Synthesis of 2-[4-(4-Chlorophenyl)piperazin-1-yl]-2-methylpropanoic Acid Ethyl Ester

spectroscopy, SYNTHESIS, Uncategorized Comments Off

Dec 202016

2-[4-(4-Chlorophenyl)piperazin-1-yl]-2-methylpropanoic Acid Ethyl Ester

1-Piperazineacetic acid, 4-(4-chlorophenyl)-α,α-dimethyl-, ethyl ester

2-[4-(4-Chlorophényl)-1-pipérazinyl]-2-méthylpropanoate d‘éthyle

Ethyl 2-[4-(4-chlorophenyl)-1-piperazinyl]-2-methylpropanoate

Ethyl-2-[4-(4-chlorphenyl)-1-piperazinyl]-2-methylpropanoat

1206769-44-9

2-[4-(4-Chlorophenyl)piperazin-1-yl]-2-methylpropanoic Acid Ethyl Ester (en)

AGN-PC-0JIRMK

AKOS016034964

ethyl 2-[4-(4-chlorophenyl)piperazin-1-yl]-2-methylpropanoate

MWt310.819

MFC16H23ClN2O2

NMR IS EASY

1H NMR PREDICT

ACTUAL VALUES……..¹H NMR (400 MHz, CDCl₃): δ ppm 1.27 (t, 3H, J = 7.2 Hz, -CH₂-CH₃), 1.35 (s, 6H, 2 x CH₃), 2.74-2.76 (m, 4H, J = 4.8 Hz, -CH₂-N-CH₂-), 3.14-3.17 (m, 4H, J = 4.8 Hz, -CH₂-N-CH₂-), 4.20 (q, 2H, J = 7.2 Hz, -CH₂-CH₃), 6.81-6.83 (d, 2H, J = 6.8 Hz, phenyl protons), 7.17-7.20 (d, 2H, J = 6.8 Hz, phenyl protons).

13C NMR PREDICT

ACTUAL VALUES……..¹³C NMR (100 MHz, CDCl₃): δ ppm 14.3 (CH₃), 22.7 ((CH₃)₂), 46.6 (-CH₂-N-CH₂-), 49.7 (-CH₂-N-CH₂-), 60.5 (O-CH₂), 62.4 (N-C-), 117.0, 124.3, 128.8, 149.8 (aromatic carbons), 174.3 (C=O).

Paper

To a solution of 4-(4-chlorophenyl)piperazine dihydrochloride 1 (5.0 g, 0.0185 mol) in DMSO (30 ml), anhydrous cesium carbonate (30.0 g, 0.0925 mol), sodium iodide (1.39 g, 0.0093 mol) and ethyl 2-bromo-2-methylpropanoate 2 (3.97 g, 0.02 mol) were added. The resulting mixture was stirred at 25-30^oC for 12 hours. The reaction mass was diluted with water (200 ml) and extracted with ethyl acetate (2 x 200 ml). The ethyl acetate layer was washed with water (2 x 100 ml), dried over anhydrous sodium sulfate (10.0 g) and concentrated under vacuum. The crude product thus obtained was purified by column chromatography (stationary phase silica gel 60-120 mesh; mobile phase 10% ethyl acetate in hexane). The title compound 3 was obtained as a white solid (4.73 g, 82 %).

Melting Point: 56^oC.

EI-MS m/z (rel. int. %): 311 (100) [M+1]⁺, 236(40), 197(60), 154(45).

IR ν _max (KBr) cm^-1: 2839-2996 (C-H aliphatic); 1728 (C=O), 1595, 1505 (C=C aromatic), 1205 (C-O bending), 758 (C-Cl bending).

¹H NMR (400 MHz, CDCl₃): δ ppm 1.27 (t, 3H, J = 7.2 Hz, -CH₂-CH₃), 1.35 (s, 6H, 2 x CH₃), 2.74-2.76 (m, 4H, J = 4.8 Hz, -CH₂-N-CH₂-), 3.14-3.17 (m, 4H, J = 4.8 Hz, -CH₂-N-CH₂-), 4.20 (q, 2H, J = 7.2 Hz, -CH₂-CH₃), 6.81-6.83 (d, 2H, J = 6.8 Hz, phenyl protons), 7.17-7.20 (d, 2H, J = 6.8 Hz, phenyl protons).

