Chemical Intermediates, key functional building blocks - Nouryon

05 Jun.,2025

 

Chemical Intermediates, key functional building blocks - Nouryon

A chemical intermediate is reacted with other chemicals to obtain the desired product.

We have been focusing on the production of chemical intermediates owing to its wide application in various end-use industries such as agriculture, pharmaceuticals, pulp and paper, detergents, textiles and polymer productions.

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We operate world leading chemical intermediate product lines and supply various chemical intermediates from our state-of-art manufacturing facilities. The chemical intermediates products we supply are Ethylene amines, Sulfur products, Monochloroacetic Acid (MCA), Hydrogen peroxide and Sodium chlorate. These chemicals are widely used in agriculture, pharmaceuticals, pulp and paper, detergents, textiles and polymer productions.

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Chemical Intermediates - BOC Sciences

Products List Background

Introduction

Intermediates refer to substances generated during chemical reactions, typically compounds produced during the conversion of the starting substance into the target product. They have a shorter existence time and higher reaction activity, serving as a bridge connecting different reaction steps. They can be further converted into final products and can also be used to generate other intermediates. Intermediates are often used in organic chemical synthesis to carry or transfer chemical groups, introduce new functional groups, or extend chains to achieve specific synthesis routes.

Pharmaceutical intermediates (IM) are actually some chemical raw materials or products used in the process of drug synthesis. In drug research and development along with production, intermediates are so crucial that they represent a key step in converting active therapeutic molecules into final drug products. They do not require a drug production license and can be produced in ordinary chemical plants. As long as they reach a certain level, they can be used for drug synthesis. Optimizing the synthetic pathway of intermediates and reaction conditions can pave the way for high-performance drug production. As a professional biotech company, BOC Sciences has directed sincere efforts toward providing customers a broad range of quality pharmaceutical intermediates at very competitive costs.

Categories of Intermediates

There are many types of specific pharmaceutical intermediate products, incorporating imidazole, furan, phenolic, and aromatic intermediates. It also includes pyrrole, pyridine, biochemical reagents, sulfur, ammonia, and halogen compounds. Heterocyclic compounds, starch, mannitol, microcrystalline cellulose, lactose, dextrin, glycol, sugar powder, inorganic salts, ethanol intermediates, stearates, amino acids, ethanolamines, potassium salts, sodium salts, and various other intermediates are also encompassed within the range.

Classification by Application Field

According to the application classification, IMs can be divided into antibiotics, antipyretic and analgesic, cardiovascular system and anticancer pharmaceutical intermediates.

Classification by Source

  • Chemical Synthesis

This type of intermediates are compounds formed during drug synthesis, including various organic synthesis intermediates and reactants, such as alcohols, ketones, acids, esters, etc.

Landis et al. reported the enantioselective hydroformylation of 2-vinyl-6-methoxynaphthalene catalyzed by a chiral Rh-bisdiazaphospholane complex in a tubular flow reactor leading to a key chiral intermediate (15) of the nonsteroidal anti-inflammatory drug (S)-naproxene.

Fig. 1 Continuous flow enantioselective synthesis of a chiral naproxen precursor. (Ötvös, S. B., )

  • Biosynthesis

Biosynthetic intermediates are produced in the process of biosynthesis, such as metabolites produced in the process of fermentation and intermediates formed under the catalysis of biological enzymes. Biocatalysis often offers advantages over chemical synthesis as enzyme-catalyzed reactions are often highly enantioselective and regioselective. In addition, enzymes can be overexpressed to make biocatalytic processes economically efficient and enzymes with modified activity can be tailor-made by directed evolution for increased enzyme activity, selectivity and stability.

The preparation of enantiomerically pure nonnatural (S)-amino acids is of wide importance due to pharmaceutical applications thereof. (S)-β-hydroxyvaline is a key chiral intermediate required for the total synthesis of orally active monobactam. The synthesis of (S)-1 from α-keto-β-hydroxyisovalerate by reductive amination using leucine dehydrogenase from Bacillus sphaericus ATCC has been demonstrated. The NADH required for this reaction was regenerated by either formate dehydrogenase from Candida boidinii or glucose dehydrogenase from Bacillus megaterium. The required substrate 3 was generated either from α-keto-β-bromoisovalerate or its ethyl esters by hydrolysis with sodium hydroxide in situ. In this process, an overall reaction yield of 98% and an enantiomeric excess (e.e.) of 99.8% were obtained for the (S)- 1. The reaction was scaled up to 100 g/l of substrate input to prepare the desired compound (S)- 1.

Fig. 2 Enzymatic synthesis of (S)-b-hydroxyvaline. (Patel, R. N. )

  • Natural Source

Natural intermediates are compounds extracted from natural sources, such as plant extracts, animal tissue extracts and so on. These compounds are often used to prepare drugs with natural products or to synthesize drugs simulating natural products.

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Common Pharmaceutical Intermediates

Vitamin Intermediates

For example, sorbitol used to produce vitamin C, isophytol used to synthesize vitamin E and β-ionone, an important intermediate, have great market demand and broad prospects.

Benzene Ring Intermediates

This type of intermediates are intermediate products or molecules with benzene ring structure formed in chemical reactions. Benzene ring is a cyclic structure formed by six carbon atoms, which has stability and special electronic characteristics. It widely exists in organic compounds and many natural products, and plays an important role in synthesizing new compounds, constructing organic skeletons and adjusting molecular properties. Phenol and aniline are common benzene ring intermediates.

