Automatic synthesis apparatus

• US 5,239,484 A
• Filed: 10/13/1992
• Issued: 08/24/1993
• Est. Priority Date: 03/31/1988
• Status: Expired due to Fees

• Current Assignee: Takeda Chemical Industries, Ltd. (Takeda Pharmaceutical Company Limited)
• Original Assignee: Takeda Chemical Industries, Ltd. (Takeda Pharmaceutical Company Limited)
• Inventors: Hayashi, Nobuyoshi, Sugawara, Tohru
• Primary Examiner(s): Teska, Kevin J.
• Application Number:
  US07/960,258
• Time in Patent Office: 315 Days
• Field of Search: 364/500, 364/502, 364/496, 364/148, 364/152, 364/166, 364/479, 364/468, 73/61.41
• US Class Current: 700/268
• CPC Class Codes: B01J 19/004 Multifunctional apparatus for automatic manufacturing of various chemical products sequential reactions B01J19/0046

Abstract

A computerized compound synthesization for producing an aimed product by controlling a synthesis reaction process including steps of supplying raw material compounds, reagents and solvents, a synthesis reaction step, a purification step and a product extraction step in accordance with a control program. Optimal condition for the reaction is established by determining discrete time points at which the reagent is added and volumes of the reagent to be added at the time points, respectively, on the basis of parameters including reaction rate constant, equilibrium, constant, initial concentration of starting material mixture, ratio of concentration of intermediate product to theoretical equilibrium concentration, stoichiometrical ratio between the reagent and the intermediate and concentration of the reagent in accordance with a relation established among these parameters.

Claims

1. A method of manufacturing a desired chemical product from a chemical reaction between a raw material mixture and a reagent, the method comprising the steps of:

measuring an initial concentration ratio of the raw material mixture; and

adding a variable volume of reagent to said raw material mixture at discrete time intervals, a first time interval being t., and being determined by the formula ##EQU4## where k₁ represents a reaction rate constant,

K represents an equilibrium constant,

A represents said initial concentration of the raw material mixture,

α

represents a ratio of concentration of an intermediate product to a theoretical equilibrium concentration,

and subsequent time intervals being determined by the formula ##EQU5## where i is incremented after each time interval, said volume of reagent being determined by the formula ##EQU6## where V represents a volume of the raw material mixture at a start of the reaction,

V_i represents volumes of the reagent added at the time points t_i, respectively,

β

represents a stoichiometrical ratio between the reagent and an intermediate product, and

y represents a concentration of the reagent.

2. A chemical product manufacturing method set forth in claim 1, wherein said reaction rate constant (k₁) and said equilibrium constant (K) are determined on the basis of a substitute constant (E₂) in the following formulas:

space="preserve" listing-type="equation">k.sub.1 =A exp (B·

E.sub.s)

space="preserve" listing-type="equation">K=C exp (D·

E.sub.s)

where A, B, C and D represent constants specific to said reaction.

3. A chemical product manufacturing method set forth in claim 1, wherein data of said time points (t.sub.°

, t_i) and said amounts (V_i), calculated by said expressions (1), (2) and (3), are stored together with information identifying said reaction in a memory of a computerized controller for reuse in carrying out another reaction.

4. A chemical product manufacturing method set forth in claim 1, wherein different types of reagents are added at several ones of said discrete time intervals, respectively.

5. An automated synthesis system for manufacturing a desired chemical product from a chemical reaction between a raw material mixture and a reagent, the system comprising:

synthesis processing means for containing the raw material mixture, dispensing a variable amount of the reagent at discrete time intervals, purifying the raw material mixture, and extracting the desired chemical product; and

synthesis control means for determining a volume of said variable amount of the reagent dispensed by said synthesis processing means and for determining said time intervals for said dispensing of the reagent, a first time interval being t.sub.°

, and being determined by the formula ##EQU7## where k₁ represents a reaction rate constant,

K represents an equilibrium constant,

A represent said initial concentration of the raw material mixture,

α

represent a ratio of concentration of an intermediate product to a theoretical equilibrium concentration,

and subsequent time intervals being determined by the formula ##EQU8## where is incremented after each time interval, said volume of reagent being determined by the formula ##EQU9## where V₂₀ represents a volume of the raw material mixture at a start of the chemical reaction,

V_i represents volumes of the reagent added at time points t_i, respectively,

β

represents a stoichiometrical ratio between the reagent and an intermediate product, and

y represents a concentration of the reagent.