¹³C NMR (100 MHz, CDCl₃): δ ppm 14.3 (CH₃), 22.7 ((CH₃)₂), 46.6 (-CH₂-N-CH₂-), 49.7 (-CH₂-N-CH₂-), 60.5 (O-CH₂), 62.4 (N-C-), 117.0, 124.3, 128.8, 149.8 (aromatic carbons), 174.3 (C=O).

Elemental analysis: Calculated for C₁₆H₂₃ClN₂O₂: C, 61.83%, H, 7.46%, N, 9.01%; Found: C, 61.90%, H, 7.44%, N, 8.98%.

Molbank 2009, 2009(3), M607; doi:10.3390/M607

http://www.mdpi.com/1422-8599/2009/3/M607

Synthesis of 2-[4-(4-Chlorophenyl)piperazin-1-yl]-2-methylpropanoic Acid Ethyl Ester

Hari N. Pati^1,* ,Bijay K. Mishra¹ andVijay S. Satam²

¹Department of Chemistry, Sambalpur University, JyotiVihar-768019, Orissa, India

²Institute of Chemical Technology (ICT), Matunga, Mumbai-400019, Maharashtra, India

^*Author to whom correspondence should be addressed.

Received: 17 May 2009 / Accepted: 30 June 2009 / Published: 27 July 2009

Abstract

The title compound was synthesized by N-alkylation of 4-(4-chlorophenyl)piperazine with ethyl 2-bromo-2-methylpropanoate and its IR, ¹H NMR, ¹³C NMR and Mass spectroscopic data are reported.

Keywords: 2-[4-(4-Chlorophenyl)piperazin-1-yl]-2-methylpropionic acid; N-alkylation; 4-(4-Chlorophenyl)piperazine

/////////

CCOC(=O)C(N1CCN(CC1)c1ccc(cc1)Cl)(C)C

The Water Purification Process

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Jun 042015

The Water Purification Process

Water purification is the process of removing undesirable chemicals, biological contaminants, suspended solids and gases from contaminated water. The goal is to produce water fit for a specific purpose. Most water is disinfected for human consumption (drinking water), but water purification may also be designed for a variety of other purposes, including fulfilling the requirements of medical, pharmacological, chemical and industrial applications. The methods used include physical processes such as filtration, sedimentation, anddistillation; biological processes such as slow sand filters or biologically active carbon; chemical processes such as flocculation andchlorination and the use of electromagnetic radiation such as ultraviolet light.

Purifying water may reduce the concentration of particulate matter including suspended particles, parasites, bacteria, algae, viruses, fungi, as well as reducing the amount of a range of dissolved and particulate material derived from the surfaces that come from runoff due torain.

The standards for drinking water quality are typically set by governments or by international standards. These standards usually include minimum and maximum concentrations of contaminants, depending on the intended purpose of water use.

Visual inspection cannot determine if water is of appropriate quality. Simple procedures such as boiling or the use of a household activated carbon filter are not sufficient for treating all the possible contaminants that may be present in water from an unknown source. Even natural spring water – considered safe for all practical purposes in the 19th century – must now be tested before determining the kind of treatment, if any, is needed. Chemical and microbiological analysis, while expensive, are the only way to obtain the information necessary for deciding on the appropriate method of purification.

According to a 2007 World Health Organization (WHO) report, 1.1 billion people lack access to an improved drinking water supply, 88 percent of the 4 billion annual cases ofdiarrheal disease are attributed to unsafe water and inadequate sanitation and hygiene, while 1.8 million people die from diarrheal diseases each year. The WHO estimates that 94 percent of these diarrheal cases are preventable through modifications to the environment, including access to safe water.^[1] Simple techniques for treating water at home, such as chlorination, filters, and solar disinfection, and storing it in safe containers could save a huge number of lives each year.^[2] Reducing deaths from waterborne diseases is a major public health goal in developing countries.

