21
The correct answer is the 1,2-addition product (i.e. the allylic alcohol 1). In general, Grignard reagents and organolithium reagents add directly to the carbonyl carbon, while organocuprates (organocopper reagents) add to the beta-position of an unsaturated ketone.
This exact transformation was reported by Akai and coworkers recently (Org. Lett. 2010, 12, ...
21
Ammonium chloride ($\ce{NH4Cl}$) is the work-up reagent that quenches the magnesium alkoxide product of the Grignard addition. It is the reagent of choice as it is a proton source without being acidic; acidic conditions could result in protonation of the tertiary alcohol product and elimination to the alkene. It also ensures that all inorganic salts of Mg ...
19
Sara Jane: Lest you miss the point of the stimulating discussion between Waylander and Zhe, I would like to sum up their thoughts with a diagram. Your first clue should have been the opening line: "Recall that epoxides rearrange with Lewis acid...". It is common that catalytic Lewis acids rearrange 2,3-dialkyl oxiranes [epoxides] to ketones. In the case of ...
13
It seems like an idea of using magnesium anthracene systems for the $\ce{MgH2}$ production persisted since 1980s [1] till late 2000s, when new more efficient method with better scalability for industrial use was established.
One of the recent reviews in hydrogen-storage applications [2, p. 220] compares the older two-step process of $\ce{MgH2}$ synthesis:
...
13
The Grignard reaction, although very well examined, there are still arguments about the mechanism and the overall process. The reagent is usually best described via the Schlenk equilibrium, but that is not only dependent on $\ce{X}$, but also on the solvent:
$$\ce{2RMgX <=> R2Mg + MgX2}$$
There also have been some dimeric structures reported, i.e. ...
12
It is known that $\ce{Mg}$ will reduce ketones. The articles (Ref.1 and 2) in the References section confirm this fact.
If you want to form the Grignard reagent of a molecule that also happens to contain a carbonyl group, then the usual practice is to protect it first. A cyclic ketal/acetal, which are stable under basic conditions, is often the first choice ...
10
The addition of Grignards to propargyl alcohols occurs via the alkoxide salt, after deprotonation:[1]
Here:
the reactivity may be explained by the stabilising influence of complexation;
the regioselectivity may be explained by the preference of a five-membered chelate ring over a four-membered one; and
the stereoselectivity arises because syn addition ...
9
Your approach, which uses $\ce{Br2}$ to convert 2-butene into 2,3-dibromobutane and react that with ethylmagnesium bromide $\ce{CH3CH2MgBr}$ has two flaws:
This approach removes the alkene and there is no obvious way to get it back (there is a way)
More seriously, Grignard reagents are pretty terrible for $\text{S}_N 2$ reactions. They are very strong bases,...
8
Here's the thing about Grignard reagents. Though we typically want them to do nucleophilic addition to something, these powerful bases tend to go for protons -- a faster reaction -- if there is just about anything that might make the proton vulnerable. Attaching the proton to an electronegative atom like nitrogen is enough, so primary and even secondary ...
8
Grignard reagents are capable of rearranging, especially in this situation where there is significant strain. The specific vinyl bromide you drew here has been studied: J. Org. Chem., 1974, 39 (10), pp 1411–1416. The table of data shown below is hard to read without including more of the text, but it was found that at 66 C in THF, after 5-10 minutes, 41% of ...
8
This paper says it does and notes that while the yield of alcohols from aliphatic Grignards is 60-90%, formation of phenols is much less satisfactory. Other methods exist for the formation of phenols from aryl organometallics with much better yields.
8
You get sulfinic acids $\ce{RSO2H}.$
This paper by Dowson et al. [1] states that Grignard plus $\ce{SO2}$ gives sulfinic acids and as a reference quotes an older article by Allen Jr. et al. [2] which states
The reaction between sulfur dioxide and Grignard reagent has been widely used for the preparation of aromatic and aliphatic sulfinic acids.
I would ...
8
In all likelihood the halide ion does attack the substrate. But, the product such a reaction mode would form does not accumulate whereas the alkylated product does.
Recall that in a nucleophilic reaction halide ions are good leaving groups, at least if you stay away from fluorides which are rarely used for Grignard reagents. So while the halide ion may add ...
8
Because the target structure contains the motif of a cyclohexane-1,2-diol, I suggest an approach including a Diels-Alder reaction (DA in the illustration below) of 1,3-butadiene and the commercially available diethyl acetal of propargyl aldehyde:
The hydrolysis of the acetal then sets the stage to install the methyl group with the cuprate and 1,4-...
7
I have prepared many aryl Grignards in my career. Generally the aryl bromide or iodide is easier than the chloride, but it can be done. THF is certainly fine for this, run under inert atmosphere, of course. Magnesium powder may prove to have more of an oxide film than turnings and hence be less reactive. Most Grignard preps use turnings. It might be helpful ...
6
According to this reference $\ce{HMgX}$ compounds are a thing. You can't make them with magnesium +$\ce{HX}$, of course (what actually happens?), but you can get them from magnesium halide salts plus an "active" form of magnesium hydride in THF. They act as hydride ion sources for reaction with $\ce{AlH3}$ and $\ce{BH3}$ (forming mixed ...
