proposed unit of apis & api intermediates in pipodara, tal: mangrol, dist: surat...

1

FORM-1

for

PROPOSED UNIT OF APIs & API INTERMEDIATES IN

PIPODARA, TAL: MANGROL, DIST: SURAT

of

M/S. VASOYA INDUSTRIES P. LTD.

PLOT NO. A2/N-59, EAKTA INDUSTRIAL ESTATE,

TEMPA GALI, N.H. 8, PIPODARA, TAL: MANGROL, DIST:

SURAT (GUJ.)

NABL Accredited Testing Laboratory

ISO 9001:2008 Certified Company

Aqua-Air Environmental Engineers P. Ltd.

403, Centre Point, Nr. Kadiwala School, Ring

Road, Surat - 395002

Prepared By:











Prepared By:

2

APPENDIX I

(See paragraph - 6)

FORM 1

(I) Basic Information

Sr.

No.

Item Details

1. Name of the project/s M/s. VASOYA INDUSTIRES P. LTD.

2. S. No. in the schedule 5(f)

3. Proposed capacity/area/length/tonnage to

be handled/command area/lease

area/number of wells to be drilled

Please refer Annexure – I

4. New/Expansion/Modernization New

5. Existing Capacity/Area etc. NA

6. Category of Project i.e. ‘A’ or ‘B’ ‘A’

7. Does it attract the general condition? If yes,

please specify.

No

8. Does it attract the specific condition? If yes,

please specify.

No

9. Location Plot No. A2/N-59, Eakta Industrial Estate,

Tempa Gali, N.H. 8, Pipodara, Tal: Mangrol, Dist:

Surat (Guj.)

Plot/Survey/Khasra No. A2/N-59,

Village Eakta Industrial Esate, Pipodara

Tehsil Kim

District Surat

State Gujarat

10. Nearest railway station/airport along with

distance in kms.

Nearest Railway Station: Kim (15 km)

Nearest Airport: Surat (35 km)

11. Nearest Town, city, District Headquarters

along with distance in kms.

Town: Kim = 15 km

District Headquarter: Surat = 35 km

12. Village Panchayats, Zilla Parishad, Municipal

Corporation, local body (complete postal

address with telephone nos. to be given)

Pipodara

13. Name of the applicant M/s. VASOYA INDUSTRIES P. LTD.

14. Registered Address M/s. VASOYA INDUSTRIES P. LTD.

Plot No. A2/N-59, Eakta Industrial Estate,

Tempa Gali, N.H. 8, Pipodara, Tal: Mangrol,

Dist: Surat (Guj.)

15. Address for correspondence:

Name Mr. Rajeshbhai S. Vasoya

Designation (Owner/Partner/CEO) Director

Address M/s. VASOYA INDUSTRIES P. LTD.

E-202, Rushikesh Township, Sarathana

Jakatnaka, Varachha, Surat-395006 (Guj.)

Pin Code 395006

E-mail [email protected]

Telephone No. Mobile: +919898083583

Fax No. --

3

16. Details of Alternative Sites examined, if any.

Location of these sites should be shown on a

topo sheet.

NA

17. Interlinked Projects No

18. Whether separate application of interlinked

project has been submitted?

No

19. If yes, date of submission No

20. If no, reason No

21. Whether the proposal involves

approval/clearance under: if yes, details of

the same and their status to be given.

(a) The Forest (Conservation) Act, 1980?

(b) The Wildlife (Protection) Act, 1972?

(c) The C.R.Z. Notification, 1991?

No

22. Whether there is any Government

Order/Policy relevant/relating to the site?

No

23. Forest land involved (hectares) No

24. Whether there is any litigation pending

against the project and/or land in which the

project is propose to be set up?

(a) Name of the Court

(b) Case No.

(c) Orders/directions of the Court, if any and

its relevance with the proposed project.

No

Capacity corresponding to sectoral activity (such as production capacity for manufacturing, mining

lease area and production capacity for mineral production, area for mineral exploration, length for

linear transport infrastructure, generation capacity for power generation etc.,)

(II) Activity

1. Construction, operation or decommissioning of the Project involving actions, which will cause

physical changes in the locality (topography, land use, changes in water bodies, etc.)

Sr.

No.

Information/Checklist confirmation Yes/

No

Details thereof with approximate

quantities frates, wherever possible) with

source of information data

1.1 Permanent or temporary change in land

use, land cover or topography including

increase intensity of land use (with

respect to local land use plan)

No Proposed project site is within Pipodara.

Capital Cost of the project is Rs. 800 Lakh

1.2 Clearance of existing land, vegetation and

Buildings?