Heterocyclic Intermediates

Heterocyclic intermediates refer to cyclic molecules with at least one non-carbon atom (usually nitrogen, oxygen, sulfur, etc.) formed in chemical reactions. In organic synthesis, it is helpful to construct complex molecular skeleton and introduce specific functional groups, so as to realize the synthesis and adjustment of target compounds. The main heterocyclic compounds are imidazole, thiazole, triazole, pyridine, pyrimidine, piperazine and triazine and some of their derivatives.

Pyridine Intermediates

These are intermediate molecules with pyridine ring structure formed in chemical reactions. Pyridine is a six-membered heterocyclic ring consisting of five carbon atoms and one nitrogen atom. Its stability and unique electronic properties make these intermediates very valuable in building complex molecular skeletons, introducing specific functional groups and regulating molecular properties, and can be applied to the fields of organic synthesis and drug research and development. 4- aminopyridine is used to treat multiple sclerosis and myasthenia gravis, which can improve muscle control and relieve symptoms by increasing nerve conduction velocity.

Deuterated Intermediates

Deuterated intermediates refer to intermediate products or molecules containing deuterium (deuterium replaces hydrogen) formed in chemical reactions. Deuterium is an isotope of hydrogen, and its nucleus contains a proton and a neutron, which is heavier than the proton of ordinary hydrogen. Deuterated intermediates can be used to study reaction mechanism, change chemical properties and analyze nuclear magnetic resonance in the fields of organic synthesis and drug research and development. Deuterated anisole can be used to study the reaction mechanism, explore the ion exchange process and analyze the nuclear magnetic resonance spectrum (NMR).

Fluorine-Containing Compounds

The most successful application of introducing new elements into pharmaceutical intermediates is fluorine. At present, there are hundreds of fluorine-containing drugs at home and abroad, and many drugs have become the main varieties to treat certain diseases. Fluorine-containing drugs have the characteristics of low dosage, low toxicity, high efficacy and strong metabolic ability, and play an important role in the pharmaceutical industry.

Nucleotide Intermediates

Nucleotide intermediates refer to compounds with nucleotides as the basic structural unit, mainly used for synthesizing antiviral and anti-tumor drugs.

Chiral Compounds

Compounds obtained by asymmetric synthesis or resolution on the basis of stereochemistry. Chiral compounds have a wide range of uses and are a very important class of organic compounds.

With the development of biotechnology, new special enzymes and microbial strains for chiral product resolution have been developed, which can be used to produce various chiral amines, chiral amino acids and other chiral intermediate products.

Fig. 3 Representative biocatalysis using lyases. a. Production of 3-methyl-L-tyrosine from toluene with enzyme cascade combining P450 BM3 and tyrosine phenol lyase. b. D-substituted phenylalanines synthesis from cinnamic acids via an amination and deracemization cascade. c. The ammonia lyase EncP catalyzed methyl-β-phenylalanine sysnthesis. (Sun, H., )

Biological Compounds

Using DNA recombination technology, cell engineering technology and enzyme engineering technology to study and treat cardiovascular diseases, diabetes, hepatitis, tumors, anti-aging drugs, and applying modern biotechnology to transform the traditional pharmaceutical industry.

Pharmaceutical Intermediates and APIs

APIs: The active ingredients of drugs, which are the basic substances that constitute the pharmacological effects of drugs, and are prepared by chemical synthesis, plant extraction or biotechnology.

IMs: chemical raw materials or products used in the process of drug synthesis, which are intermediate products in the process of producing APIs and can be further processed into APIs.

  • Analyzing the definition, intermediates emerge as critical products in the initial process of manufacturing APIs and their structures differ from APIs.
  • Contemplating from the viewpoint of new drug development, APIs have undergone sufficient pharmaceutical research ensuring their safe usage for diagnosis and treatment. However, intermediates are merely compounds in the API synthesis process and may not necessarily possess therapeutic effects or toxicity. It's worth noting that some intermediates used in the synthesis of APIs also qualify as APIs.
  • Addressing drug management perspective, APIs are required to apply for a registration in accordance with local drug administration laws, and production can only commence after gaining the approval number in GMP-compliant factories. Conversely, intermediates are mere by-products in the API synthesis process and do not require an approval number.

Case Study

  • Case Study 1

Nucleoside 5'-triphosphate can be synthesized via a mixed P(III)-P(V) intermediate. The Huang research group reported a method based on the hypothesis that a bulky phosphitylation reagent would react selectively with the primary 5'-OH group versus the secondary 2'- and 3'-OH groups, thus avoiding extra steps of synthesis (introduction and removal of protecting groups). New reagent 183 was generated in situ through the reaction of salicylic chlorophosphite 180 with excess tetra(tri-n-butylammonium) pyrophosphate. Regioselective phosphitylation of the 5'-position of unprotected nucleosides generated the cyclic intermediates 184-187, which were oxidized by iodine in pyridine and water and subsequently hydrolyzed to give NTPs. Conversion was estimated to be about 10-50% of the crude material, and HPLC purification was subsequently carried out. This method was recently applied to the synthesis of ATP analogues.

Fig. 4 Synthesis of the cyclic intermediates. (Roy, B., )