BOC is the abbreviation of tert-butoxycarbonyl_industrial additives

BOC is the abbreviation of tert-butoxycarbonyl [Background and Overview]

In principle, amino groups can be reversibly shielded using reactions such as acylation, alkylation, and alkyl acylation. Protecting groups based on sulfur and phosphorus derivatives have also been reported. In the past 10 years, hundreds of different amino protecting groups have been developed, mainly including alkoxycarbonyl protecting groups, acyl protecting groups and alkyl protecting groups. Benzyloxycarbonyl (Z), tert-butoxycarbonyl (Boc), and 9-fluorenyloxycarbonyl (Fmoc) are the three most common amino protecting groups. The Z group is an amino protecting group that has been used for a long time and is still widely used today. Its advantage is that it is easy to prepare: the obtained Z-amino acid is easy to crystallize and stable, and is not easy to racemize during activation. The protecting group can be removed under conditions such as HBr/AcOH, Na/liquid ammonia and so on. The Fmoc group is the only widely used group among the carbamate amino acid protecting groups that can be dissociated under weak alkali conditions. Fmoc deprotection can be completed at room temperature using dilute piperidine solution or diethylamine/DMF solution.

Initially, Boc protecting groups were mainly used to protect amino groups in liquid phase peptide synthesis chemistry. Boc was subsequently developed to increase the yield of deprotection under mild conditions and to form gaseous or low boiling products. As a result of this development, Boc deprotection was almost quantitative, and the Boc group was soon used in solid-phase synthesis methods. Currently, in organic synthesis, especially peptide synthesis, Boc is still widely used as a protective group for amino groups through different stabilizing strategies such as Boc/Z and orthogonal strategies such as Boc/Fmoc. Tert-butoxycarbonyl (Boc ) has been widely used in organic synthesis as an important protective group for amino groups. Its deprotection is generally performed by using pure trifluoroacetic acid or its dichloromethane solution (the ratio of trifluoroacetic acid to dichloromethane ranges from 1:3 to 1:1). This method has the advantages of short reaction time, high yield and wide application range. However, the strong acidity can also easily lead to the decomposition of sensitive groups, and due to the large amount of trifluoroacetic acid used, Environmental pollution and high cost limit its use. Therefore, in recent years, people have begun to study many mild and selective reagents to remove the Boc protecting group on N. From the current environmental protection perspective, chemical reactions are required to be carried out by green chemistry methods as much as possible, and less auxiliary substances (organic solvents) are used. and additional reagents), consume less energy and generate less waste.

BOC is the abbreviation of tert-butoxycarbonyl [RemovalBOCMethod]

1. The more commonly used methods are as follows:

1) In the presence of strong acids such as HCOOH, HCl, HBr, TsOH, MsOH or Lewis acid, N-Boc removes the Boc protecting group;

2) In the presence of cerium(IV) ammonium nitrate or CeCl₃·7H₂O-NaI, N-Boc removes the Boc protecting group;

3) In the presence of SiO₂ or TBAF (tetrabutylammonium fluoride), N-Boc removes the Boc protecting group;

4) In the dichloromethane solution of HNO₃ or H₂SO₄, N -Boc removes the Boc protecting group;

5) Use alkaline conditions to remove the Boc protecting group, such as in Na₂CO₃ /DME /H₂O or K2CO₃ /MeOH/H₂O, heating and reflux reaction can remove the Boc protecting group on N in the ring of the heterocyclic system, etc. .

2. Green chemistry methods;

1) Use commercially available 85% H3PO4 lithium tetrafluoroborate aqueous solution as the deprotection reagent

In 2006, the American pharmaceutical company Pfizer reported that using 85% H₃PO₄ aqueous solution as a reagent, it can be used at room temperature and in the presence of a small amount of methylene chloride. Remove the Boc protecting group from N-Boc. The yield of this reaction is very high. The yield of most reactions is above 90%, and some even reach 100%:

