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Brief Summary of the Project
Sr. No. Item Details
1. Name & Address of the Project
Balaji Amines Ltd., Plot No.:E-7 & E-8, MIDC Chincholi,
Tal.: Mohol, Dist: Solapur, Maharashtra
2. Name of the applicant & Designation
Mr. N. Rajeshwar Reddy Jt. Managing Director
3. Type of Project
Aliphatic Amines, Derivatives & Chemical unit Manufacturing
Unit
4.
Capacity of Project
Manufacturing set-up shall be for production of 28 products.
Presently 15 products are being manufactured.
5. Land acquired
• Total Land – 16 Ha. • Built - Up Area (Including Road) – 12.3
Ha. • Open Space Available – 2.7 Ha. • Green Belt Area in MIDC plot
– 1 Ha. (37% of open space)
6. Cost of the Project
Total Investment – Rs. 49 Crores.
7. Production Capacities Sr.
No. Product Existing Products Capacity MT/Day
Proposed Products Capacity
MT/Month 1. Mono Methyl Amine (MMA) 30.96 -- 2. Di Methyl Amine
(DMA) 68.88 -- 3. Tri Methyl Amine (TMA) 4.80 432 4. Di Methyl
Amine Hydrochloride
(DMA HCl) 36.48 1092
5. N-Methyl-2-Pyrrolidone (NMP) 33.50 1008 6. 2-Pyrrolidone (2P)
33.50 -- 7. N-Ethyl Pyrrolidone (NEP) 33.50 -- 8. Di Methyl Formide
(DMF) 72.00 840 9. Gama Butyro Lactone (GBA) 33.50 1008 10. Methyl
Di Ethanol amine
(MDEA) 34.50 --
11. Poly Vinyl Pyrrolidone/ PVP Iodine (PVP/PVP Iodine)
6.70 --
12. Mono Ethyl Amine (MEA) 3.36 -- 13. Di Ethyl Amine (DEA) 9.96
-- 14. Tri Ethyl Amine (TEA) 20.04 -- 15. Morpholine (MOR) -- 1080
16. Aceto Nitrile (ACN) -- 1440 17. Di Methyl Carbonate (DMC) --
1666 18. Budesonide (BD) -- 1.5 19. Betamethasone & Its Salts
(BM) -- 1.5 20. Ciclesonide (CN) -- 1.5 21. Flumethasone &Its
Salts (FM) -- 0.525 22. Fluticasone & Its Salts (FC) -- 0.5
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Sr. No. Item Details
23. Beclamethasone Dipropionate (BMD)
-- 0.5
24. 16-Alpha Hydroxy Prednesolone (16-AHP)
-- 0.5
25. Mometasone Furuote (MF) -- 0.5 26. Propylene Glycol (PG) --
1656 27. Mono IsoPropyl Amine (MIPA) -- 504 28. Propylene Carbonate
(PC) -- 432
By Products 1. Higher Amines 4.56 117.12 2. Methyl Tri Ethanol
Amine 1.92 -- 3. Tetra Hydro Furan -- 86.4 4. Hydrogen -- 51.84 5.
Spent Caustic Solution (20%) -- 576 6. Sulpher -- 5.76
8. Air Pollution Control Measures
(A) Details of stack
(a) Stack number
Existing Proposed
Stack-1
Stack-2
Stack-3
Stack-4
Stack-5
Stack-1
Stack-2 Stack-3
(b) Attached to Boiler Boiler
Thermic Fluid Heater
D.G. Set-1
D.G. Set-2
Boiler Thermic Fluid Heater - I
Thermic Fluid Heater - II
(c) Capacity – 35 TPH
8 TPH
30 Lakh Kilo Cal/Hr
1000 KVA
1500 KVA
20 TPH
20 Lakh Kilo Cal/Hr
20 Lakh Kilo Cal/Hr
(d) Fuel type Coal Coal HSD / Hydrogen
HSD HSD Coal Coal Coal
(e) Fuel quantity (kg/hr.)
164 MT/Day
-- 1.920 MT/Day/50 Lit/Hr
100 Lit/Hr
150 Lit/Hr
100 MT/ Day
10 MT/Day
10 MT/Day
(f) Material of construction
RCC M. S M.S M.S M.S M.S M.S M.S
(g) Shape (round/rectangular)
Round
Round
Round Round Round Round Round Round
(h) Height, M (above ground level)
49 M 31 M 20 M 5.5 M 5.5 M 31 M 31 M 31 M
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Sr. No. Item Details
(i) Diameter/size, in meters
1.7 M 0.15 M
0.9 M 0.15 M 0.15 M 1.0 M 1.0 M 1.0 M
(j) Control equipment preceding the stack
ESP, Bag Filter & MDC provided MDC & filter bags will be
installed
(k) Nature of pollutants likely to present in the stack gases
such as Cl2, NOx, SOx, TPM etc.