6. An automated synthesis system as set forth in claim 5, wherein:

said reaction rate constant (k₁) and said equilibrium constant (K) are determined in said synthesis control means on the basis of a substitute constant (E_s) by the following formulas,

space="preserve" listing-type="equation">k.sub.1 =A exp (B.sub.1 ·

E.sub.s)

space="preserve" listing-type="equation">K=C exp (D·

E.sub.s)

where A, B, C and D represent constants specific to said reaction.

7. An automated synthesis system as set forth in claim 5, wherein:

said time intervals (t.sub.°

, t_i) and said variable volumes (V_i) calculated by said formulas (1), (2) and (3) and are stored together with information identifying said reaction in a memory of said synthesis control means for reuse in controlling said dispensing of said reagent when carrying out a same synthesis reaction, said synthesis control means controlling the chemical reaction.

8. An automated synthesis system as set forth in claim 5, wherein:

different types of reagents are added by said synthesis control means at several ones of said discrete time intervals, respectively.

9. An automated compound synthesizing apparatus for producing a desired product through a series of synthesis processes, the apparatus comprising:

a synthesis reaction unit;

means for charging a mixture of raw materials and a solvent to said synthesis reaction unit and forming an intermediate product from said raw materials, said intermediate product being in an equilibrium state with said raw materials;

reagent adding means for adding a reagent to said mixture within said synthesis reaction unit, said reagent reacting with said intermediate product to produce the desired product;

means for determining an amount of said mixture of raw materials prior to said adding of said reagent;

means for determining an initial concentration of said raw material in said synthesis reaction unit;

means for determining an initial concentration of said intermediate product in said synthesis reaction unit;

means for determining a ratio of said concentration of said intermediate product to a theoretical equilibrium concentration;

means for determining a stoichiometrical ratio between said reagent and said intermediate product;

means for determining a concentration of said reagent;

computer-based synthesis control means for controlling said reagent adding means such that said reagent is successively added at discrete time intervals and in volumes described by the following formulas ##EQU10## where t_o represents a time duration fulfilled before said reagent is initially added,

t_i represents said discrete time intervals at which said reagent is to be adding after said time duration t_o is fulfilled,

V.sub.°

represents said volume of the raw material mixture before said reagent is initially added,

V_i represents said volumes of the reagent added at time intervals t_i, respectively,

k₁ represents a reaction rate constant specific to said reaction,

K represents an equilibrium constant specific to said reaction,

A represents said initial concentration of the raw material mixture,

α

represents said ratio of concentration of said intermediate product to said theoretical equilibrium concentration,

β

represents said stoichiometrical ratio between said reagent and said intermediate product, and

y represents said concentration of said reagent.

10. An apparatus as set forth in claim 9, wherein:

said means for determining an initial concentration of said raw material in said synthesis reaction unit, and said means for determining an initial concentration of said intermediate product in said synthesis reaction unit, include a concentration sensor; and

said synthesis reaction unit include a gas-liquid boundary sensor and a liquid-liquid boundary sensor;

11. A method of manufacturing a desired chemical comprising the steps of:

providing a synthesis reaction unit;

adding a plurality of raw materials to the synthesis reaction unit;

combining the plurality of raw materials in the synthesis reaction unit to form an intermediate product;

measuring an initial volume of the plurality of raw materials;

measuring an initial concentration ratio of the plurality of raw materials;

measuring a concentration ratio of the intermediate product;

determining a ratio of said concentration of said intermediate product to a theoretical equilibrium concentration;

determining a stoichiometrical ratio between a reagent and said intermediate product;

determining a concentration of said reagent;

adding a variable volume of said reagent to the synthesis reaction unit at discrete time intervals, a first time interval being t.sub.°

, and being determined by the formula ##EQU11## where k₁ represents a reaction rate constant,

K represents an equilibrium constant specific to said reaction,

A represents said initial concentration of the raw materials,

α

represents said ratio of concentration of the intermediate product to said theoretical equilibrium concentration,

and subsequent time intervals being determined by the formula ##EQU12## where i is incremented after each time interval, said volume of reagent being determined by the formula ##EQU13## where V.sub.°

represents said initial volume of the plurality of raw materials,

V_i represents volumes of the reagent added at the time points t_i, respectively,

represents said stoichiometrical ratio between the reagent and the intermediate product, and

represents said concentration of the reagent;

combining said reagent and said intermediate product in said synthesis reaction unit to react and form the desired chemical;

purifying the desired chemical; and

extracting the desired chemical.