Water purity is extremely important to pharmaceutical and biochemical industries. Suspended or dissolved particles, organic compounds, impurities and other contaminants prohibit the usage of tap water in laboratory applications and scientific research. Parameters such as resistivity, conductivity, size of particulate matter and concentration of microorganisms are used to categorize water quality and, therefore, specify intended uses for water. Some applications can tolerate the presence of specific impurities in the water, but others, such as High Performance Liquid Chromatography (HPLC) require removal of the majority of contaminants.

Contaminants

Water is an excellent solvent and can be sourced from almost anywhere on Earth. This property makes it prone to all kinds of contamination.

Particulates: Silt and debris which can be removed by passing water through a 10 to 20 micron filter (or less if necessary).
Microorganisms: Bacterial agents constitute a real challenge for water purification systems. Their growth rate, size and robustness require an efficient design (detection, removal from water inlet, inhibition of growth, etc.). Bacteria are measured in colony forming units per milliliter and can be killed with disinfectants. As a result, their secretions and cellular fragments must also be removed to avoid contamination.
Endotoxins, pyrogens, DNA and RNA: Cellular fragments and bacterial by-products. Harmful to tissue cultures. Can be detected with a Limus Amoebocyte Lysate (LAL) test.
Dissolved inorganic elements: Include phosphates, nitrates, calcium and magnesium, carbon dioxide, silicates, iron, chloride, fluoride, and any other natural or man-made chemicals resulting from exposure to the environment. Electrical conductivity (μSiemens/cm) is used to monitor high concentration of ions, while resistivity (MÙcm) is used to identify ions if present in small concentrations. These contaminants affect water hardness and alkalinity/acidity.
Dissolved organic elements: Pesticides, plant and animal remains or fragments. Total Organic Carbon (TOC) analyzers are used to measure CO2 emitted by organics subjected to oxidization. Organic-free water is mainly used in applications where analysis of organic substances is carried out (e.g. HPLC, chromatography and mass spectrometry).

Scientific applications require elimination of certain types of contaminants. On the other hand, pharmaceutical productions require, in most cases, near-total removal of impurities (criteria dictated by specific standards or local/international regulatory bodies).

Purification Process

There are a number of methods commonly used to purify water. Their effectiveness is linked to the type of contaminant being treated and the type of application the water will be used for.

Filtration: This process can take the form of any of the following:
- Coarse filtration: Also called particle filtration, it can utilize anything from a 1 mm sand filter, to a 1 micron cartridge filter.
- Micro filtration: Uses 1 to 0.1 micron devices to filter out bacteria. A typical implementation of this technique can be found in the brewing process.
- Ultra filtration: Removes pyrogens, endotoxins, DNA and RNA fragments.
- Reverse osmosis: Often referred to as RO, reverse osmosis is the most refined degree of liquid filtration. Instead of a filter, it uses a porous material acting as a unidirectional sieve that can separate molecular-sized particles.

Distillation: Oldest method of purification. Inexpensive but cannot be used for an on-demand process. Water must be distilled and then stored for later use, making it again prone to contamination if not stored properly.
Activated carbon adsorption: Operates like a magnet on chlorine and organic compounds.
Ultraviolet radiation: At a certain wavelength, this might cause bacteria to be sterilized and other micro organics to be broken down.
Deionization: Also known as ion exchange, it is used for producing purified water on-demand, by passing water through resin beds. Negatively charged (cationic) resin removes positive ions, while positively charged one (anionic) removes negative ions. Continuous monitoring and maintenance of the cartridges can produce the purest water.

Hot Water Sanitization

Sanitization of water purification equipment with hot water is achieved via an appropriate combination of exposure time and temperature. A primary use for this process is to deactivate viable microbes. It is worth mentioning that Endotoxin reduction is not achieved as a direct result of the hot water sanitization process.
Based on the feed water source, system operating conditions and the end-user’s operating and maintenance procedures, traditional chemical cleaning processes may still be required.
Sanitization using hot water involves incorporating heat exchangers into the traditional clean in place (CIP) system to gradually heat and cool water circulating through the reverse osmosis membrane system. Membrane manufacturers commonly stipulate a controlled heating and cooling rate to protect against irreversible damage to the membrane and ensure the system’s long-term performance.
A typical hot water sanitization sequence would consist of the following phases:

Initialization (conditions checking)
Heating
Holding
Cooling

A control system must therefore provide flexibility in the way in which accurate and repeatable control of the sterilization is achieved and will

include the following features:

Precise loop control with setpoint profile programming
Sequential control for sanitation/sterilization
Onscreen operator messaging
Duty standby pump control
Secure collection of on-line data from the purified water system for analysis and evidence
Local operator display with clear graphics and controlled access to parameters

Control room and schematics of the water purification plant to Lac de Bret, Switzerland

Bottle for distilled water in theFarmacia Real in Madrid

Large cation/anion ion exchangersused in demineralization of boiler feedwater

Pharmaceuticals can enter the water supply in a variety of ways. Debates continue over how dangerous this is. Source: GAO

Information sheet: Pharmaceuticals in drinking-water

(This information sheet is a summary of the key findings, recommendations and conclusions of the WHO technical report on Pharmaceuticals in drinking-water and the inputs of additional expert peer-reviewers)

Background and scope

Pharmaceuticals are synthetic or natural chemicals that can be found in prescription medicines, over-the-counter therapeutic drugs and veterinary drugs. Pharmaceuticals contain active ingredients that have been designed to have pharmacological effects and confer significant benefits to society. Pharmaceuticals can be introduced into water sources through sewage, which carries the excreta of individuals and patients who have used these chemicals, from uncontrolled drug disposal (e.g. discarding drugs into toilets) and from agricultural runoff comprising livestock manure. They have become chemicals of emerging concern to the public because of their potential to reach drinking-water.

Occurrence of pharmaceuticals in drinking-water

The ubiquitous use of pharmaceuticals (both prescribed and over the counter) has resulted in a relatively continuous discharge of pharmaceuticals and their metabolites into wastewater. In addition, pharmaceuticals may be released into water sources in the effluents from poorly controlled manufacturing or production facilities, primarily those associated with generic medicines.

Following advances in the sensitivity of analytical methods for the measurement of these chemicals at very low concentrations, a number of studies found trace concentrations of pharmaceuticals in wastewater, various water sources and some drinking-waters. Concentrations in surface waters, groundwater and partially treated water were typically less than 0.1 µg/l (or 100 ng/l), whereas concentrations in treated water were generally below 0.05 µg/l (or 50 ng/l). These investigations suggested that pharmaceuticals are present, albeit at trace concentrations, in many water sources receiving wastewater effluents.

The presence of specific pharmaceuticals in a water source will vary from place to place depending upon the type of pharmaceutical and the extent of discharge into water bodies. Key factors include the pharmaceuticals prescribed, used or manufactured in the area and the size of the population in the catchment. The occurrence and concentration of pharmaceuticals in receiving water sources, which are the primary pathway into drinking-water, are dependent on dilution, natural attenuation and the degree of wastewater treatment applied.

Risk assessment of pharmaceuticals in drinking-water

There are currently few systematic monitoring programmes or comprehensive studies available on human exposure to pharmaceuticals from drinking-water. Therefore, a key challenge in assessing the potential human health risk associated with exposure to very low concentrations of pharmaceuticals in drinking-water is the limited occurrence data available for the diverse group of pharmaceuticals in use today and their active metabolites.

However, several approaches for screening and prioritizing pharmaceuticals for human health risk assessment for exposure through drinking-water have been published in the peer-reviewed literature. These approaches usually apply the principle of the “minimum therapeutic dose” (also known as the “lowest clinically effective dose”) or the acceptable daily intake, in conjunction with safety factors or uncertainty factors for different groups of pharmaceuticals, to derive a margin of safety, or margin of exposure, between the worst-case exposure observed or predicted and the minimum therapeutic dose or acceptable daily intake.

Current observations suggest that it is very unlikely that exposure to very low levels of pharmaceuticals in drinking-water would result in appreciable adverse risks to human health, as concentrations of pharmaceuticals detected in drinking-water (typically in the nanogram per litre range) are several orders of magnitude (typically more, and often much more, than 1000-fold) lower than the minimum therapeutic dose.

Control measures and risk management

Concentrations of the vast majority of pharmaceuticals in the water environment can be reduced through natural processes (e.g. adsorption onto sediment, solar photodegradation and biological degradation) or during subsequent drinking-water and wastewater treatment processes.

