FORM 2
THE PATENTS ACT, 1970 (39 of 1970)
&
THE PATENTS RULES, 2003
PROVISIONAL SPECIFICATION
[See section 10, Rule 13]
CONTINUOUS NEUTRALIZER MIXER
REACTOR AND A CONTINUOUS
PROCESS FOR QUENCHING
CHLORINATION REACTION MIXTURE IN PRODUCTION OF CHLORINATED SUCROSE;
PHARMED MEDICARE PVT. LTD., A COMPANY INCOPORATED UNDER THE COMPANIES ACT, 1956, WHOSE ADDRESS IS 141 WALCHAND HIRACHAND MARG, MUMBAI - 400 001, MAHARASHTRA, INDIA.
THE FOLLOWING SPECIFICATION DESCRIBES THE INVENTION.

TECHNICAL FIELD
The present invention relates to method of neutralization of the chlorinated reaction mixture as a continuous process in a novel neutralizer mixer reactor used in the production of halo (chlorinated) sugars including 1'-6'-Dichloro-1'-6'-DIDEOXY-p-Fructofuranasyl-4-chloro-4-deoxy-galactopyranoside (TGS)
DESCRIPTION
Strategies of prior art methods of production of 4,1', 6' trichlorogalactosucrose (TGS) predominantly involve chlorination of sucrose-6-ester by use of Vilsmeier-Haack reagent derived from various chlorinating agents such as phosphorus oxychloride, oxalyl chloride, phosphorus pentachloride etc, and a tertiary amide such as dimethyl formamide (DMF) or dimethyl acetamide to chlorinate Sucrose-6-ester, to form 6 acetyl 4,1', 6'trichlorogalactosucrose. After the said chlorination reaction, the reaction mass is neutralized to pH 7.0 -7.5 using appropriate alkali hydroxides of calcium, sodium, etc. to deesterify / deacetylate the 6 acetyl 4,1', 6'trichlorogalactosucrose to form 4,1', 6' trichlorogalactosucrose (TGS).
After the said chlorination reaction, which takes place at elevated temperature, the reaction mass is highly acidic and has to be neutralized prior to purification and isolation of TGS. The neutralization of the chlorinated mass is carried out by addition of solution of hydroxides, carbonates and bicarbonates of alkali or alkaline earth metals. Also

ammonia gas or various strength of ammonia solution can be used for neutralization.
This neutralization when carried out in the conventional reactor, several problems arise due to foaming, improper mixing of solution, improper temperature control and the like. These problems adversely affect the TGS content in the chlorinated mass during the neutralization stage. Hence the neutralization stage is a very crucial stage which needed to be controlled properly to ensure complete recovery of TGS from the chlorinated mass.
Further, during neutralization stage, in conventional methods, the volume of chlorinated mass increase to about 3-4 . Thus it becomes necessary that in any scale up of the reaction, the reactor of neutralization / quenching reactor should at least be three times that of the chlorination reactor. As the size of the reactor increases, the efficiency of temperature, pH control and agitation comes down.
This problem was very effectively solved by designing a continuous neutralizer mixer and a process of continuous quenching of chlorinated mass with efficient temperature, pH and volume control. This resulted in greatly reducing the size of the neutralizer reactor. The continuous neutralizer / quencher is as shown in the figure 1.
This system of a Continuous Neutralizer Mixer reactor reported here consists of a reactor where the neutralization takes place, a closed loop circulation of the neutralized mass from the reactor bottom through a heat exchanger for the purpose of keeping the temperature low and the reactor

also has an overflow from where continuously the neutralized solution flows out. The reactor is equipped with the pH controller which controls the inflow of the acid /alkali for pH adjustment in the reactor.
The chlorinated mass is fed into the reactor at a fixed flow rate and the solution for pH adjustment (hydroxides, carbonates and bicarbonates of alkali or alkaline earth metals, ammonia solution, etc) also flows simultaneously into the reactor and is mixed thoroughly. An online pH meter measures the pH as the solution gets mixed and a control system monitors the flow of the solution for pH adjustment. The neutralized mass continuously flows from the bottom of the reactor through a heat exchanger, where the temperature is maintained and flows back to the reactor. This loop of passing through the heat exchanger is kept continuous and hence the temperature is well controlled in the reactor. The reactor is provided with an overflow at the top corner of the reactor through which the neutralized mass in the reactor continuously flows out and gets collected in a tank, which is taken for further purification.
Significant achievement of this inventive method of neutralization was that the typical size of a continuous neutralizer mixer required to handle the output from a chlorination reactor on a continuous basis was about half the size of the chlorination reactor. This resulted in a huge reduction in the size of the equipment meant for neutralization and also the utility requirement.
The results given below are an account of interim results, which shall be improved upon by further work and fine tuned until complete specification is submitted. The details of work done so far disclosed below serve as

illustrations and do not limit the scope of actual techniques used or scope of reaction conditions or process conditions or specifications of equipment or dimensions of the equipment or design of the equipment or layout and capacities of the equipment claimed and used. The techniques, reaction conditions, process conditions, design of equipment, dimensions of the equipment, layout of the equipment and the like disclosed below are subject matter of ongoing trials and fine tuning or trials in alternative or better conditions in method for quenching of the chlorinated mass. An adaptation to the disclosed invention obvious to an ordinary skilled person is also included within the scope of this disclosure.
In an experiment, 150 L of DMF and 30 % of 25% ammonia solution in water was charged to the Continuous Neutralizer reactor. This solution was continuously circulated through the heat exchanger loop and was cooled to 10°C.
Addition of the chlorinated mass (~ 950 L containing 28 kg 6-acetyl TGS) was started at a flow rate of 120 L/hr through a dip pipe arrangement. The reactor was also connected to a 7% ammonia solution tank through which the ammonia solution also was added simultaneously to the reactor. Temperature through the loop cycle was running continuously and was maintained at 20°C. The pH was monitored online and was controlled between 7.0 - 7.5 by the flow of the ammonia solution.
The quenched mass was collected through the overflow point provided in the reactor. The total quenched mass volume obtained was about 2500 L in 8 hrs. from a chlorinated reaction mass of 900 liters. The capacity of the neutralizer mixer reactor was 500 L. The quenched mass obtained by

the method was analyzed for TGS content by HPLC. The overall efficiency of quenching was found to be 98%.
Dated this day of April, 2006.
FOR PHARMED MEDICARE PVT. LTD. By their Agent

(DR. VASANT ANANTRAO SAVANGIKAR) KRISHNA & SAURASTRI