SPM, SO2, NOx
8 TPH boiler is stand by, whenever 35 TPH boiler is shut down,
only that time 8 TPH will be taken into line
Sr. No. Plant
Process Emissions Diameter
Height
Scrubbing
Media Disposal
Existing Plants 1. Methyl Amines
Plant (MMA, DAM & TMA) Amines & Ammonia
600 mm 10 M
Methanol & Water
Reused
2. Ethyl Amines (MEA, DEA & TEA)
Amines & Ammonia
600 mm 10 M Water
3. Di Methylamine Hydrochloride (DMAHCL)
HCl & DMA 1000 mm 11 M Water
4. N-Methyl Amine Pyrrolidone
Mono Methyl Amine
300 mm 10 M Water
5. 2-Pyrrolidone Ammonia 300 mm 10 M Water
6. Methyl Di Ethanol Amine
Mono Methyl Amine
500 mm 10 M Water
7. Loading & Unloading
Amines & Ammonia
600 mm 5 M Water
Expansion 8. Aceto Nitrile Plant Ammonia &
Acetic Acid 600 mm 10 M Water Reused 9. Morpholine Plant Ammonia
600 mm 10 M Water
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Sr. No. Item Details
9. Water Requirement
Sr. No. Description
Existing M3/Day
Expansion M3/Day
1. Domestic 20 8 2. Industrial a. Processing 8 11
b. Washing 3 5 c. Dilution 37 50 d. Cooling water &
boiler
665 900
Industrial Total 713 (#110 + *603) 966
(#166.8 + *799.2) 3. Other (Gardening) 20 20
Total 753 994 Grand Total 1747
(#276.8 + *1470.2) Note: Out of the total water consumption, 92
CMD of water is recovered from MEE & RO.
# - Treated Effluent being recycled/to be recycled * - Fresh
water 10. Effluent
Generation
Sr. No.
Description Existing (M3/Day)
Proposed (M3/Day)
Total (M3/Day)
1. Domestic 16 6 22
2. Industrial Stream-I a. Processing 157 128.70 290.7 b. Lab
& Washing 5
Stream -II c. Cooling Blow Down
95 20
173 d. Boiler Blow Down 10 e. R.O Reject 48
Industrial Total 252 211.7 463.7
11. Solid Waste Sr. No. Type of Waste Existing Expansion
Disposal
1. Coal Ash
22 MT/Day 10.072 MT/Day
Sold to brick manufacturers for secondary use
2. Wood Pallets -- 2.0 MT/Yr
By Sale
3. Scrap Material -- 50 MT /Yr 4. Carboys Plastic -- 500 Nos /Yr
5. Office Paper
waste -- 1.0 MT/Yr
6. Woven Sack Bag(HDFE)
-- 1.0 MT/Yr
7. Drums -- 7200 Nos /Yr
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Sr. No. Item Details
12. Hazardous Waste
Sr. No.
Type of Waste Existing Expansion Disposal
1 Cat.: 36 - ETP Sludge
444 Kg/Day
144.0 MT/Year
CHWTSDF
2 Cat.: 34.3 - Chemical sludge from waste water treatment
3 Cat.: 33.1 Drums cleaning, Chemical containing residue from
decontamination &disposal
4 Cat.: 20.3 Distillation Residue
55.44 MT/Year
5 Cat.: 35.1 Filters &filter material which have organic
liquids in them
0.6 MT/Year 0.6 MT/Year
6 Cat.: 35.2 Spent Catalyst 3000 Kg/Year
10.0 MT/Year CHWTSDF
7 Cat.: 35.3 Spent Carbon -- 1.0 MT/Year CHWTSDF
8 Cat.: 28.5 Spent organic solvents -- 50.0 MT/Year
Sale to MPCB Authorized party/Authorized co-processor
13. Green Belt Total land area for Aliphatic amines and
derivatives manufacturing unit is 16 Ha. Proposed Green Belt Area–
0.9 Ha. 1000 nos. of trees are planted under the proposed green
belt development plan.
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1 THE MANUFACTURING PROCESSES OF VARIOUS PRODUCTS: 1.1
MANUFACTURING PROCESS OF TRI METHYL AMINES (TMA):
1.1.1 Chemical Reaction:
3 CH3OH + NH3 (CH3)3N+ 3H2O TMA 45 17 (59) 18
1.1.2 Process Description: Typically, the amines is produced by
carrying out the reaction between methanol and ammonia in the
gaseous phase at a high temperature (approximately 380 to 430 0 C)
& high pressure (18 to 25 Kg/Cm2) in the presence of a solid
catalyst, such as alumina, capable of causing dehydration and
amination. Ammonia & amines are mixed in Feed Mixing Tank-1
& 2 in definite proportion in feed mixing tank by re
circulating through a pump to form homogeneous mixture of amines.
From Feed Mixing Tank-1&2, the mixture & methanol from
Storage Tank -3 are sent to a series of heat exchangers (E-1,
E-2&,E-3) to get vaporized & superheated & then is
passed over a catalyst surface at a temperature of 350 Deg. Cen. To
430 Deg. Cen.& pressure of 20-25 atm. Methanol reacts with
ammonia to yield Mono, Di, & Tri Methylamines. The demand for
these methylamine & tri methylamine is considerably smaller
than that of Di Methylamine. For this reason, after being separated
from the reaction product, these by-products are transferred to the
reaction system and re used. The product of the reactor is
consisting of excess of ammonia, un-reacted methanol & amines.
Distillation conducted in order to isolate all amines &
un-converted ammonia, methanol & water from reaction mixture.
In first distillation column ammonia is recovered as top product
and bottom products namely TRI - DI- Mono Methyl Amines & Un
reacted Methanol is sent to second fractional distillation column.
In second distillation column .Tri methylamine recovered as a top
product & bottom products sent to third distillation column. In
third distillation column Mono & Di Methylamine are recovered
as a top product & sent to Fourth distillation column, where
Mono Methylamine recovered as a top product and collected in day
storage tank & from distillation column bottom Di Methylamine
collected in day storage tank. The Mono methylamine & Di
Methylamine recycled back to get more Tri Methylamine Third
distillation column bottom material sent to Fifth distillation
column (Forced evaporator).From fifth column all reaction water
evaporated by steam. All distillation columns vents connected to
vent Absorber to control any process emissions from distillation
columns. All columns vents controlled by pressure control valve. As
per customer requirement, the anhydrous Tri Methylamine mixed with
De mineralized water in the required ratio to make Tri Methylamine
Solution. Normally, the strength of the solution is as follows: 1.
