Preparation method of o-aryl primary amide

Abstract

The invention relates to a preparation method of o-aryl primary amide, which comprises the steps of mixing alpha-silicon nitrile and aryl sulfoxide in a solvent, adding acid, stirring, heating to the temperature of 40-80 DEG C, stirring, and reacting to obtain the o-aryl primary amide, wherein the chemical structural formula of the alpha-silyl nitrile is shown in the description, Si is a silyl group selected from a trimethylsilyl group, a tert-butyl dimethyl silyl group, a dimethyl phenyl silyl group, a triethyl silyl group, a triisopropyl silyl group or a tert-butyl diphenyl silyl group; R1 is substituted or unsubstituted alkyl; the chemical structural formula of the aryl sulfoxide is shown in the description, Ar is a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group or a substituted or unsubstituted aromatic heterocyclic ring; R2 is a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group, a substituted or unsubstituted heteroaromatic ring, or a substituted or unsubstituted alkyl group; and the chemical structural formula of the o-aryl primary amide is shown in the description.

Description

technical field [0001] The invention relates to the field of organic synthesis, in particular to a preparation method of ortho-aryl primary amides. Background technique [0002] Primary amides (RCONH 2 ) is a very important organic functional group, not only often used as a synthetic intermediate, but also widely present in a variety of natural products, bioactive molecules and drugs. [0003] One of the methods for preparing primary amides in the prior art is to use a compound containing a nitrile group to obtain it by hydrolysis under strong acid or strong alkali conditions. The disadvantage of this method is that it is not easy to control the amide stage, because the amide is easy to continue to hydrolyze to produce a carboxylate that is not easy to separate. Acids, or other by-product impurities; and many functional groups are not resistant to strong acids and strong bases, so the functional group compatibility of this type of reaction is not high (Org. Process Res. Dev...

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Problems solved by technology

[0003] One of the methods for preparing primary amides in the prior art is to use a compound containing a nitrile group to obtain it by hydrolysis under strong acid or strong alkali conditions. The disadvantage of this method is that it is not easy to control the amide stage, because the amide is easy to continue to hydrolyze to produce a carboxylate that is not easy to separate. Acids, or other by-product impurities; and many functional groups are intolerant to strong acids and bases, so the functional group compatibility of this type of reaction is not high (Org. Process Res. Dev., 2019, 23, 1918-1925)

[0004] In addition, a widely used in the preparation of o-aryl tertiary amides in the prior art The most common method is to use transition metal catalyzed ortho arylation of amides (J.Am.Chem.Soc., 2006, 128, 4976-4985), but this type of technology is limited to tertiary amide substrates without hydrogen on the nitrogen, if Nitrogen contains hydrogen, and arylation will preferentially occur on nitrogen (Org. Lett., 2000, 2, 1101-1104)

There is also a recent technique to prepare ortho-aryl secondary amides using a temporary protecting group strategy, but this technique is ineffective for ortho-aryl primary amides (J.Am.Chem.Soc.,2019,141,11749-11753)

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