CONTRACTED SYNTHESIS

Improvement of crystal shape by improving crystallization conditions

We consider the optimization of reaction conditions and crystallization conditions using a reaction vessel and stirring blade with a shape similar to that of the actual machine. On the lab scale, we check how the reaction speed and product quality are affected by the difference in the stirring blade, and consider necessary measures.
Since we have a lot of knowledge about improving the crystal shape, we can control the crystal shape and particle size distribution by making full use of various crystallization processes such as evaporation crystallization, cooling crystallization, and poor solvent crystallization, allowing us to shorten the separation time and drying time and to improve handleability at the time of customer use.

Development using inline analysis equipment

We conduct research and development utilizing process analysis technology (PAT), which measures by inserting a probe directly into the system. It is possible to measure changes in the particle size distribution and the number of particles, and to see the particles being crystallized in real time using an in-line particle size distribution meter. The reaction trend can be monitored by continuously measuring a specific wavelength with IR, and important information can be quickly obtained in advancing research and development and optimization of the reaction process. It is especially useful for reaction tracking in systems where sampling is difficult, and for optimization studies in systems where the crystal shape changes continuously, such as crystal polymorph.

Safe formulation design through calorimetric measurement

Hazard prediction and safe process development during scale-up is carried out efficiently by utilizing calorimetric measurement equipment such as RC-1 and DSC. It is of utmost importance to design a process with well-controlled reactions. We develop safe processes based on data such as accumulation of unreacted substances, heat generation behavior, and heat removal capacity of manufacturing facilities.
We consider the identification of issues associated with scale-up, such as heat generation due to reactions and prediction of quality effects due to extended process time, and the countermeasures.

Liquid-phase air oxidation

Liquid-phase air oxidation is a core technology that uses special equipment and uses oxygen in the air as an oxidizing agent. It has a long track record of use for supplying a wide range of carboxylic acid derivatives. We also use this technology to supply distinctive functional polymer materials.

Characteristics

• Environmentally friendly oxidation method that uses oxygen in the air as an oxidizing agent
• Unlike chemical oxidation, it can be used to perform synthesis using a small amount of catalyst
• AWPC　has special equipment
• AWPC has extensive experience in avoiding explosion limits

Acid anhydride development

We can provide various acid dianhydrides, which are polyimide monomers, by using our expertise with liquid-phase air oxidation and coupling reactions.

Patents held by AWPC

(1) JP 5280115 B2 "Method for producing p-phenylenebis (trimellitic acid monoester anhydride)"
(2) JP 5432605 B2 "Method for producing aromatic carboxylic acid dianhydride with ester radicals"
(3) JP 5525216 B2 "Method for producing trimellitic anhydride diester"

Proposal of processes

We propose efficient processes for the chemicals you desire, based on our abundant accumulation of synthesis and refining technologies for fine chemical products such as electronic materials and agrochemicals.

Examples

① Development of manufacturing method for rational process

We have developed a unique method to introduce a nitro group directly at the 7-position without altering the indole structure.

Conventional method ① Derived from nitrobenzenes

An indole structure is made by the Fischer method or the like using a raw material having a nitro group in advance.
Difficulty: Harmful raw materials used, many by-products

Conventional method ② Derived from indoline reduction

Converted to indoline and then nitrated
Difficulty: Harmful raw materials used, many processes

②Process development based on the safety evaluation system

[Ensure safety and quality by formulation design using calorimetric measurement (RC1e)]
We measure the heat of reaction, etc. at the time of investigation in the laboratory, predict the danger during actual manufacturing, and ensure safety. It is possible to predict the impact on product quality due to heat generation and extended process time, and identify issues. We propose manufacturing formulations that ensure safety and quality to our customers.

③Impurity control (metallic foreign matter, ionic impurities, etc.)

[Reduce metallic foreign matter and ionic impurities by making full use of magnetic separators, filters, resins, etc.]
We have been involved in the development and manufacture of electronic materials for many years, and possess expertise to reduce metallic foreign matter and ionic impurities. Upon your request, we will propose a process to reduce metallic foreign matter and ionic impurities, then carry out mass production.

Manufacturing facilities for active pharmaceutical ingredients: Sun Chemical GMP 8th Plant

Sun Chemical Co., Ltd., an affiliate company, started manufacturing amino acids when it was founded in June 1970. Since then, we have accumulated manufacturing results centered on pharmaceutical intermediates. The active pharmaceutical ingredient plant was completed in 2002. We have obtained a pharmaceutical manufacturing license and have manufactured many active pharmaceutical ingredients (APIs) to date and supply them to pharmaceutical manufacturers.
(Pharmaceutical Master File (MF): 10 items; Pharmaceutical Intermediates: Many)

In the manufacture of active pharmaceutical ingredients, we have established a GMP-compliant pharmaceutical manufacturing and quality control system. We regularly undergo GMP audits and regulatory inspections by domestic and overseas pharmaceutical manufacturers and receive high praise from users. We provide products and services that satisfy our customers through the enhancement and development of quality assurance activities that always prioritize quality in compliance with laws and regulations.
(GMP on-site audits: 10 or more cases/year [including PMDA and overseas users])
(Quality assurance/Quality control members: 13)

API manufacturing facility

Scale: Site area of 170 m2, 4-story building
Clean room: Most of the manufacturing area
Level: Class 100,000—Up to 100,000 airborne particles of 0.5 μ per ft3 (up to 3.53 million/m3)
Refining pot: 5 m3 (GL)
Centrifuge: 48 inches (Teflon)
Dryer: Conical (GL)
Crushing: Pin mill, etc.
Switching washability: Good

Specialty technology

Amino acid derivative manufacturing (Strecker reaction, esterification, SBH reduction, reductive amination, N-protection, optical resolution, dipeptide), Grignard reaction, liquid-phase air oxidation reaction, cyclization reaction, hydrogenation reaction, and cross-coupling

Main reactions: alkylation, Wittig reaction, epoxidation, metal reduction, Claisen rearrangement, acid chlorination, dehydrogenation, Parikin-Doering oxidation, oxone oxidation, acid anhydrideization, dipeptide synthesis, Stobbe condensation, Bucher-Bergs reaction, Suzuki coupling, Chan-Lam coupling, sulfonation, and thiolation

Molecular design technologies

Sumikin Coke Company, Ltd., which is one of our roots, has developed a condensed polycyclic aromatic (COPNA) resin using tar distilled products—the main product at that time—as a raw material. Starting with this, we are still developing and proposing functional resins for various advanced applications in-house. In particular, we are good at material design of thermosetting resins.
Please feel free to contact us for other molecular designs. We will propose materials that can flexibly respond to the coming paradigm shift using our accumulated development expertise.

Main applications

Semiconductor-related materials (sealing materials, other adhesives), circuit-related materials (rigid/flexible), etc.

Design examples

• [Phenol type]

  

  Features
  ・ High liquidity
  ・ High heat resistance
  ・ High flame resistance
  ・ Low elastic modulus
  etc.

• [Phenolic hydroxyl group protection type]

  

  Features
  ・ High liquidity
  ・ High heat resistance
  ・ Quick hardening
  ・ Low dielectric constant, low dielectric loss factor
  etc.

• [Imide type]

  

  Features
  ・ Highly soluble (solvent, water, etc.)
  ・ Low dielectric constant, low dielectric loss factor
  etc.