Grignard reactions often start slowly. First, there is an induction period during which reactive magnesium becomes exposed to the organic reagents. After this induction period, the reactions can be highly exothermic. Alkyl and aryl bromides and iodides are common substrates. Chlorides are also used, but fluorides are generally unreactive, except with specially activated magnesium, such as Rieke magnesium.
Many Grignard reagents, such as methylmagnesium chloride, phenylmagnesium bromide, and allylmagnesium bromide are available commercially in tetrahydrofuran or diethyl ether solutions.
Using the Schlenk equilibrium, Grignard reagents form varying amounts of diorganomagnesium compounds (R = organic group, X = halide):
Many methods have been developed to initiate Grignard reactions that are slow to start. These methods weaken the layer of MgO that covers the magnesium. They expose the magnesium to the organic halide to start the reaction that makes the Grignard reagent.
Mechanical methods include crushing of the Mg pieces "in situ", rapid stirring, or using ultrasound (sonication) of the suspension. Iodine, methyl iodide, and 1,2-dibromoethane are commonly employed activating agents. Chemists use 1,2-dibromoethane because its action can be monitored by the observation of bubbles of ethylene. Also, the side-products are innocuous:
The amount of Mg consumed by these activating agents is usually insignificant.
The addition of a small amount of mercuric chloride will amalgamate the surface of the metal, allowing it to react.
Grignard reagents are produced in industry for use in place, or for sale. As with at bench-scale, the main problem is that of initiation. A portion of a previous batch of Grignard reagent is often used as the initiator. Grignard reactions are exothermic; this exothermicity must be considered when a reaction is scaled-up from laboratory to production plant.
Grignard reagents will react with a variety of carbonyl derivatives.
The most common application is for alkylation of aldehydes and ketones, as in this example:
Note that the acetal function (a masked carbonyl) does not react.
Such reactions usually involve a water-based (aqueous) acidic workup, though this is rarely shown in reaction schemes. In cases where the Grignard reagent is adding to a prochiral aldehyde or ketone, the Felkin-Anh model or Cram's Rule can usually predict which stereoisomer will form.
In addition, Grignard reagents will react with electrophiles.
Another example is making salicylaldehyde (not shown above). First, bromoethane reacts with Mg in ether. Second, phenol in THF converts the phenol into Ar-OMgBr. Third, benzene is added in the presence of paraformaldehyde powder and triethylamine. Fourth, the mixture is distilled to remove the solvents. Next, 10% HCl is added. Salicylaldehyde will be the major product as long as everything is very dry and under inert conditions. The reaction works also with iodoethane instead of bromoethane.
The Grignard reagent is very useful for forming carbon–heteroatom bonds.
A Grignard reagent can also be involved in coupling reactions. For example, nonylmagnesium bromide reacts with methyl "p"-chlorobenzoate to give "p"-nonylbenzoic acid, in the presence of Tris(acetylacetonato)iron(III), often symbolized as Fe(acac), after workup with NaOH to hydrolyze the ester, shown as follows. Without the Fe(acac), the Grignard reagent would attack the ester group over the aryl halide.
For the coupling of aryl halides with aryl Grignards, nickel chloride in tetrahydrofuran (THF) is also a good catalyst. Additionally, an effective catalyst for the couplings of alkyl halides is dilithium tetrachlorocuprate (LiCuCl), prepared by mixing lithium chloride (LiCl) and copper(II) chloride (CuCl) in THF. The Kumada-Corriu coupling gives access to [substituted] styrenes.
The oxidation of a Grignard reagent with oxygen takes place through a radical intermediate to a magnesium hydroperoxide. Hydrolysis of this complex yields hydroperoxides and reduction with an additional equivalent of Grignard reagent gives an alcohol.
formula_1
A reaction of Grignards with oxygen in presence of an alkene makes an ethylene extended alcohol. These are useful in synthesizing larger compounds. This modification requires aryl or vinyl Grignard reagents. Adding just the Grignard and the alkene does not result in a reaction, showing that the presence of oxygen is essential. The only drawback is the requirement of at least two equivalents of Grignard reagent in the reaction. This can addressed by using a dual Grignard system with a cheap reducing Grignard reagent such as n-butylmagnesium bromide.
Grignard reagents are nucleophiles in nucleophilic aliphatic substitutions for instance with alkyl halides in a key step in industrial Naproxen production:
In the Boord olefin synthesis, the addition of magnesium to certain β-haloethers results in an elimination reaction to the alkene. This reaction can limit the utility of Grignard reactions.
Grignard degradation at one time was a tool in structure identification (elucidation) in which a Grignard RMgBr formed from a heteroaryl bromide HetBr reacts with water to Het-H (bromine replaced by a hydrogen atom) and MgBrOH. This hydrolysis method allows the determination of the number of halogen atoms in an organic compound. In modern usage, Grignard degradation is used in the chemical analysis of certain triacylglycerols.
An example of the Grignard reaction is a key step in the industrial production of Tamoxifen. (Tamoxifen is currently used for the treatment of estrogen receptor positive breast cancer in women.):
Peach (disambiguation)
Peach can mean:
Giant Magellan Telescope
The Giant Magellan Telescope (GMT) will be the world's largest telescope when it is completed in 2025. Instead of one large mirror, the GMT will have seven separate mirrors working together. This will mean its collecting area is bigger than the actual mirror surfaces. It will be made of seven diameter mirror parts. It will have a the resolving power of a mirror. Its collecting area will be the same as a mirror. The telescope will have over four times the ability to gather light than existing telescopes. It will produce images up to ten times clearer than the Hubble Space Telescope. It will cost $700 million.
The location of the telescope is the Las Campanas Observatory, which is also the site of the Magellan Telescopes, some northeast of La Serena, Chile. This area has clear weather for most of the year. The night sky in most of the surrounding Atacama Desert region is free from atmospheric pollution. With few cities nearby this is probably one of the places least affected by light pollution. All of this makes the area one of the best spots on Earth for long-term astronomical observation.
The telescope is unique because it will use seven mirror sections, each in diameter. These segments will then be arranged to form a single optical surface. This is difficult as the surface of the outer six mirror segments is not radially symmetrical (that is, they are off-axis). This requires a small change in the way mirrors are usually polished. All seven mirrors will be arranged so that the reflecting surface of each of them is on a common axis. One mirror will be in the center and the other six arranged symmetrically around the center. A focal plane will be on-axis with the entire assembly. The plan is to build seven identical off-axis mirrors. The spare mirror has been made to replace a mirror when it needs recoating, a 1–2 week (per segment) process required every 1–2 years.
The Steward Observatory, at the University of Arizona, is making the mirrors in a laboratory beneath the university's football stadium. It is using a rotating furnace to make the mirror. The casting of the first mirror was completed on November 3, 2005. But the time-consuming shaping and polishing will be completed in the autumn of 2011.
The telescope will make use of adaptive optics.