PEG for Chemical Synthesis

The application of PEG in chemical synthesis has a long history. It has been widely used in combinatorial chemistry and organic chemistry. It can provide homogeneous reaction conditions and has the advantages of easy purification and easy analysis. Therefore, using PEG as a solvent and/or catalyst has been increasingly applied in laboratory research and industrial production.

PEG as A Solvent

As a solvent, research in recent years tends to be "green" of PEG. With the excellent viscosity, low toxicity, thermal stability, low price, non-volatility, biodegradability, and environmentally friendly characteristics at both room temperature and high temperature, PEG has received more and more attention in synthetic chemistry and heterogeneous catalysis, such as Heck reaction, Suzuki coupling reaction, oxidation reaction, reduction reaction, addition reaction and asymmetric Aldo reaction.

  • Heck Reaction

Heck-ReactionFig 1. Chemical synthesis route of Heck reaction. (Organic letters 2002, 4 (25), 4399-4401)

Heck reaction refers to the reaction of halogenated hydrocarbons and activated unsaturated hydrocarbons to produce trans products under palladium catalysis. Using poly(ethylene glycol) (PEG) with molecular weight 2000 (or lower) as an efficient reaction medium for Pd-catalyzed C-C bond formation is more rapid and high yielding, and the catalyst is easily recycled with high efficiency.

  • Suzuki Reaction

Suzuki-ReactionFig 2. Chemical synthesis route of Suzuki reaction. (Journal of Molecular Liquids 2015, 207, 73-79)

Suzuki reaction (also known as Suzuki–Miyaura reaction) is a palladium catalyzed carbon–carbon bond formation between organoboron compounds with aromatic halides. The research reported in 2001 shown that this reaction was preceded in high yield in PEG400 as an inexpensive and non-toxic reaction medium.

  • Sonogashira Coupling Reaction

Sonogashira-Coupling-ReactionFig 3. Chemical synthesis route of Sonogashira reaction. (Journal of Molecular Liquids 2015, 207, 73-79)

Pd-catalyst carbon–carbon bond formation between a terminal alkyne and an aryl or vinyl halide is known as Sonogashira coupling reaction. The first study of this reaction was performed in PEG 6000 as reaction medium and a polymeric PEG-PdL catalyst with high catalytic reusability potential for ten times in the Sonogashira reaction of 4-bromoacetophenone and phenylacetylene.

  • Hiyama reaction

Hiyama-reactionFig 4. Chemical synthesis route of Hiyama reaction. (Journal of Molecular Liquids 2015, 207, 73-79)

The Hiyama-coupling is a palladium-catalyzed cross-coupling reaction of organosilanes with organic halides discovered by Hiyama and Hatanaka in 1988. In 2007, researchers first developed a fluoride-free catalyst system employing Pd(OAc)2 in a mixture containing 3 mL of H2O and 3 g of PEG2000 as solvent.

  • Ullmann's Homocoupling Reaction

Ullmann-s-Homocoupling-ReactionFig 5. Chemical synthesis route of homocoupling of aryl halides in PEG 4000. (Journal of Molecular Liquids 2015, 207, 73-79)

PEG 4000 is very useful for preparation of symmetrical biaryls is Ullmann homocoupling reaction of aryl halides(I and Br). In this reaction, PEG acts as solvent, phase transfer catalyst (PTC) and as a reducing agent. The flexibility of this catalytic system also provides suitable condition for cross coupling reactions of aryl iodide with aryl bromide.

  • Michael addition

Michael-additionFig 6. Chemical synthesis route of asymmetric Michael addition in PEG 400 as solvent. (Journal of Molecular Liquids 2015, 207, 73-79)

Asymmetric organocatalytic Michael reaction is a powerful tool for carbon–carbon bonds formation since the products participate in the important biologically active compounds. As shown in Fig 5, nitrostyrene substrates bear the β-aryl substituent with withdrawing -NO2 group gave the corresponding Michael derivative in quantitative yield with good diastereomeric ratios.