Despite their unique pharmacological properties, pharmaceuticals respond to treatment no differently from other organic chemicals, with removal rates depending on their physicochemical properties and the treatment technology being used. Conventional water treatment processes, such as chlorination, can remove approximately 50% of these compounds, whereas more advanced treatment processes, such as ozonation, advanced oxidation, activated carbon, nanofiltration and reverse osmosis, can achieve higher removal rates; reverse osmosis, for example, can remove more than 99% of large pharmaceutical molecules.

Funding for any water safety improvements, like any public health intervention, draws on limited resources that need to be carefully allocated with due consideration of their beneficial impact. However, implementing additional specialized and costly drinking-water treatment, specifically with the intention of reducing trace concentrations of pharmaceuticals, is not considered necessary at this time, as the human health benefit would be limited.

The most appropriate approach to minimize the presence of pharmaceuticals in drinking-water and reduce human exposure is to prevent or reduce their entry into the water environment as far as reasonably practical. This can be achieved through a combination of preventive measures, including enhanced communication to the public on rational drug use and disposal of pharmaceuticals (e.g. avoid flushing unused drugs down the toilet), education for prescribers and systematic drug take-back programmes.

However, in line with the water safety plan principle of control of contaminants at the source, it would be appropriate to investigate improvements in wastewater treatment to remove pharmaceuticals and other potential contaminants of concern from their main route of entry into the water environment.

Monitoring of pharmaceuticals in water

In the absence of regulatory mandates, routine monitoring for pharmaceuticals in water sources and drinking-water on a national basis would not be desirable except in cases where local circumstances indicate a potential for elevated concentrations (e.g. manufacturing facilities with uncontrolled effluent discharge upstream of a drinking-water source). In these circumstances, investigative monitoring of, for example, surface water, groundwater and wastewater effluent can be undertaken to assess possible occurrence levels and exposure; if necessary, screening values can be developed in conjunction with an assessment of the potential risks to human health from exposure through drinking-water.

Based on the results of this risk assessment, an evaluation of possible control options could be considered as part of a water safety plan. Practical difficulties associated with implementing monitoring programmes for pharmaceuticals include the lack of standardized sampling and analysis protocols, high costs and the limited availability of the analytical instruments required to measure the diverse range of pharmaceuticals that may be present.

Investigative surveys should be tailored to local circumstances, taking into account existing wastewater and water treatment processes and pharmaceuticals (and their metabolites) that are commonly prescribed, used or manufactured within the catchment area of concern. Such studies should be carried out with appropriate rigorous quality assurance and verification and designed to confirm whether drinking-water is a significant risk.

Knowledge gaps

Although current risk assessments indicate that the very low concentrations of pharmaceuticals found in drinking-water are very unlikely to pose any appreciable risks to human health, knowledge gaps exist. These include the assessment of risks to human health associated with long-term exposure to low concentrations of pharmaceuticals and the possible combined effects of mixtures of pharmaceuticals.

Although the margins of exposure are substantial, it would be of value to ensure that these margins are adequate for possibly sensitive subpopulations and to better characterize health risks, if any, from long-term, low-level exposures. In addition, future research should focus on developing methods or protocols for prioritizing pharmaceuticals in the context of an overall risk assessment for all drinking-water hazards.

Summary

Currently, analysis of the available data indicates that there is a substantial margin of safety between the very low concentrations of pharmaceuticals that would be consumed in drinking-water and the minimum therapeutic doses, which suggests a very low risk to human health. Based on this finding, the development of formal health-based guideline values for pharmaceuticals in the World Health Organization’s (WHO) Guidelines for drinking-water quality is currently not considered to be necessary.

Concerns over pharmaceuticals in drinking-water should not divert water suppliers and regulators from other priorities for drinking-water and health, most notably microbial risks, such as bacterial, viral and protozoan pathogens, and other chemical risks, such as naturally occurring arsenic and excessive levels of fluoride.

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Scaling from Milligrams to 1-2Kg

PROCESS Comments Off

Jan 142015

Dr John Knight

Scaling from Milligrams to 1-2Kg

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The aim of this professional development course is to provide a good basis to work from when involved in taking development candidates to the first in human trials and with a view on some longer-term requirements. The course content will focus on the necessary early phases of chemical development, as would typically be required to support production of up to about 2kg.

