Английская Википедия:4-Formylphenylboronic acid
4-Formylphenylboronic acid (4-FPBA) is a versatile synthetic building block and an important intermediate in the preparation of agrochemical and pharmaceutical active ingredients. The substance finds industrial application as a stabilizer and inhibitor for enzymes[1] and as a bactericide.
Synthesis
The synthesis of 4-formylyphenylboronic acid was reported by the group of Heinrich Nöth in 1990. 4-Bromobenzaldehyde was used as starting material.[2] The acetalization of the aldehyde group was carried out by standard methods[3] using diethoxymethoxyethane and ethanol to give 1-bromo-4-(diethoxymethyl)benzene. The formation of the Grignard compound with magnesium requires 1,2-dibromoethane and activation with ultrasound. Reaction with tri-n-butyl borate leads to the protected aryl boronic ester which gives after acidic work-up the target product in 78% yield.
The same reactants are forming with the aryl boronic ester at -60 °C 4-formylyphenylboronic acid with a 99% yield when activated with sodium bis(2-methoxyethoxy)aluminiumhydride, also on the kilogram scale.[4]
When the aryllithium compound of 1-bromo-4-(diethoxymethyl)benzene is used with triisopropylborate at -78 °C instead of the Grignard compound (via n-butyllithium) 4-formylphenylboronic acid is obtained in 99% crude yield.[5]
Disadvantages of both routes are the high price of the educts used (such as 4-bromobenzaldehyde, boronic esters of higher alcohols and butyllithium) as well as in the Nöth route the difficult workup after the hydrolysis by n-butanol. More recently, an improved process has been patented using less expensive starting materials such as 4-chlorobenzaldehyde, metallic lithium and trimethyl borate.[6]
4-Formylphenylboronic acid can also be prepared by hydrolysis of potassium 4-formylphenyl-trifluoroborate by means of acidic alumina[7] or silicon dioxide.[8] As a rule, phenylboronic acids serve as starting compounds for the corresponding potassium aryl trifluoroborates.[9]
Properties
4-Formylphenyl boronic acid crystallizes in colorless needles[2] or is obtained as an odorless, whitish powder, which dissolves little in cold but better in hot water. The compound is quite stable[4] and readily forms dimers and cyclic trimeric anhydrides, which complicate purification and tend to protodeboronize, a secondary reaction that occurs frequently in the Suzuki coupling, with elimination of the boronic acid function.[10]
Applications
4-Formylphenylboronic acid is used in Suzuki couplings, for example in the build up of pharmacologically active biphenyl compounds such as a precursor of the antihypertensive AT1 antagonist telmisartan in an improved synthesis:[11]
Also palladium-catalyzed aryl heteroaryl linkages after Suzuki use 4-formylphenylboronic acid as a molecular building block, as for instance in the synthesis of aryl-benzimidazole derivatives (which bind to peroxisome-proliferator-activated receptors (PPARγ) and activate the expression of a variety of genes):Шаблон:Cn
In a copper-mediated fluoroalkylation reaction, the boronic acid group of the 4-FPBA can be replaced with perfluorinated alkyl iodides (Rf-I) by a perfluoroalkyl chain under mild conditions.[12]
4-Formyphenylboronic acid is used industrially as an enzyme stabilizer for proteases and in particular for lipases in liquid detergent preparations.[1] The addition of 4-FPBA in amounts < 0.08 wt% in the formulation reduces the loss of hydrolytic activity of the enzymes used and increases the storage stability of enzyme-containing liquid detergents.[13]
References
- ↑ 1,0 1,1 Шаблон:Cite patent
- ↑ 2,0 2,1 Шаблон:Citation
- ↑ Autorenkollektiv, Organikum, 24. Auflage, S. 481, Wiley-VCH, Weinheim, 2001, Шаблон:ISBN
- ↑ 4,0 4,1 Шаблон:Citation
- ↑ Шаблон:Citation
- ↑ Шаблон:Cite patent
- ↑ Шаблон:Citation
- ↑ Шаблон:Citation
- ↑ Шаблон:Citation
- ↑ Шаблон:Citation
- ↑ Шаблон:Citation
- ↑ Шаблон:Citation
- ↑ Шаблон:Cite patent
