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

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

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

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

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.

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.

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.

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.

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

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

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

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

4

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