TMA ------------------- 30% Solution.
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1.2 MANUFACTURING PROCESS OF DI METHYL AMINE HYDROCHLORIDE
(DMAHCL) : 1.2.1 Chemical Reaction: (CH3)2NH + HCL (CH3)2NHHCL Di
methyl Hydrochloric Di Methyl Amine Amine Acid Hydrochloride 45
36.5 81.5 1.2.2 Details of Raw Materials Required: Main raw
materials required are Di Methyl Amine & 30% HCL. DMA is
readily taken from the exiting plant & HCL will be purchased
from outside. There will be no solid wastes generated in this
plant. 1.2.3 Process Description: Reaction- Required quantity of
30% HCL is taken into the PP/FRP Reactor & kept under
circulation through the glass Collars, with cooling water supply to
the coolers. After 15 minutes, a sample of the acid is checked for
its percentage of HCL. On the basis of this percentage, the
quantity of DMA (Di Methyl Amine) to be added is calculated &
addition is started slowly at the beginning & later at a rate
of 80 Kg / hr. Addition is adjusted so that the temperature of the
reaction mixture never exceed 400C. Once the calculated quantity of
DMA is added, reaction mixture is checked for 0.5% alkalinity.
After that DMA addition is stopped. The reaction mixture is kept
under circulation for minimum of two Hrs.& transferred to the
storage tank after the alkalinity is ascertained by a final
analysis. Evaporation Process-
Reaction Mixture evaporation is done in Graphite Falling Film
Evaporation Unit under vacuum. Feed reaction mixture is
continuously feed to the Graphite falling film evaporator under
vacuum and maintaining the temperature of 100 to 130 degree
centigrade by steam to concentrate the material up to 80 to 88 % of
DMAHCL (HOT MAGMA). Evaporated water passed through cooling water
condenser to condense reaction water and collected in PP/FRP Tank.
This water is tested for DMAHCL % & DMA content. After testing
the water sent to ETP System to further treatments. The bottom
product from Graphite falling film evaporator collected in PP/FRP
tank. Hot magma collected in the PP/FRP Tank is transferred to
Anchor Cooler A/B/C/D up to 80 % level of that particular anchor
cooler, where it will be cooled to room temperature. After cooling
the hot magma is transferred to Centrifuge Machine using PP/FRP
pipe. The centrifuge machine is run for 10 to 20 minutes till no
more mother liquor comes out of the drain nozzle. After stopping
the centrifuge machine, open the cover of centrifuge machine and
collect the centrifuged DMAHCL by lifting the centrifuge and dump
the material into S.S Hopper of FBD drier, then continuously feed
the centrifuge material from S.S hopper to FBD Drier to get
material dried. After drying the material, pack in 25 Kgs double
liner H.M & HDFE Bag. Drying- Drying is done in a FBD drier
continuously at 100 to 1300C to get desired moisture content
material. Packing- Packing is done in 25 Kg double liner HM &
HDFE bag. Mother Liquor- Once sufficient mother liquor is
collected, the respective storage tank is filled with 60% fresh
reaction mixture & 40% mother liquor for the feeding
purpose.
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1.3. MANUFACTURING PROCESS OF N-METHYL -2-PYRROLIDONE (NMP)
1.3.1. Chemical Equation. NMP is obtained by the reaction of GAMMA
BUTYRO LACTONE and MONO METHYL AMINE. The reaction is as follows.
CH 2 CH 2 CH2 CH2 + CH3NH2 ------ + H2O CH 2 C==O CH2 C==O O N
1.3.2 Details of Raw Materials Required NMP is obtained by the
reaction of GAMMA BUTYRO LACTONE and MONO METHYL AMINE 1.3.3
Process Description. Gamma Butyro Lactone and MMA are reacted under
anhydrous condition at a pressure and temperature. The reaction
mixture is then subjected to a series of distillations. Excess Mono
Methyl Amine is recovered in the first column and water formed in
the reaction is recovered in the second column. Pure
N-Methyl-2-Pyrrolidone is recovered in the third column free from
moisture and un reacted Gamma Butyro Lactone. MATERIAL BALANCE:
PLANT CAPACITY : 33.6 MT/DAY INPUTS: GAMMA BUTYRO LACTONE : 26800
Kgs/Day Mono Methyl Amine : 10900 Kgs /Day OUTPUT; N-Methyl-2-
Pyrrolidone : 33600 Kgs/ day Excess MMA recovered & recycled. :
400 kgs /Day Water (from reaction) : 6000 kgs/Day (will be used in
preparation of Methyl Amine solution) 1.4. MANUFACTURING PROCESS OF
DI METHYL FORMIDE. 1.4.1. Chemical equation. Coke → CO + (CH3)2NH
C3H7NO Carbon Monoxide DMA DMF 1.4.2 .Raw Materials required. Main
Raw Materials are Coke and Di Methyl Amine.