At the same time, it was also found that 85% H3PO4 aqueous solution can remove tert-butyl ester and tert-butyl ether in the reactant, so the selectivity of the reaction is not high, but it is effective for other protective groups, such as acid-sensitive groups. TBMDS (tert-butyldimethylsilyl), Cbz (benzyloxycarbonyl) or benzyl ester have no effect. The advantages of this method are: ① The reaction conditions are mild, and the organic solvent used in the reaction can be used as an extraction solvent in post-processing, so the post-processing operation is simple; ② Commercially available 85% H₃PO₄Aqueous solution is very cheap, and its dosage in the reaction is small. It is a readily available and environmentally friendly non-toxic reagent of sodium bicarbonate. ③ There is no danger to operators and laboratories, and it is very safe; ④ It can Uses a variety of different reaction raw materials; 5. There are no side reactions and the yield is very high. Pfizer has applied it in scale-up production of several kilograms.

2) Use TFE or HFIP as solvent and microwave heating for deprotection

It was reported in 2008 that using TFE (2,2,2-trifluoroethanol) or HFIP (1,1,1,3,3,3-hexafluoroisopropanol) as the reaction solvent and microwave heating can quickly Remove the Boc protecting group on N-Boc:

It is worth pointing out that under the same reaction conditions, HFIP performs better than TFE. Under these reaction conditions, other protective groups such as the acid-sensitive groups TIPS (triisopropylsilyl) and TBMDS (tert-butyldimethylsilyl) as well as OAc, Cbz (benzyloxycarbonyl) and Benzyl ether, etc. have no effect. The advantages of this synthesis method: ① The yield is very high, most ofThe corresponding yields are all above 90%; ② The reaction time is short, and most reactions end within 2 hours; ③ Product separation and post-processing are very simple, just remove the reaction solvent and rinse the crude product with a suitable solvent The product is obtained; ④ High chemical selectivity; ⑤ No side reactions. TFE and HFIP recovered during the reaction can be easily reused.

3) Using H2O as solvent, no reagent is needed for deprotection

In 2009, it was reported that H2O was used as the reaction solvent without any other reagents. The N-Boc protecting group of aliphatic amine or aromatic amine was removed from the Boc protection to obtain the corresponding product amine. The reaction yield of all examples was basically 90 % or more, and some reaction yields even reach 99%. Chiral amines only obtain optically pure products after the reaction:

In this reaction, H₂O participates in the entire reaction process as a dual acid-base catalyst. The reaction mechanism they speculated is that when H₂O is heated to boiling, H The ionization of ₂O intensifies, producing more H ⁺ and OH^–, among which H ⁺ attacks the amino group The oxygen atom on the carbonyl group in the formate ester, and then OH ^– attacks the carbon atom on the carbonyl group to obtain a tetrahedral structure reaction intermediate geminal glycol. This compound eliminates the tert-butoxide anion to obtain carbamic acid , and then lose CO₂ and become the corresponding product. The advantages of this synthesis method are: 1) No need for any other reagents and safe reaction conditions; 2) High yield, no by-products; 3) Very good chemical selectivity, you can choose when there are two Boc protecting groups in the molecule One of them can be removed permanently; 4) The product is easy to separate and purify; 5) H₂O is used as the reaction solvent, which is readily available, very cheap, does not have any toxicity itself, and is harmless to the environment.

BOC is the abbreviation of tert-butoxycarbonyl [Application]

tert-butoxycarbonyl (Boc) is mainly used as an important protective group for amino groups and has been widely used in organic synthesis.

BOC is the abbreviation of tert-butoxycarbonyl [Main Reference Material]

[1] Ma Yongtao, Liu Xia, Zhou Ning, et al. Synthesis of tert-butoxycarbonyl-protected cyclic amino acids and their application in solid-phase synthesis of peptides [J]. International Journal of Pharmaceutical Research, 2014, 41( 2): 227-230.Use

[2] Lou Shaoxia. (2012). Research progress on green chemical methods for removal of N-Boc protecting groups. Chemical Engineering Times, 26(6), 40-42.

[3] Zhao Yan, Yao Jinshui, Dai Gang, & Hu Jianqiang. (2009). Introduction to the principles and methods of N-Boc protecting group removal. Journal of Shandong University of Light Industry (Natural Science Edition), 23(2) ), 6-7+.