C-H stretching peaks between 2850-2970 cm-1.

IV. Conclusions

The reaction of phenylmagnesium bromide with methyl benzoate was successful in forming triphenylmethanol. The IR spectrum of the recovered product confirms that the product was pure triphenylmethanol. The spectrum also confirms the loss of a C=O, and the gaining of an O-H bond. In the reaction the ester (methyl benzoate) underwent nucleophilic addition and the result was the production of tertiary alcohol (triphenylmethanol). The wide and lower melting point range is due to the lack of purifying the crude sample prior to taking the melting point. In the future it would be useful to calibrate the melting point apparatus to ensure accurate readings. It would also be helpful to perform this lab in two parts in order to have sufficient time to purify the product.

Reference:
Gilbert, John C., and Stephen F. Martin. Experimental Organic Chemistry A Miniscale and Microscale Approach. 5th ed. Boston: Cengage Learning, 2011. Print.