Phenol formylation

REIMER TIEMANN Phenol formylation 314 REISSERT-GROSHEINTZ FISCHER Cyanoamme reaction 315 REPPE Acetylano reaction 3t6 von RICHTER Aromatic carboxylalion 317 von RICHTER - WIDMAN - STOERMER Cmndme synthesis 3t8 RILEY Selenaim dioxide oxidation 319 Rimmi 4... 

In the cases of phenols, formylations by CO / HF / BF3 system require pressures of carbon monoxide of about 50 to 100 bars to obtain good yields (refs. 12, 13) (Fig. 4). 

Attempted phenol formylation with excess aluminum trichloride did not yield any aldehyde products, even at elevated CO pressures and extended reaction times (Table... 

Aromatics containing electron releasing groups such as phenols, dim ethyl am in oben 2en e and indole are formylated by 2-ethoxy-l,3-dithiolane in the presence of boron trifluoroetherate, followed by hydrolysis (114). The preformed dithiolanium tetrafluoroborate also undergoes Friedel-Crafts reaction with aromatics such as dim ethyl am in oben 2en e and indole (115), and was used to generate dithiolanium derivatives (formyl precursors) from the enoltrimethylsilyl ether derivatives (116). 

Formylation of phenols and anilines with hexanethylane tetramine. 

REIMER - TIEMANN Phenol Pormylation Formylation ot phenols with CHCt3-base (dichiorocarbene)... 

Tetramethoxyisoflavone (5) was the target of the cyclisation reaction of 3,4-dimethoxy-phenol (7) with formyl-(3,4-dimethoxyphenyl)acetic acid (2) in the presence of polyphosphoric acid. 

The idea that dichlorocarbene is an intermediate in the basic hydrolysis of chloroform is now one hundred years old. It was first suggested by Geuther in 1862 to explain the formation of carbon monoxide, in addition to formate ions, in the reaction of chloroform (and similarly, bromoform) with alkali. At the end of the last century Nef interpreted several well-known reactions involving chloroform and a base in terms of the intermediate formation of dichlorocarbene. These reactions included the ring expansion of pyrroles to pyridines and of indoles to quinolines, as well as the Hofmann carbylamine test for primary amines and the Reimer-Tiemann formylation of phenols. 

The Reimer-Tiemann formylation of several phenols in the quinohne and pyrimidine series is known, but the reaction is unsuccessful with hydroxypyridines 3-hydroxypyridine gave a polymer. No 2-hydroxyquinoline appears to have been studied the 4-hydroxy... 

The applicability of the Gattermann synthesis is limited to electron-rich aromatic substrates, such as phenols and phenolic ethers. The introduction of the formyl group occurs preferentially para to the activating substituent (compare Friedel-Crafts acylation). If the /jara-position is already substituted, then the ort/zo-derivative will be formed. 

The formylation of a phenol 1 with chloroform in alkaline solution is called the Reimer-Tiemann reaction. It leads preferentially to formation of an ortho-formylated phenol—e.g. salicylic aldehyde 2 —while with other formylation reactions, e.g. the Gattermann reaction, the corresponding /jara-formyl derivative is obtained as a major product. The Reimer-Tiemann reaction is mainly used for the synthesis of o-hydroxy aromatic aldehydes. 

In alkaline solution, the phenol 1 is deprotonated to the phenolate 4, which reacts at the ort/zo-position with dichlorocarbene 3. The initial addition reaction product 5 isomerizes to the aromatic o-dichloromethyl phenolate 6, which under the reaction conditions is hydrolyzed to the o-formyl phenolate." ... 

The applicability of the Reimer-Tiemann reaction is limited to the formylation of phenols and certain reactive heterocycles like pyrroles and indoles. Yields are usually below 50%. In contrast to other formylation procedures, the Reimer-Tiemann reaction is ort/zo-selective it is therefore related to the Kolb e-Schmitt reaction. 

With respect to aromatic substrates, the Vilsmeier formylation reaction works well with electron-rich derivatives like phenols, aromatic amines and aromatic heterocycles like furans, pyrroles and indoles. However various alkenes are also formylated under Vilsmeier conditions. For example the substituted hexatriene 6 is converted to the terminal hexatrienyl aldehyde 7 in 70% yield ... 

Synthesis of the remaining half of the molecule starts with the formation of the monomethyl ether (9) from orcinol (8). The carbon atom that is to serve as the bridge is introduced as an aldehyde by formylation with zinc cyanide and hydrochloric acid (10). The phenol is then protected as the acetate. Successive oxidation and treatment with thionyl chloride affords the protected acid chloride (11). Acylation of the free phenol group in 7 by means of 11 affords the ester, 12. The ester is then rearranged by an ortho-Fries reaction (catalyzed by either titanium... 