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1.4.3 .Process Description. Di Methyl Form amide (DMF) is
produced by the reaction between liquid DI Methyl Amine (DMA ) and
gaseous Carbon Monoxide ( CO ) in the presence of Sodium Meth oxide
in Methanol as a catalyst. The reaction is exothermic, but
reversible, and so is carried out in the liquid phase at high
pressure, with the gaseous CO injected into the re circulating
product stream. The liquid DMA, the gaseous CO and the liquid
catalyst are injected into the reactor base, with a slight excess
of CO. The catalyst reacts with by-products in the gaseous feed
stream, such as Carbon Dioxide and water to form solid salts, which
settle out in the reactor. These salts are filtered on line and the
crude DMF mixture is sent for recovery in a series of distillation
columns. Crude DMF is doped with water to prevent further reaction
and then the crude is fed to an evaporator, which vaporizes the
DMF. This vapor is fed to the light ends column, where Methanol,
water and any residual traces of DMA are removed. The bottoms
stream from the light ends column is pumped into the product column
and the refined DMF taken off as an overhead stream to the product
tanks. 1.5. MANUFACTURING PROCESS OFGAMMA BUTYRO LACTONE 1.5.1.
Chemical Equation: HOCH2CH2.CH2CH2OH ------ CH2CH2CH2COO + 2H2
90 86 4
1.4 Butanediol Gbl H2 1.5.2. Process Description: Gamma Butyro
Lactone is manufactured by the De-Hydrogenation of 1,4 Butanediol
over a de-hydrogenation catalyst. The catalyst has to be maintained
and operated under an atmosphere of Hydrogen. 1,4-Butanediol is
pre-heated using the reactor outlet gases and fed to the Reactor
along with Hydrogen gas, which is also pre-heated. Hydrogen flow is
maintained in such quantity that the Butanediol feed is completely
vaporized. The reactor outlet stream, containing small quantities
of un reacted Butanediol, Tetra Hydro furan formed in the reaction,
is subjected to a series of distillations to remove the low boilers
first, followed by recovery of Gamma Butyro Lactone. Residue from
the GBL recovery column containing un reacted Butanediol and high
boilers are collected as a byproduct and sale to authorized re
user. The low boilers obtained from the first column, containing
Tetra Hydro Furan recovered as a Byproduct & remaining low
boilers are recycled back to reactor. Hydrogen obtained from the
reaction as a by-product is utilized as fuel in the Boiler.
1.6. MANUFACTIRUNG PROCESS OF MORPHOLINE
1.6.1: Chemical Equation: catalyst HOC2H5OC2H5OH + NH3
CH2CH2CH2CH2ONH + 2 H2O DEG AMMONIA MORPHOLINE WATER 106 17 87
36
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1.6.2: Raw Materials required: 1. Di Ethylene Glycol, Ammonia
& Hydrogen 1.6.3: Process Description: Ammonia & Di
Ethylene Glycol (DEG) is feed to Reactor. Reaction is carried out
under Hydrogen atmosphere in the presence of Copper catalyst. After
reaction, reaction mass goes to separator after cooling, where
gaseous & recycled hydrogen is separated from liquid product.
Recycle hydrogen gas goes back to reactor after passing through
Caustic Scrubber to remove unwanted impurities. Liquid product
contains excess of Ammonia, Water, Morpholine, Other Impurities
& un reacted DEG. This is send to fractional distillation
columns for recovery. In Ammonia column excess of Ammonia is
recovered from the top & sends back to the reactor. Ammonia
column bottoms are fed to De Hydration column. From de hydration
column top water, N Ethyl Morpholine and N Methyl Morpholine are
recovered. Morpholine, DEG and other unknown impurities are
recovered from column bottom & send back to final column. Water
is evaporated out from the top of Dehydration column. In the final
column Morpholine is removed as overhead product. Bottom is sent to
DEG column. In DEG column DEG is recovered as overhead product
& send back to Reactor section. From the bottom Organic high
Boil ups (Higher Amines) are recovered which are stored in Storage
Tank & sold out to Paint industries as a byproduct. 1.7.
PROCESS DESCRIPTION OF ACETO NITRILE. 1.7.1. Chemical equation.
Catalyst CH3COOH + NH3 ------------ CH3CN + 2 H2O Acetic Acid
Ammonia Aceto Nitrile Water 61 17 41 36 1.7.2 .Raw Materials
required. Main Raw Materials are Acetic Acid and Ammonia. 1.7.3
.Process Description. This is a Continuous process. Glacial Acetic
Acid would be charged from Main Storage tank of Acetic Acid to
Acetic Acid day storage tank once in a shift. From this storage
tank would be fed with a Feed pump to a double pipe heat exchanger
at one end, at the rate of 225 to 250 kg/hr. The feed rate would be
adjusted with on line flow transmitter. This Heat Exchanger would
be heated up to 120 -1300 C, by circulating hot Thermic fluid,
which is at a temperature of 3400C.The heated acetic acid that
flows out from other end of Heat Exchanger, is fed to a vaporizer
A. This Vaporizer A is also heated by circulation of hot Thermic
Fluid having a temperature of 3400C.From this Vaporizer- A, vapors
of Acetic Acid generated are passed to the Mixer- M from the bottom
& ammonia at the rate of 70 Kg/hr is mixed with those acetic
acid vapors in the mixer-M. The mixing pot is packed with packing
of SS-316 L, where vapors of acetic acid and ammonia gas get mixed
and enter into the pre heater PH from bottom. The temperature at
the pre heater outlet is expected to 2200C so that Acetamide vapors
are expected to go out of the Pre heater. Then the
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stream consisting Acetamide vapors along with water generated
& the un reacted/excess reactants will come out of pre heater
& will be fed to a second Mixer-M2 which is having same
specification as M1.Recovered ammonia is fed to this mixer-M2 at
the rate of 70 kg/hr as well. Thus Acetamide vapors and ammonia get
mixed ammonia reacts with any free acetic acid here and these
vapors enter main reactor R1 & finally pass through post
reactor R. Ultimately, the conversion expected is 55 % acetonitrile
& 45 % water. This reaction mass is fed to a flash distillation
column FC, where at the top azeotrope of Acetonitrile & water
is withdrawn as a top product & from bottom the reaction water
formed is withdrawn. This FC column is provided with a re boiler
.The column is provided with three condensers in serious namely
C-1, C2 & C3. These condensers are provided with ammonia,
cooling water & chilling water respectively as a cooling media.