Yes Minor site clearance activities shall be

carried out.

1.3 Creation of new land uses?

No

1.4 Pre-construction investigations e.g. bore

Houses, soil testing?

No

1.5 Construction works?

Yes For detail Please refer Annexure – II

1.6 Demolition works? No --

1.7 Temporary sites used for construction No --

4

works or housing of construction

workers?

1.8 Above ground buildings, structures or

earthworks including linear structures,

cut and fill or excavations

Yes For detail Please refer Annexure – II

1.9 Underground works mining or tunneling?

No

1.10 Reclamation works?

No

1.11 Dredging?

No

1.12 Off shore structures?

No

1.13 Production and manufacturing processes?

Yes For detail Please refer Annexure -III

1.14 Facilities for storage of goods or

materials?

Yes Areas for storage of raw materials and

finished products will be available.

1.15 Facilities for treatment or disposal of solid

waste or liquid effluents?

Yes Details of the Liquid Effluent is given as

Annexure – V and details of solid waste is

given as Annexure –VI.

1.16 Facilities for long term housing of

operational workers?

No

1.17 New road, rail or sea traffic during

Construction or Operation?

No

1.18 New road, rail, air waterborne or other

transport infrastructure including new or

altered routes and stations, ports,

airports etc?

No

1.19 Closure or diversion of existing transport

routes or infrastructure leading to

changes in traffic movements?

No

1.20 New or diverted transmission lines or

Pipelines?

No

1.21 Impoundment, damming, culverting,

realignment or other changes to the

hydrology of watercourses or aquifers?

No

1.22 Stream crossings?

No

1.23 Abstraction or transfers of water form

ground or surface waters?

Yes Water Source: Ground Water

1.24 Changes in water bodies or the land

surface

No

5

Affecting drainage or run-off?

1.25

Transport of personnel or materials for

construction, operation or

decommissioning?

Yes The construction material including

cement, structural steel, stones, sand,

bricks, tiles, etc. will be transported via

trucks/ trailers to the site. Also the

construction job will be given on contract

basis thus manpower will be arranged by

the same party. The separate project team

will be allocated for this project.

1.26 Long-term dismantling or

decommissioning or restoration works?

No

1.27 Ongoing activity during decommissioning

which could have an impact on the

environment?

No

1.28

Influx of people to an area either

temporarily or permanently?

Yes As the construction party will be on

contract basis, it will temporary increase

population. But after construction stage,

the new recruitment of the employees will

be done from local area which can have

minor impact on the population.

1.29 Introduction of alien species?

No

1.30 Loss of native species or genetic diversity?

No

1.31 Any other actions? No

6

2. Use of Natural resources for construction or operation of the Project (such as land, water, materials

or energy, especially any resources which are non-renewable or in short supply):

Sr.

No.

Information/checklist confirmation Yes/No Details there of (with approximate

quantities frates, wherever possible) with


2.1 Land especially undeveloped or agricultural

land (ha)

No

2.2 Water (expected source & competing users)

unit: KLD

Yes Water Source: Ground Water

Please refer Annexure – IV.

2.3 Minerals (MT) No

2.4 Construction material - stone, aggregates,

and / soil (expected source - MT)

Yes Construction materials, like steel, cement,

crushed stones, sand, rubble, etc. required

for the project shall be procured from the

local market of the region.

2.5 Forests and timber (source - MT) No.

2.6 Energy including electricity and fuels

(source, competing users) Unit: fuel (MT),

energy (MW)

Yes Power requirement:

150 KVA

Source :DGVCL

DG Set = 150 KVA

(It will be kept for emergency power back

up)

Fuel Requirement:

Diesel = 200 Lit/Month

Natural Gas = 690 Sm3/Month

2.7 Any other natural resources (use

appropriate standard units)

No

3. Use, storage, transport, handling or production of substances or materials, which could be

harmful to human health or the environment or raise concerns about actual or perceived risks to

human health.

Sr.

No.

Information/Checklist confirmation Yes/No Details there of (with approximate

quantities/rates, wherever possible) with


3.1 Use of substances or materials, which are

hazardous (as per MSIHC rules) to human

health or the environment (flora, fauna, and

water supplies)

Yes For detail please refer Annexure – VIII

3.2 Changes in occurrence of disease or affect

disease vectors (e.g. insect or water borne

diseases)

No

3.3 Affect the welfare of people e.g. by changing

living conditions?

No

7

3.4 Vulnerable groups of people who could be

affected by the project e.g. hospital patients,

children, the elderly etc.

No

3.5 Any other causes No

4. Production of solid wastes during construction or operation or decommissioning (MT/month)

Sr.