The course will introduce and discuss the following:

Requirements in order to move from small (less than 1g) supplies to the first 100g or so for preclinical work
Further scaling to 1-2kg non-cGMP
Requirements to make material for use in clinical trial – an introduction to cGMP coupled with the scaling issues
An overview of the requirements to move processes to fixed vessels, assuming cGMP is required – what operations can readily be transferred and those that should ideally be developed out
The phases of development and indicative timelines with quality requirements
The importance of physical form selection, understanding and control
Impurities and their control, with specific discussion on genotoxic impurities and developing the specification for the API as it moves from preclinical batch preparation to cGMP batches for clinical trials

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Project managers and those involved in technical outsourcing
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What will you take away from this course…

How long it takes to get from milligrams to 1-2kgs suitable for human clinical trials
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What can be left out and what must be included
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Ensuring Process Stability with Reactor Temperature Control Systems

PROCESS, spectroscopy, SYNTHESIS Comments Off

Dec 272014

Temperature control plays an important role in industrial processes, pilot plants, and chemical and pharmaceutical laboratories. When controlling reactors, both exothermic and endothermic reactions must be offset with high speed and reliability. Therefore, different conditions and effects must be taken into account when specifying an optimum and highly dynamic temperature control system.

Temperature Control of Reactors

Most temperature control systems are used with chemical reactors made of either steel or glass. The former is more rugged and long-lasting, while the latter enables chemists to observe processes inside the reactor.

However, in the case of glass reactors, extensive precautions have to be followed for safe usage. Reactors usually include an inner vessel to hold the samples, which need temperature control. This inner vessel is enclosed by a jacket containing heat-transfer liquid. This reactor jacket is linked to the temperature control system.

In order to control the reactor’s temperature, the temperature control system pumps the heat-transfer liquid through the reactor’s jacket. Rapid temperature change inside the reactor is balanced by instant cool-down or heat-up, and the liquid is either cooled or heated inside the temperature control system. Figure 1 shows a schematic of a simple temperature control system.

Figure 1. Functional view of reactor temperature control

Process Stability

Both materials and reactor design can affect the temperature control of highly dynamic reactor systems. However, the heat transferred by a glass-walled vessel will be different than that transferred by a steel-walled vessel. In addition, both wall thickness and surface area can also affect accuracy. Therefore, proper mixing of the initial materials inside the reactor is important to obtain good uniformity, which in turn will guarantee optimal heat exchange.

For each type of reactor, maximum pressure values have been provided as per the specifications established by reactor manufacturers and in the Pressure Equipment Directive 97/23/EG. Regardless of any temperature control application, these limit values may not be surpassed during operation under any situations. Prior to starting a temperature control application, the applicable limits must be programmed within the temperature control unit.

Another important criterion in reactors is the maximum permissible temperature difference, which is referred to as Delta-T limit. It defines the highest difference between the temperature of the contents of the reactor and the actual thermal fluid temperature.

When compared to steel reactors, glass reactors are more susceptible to thermal stress. For that matter, any temperature control system should enable users to program reactor-specific values for the Delta-T limit per time unit. Within the temperature control equipment itself, three components considerably affect the stability of the process and these include heat exchanger, pump, and control electronics.

Heat Exchanger

It is important to ensure that a temperature control system has sufficient heating and cooling capacity, as this can significantly affect the speed to reach the preferred temperatures. In order to determine the preferred heating and cooling capacities, users must consider the essential differences in temperature, the volume of the samples, the preferred heat-up and cool-down times, and the specific heat capacity of the temperature control medium.

Highly dynamic temperature control solutions are commercially available in the market with water or air cooling. Air-cooled systems do not utilize water and may be deployed where there is sufficient air flow.

The heat thus removed from the reactor is eventually transferred to ambient air. Water-cooled systems need to be joined to a cooling water supply, but they operate more quietly and do not add surplus heat in small labs. These units could be completely enclosed by the application, if required.

Pump

The integrated pump of the temperature control unit equipment must be sufficiently strong to obtain the preferred flow rates at stable pressure. To ensure that pressure limit values mentioned above are not exceeded, the pump should provide the preferred pressure quickly and with maximum control.