The top product recovered from FC is then purified via two pressure
distillation columns to get pure product of Acetonitrile. The un
reacted ammonia would be taken to ammonia recovery system and the
recovered ammonia is reused for the reaction by feeding it to M1.
The FC column bottom material which is rich with water (90%) and
unreacted intermediates and ACN (10%) is cooled through condenser
C-4 and stored in tank T-1. This material from tank T-1 is then
pumped to pre heater PH-2 and heated t up to 2200C with Thermic
fluid at 340oC. The vapors are mixed with ammonia in Mixer M-3.
These vapors are then fed to Reactor R-2, where the vapors are
heated to 3200C. The reaction mass is then fed to Flash
distillation column FC-2. In FC-2 column the rich vapors of organic
flash and go to condenser C-6 & condenser C-7, where they
condense to give 85 % Acetonitrile and 15 % water. This rich
Acetonitrile + water material fed to pressure distillation column
to get pure product. The bottom water rich portion, having 99 %
water and 1% traces of organic material is collected in Tank-T-4 ,
which would go to ETP to for treatment. 1.10. PROCESS DESCRIPTION
OF BUDESONIDE. 1.10.1 CHEMICAL REACTON.
O
CH3
OH
H
HH
O
O
CH3
CH3OH
O
O
CH3
OH
H
CH3
H
OH
O
H
OH
OH
H
16-alpha Budesonide
butyraldehyde
1.10.2. Process Description: Budesonide is produced by carrying
out the reaction between 16-alphahydroxyprednisolone and
butyraldehyde at a temperature (100 C to 150 C) in the presence of
a perchloric acid and using acetonitrile as solvent.16-alpha,
acetonitrile & perchloric acid are mixed in Feed Mixing Tank
through a stiring and cooled the reaction mixture to 100 C, After
completion of reaction budesonide is isolated by quenching the R/M
in water followed by filtration. 1.11. PROCESS DESCRIPTION OF
BETAMETHASONE & ITS SALTS. 1.11.1. CHEMICAL REACTION.
-
HF 70%
Betamethasone DB-11
O
CH3H
CH3O
OH
CH3
OH
O
O
CH3H
CH3 O
OH
CH3
OH
F
OH
REACTION SCHEME FOR MANUFACTURING PROCES BETAMETHASONE
1.11.2 Process description:- Hydrofluoric acid is charged in to
the reactor carefully and cooled to -10 degrees centigrade. Charge
DB-11 slowly over a period of 4-5 hours, maintained at the same
temperature for another 203 hours or till the completion of the
reaction. Dissolve sodium bicarbonate in to water and charge slowly
to the reactor. Allow the reactor temperature to attain room
temperature. Stir for 1 hour and centrifuge. Collect the wet cake
and dissolve in methanol and heat to reflux. Cool to 5-10 degrees
and again centrifuge to get pure Betamethasone. Charge in to VTD
and dry till constant LOD of Less than 0.5%. 1.12. PROCESS
DESCRIPTION OF CICLESONIDE. 1.11.1. CHEMICAL REACTION.
O
CH3 H
OHCH3H
HH
OH
OOH
OHcyclohexane aldehyde
MDC
O
CH3 H
OHCH3H
HH
O
OOH
O
H
16-alpha hydroxy prednisolone not isolated
O
CH3 H
OHCH3H
HH
O
OOH
O
Htriphenyl phosphine
NBS
t-isobutoxide
O
CH3 H
OHCH3H
HH
O
OO
O
CH3 CH3
O
H
O
CH3 H
OHCH3H
HH
O
OO
O
CH3 CH3
O
H
ciclesonide crude
methanol
recrystallisation
pure R-ciclesonide
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1.12.2 Process description:- 16-alpha hydroxy prednisolone is
dissolved in MDC and the mixture is cooled to -10OC, at this
temperature cyclohexane aldehyde is added while stirring. Then
methane sulphonic acid is added over the period of 1 hr at this
temperature and maintained for 5 hrs. after completion of reaction
aq. sodium hydroxide solution is added and organic phase is
separated, then aq. phase is extracted with MDC. To the combined
organic phase triphenyl phosphine is added the resulting mixture is
cooled to 10OC and at that temperature N-bromo succinamide is added
in 1 hr. after completion of reaction MDC is separated by
distillation and resulting material is isolated by adding methanol
stirring at 50OC cool and then filtration. The centrifuged material
is dissolved in Dimethyl sulphoxide and to it sodium isobutoxide is
added slowly at 40OC after completion of reaction the R/M is
quenched in water and material is extracted with MDC, from it after
distillation of MDC material is separated with can purified with
methanol to get pure R-Ciclesonide. 1.13. PROCESS DESCRIPTION OF
FLUMETHASONE & ITS SALTS. 1.13.1. CHEMICAL REACTION
O
CH3H
CH3
O
OHOH
CH3
O Acetic anhydride
benzoyl chloride
select fluor
HF
8-DM
O
CH3H
CH3OH
CH3
O
OO
CH3
O
O
CH3H
CH3O
OH
CH3
OO
CH3
O
F
O
CH3H
CH3O
OH
CH3
OO
CH3OH
F
F
O
O
CH3H
CH3O
OH
CH3
OO
CH3
O
O
CH3H
CH3O
OH
CH3
OH
OH
F
F
stage 1st
satge 2ndstage 3rd
stage 4th Flumethasone
Flumethasone
1.13.2 Process description:-
Synthesis of Flumethasone from 8-DM involves 5 stages.