6
t-butanol + allyltrimethylsilane + Lewis acid
This is called the Hosoni-Sakurai Reaction (see J. Org. Chem. 2006 71 8516)
Can only find an image for the more common addition to carbonyl compounds but there are examples of additions to alcohols (see the JoC reference)
6
Nucleophilic acetyl substitution is common among carboxylic acid, acid chlorides, anhydrides, esters, and amides.
Two very common examples are anhydride decomposition and esterification of carboxylic acids. For example, if you look at esterification, carboxylic acid and alcohol first make an addition, giving tetrahedral intermediates 1 and 2. Intermediate 2 ...
answered Jun 11 '19 at 22:41
Mathew Mahindaratne
33.6k17 gold badges44 silver badges95 bronze badges
6
There are quite a few reasons why the episulfide might open before the epoxide:
Sulphur is less electronegative than oxygen. Therefore, by Bent's rule , more atomic s-character will be directed by the ring towards sulphur in the episulfide as compared to the oxygen in the epoxide. An increased s-character will lead to a bigger increase in the $\ce{C-S-C}$ ...
6
For the compound given in the question, the priority order of Grignard reagent attack follows,
$\ce{R-OH > R-CO-R' > R-COOR'}$
Reason:
Acid-base neutralisation are very fast.
Carbonyl carbon is more nucleophilic than carboxylic carbon, as the latter one is stabilized by resonance.
Therefore, first alcohol is attacked and hence P is (a), then the ...
5
As requested by the OP - the route that lab chemists use to form phenols from aryl halides (not aryl fluorides) is via formation of the aryl boronic acid or boronate. These may be formed by either metallation of the aryl halides to form the aryl lithium or Grignard and reaction with a trialkyl borate $\ce{B(OR)3}$, or by Pd catalysed reaction with pinacol ...
5
The $\ce{N-H}$ protons are relatively weakly acidic and this makes deprotonation kinetically less favored if an alternative nucleophilic attack mechanism is available. With $\ce{NH3}$ no such alternative is there, due to lack of a decent leaving group, so deprotonation ultimately prevails; but $\ce{NH2Cl}$ allows displacement of a chloride ion and thus ...
5
I am not sure if Gilman reagents are harder to make than Grignard but they are softer nucleophiles and so they are used to perform 1,4-(conjugate) additions on $\ce\alpha,\beta-$unsaturated electrophiles. Grignard reagents will generally go for 1,2-attack instead. See this Wikipedia article for more info:
5
Cyclobutyne cannot exist. There is no way to enforce 90° bends at both ends of a triple bond, but the carbanion formed by the Grignard reagent synthesis finds an easy way around this problem.
Let's say the magnesium reacts at position 1. Then the negative charge would couple with the conjugated triple bond to spread to position 3:
$\ce{Br\overset{+}{Mg}\...
5
There is no step 1 and step 2 in this reaction. Both are consecutive and second one is fast because it is an acid-base reaction:
Note that approximate $\mathrm{p}K_\mathrm{a}$ values of ring $\ce{C-H}$ and $\ce{N-H}$ are 50 and 40, respectively. Thus, as soon as Grignard reagent is formed, it exchanges relatively acidic protons of $\ce{N-H}$ fast (Remember, ...
answered Aug 17 '20 at 17:44
Mathew Mahindaratne
33.6k17 gold badges44 silver badges95 bronze badges
5
You seem to have got the uses of the compounds right, but could not bring that knowledge together to apply it here. As you said, you first use the Grignard to add a methyl group to D
Let's call this compound K. Then, we use $\ce{NaCN}$ to convert the alcohol into a nitrile, then to a carboxylic acid rather than an amide, as this would be easier to work with ...
4
In terms of regioselectivity, at least for the first addition of the Grignard reagent, I suggest to have a look on the cumarin, that may be seen as an α,β-unsaturated carbonyl compound. Hard nucleophiles (in terms of HSAB principle) like $\ce{MeLi}$ would almost exclusively react with the carbonyl carbon, as you drew in your reaction equation. Soft ...
4
Ben is right that your product is simple dimer of substrate. However, there is much easier approach to conduct dimersisation of butene - it happens easily if you use strongly acidic catalyst, like conc. sulfuric acid or ion-exchange resin, such reaction is used for example in production of isooctane. It's similar to cationic polymerization of alkenes, so ...
4
I've done this with aromatic Grignards, but I have no reference and no database access any longer.
I think when I did it, I was relying on an older colleague's instructions. It was pretty much generate your Grignard from ArBr + Mg in THF, cool in ice bath, stir vigorously and add elemental sulfur. You may need to introduce a reductive step as you can ...
4
Aromatic nitro groups are not compatible with Grignards as they react with the nitro group. An example of this being useful is the Bartoli synthesis of indoles from vinyl Grignards (Tet. Letts. 1989, 30 2129, Curr. Org. Chem.. 2005, 9, 163). The first step of the Bartoli is addition of the vinyl Grignard to the O of the N=O of the nitro group so I presume ...
Only top voted, non community-wiki answers of a minimum length are eligible