PEG as A Catalyst

In terms of catalysis, since the chain structure of PEG can be folded into holes of different sizes, the chain links can be folded into spiral and free sliding chains to form a shape similar to crown ether, so it can complex with metal ions of different sizes to carry out the phase transfer catalytic reaction. Although the reaction effect is not good in liquid-liquid phase, it still has a good catalytic effect on the reaction of sodium, potassium and other metal salts. For reactions involving different salts, PEG 400-1000 is a commonly used phase transfer catalyst (PTC). Studies have shown that PEG 400, due to its moderate molecular weight, especially the high relative ratio of two polar terminal hydroxyl groups, is more suitable for catalyzing sodium and potassium salts in many liquid-liquid, gas-liquid, and gas- solid, solid-liquid two-phase organic chemical reactions. Because of the strong water solubility, the catalyst and salt by-products can be easily washed away with water after the reaction is completed, greatly simplifying the post-processing.

  • Williamson Ether Synthesis

Williamson synthesis is a method of preparing mixed ethers. It is an important nucleophilic substitution reaction (SN2) and involves the synthesis of an ether using an alkyl halide and an alkoxide in an alcoholic solvent. The novel Williamson reaction has been successfully conducted in a liquid–solid or liquid–liquid biphasic system using PEG as PTC with or without organic solvent. The yield of decan-1-ol during etherification using PEG-2000 as PTC is equal to that found by using 18-crown-6, and higher than that found by using cryptand, which are both expensive and toxic.

  • Substitution Reactions

One of the most common reactions for the application of PEGs as PTCs is in nucleophilic substitution reaction. For example, the diaryl 1,4-phenylenedioxydiacetic acid and diaryl 1,4-phenylenedioxydiacetate synthesis using PEG 400 as PTC showed good to excellent yields under mild conditions, with short reaction times and simple operation. N-Acylation reactions, normally considered difficult, could be conducted using PEG 400 as PTC with high yield.

  • PEG-supported PTC

Apart from its own catalytic activity, PEG has also been used as a polymer support for other PTCs. PEG has been modified with some typical PTCs such as crown ethers, ammonium salts, cryptands, and polypodands to enhance phase-transfer in two-phase reactions. For instance, 16-crown-5, 19-crown-6, and 18-crown-6 ethers have been attached to PEG 3400 and PEG 6800 and demonstrated effective transfer of metal picrates from H2O into CH2Cl2, which were able to catalyze the reaction of CH3COOK with benzyl bromide.


  1. Chen, J.; Spear, S. K.; Huddleston, J. G.; Rogers, R. D., Polyethylene glycol and solutions of polyethylene glycol as green reaction media. Green Chemistry 2005, 7 (2), 64-82.
  2. Chandrasekhar, S.; Narsihmulu, C.; et al. Poly (ethylene glycol)(PEG) as a reusable solvent medium for organic synthesis. Application in the Heck reaction. Organic letters 2002, 4 (25), 4399-4401.
  3. Vafaeezadeh, M.; Hashemi, M. M., Polyethylene glycol (PEG) as a green solvent for carbon–carbon bond formation reactions. Journal of Molecular Liquids 2015, 207, 73-79.

Why BOC Sciences?

  • Large Stock

    More than 2000+ products in inventory

  • Global Delivery

    Warehouses in multiple cities to ensure fast delivery

  • mg to kg

    Multi specification for academic research and industrial production

  • 24/7 Technical Support

    Strict process parameter control to ensure product quality



Our Feature

BOC Sciences supplies a unique variety of PEG derivatives and functional PEG polymers. Our products offer the most diverse collection of reactivity, ready-to-use functionality, and molecular weight options that you will not find anywhere else.

  • Our Feature icon1
  • Our Feature icon2
  • Our Feature icon3
  • Our Feature icon4
PEGylation of Peptides and Proteins

PEGylation of Peptides
and Proteins

Reduce the Immunogenicity of Peptide/Protein Drugs

Learn More



PEG linkers For Drug

Improved Circulation Half-Life

Learn More

Have Customer Reviewed On Us?


Chat With Us

Online Inquiry

Verification code

Copyright © 2024 BOC Sciences. All rights reserved.