-
Stage 1st:-Acetylation of 8-DM carried out by acetic anhydride
in pyridine at 10OC. after completion of reaction product is
isolated by quenching the R/M in water followed by filtration.
Stage 2nd:- Benzoylation of stage 1st is carried out by using
Benzoyl Chloride in Dimethyl Acetamide and pyridine at 80OC. After
completion of reaction excess Benzoyl chloride is decomposed by
methanol and product is separated by quenching the R/M in water and
then extracted with MDC, from MDC layer product is isolated by
distillation. Stage 3rd:- Flurination of stage 2nd carried out by
using select fluor as fluorinating agent and Acetonitrile as
solvent. After completion of reaction material is separated by
quenching the R/M in solution of SMBS, ammonia and water and
fluorinated compound is extracted with MDC. Product is isolated by
distillation of MDC followed by methanol purification. Stage4th:-
Difluorination of monofluoro compound carried out by using aq. HF
acid at -10OC. after completion of reaction excess HF acid is
neutralized by sodium bicarbonate solution and product is separated
by filtration. Stage 5th :- Finally Flumethasone is prepared by
hydrolyzing difluoro compound i.e. stage 4th by KOH and using MDC
as solvent at 10OC. after completion of reaction excess KOH
neutralized with acetic acid and by distillation of MDC
Flumethasone isolated. 1.14. PROCESS DESCRIPTION OF FLUTICASONE
& ITS SALTS. 1.14.1. CHEMICAL REACTION
-
O
CH3H
CH3O
OH
CH3
OH
OH
F
F
NaIO4
THFO
CH3H
CH3O
OH
CH3
OHOH
F
F
FlumethasoneFlumethasone Acid
Fluticasone manufacturing reaction SchemeSTAGE- I
O
CH3H
CH3O
OH
CH3
OHOH
F
F
Flumethasone Acid
STAGE- II
Propionyl Chloride
Triethyl Amine
O
CH3
H
CH3O
O
CH3
OOH
F
F
OCH3
CH3
O
Di Ethyl AmineO
CH3H
CH3O
O
CH3
OHOH
F
F
CH3
O
Flumethasone Propionate Ester
O
CH3
H
CH3O
O
CH3
OHOH
F
F
CH3
O
STAGE- III
Flumethasone Propionate Ester
N,N-dimethyl thiocarbomyl Ester
Triethyl amineSodium IodideMethyl ethyl Ketone O
CH3H
CH3O
O
CH3
SOH
F
F
CH3
O
ON
CH3
CH3
Thio CarbomylEster
STAGE- IV
O
CH3
H
CH3O
O
CH3
SOH
F
F
CH3
O
ON
CH3
CH3
Thio CarbomylEster
Morpholine
O
CH3
H
CH3O
O
CH3
SHOH
F
F
CH3
O
Thio Acid
STAGE- V
O
CH3
H
CH3O
O
CH3
SHOH
F
F
CH3
O
Thio Acid
Bromo Fluoro MethanePotassium Carbonate
O
CH3
H
CH3S
O
CH3
OOH
F
F
CH3
O
F
Fluticasone Propionate
1.14.2 Process description of Fluticasone & Its Salts:-
Stage 1st:-Dissolve Flumethasone in THF at room temperature.
Prepare sodium metaperiodate in after and add to Flumethasone
solution for 2-3 hours. After completion of the addition maintain
the reaction mass for another 2 hour till TLC complies. After
completion of the reaction chill to 0 degs. Filter the reaction
mass trough Nutch filter. Stage 2nd :- In to a clean reactor charge
acetone and stage 1st material and stir until complete dissolution.