Operating conditions and pressure specifications of the reactor must always be taken into account, and regulation of pump capacity must be done by presetting a limit value. Sophisticated temperature control solutions include pumps that balance the variations of the viscosity of the heat transfer liquid to make sure that energy efficiency is maintained continuously.

This is because viscosity influences flow and hence the heat transfer. An additional advantage provided by magnetically coupled pumps is that they guarantee a hydraulically-sealed thermal circuit. Also, self-lubricated pumps are beneficial as they require only minimum maintenance.

The closed loop circuit prevents contact between the ambient air and the heat transfer liquid. This not only prevents permeation of oxidation and moisture, bit also prevents oil vapors from entering into the work environment.

Additionally, an internal expansion vessel must permanently absorb temperature-induced volume variations inside the heat exchanger. Individual cooling of the expansion vessel will help in ensuring that the temperature control unit does not overheat and ultimately ensures operator safety.

A temperature control equipment should operate consistently even at high ambient temperatures. In majority of cases, the real work environment will diverge from the ideal temperature of 20°C. During hot summer months, temperature control solutions are exposed to adverse conditions. In laboratories, ambient temperatures are usually higher because of energy saving measures. These instances demonstrate the benefits of temperature control solutions that work consistently at temperatures as high as 35°C.

Control Electronics

Temperature control equipment includes advanced control electronics that monitor and control the process inside the reactor and also the internal processes of the system. When a control variable changes, the system is capable of readjusting the variable to the setpoint sans overshooting.

Accurate control electronics are needed to maintain the stability of a temperature control application. One option to assess control electronics is to look at the effort needed to set parameters. In a temperature control unit, users can enter a setpoint. Control electronics must be self-optimizing throughout the temperature control process to ensure optimum results.

Conclusion

To sum up, the process safety and stability during reactor temperature control relies on the effectiveness of heat transfer, the type of reactor, and the efficiency of the components within the temperature control unit. Therefore, different conditions and effects must be considered when specifying a highly dynamic temperature control system.

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TRAINING COURSE 2-3 DEC 2014

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Chemical process research and development is recognised as a key function during the commercialisation of a new product particularly in the generic and contract manufacturing arms of the chemical, agrochemical and pharmaceutical industries.

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Process robustness testing and reaction optimisation via stastical methods will also be covered.

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The use of engineering and technology solutions to reduce costs will be discussed and throughout the course the emphasis will be on minimising costs and maximising returns.

Conference 4-5 DEC 2014

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Subtitle:The 32nd International Conference and Exhibition

When:04.12.2014 – 05.12.2014

Where:National Chemical Laboratory – Pune, India

Brochure:View Brochure

Organic Process Research & Development - India

for

Process Research & Development Chemists
Chemical Engineers in Industry
Heads of Departments & Team Leaders

Benefits

Invest in yourself: keeping up to date on current developments and future trends could mean greater job security.
Learn from a wide range of industrial case studies given by hand-picked industrial speakers.
Take home relevant ideas and information that are directly applicable to your own work with the full proceedings and a CD of the talks.
Save time. Our intensive, commercial-free programme means less time away from work.
Meet and network with the key people in the industry in a relaxed and informal atmosphere.

Do you want to improve efficiency and innovation in your synthetic route design, development and optimisation?

The efficient conversion of a chemical process into a process for manufacture on tonnage scale has always been of importance in the chemical and pharmaceutical industries. However, in the current economic and regulatory climate, it has become increasingly vital and challenging to do so efficiently. Indeed, it has never been so important to keep up to date with the latest developments in this dynamic field.

At this Organic Process Research & Development Conference, you will hear detailed presentations and case studies from top international chemists. The hand-picked programme of speakers has been put together specifically for an industrial audience. They will discuss the latest issues relating to synthetic route design, development and optimisation in the pharmaceutical, fine chemical and allied fields. Unlike other conferences, practically all our speakers are experts from industry, which means the ideas and information you take home will be directly applicable to your own work.

The smaller numbers at our conferences create a more intimate atmosphere. You will enjoy plenty of opportunities to meet and network with speakers and fellow attendees during the reception, sit-down lunches and extended coffee breaks in a relaxed and informal environment. Together, you can explore the different strategies and tactics evolving to meet today’s challenges.