Mn(II) > Mg(II).270 It should be underlined that titanium and zirconium alkoxides are efficient catalysts for both stages of reaction. Lanthanide compounds such as 2,2/-bipyridyl, acetylacetonate, and o-formyl phenolate complexes of Eu(III), La(III), Sm(III), Er(III), and Tb(III) appear to be even more efficient than titanium alkoxides, Ca or Mn acetates, Sb203, and their mixtures.273 Moreover, PET produced with lanthanides has been reported to exhibit better thermal and hydrolytic stability as compared to PET synthesized with the conventional Ca acetate -Sb203 catalytic system.273... 

Formaldehyde-to-phenol ratios, 404 V-Formyl amines, 158 Fourier transform infrared (FTIR) spectrometry, 116, 300, 387, 407-408 Fradet, Alain, 17 Free-radical copolymerization, 59 Friedel-Crafts acrylation polymerization, 332-334... 

Auch Li t hi urn a I ana t reduziert die o- und p-standig mit elektronenliefemden Gruppen (z.B. Amino, Dial-kylamino, Methoxy) substituierten aromatischen Aldehyde und Ketone mcist nur unter cncrgischen Bedingun-gen zu Kohlenwasserstoffen (z. B. in Dibutylather mehrere Tage bei 80-90°). Formyl- und Acyl-phenole werden nicht reduziert1. 

The reaction with disubstituted formamides and phosphorus oxychloride, called the Vilsmeier or the Vilsmeier-Haack reaction,is the most common method for the formylation of aromatic rings. However, it is applicable only to active substrates, such as amines and phenols. An intramolecular version is also known.Aromatic hydrocarbons and heterocycles can also be formylated, but only if they are much more active than benzene (e.g., azulenes, ferrocenes). Though A-phenyl-A-methyl-formamide is a common reagent, other arylalkyl amides and dialkyl amides are also used. Phosgene (COCI2) has been used in place of POCI3. The reaction has also been carried out with other amides to give ketones (actually an example of 11-14),... 

Formylation with Zn(CN)2 and HCI is called the Gatterman reaction It can be applied to alkylbenzenes, phenols and their ethers, and many heterocyclic compounds. However, it cannot be applied to aromatic amines. In the original version of this reaction, the substrate was treated with HCN, HCI, and ZnCl2, but the use of Zn(CN)2 and HCI (HCN and ZnCF are generated in situ) makes the reaction more... 

The Gattermann-Koch formylation was found unsuited to the preparation of aldehydes from phenols and phenol ethers such aldehydes may be obtained by Gattennann s aldehyde reaction. 

An attempt to formylate phenol by heating a mixture with nitromethane and aluminium chloride in an autoclave under carbon monoxide at 100 bar pressure at 110°C led to a high-energy explosion after 30 min. 

Aldred, R. Johnston, R. Levin, D. Neilan, J. Magnesium-mediated ortho-specific formylation and formaldoxima-tion of phenols. J. Chem. Soc., Perkin Trans. 1 1994, 1823-1831. 

In this route a dihydroisoquinoline (58) is N alkylated with a highly functionalized o -bromoacetophenone (59) to give a quaternary salt (60), which is treated with base and cyclizes to a pyrroloisoquinoline (60). The pyrrole nucleus is then formylated under Vilsmeier-Haack conditions at position 5 and a proximate mesylated phenolic group is deprotected with base to yield a pen-tasubstituted pyrrole (61). Subsequent oxidative cyclization of this formylpyr-role produces the 5-lactone portion of lamellarin G trimethyl ether (36). This sequence allows for rapid and efficient analog synthesis as well as the synthesis of the natural product. 

Alkyl-substituted phenols and alkanes were also oxidized to give the corresponding oxygenated products. In the case of isophorene, 3-formyl-5,5-dimethyl-2-cyclohexen-l-one was obtained selectively [110], The regioselectivity of the oxidation was remarkably different from that observed with the corresponding homogeneous analog, which produced 1,4-diketone as a major product [110] ... 

In 1983, Nixon and Scheimann reported that 2-acyl(or formyl, methoxycarbonyl)-phenol can add to 4-(methoxycarbonyl)-2,3-butenoate to yield 4-(methoxycarbonyl)-3-(phenoxy)-3-buteneate 522. o-Hydroxyphenyl ketone, o-hydroxybenzaldehyde or o-hydroxybenzoic acid esters reacted with 4-methoxycarbonyl-2,3-butenoate in a... 

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