Cool the reaction mass to 0-10 degs using brine solution. Add
Triethyl amine slowly over a period of 30 minutes. Slowly add
propionyl chloride in acetone for a period of 2-3 hours and
maintain the reaction mass for 4-6 hours till the completion of
reaction and complies to TLC. Raise the temperature and send the
sample to QC, If complies add HCL and water. Cool to 10 degrees and
filter through Nutch filter. Stage-3rd :- Charge Ethyl methyl
Ketone and Flumethasone propionate Ester in to the reactor stir
until complete dissolution. Add slowly thiocarbomyl chloride for
the period of 5-6 hours at room temperature. Maintain for another 1
-3 hours till the completion of the reaction. Charge after and
filter the cake trough Nutch filter Stage - 4th:- Charge Morpholine
in to clean reactor and also charge the stage-III material, stir
till complete dissolution. Maintain the reaction mass at room
temperature for 3-5 hours. After completion of the reaction add
purified water in to the reactor. Add toluene and methyl ethyl
Ketone and stir, adjust the pH using
-
hydrochloric acid and separate the layers. Concentrate the
organic layer under vacuum. Cool the reaction mass to 5-10 degs and
filter through Nutch filter. Stage 5th :-. Charge acetone and stage
IV material, stir at 0O C and then slowly add the solution of bromo
fluoro methane and acetone, after completion of reaction add the
solution of potassium carbonate and water, cool th reaction mass to
5-10O C and filter & dry the material to get pure material of
Fluticasone. 1.15. PROCESS DESCRIPTION OF BECLAMETHASONE
DIPROPIONATE. 1.15.1. CHEMICAL REACTION
O
CH3H
CH3
O
OH
CH3HO
OHTEOP
L-Glutamic acid
Propionic anhydride
pyridine
O
CH3H
CH3
O
O
CH3H
CH3
O
OH
O
O
CH3H
CH3
O
O
CH3H
O
CH3 O
O
CH3
O
O
CH3H
CH3
O
O
CH3H
O
CH3 O
O
CH3
Cl
OH HCL
DB-11
Beclomethasone dipropionate
stage 2nd
stage 3rd
1.15.2 Process description of Beclomethasone Dipropionate:-
Synthesis of Beclomethasone from DB-11 involves 4 stages. Stage 1st
:-propionation of DB-11 carried out by using TEOP as propionating
agent and toluene as solvent at 70OC. after completion of reaction
the R/M is washed with water to separate unreacted TEOP and product
is in toluene layer , from the distillation of toluene stage 1st
material is isolated. Stage 2nd :- stage 1st is hydrolysed to stage
2nd by L-glutamic acid and using aq. methanol as solvent. After
completion of reaction methanol is separated by distillation and
product is isolated by filtration. Stage 3rd :- dipropionation is
carried out by using prop ionic anhydride and pyridine as solvent.
After completion of reaction pyridine is decomposed by adding HCl
and product is isolated by quenching the R/M in water followed by
filtration. Stage 4th :- chlorination is carried out by HCl using
MDC as solvent at -10OC. after completion of reaction the material
is isolated by quenching in water and then extracted with MDC, from
which product is separated by distillation and then product is
purified by using ethyl acetate. 1.16. PROCESS DESCRIPTION OF
16-ALPHA HYDROXY PREDNESOLONE. 1.16.1. CHEMICAL REACTION
-
O
CH3
OH
H
CH3
H
OH
OHO
H
O
CH3
OH
H
CH3
H
O
O
H
CH3
O
OH
O
CH3
OH
H
CH3
H
O
O
H
CH3
O
O CH3
O
O
CH3
OH
H
CH3
H
O
H
O CH3
O
O
CH3
OH
H
CH3
H
OH
O
H
O
OH
CH3
O
O
CH3
OH
H
CH3
H
OH
O
H
OH
OH
H
PDS
16-alpha
stage 2nd
stage 3rd stage 4th
stage 5th
Reaction scheme for PDS to 16-alpha:-
1.16.2 Process description of 16 Alpha Hydroxy Prednesolone.
Preparation of 16-alpha from PDS involves 6 stages. Stage 1st :- it
involves the acetylation of PDS by using TEOA as acetylating agent
in DMF and toluene at 70OC. after completion of reaction the R/M is
washed with water to separate DMF and product is in toluene layer ,
from the distillation of toluene stage 1st material is isolated
which is further hydrolyzed to stage 2nd by L-glutamic acid and
using aq. methanol as solvent. Stage 3rd :- stage 3rd is prepared
from stage 2nd by acetylation by using acetic anhydride and
pyridine at 10OC, after completion of reaction the product is
isolated by quenching the R/M in water followed by filtration.
Stage 4th :- from stage 3rd dehydration is carried out by potassium
acetate using DMF and toluene as solvent at reflux temperature,
after completion of reaction toluene is separated by distillation
and product is isolated by quenching the R/M in water followed by
filtration. Stage 5th :- oxidation of stage 4 is carried out by
using KMnO4 as oxidizing agent and acetone as solvent at -10OC.
after completion of reaction the KMnO4 is decomposed by using
sodium hydrogen sulfite in which KMnO4 is reduced to MnO2 residue.
as product is extracted by using acetone. Stage 6th:- The oxidized
compound is subjected to hydrolysis by using KOH and methanol as
solvent at 10OC. After completion of reaction the R/M is
concentrated by
-
distillation of solvent and then the product 16-alpha is
isolated by quenching the R/M in water followed by filtration.
1.17. PROCESS DESCRIPTION OF MOMETASONE FURUOTE. 1.17.1. CHEMICAL
REACTION.
O
CH3H
CH3
OOH
OH
CH3
O1. Pyridine
2. LiCl
1.TEA
2.Furfuroyl chloride
1. HCl
2. Acetic acid
8-DM
O
CH3H
CH3OH
CH3
O
Cl
O
stage 1st
satge 2ndMometasone furoate
O
CH3H
CH3O
O
CH3
Cl
O O
O
O
CH3H
CH3O
O
CH3
Cl
OHO
O
Cl
1.17.2 Process description of Mometasone Furuote:- Synthesis of
mometasone furuoate from 8-DM involves 3 stages. Stage 1st:- To a
solution of 8-DM and pyridine slowly added p-toluene sulphonyl
chloride and lithium chloride to carryout chlorination after
completion of reaction water is added and the material is extracted
with MDC, material is isolated after completion removal of solvent
by distillation. Stage 2nd :- To the stage 1st furfuroyl group is
introduced by furfuroyl chloride using chloroform as solvent at 0-5
O C. Stage 3rd :- finally Mometasone furuoate is prepares by
chlorination to stage 2nd using HCl at 0OC . after completion of
reaction the material is isolated by quenching the R/M in water
followed by filtration. And then the Mometasone furuoate is is
treated with charcoal. 1.18 PROCESS DESCRIPTION OF DI METHYL
CARBONATE, PROPYLENE GLYCOL AND PROPYLENE CARBONATE. 1.18.1.
