Ketone Grignard reaction

With l,4,6-triene-3-ones, addition occurs exclusively at the 1,2-double bond to yield la-methyl-A -S-ketones. Grignard reaction and reacetylation of 17)5-acetoxyandrosta-l,4,6-trien-3-one (23) gives the la-methyl-4,6-dien-3-one (24) in a crude yield of 85%. ° ... 

Type of reaction C-C bond formation Reaction condition solid-state Keywords ketone, Grignard reaction, alcohol... 

Nucleophilic Addition to Ketones Grignard reaction Reduction ketone to alcohol via hydrosilylation... 

Section 20 20 Nitriles are useful starting materials for the preparation of ketones by reaction with Grignard reagents... 

Barbier reported (1) in 1899 that a mixture of methyl iodide, a methyl ketone, and magnesium metal in diethyl ether produced a tertiary alcohol. Detailed studies by his student Victor Grignard are documented in his now classical doctoral thesis, presented in 1901. Grignard estabUshed (2) that the reaction observed by Barbier could be separated into three distinct steps Grignard reagent formation, Grignard reaction, and hydrolysis. 

With care, the monosubstituted Grignard reagent can be formed and it reacts with aldehydes and ketones to produce carbinols (see Grignard reactions). 

Reactions of titanium alkyls with aldehydes and ketones are generally more stereospecific and selective than the corresponding Grignard reactions (416). 

Addition of hydrogen cyanide to an aldose to form a cyanohydrin is the first step in the Kiliani-Fischer method for increasing the carbon chain of aldoses by one unit. Cyanohydrins react with Grignard reagents (see Grignard reaction) to give a-hydroxy ketones. 

Although cholest-4-en-3-one does not give a 1,4-addition product in the cuprous chloride-catalyzed Grignard reaction,the A ° -5a-2-ketone (35) reacts to give the 10a-methyl-5a-2-ketone (36). ... 

Unprotected cyanohydrins cannot be used in the Grignard reaction because of reversal to the starting ketone. However, recently" it has been... 

Cyclic enamines with an isomeric position of the double bond have been obtained by the addition of Grignard reagents to five- (78-81), six- (82-86), seven- (87-90), and thirteen- (89-91) membered lactams, whereas other medium-sized (92,93) lactams furnished amino ketones. The reaction has been extended to substituted lactams (94-98), and iminoethers (99,100). 

The classical Reformatsky reaction consists of the treatment of an a-halo ester 1 with zinc metal and subsequent reaction with an aldehyde or ketone 3. Nowadays the name is used generally for reactions that involve insertion of a metal into a carbon-halogen bond and subsequent reaction with an electrophile. Formally the Reformatsky reaction is similar to the Grignard reaction. 

Preparation of the key intermediate to this series begins by reduction of the methylene phthalide, 12a, with hydriodic acid and red phosphorus. Cyclization of the acid (26) thus obtained affords the tricyclic ketone, 27. Reaction with the Grignard reagent from 3-dimethylamino-2-methylpropyl chloride affords the... 

Nitromifene (85) is such an agent. A Grignard reaction of aryl ether and ketone leads to tertiary carbinol Tosic acid dehydration leads to a mixture of 1 and stilbenes which constitute the antiestrogen, nitromi fene (85)... 

Phthalic anhydride is reacted with phenylacetic acid to form 3-benzylidenephthalide which is then hydrogenated to 2-phenethylbenzoic acid. Conversion to the acid chloride followed by intramolecular dehydrochlorination yields the ketone, 5H-dibenzo[a,d] cyclohepten-5-one. The ketone undergoes a Grignard reaction with 3-(dimethylamino)propyl chloride to give 5-(7-dimethylaminopropylidene)-5H-dibenzo[a,d] cycloheptene. 

The ketone, preferably prepared by a Grignard reaction, was added in such a way as to maintain the ether under constant reflux. When all of the solution had been added, the mixture was refluxed for a further hour. The mixture was then allowed to stand for 12 hours at ambient temperature, after which the reaction mass was extracted with ice and ammonium chloride in known manner. 

Formation of an Alcohol The simplest reaction of a tetrahedral alkoxide intermediate is protonation to yield an alcohol. We ve already seen two examples of this kind of process during reduction of aldehydes and ketones with hydride reagents such as NaBH4 and LiAlH4 (Section 17.4) and during Grignard reactions (Section 17.5). During a reduction, the nucleophile that adds to the carbonyl... 

Formation of C—Nu The second mode of nucleophilic addition, which often occurs with amine nucleophiles, involves elimination of oxygen and formation of a C=Nu bond. For example, aldehydes and ketones react with primary amines, RNH2, to form imines, R2C=NR. These reactions proceed through exactly the same kind of tetrahedral intermediate as that formed during hydride reduction and Grignard reaction, but the initially formed alkoxide ion is not isolated. Instead, it is protonated and then loses water to form an imine, as shown in Figure 3. 

A Grignard reaction begins with an acid-base complexation of Vfg2+ to the carbonyl oxygen atom of the aldehyde or ketone, thereby making the carbonyl group a better electrophile. Nucleophilic addition of R then produces a tetrahedral magnesium alkoxide intermediate, and protonation by addition of water... 

Mechanism of the Grignard reaction. Nucleophilic addition of a carbanion to an aldehyde or ketone, followed by protonation of the alkoxide intermediate, yields an alcohol. 

How would you use a Grignard reaction on an aldehyde or ketone to synthesize the following compounds ... 

Among the most useful reactions of nitriles are hydrolysis to yield first an amide and then a carboxylic acid plus ammonia, reduction to yield an amine, and Grignard reaction to yield a ketone (Figure 20.3). 

The mechanism of this Grignard reaction is similar to that of L1AIH4 reduction. The first equivalent of Grignard reagent adds to the acid chloride, loss of (T from the tetrahedral intermediate yields a ketone, and a second equivalent of Grignard reagent immediately adds to the ketone to produce an alcohol. 

Conversion of Esters into Alcohols Grignard Reaction Esters and lactones react with 2 equivalents of a Grignard reagent to yield a tertiary alcohol in which two of the substituents are identical (Section 17.5). The reaction occurs by the usual nucleophilic substitution mechanism to give an intermediate ketone, which reacts further with the Grignard reagent to yield a tertiary alcohol. 

Acid chloride—con l d esters from, 802-803 from carboxylic acids, 794-795 Grignard reaction of, 804-805 hydrolysis of, 802 IR spectroscopy of, 822-823 ketones from, 805 mechanism of formation from carboxylic acids, 795 naming, 786... 

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