This is held in Pune, close proximity to Mumbai city, very convenient to stay and travel to either in Pune or Mumbai. I feel this should be an opportunity to be grabbed before the conference is full and having no room

Hurry up rush

References

1 http://newdrugapprovals.org/scientificupdate-uk-on-a-roll/

2 http://scientificupdate.co.uk/conferences/conferences-and-workshops.html

3 http://en.wikipedia.org/wiki/Pune

PROFILES

Will Watson

Dr Will Watson gained his PhD in Organic Chemistry from the University of Leeds in 1980. He joined the BP Research Centre at Sunbury-on-Thames and spent five and a half years working as a research chemist on a variety of topics including catalytic dewaxing, residue upgrading, synthesis of novel oxygenates for use as gasoline supplements, surfactants for use as gasoline detergent additives and non-linear optical compounds.

In 1986 he joined Lancaster Synthesis and during the next 7 years he was responsible for laboratory scale production and process research and development to support Lancaster’s catalogue, semi-bulk and custom synthesis businesses.

In 1993 he was appointed to the position of Technical Director, responsible for all Production (Laboratory and Pilot Plant scale), Process Research and Development, Engineering and Quality Control. He helped set up and run the Lancaster Laboratories near Chennai, India and had technical responsibility for the former PCR laboratories at Gainesville, Florida.

He joined Scientific Update as Technical Director in May 2000. He has revised and rewritten the ‘Chemical Development and Scale Up in the Fine Chemical & Pharmaceutical Industries’ course and gives this course regularly around the world. He has been instrumental in setting up and developing new courses such as ‘Interfacing Chemistry with Patents’ and ‘Making and Using Fluoroorganic Molecules’.

He is also involved in an advisory capacity in setting up conferences and in the running of the events. He is active in the consultancy side of the business and sits on the Scientific Advisory Boards of various companies.

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John Knight

Dr John Knight gained a first class honours degree in chemistry at the University of Southampton, UK. John remained at Southampton to study for his PhD in synthetic methodology utilizing radical cyclisation and dipolar cyloaddition chemistry.

After gaining his PhD, John moved to Columbia University, New York, USA where he worked as a NATO Postdoctoral Fellow with Professor Gilbert Stork. John returned to the UK in 1987 joining Glaxo Group Research (now GSK) as a medicinal chemist, where he remained for 4 years before moving to the process research and development department at Glaxo, where he remained for a further 3½ years.

During his time at Glaxo, John worked on a number of projects and gained considerable plant experience (pilot and manufacturing). In 1994 John moved to Oxford Asymmetry (later changing its name to Evotec and most recently to Aptuit) when it had just 25 staff. John’s major role when first at Oxford Asymmetry was to work with a consultant project manager to design, build and commission a small pilot plant, whilst in parallel developing the chemistry PRD effort at Oxford Asymmetry.

The plant was fully operational within 18 months, operating to a 24h/7d shift pattern. John continued to run the pilot plant for a further 3 years, during which time he had considerable input into the design of a second plant, which was completed and commissioned in 2000. After an 18-month period at a small pharmaceutical company, John returned to Oxford in 2000 (by now called Evotec) to head the PRD department. John remained in this position for 6.5 years, during which time he assisted in its expansion, established a team to perform polymorph and salt screening studies and established and maintained high standards of development expertise across the department.

John has managed the chemical development and transfer of numerous NCE’s into the plant for clients and been involved in process validations. He joined Scientific Update in January 2008 as Scientific Director.

Pune images

From top:1 Fergusson College, 2 Mahatma Gandhi Road, Shaniwarwada 3 the HSBC Global Technology India Headquarters, and the 4National War Memorial Southern Command

NCL PUNE

The National Chemical Laboratory is located in the state of Maharashtra in India. Maharashtra state is the largest contributor to India’s GDP. The National Chemical Laboratory is located in Pune city, and is the cultural capital of Maharashtra. Pune city is second only to Mumbai (the business capital of India) in size and industrial strength. Pune points of interest include: The tourist places in Pune include: Lal Deval Synagogue, Bund Garden, Osho Ashram, Shindyanchi Chhatri and Pataleshwar Cave Temple.