“4-Formylphenylboronic acid”的意思、由来-开放百科全书

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)aluminumhydride, 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):^[12]

In a copper-mediated fluoroalkylation reaction, the boronic acid group of the 4-FPBA can be replaced with perfluorinated alkyl iodides (R_f-I) by a perfluoroalkyl chain under mild conditions.^[13]

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.^[14]

References

1. ^¹{{cite patent|country = US|V-Nr =5972873 |Code= |title=4-Substituted-phenyl-boronic acids as enzyme stabilizers |V-Datum =1999-10-26 |A-Datum =1997-11-21 |inventor =L.K. Nielsen, A. Deane-Wray | assign1 =Novo Nordisk A/S | DB =Google}}
2. ^¹{{citation|author1=H. Feulner|author2=G. Linti|author3=H. Nöth|periodical=Chem. Ber.|title=Beiträge zur Chemie des Bors, 206. Darstellung und strukturelle Charakterisierung der p-Formylbenzolboronsäure|volume=123|issue=9|pages=1841–1843|date= 1990|language=German|doi=10.1002/cber.19901230915}}
3. ^Autorenkollektiv, Organikum, 24. Auflage, S. 481, Wiley-VCH, Weinheim, 2001, {{ISBN|978-3-527-33968-6}}
4. ^¹{{citation|author1=H. Jendralla|author2=A. Wagner|author3=M. Mollath|author4=J. Wunner|periodical=Liebigs Ann. Chem.|title=Efficient, simple procedures for the large-scale preparation of buildings blocks for angiotensin (II) receptor antagonists|volume=1995|issue=7|pages=1253–1257|date= 1995|doi=10.1002/jlac.1995199507166}}
5. ^{{citation|author1=Y. Kobayashi|author2=Y. Tokoro|author3=K. Watatani|periodical=Tetrahedron Lett.|title=Preparation of functionalized zinc borates and their coupling reactions with allylic acetates|volume=39|issue=41|pages=7537–7540|date= 1998|doi=10.1016/s-0040-4039(98)01639-6}}
6. ^{{cite patent|country = US|V-Nr =6833470 |Code=B2 |title=Method for producing formylphenylboronic acids |V-Datum =2004-12-21|A-Datum =2001-11-30 |inventor =A. Meudt, S. Scherer, F. Vollmüller, M. Erbes |assign1 =Clariant GmbH | DB =Google}}
7. ^{{citation|author1=G.W. Kabalka|author2=V. Coltuclu|periodical=Tetrahedron Lett.|title=Thermal and microwave hydrolysis of organotrifluoroborates mediated by alumina|volume=50|issue=46|pages=6271–6272|date= 2009|doi=10.1016/j.tetlet.2009.09.008}}
8. ^{{citation|author1=G.A. Molander|author2=L.N. Cavalcanti|author3=B. Canturk|author4=P.-S. Pan|author5=L.E. Kennedy|periodical=J. Org. Chem.|title=Efficient hydrolysis of organotrifluoroborates via silicagel and water|volume=74|issue=19|pages=7364–7369|date= 2009|doi=10.1021/jo901441u}}
9. ^{{citation|author1=E. Vedejs|author2=R.W. Chapman|author3=S.C. Fields|author4=S. Lin|author5=M.R. Schimpf|periodical=J. Org. Chem.|title=Conversion of arylboronic acids into potassium aryltrifluoroborates: convenient precursors of arylboron difluoride Lewis acids|volume=60|issue=10|pages=3020–3027|date= 1995|doi=10.1021/jo00115a016}}
10. ^{{citation|author1=G.K. Surya Prakash|author2=F. Pertusati|author3=G.A. Olah|periodical=Synthesis|title=HF-free, direct synthesis of tetrabutylammonium trifluoroborates|volume=2011|issue=2|pages=292–302|date= 2011|doi=10.1055/s-0030-1258370}}
11. ^{{citation|author1=A. S. Kumar|author2=S. Ghosh|author3=G.N. Mehta|periodical=Beilstein J. Org. Chem.|title=Efficient and improved synthesis of Telmisartan|volume=25|pages=6|date= 2010|doi=10.3762/bjoc.6.25}}
12. ^{{citation|author1=G. Singh|author2=A. Singh|author3=V. Singh|author4=R.K. Verma|author5=R. Mall|periodical=WJPPS|title=Novel benzimidazole derivatives as partial PPARγ agonists: synthesis, characterization, and docking studies|volume=5|issue=7|pages=1080–1091|date= 2016|doi=10.20959/wjpps20167-7143}}
13. ^{{citation|author1=Q. Qi|author2=Q. Shen|author3=L. Lu|periodical=J. Am. Chem. Soc.|title=Copper-mediated aerobic fluoroalkylation of arylboronic acids with fluoroalkyl iodides at room temperature|volume=134|issue=15|pages=6548–6551|date= 2012|doi=10.1021/ja301705z}}
14. ^{{cite patent|country = US|V-Nr =20130252315 |Code=A1 |title=Stabilized, liquid, enzyme-containing surfactant preparation |V-Datum =2013-9-26 |A-Datum =2013-5-14 |inventor =T. O’Connell, S. Tondera, T. Weber | assign1 =Henkel AG & Co. KGaA | DB =Google}}