Acetals reaction with Grignard reagents

By reaction of 3-thienyllithium with magnesium bromide, the Grignard reagent, free from entrainment Grignard reagent, was obtained,- which is useful for the preparation of 3-acetothiophene by reaction with acetic anhydride at —70 0 and for the preparation of 3-t-butoxythiophene through reaction with t-butyl perbenzoate. It is the opinion of the present author that most 3-substituted thiophenes are prepared more conveniently from 3-thienyllithium than from 3-thenyl bromide. The latter method, however, is superior if the introduction of the 3-thenyl group is desired. 

By reaction of 3-thienyllithium with magnesium bromide, the Grignard reagent, free from entrainment Grignard reagent, was obtained,- which is useful for the preparation of 3-acetothiophene by reaction with acetic anhydride at — and for the preparation... 

A complete reversed selectivity has been observed by Yamamoto [46] who, more recently, reported the chemoselective reaction of prenyl Grignard reagent 73 with primary allylic chlorides 76, versus allylic acetates in the presence of CuCN -2LiCl at 0°C to give the 8 2 product 78 with high selectivity, as shown in Eq. (24). 

Dithiophosphinic acids are produced in good yield by the reaction of the perthiophosphinic anhydride (81) with Grignard reagents. Reaction of H2S with compounds containing a P—Cl bond can, in selected cases, provide a convenient route to phosphonothioates. Thus the adduct of acetal and phosphorus pentachloride gives (82) under these conditions, and the cyclic trimeric anhydride (83) is formed from the phosphonic chloride (84). ... 

Reaction with a,p-unsaturated acetals. Under catalysis with cuprous bromide, Grignard reagents condense with a ,j3-unsaturated acetals to give enol ethers (Z-isomers predominating). The products are hydrolyzed to aldehydes by acid. The reaction can be carried out with a- or j3-substituted a, unsaturated acetals. 

We follow acetal formation with the reactions needed to complete our synthesis Convert the hromoalkane functional group to the Grignard reagent, react with formaldehyde to add the necessary carhon atom, and protonate the resulting alkoxide with aqueous acid. 

Alkynyl anions are more stable = 22) than the more saturated alkyl or alkenyl anions (p/Tj = 40-45). They may be obtained directly from terminal acetylenes by treatment with strong base, e.g. sodium amide (pA, of NH 35). Frequently magnesium acetylides are made in proton-metal exchange reactions with more reactive Grignard reagents. Copper and mercury acetylides are formed directly from the corresponding metal acetates and acetylenes under neutral conditions (G.E. Coates, 1977 R.P. Houghton, 1979). 

Other Rea.ctlons, The anhydride of neopentanoic acid, neopentanoyl anhydride [1538-75-6] can be made by the reaction of neopentanoic acid with acetic anhydride (25). The reaction of neopentanoic acid with acetone using various catalysts, such as titanium dioxide (26) or 2irconium oxide (27), gives 3,3-dimethyl-2-butanone [75-97-8] commonly referred to as pinacolone. Other routes to pinacolone include the reaction of pivaloyl chloride [3282-30-2] with Grignard reagents (28) and the condensation of neopentanoic acid with acetic acid using a rare-earth oxide catalyst (29). Amides of neopentanoic acid can be prepared direcdy from the acid, from the acid chloride, or from esters, using primary or secondary amines. 

Ullmann condensation of the sodium salt of p-chlorothiophe-nol (31) with 2-iodobenzoic (32) acid gives 33. Cyclization by means of sulfuric acid affords the thioxanthone, 34. Reaction with the Grignard reagent from 3-dimethylaminopropyl chloride affords the tertiary carbinol (35). Dehydration by means of acetic anhydride affords chlorprothixene as a mixture of geometric isomers, 36. (Subsequent work showed the Z isomer-chlorine and amine on the same side—to be the more potent compound.) Chlorprothixene is said to cause less sedation than the phenothiazines. ... 

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