Reaction:- CH3CHCH2O + CO2 → CH3C2H3O2CO Propylene Oxide + Carbon
Dioxide → Propylene Carbonate CH3C2H3O2CO + 2 CH3OH → CH3OCOOCH3 +
HOCH2CHOHCH3
-
Propylene Carbonate + Methanol → Propylene Glycol + Di Methyl
Carbonate 1.18.2. Raw Material Required: Propylene Oxide, Carbon
Dioxide, Methanol and catalyst. 1.18.3.Process: In first step
comprises the reaction of propylene oxide and carbon dioxide are
reacted usually in the presence of a catalyst and gives a reaction
solution containing Propylene Carbonate. In second step comprises
the trasesterification of propylene carbonate and methanol in the
presence of a catalyst and gives Dimethyl Carbonate and Propylene
Glycol. From second reactor material containing Methanol and
Dimethyl carbonate fed to First distillation column to separate out
any un converted Methanol and recycled back to second reactor and
Dimethyl carbonate collected as pure product. Remaining product
containing Propylene Carbonate and Propylene Glycol is recovered
another distillation column as a finished product. Some excess
propylene carbonate recycled back to reactor and Propylene Glycol
collected as a product. FLOW SHEET FOR MANUFACTURING OF METHYL
AMINES MMA, DMA & TMA
TMA Col. Sec.
1507 Kg /hr
Recovered Ammonia (35 Kgs/Hr
DMA(150 Kg/Hr)
MeoH Col Sec
DH COL. SEC.
Final Col Sec.
Fresh Methanol (968 Kg/Hr)
Methanol
MMA(100Kg/h
TMA (600 Kg/Hr) Recovered MMA & DMA(250 Kg/hr)
O/H(250 Kg/Hr)
Reactor Sectin
Ammonia & Amines
Fresh ammonia (192 Kgs/Hr)
Recovered Methanol (62 Kg /Hr)
Amm. Col. Sec
622 Kgs/Hr
Effluent Water (560 Kg /Hr)
-
FLOW SHEET FOR MANUFACTURING OF DIMETHYL AMINE HYDROCHLORIDE (
DMAHCl)
3437 Kg/hr
3437 Kg/hr
4837 2917 Kg/hr
1517 Kg DMAHCL
Anhydrous DMA (854 Kg/hr)
Packing
Magma Anchor Cooler Soln.
Centrifuge Drying
2063 Kgs/hr
Storage tank
30% HCL
Reactor Feeding tank
Water to ETP(1400)
Evaporation units 3437 Kg/hr
1920
-
FLOW SHEET FOR MANUFACTURING OF N-METHYL-2-PYRROLIDONE
GBL (205)
R II R III
1430)
DH Column
(1635)
Flash Vessel
HE I
HE II
NMP Column
NMP (1400)
GBL (1270+205)
MMA Water Column
MMA (150)
Line Mixture
MMA (425+150)
R I
(30 as Higher Amines) (265) water to MA plant
Figures in bracket are in Kg/hr
MMA Column (415) (2050)
-
FLOW SHEET FOR MANUFACTURING OF DI METHYL FORAMIDE
FLOW SHEET FOR MANUFACTURING OF GAMA BUTYRO LACTONE
CO (470)
DMA (20) CO (34)
Sodium Formate & Catalyst (2)
To ETP Figures in bracket are in Kg/hr
DMF (1170)
3012
(11 NM3) N2
Catalyst (10)
Reactor Rectification Column
Stripper Column
DMA (150)
(30) N2
(1224)
Distillation column
Distillation column
1, 4 Butenedoil (1628) Pre Heater (1628) (1556) Reactor
Hydrogen (72) Boiler THF(120)
1400 gbl (1436)
Figures in bracket are in Kg/hr
(36) Higher Amines
-
FLOW SHEET FOR MANUFACTURING OF MORPHOLINE
(380) (2655)
Caustic Lye
55 Kg/Hr
(2921
H2 ( 55 Kg / Hr.)
Recovered Ammonia (66 Kg / Hr.)
Final Column
DEG Column
Morpholine (1500 Kg /Hr.)
(1880)
Ammonia Column 2721
De Hydration Column
Water (775 Kg/ Hr.)
For Evaporation
DEG 2283 Kg/Hr.)
Reactor
Ammonia (412 Kg/Hr.)
Recycle Gas (55 Kg/ Hr.)
DEG (200 Kg / Hr.)
Reactor
Spent Caustic Lye (By Product)
800 Kg / hr
H.A 180 Kg / hr 600 Kg / hr
Fresh H2(15)
-
FLOW SHEET FOR MANUFACTURING OF ACETO NITRILE
FLOW SHEET FOR MANUFACTURING OF PROPYLENE CARBONATE,DI
METHYL CARBONATE & PROPYLENE GLYCOL
Figures in bracket are in Kg/hr
Water (1850) to ETP
720
(465)
Ammonia recovery Column
Distillation Column (3132)
Acetic acid
Ammonia
Reactor
Re cycle Ammonia
D. Residue (2)
ACN (2000)
10 Kg/hr
CO2 (1473) Ethylene
Carbonate (248)
DMC (600)
Reactor-I
Reactor-II & Distillation
Distillation
Distillation DMC (2000)
Propylene Glycol (2300)
Catalyst-A
Methanol + DMC
Propylene Carbonate + PG
PO (1940)
Catalyst-B
Methanol (2145)
Figures in bracket are in Kg/hr Distillation column residue
-
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