No.

Information/Checklist confirmation Yes/No Details there of (with approximate

quantities/rates, wherever possible)

with source of information data

4.1 Spoil, overburden or mine wastes No

4.2 Municipal waste (domestic and or commercial

wastes)

No

4.3 Hazardous wastes (as per Hazardous Waste

Management Rules)

Yes Please refer Annexure –VI

4.4 Other industrial process wastes No

4.5 Surplus product No

4.6 Sewage sludge or other sludge from effluent

treatment

Yes

Please refer Annexure- VI

4.7 Construction or demolition wastes No

4.8 Redundant machinery or equipment No

4.9 Contaminated soils or other materials No

4.10 Agricultural wastes No

4.11 Other solid wastes No

5. Release of pollutants or any hazardous, toxic or noxious substances to air (Kg/hr)

Sr. No. Information/Checklist confirmation Yes/No Details there of (with approximate



5.1 Emissions from combustion of fossil fuels

from stationary or mobile sources

Yes Please refer as Annexure – VII

5.2 Emissions from production processes Yes Please refer as Annexure – VII

5.3 Emissions from materials handling storage or

transport

Yes The construction materials such as stones,

cements, bricks & coal may pollute the air

by dust particles. But it will be controlled

by covering the trucks & trailers by

clothes during transportation.

5.4 Emissions from construction activities

including plant and equipment

Yes

During construction work, the Nearby

buildings area will be covered by sheets

or clothes to avoid dust Contamination in

air.

5.5 Dust or odors from handling of materials

including construction materials, sewage and

waste

No

5.6 Emissions from incineration of waste No

8

5.7 Emissions from burning of waste in open air

(e.g. slash materials, construction debris) No

5.8 Emissions from any other sources No

6. Generation of Noise and Vibration, and Emissions of Light and Heat:



with source of information data with


6.1 From operation of equipment e.g. engines,

ventilation plant, crushers

Yes The Noise level will be within the

prescribed limit. At noisy area, adequate

preventive & control measures will be

taken. No significant noise, vibration or

emission of light & heat from the unit.

6.2 From industrial or similar processes Yes -do-

6.3 From construction or demolition No

6.4 From blasting or piling No

6.5 From construction or operational traffic No

6.6 From lighting or cooling systems No

6.7 From any other sources No

7. Risks of contamination of land or water from releases of pollutants into the ground or into sewers,

surface waters, groundwater, coastal waters or the sea:




7.1 From handling, storage, use or spillage of

hazardous materials

No All the raw material shall be stored

separately in designated storage area

with safely measures. For detail please

refer Annexure – VIII

7.2 From discharge of sewage or other effluents

to water or the land (expected mode and

place of discharge)

No

7.3 By deposition of pollutants emitted to air

into the and or into water

No

7.4 From any other sources No

7.5 Is there a risk of long term build up of

pollutants in the environment from these

sources?

No

9

8. Risk of accidents during construction or operation of the Project, which could affect human

health or the environment




8.1 From explosions, spillages, fires etc. from

storage, handling, use or production of

hazardous substances

Yes For detail please refer Annexure – VIII

8.2 From any other causes No

8.3 Could the project be affected by natural

disasters causing environmental damage

(e.g. floods, earthquakes, landslides,

cloudburst etc)?

No

9. Factors which should be considered (such as consequential development) which could lead to

environmental effects or the potential for cumulative impacts with other existing or planned

activities in the locality

Sr. No.

Information/Checklist confirmation

Yes/No

Details there of (with approximate



9.1 Lead to development of supporting. lities, ancillary development or development stimulated by the project which could have impact on the environment e.g.

• Supporting infrastructure (roads, power

supply, waste or waste water treatment,

etc.)

• housing development

• extractive industry

• supply industry

• other

Yes For detail please refer Annexure – IX

9.2 Lead to after-use of the site, which could

have an impact on the environment

No

9.3 Set a precedent for later developments No

9.4 Have cumulative effects due to proximity

to other existing or planned projects with

similar effects

No

10

(II) Environmental Sensitivity

Sr.

No.

Areas Name/

Identity

Aerial distance (within 15km)

Proposed project location boundary

1 Areas protected under international

conventions, national or local legislation for

their ecological, landscape, cultural or

other related value

- Proposed project site is within

Pipodara, Dist: Surat

2 Areas which important for are or sensitive

Ecol logical reasons - Wetlands,

watercourses or other water bodies,

coastal zone, biospheres, mountains,

forests

-

3 Area used by protected, important or

sensitive Species of flora or fauna for

breeding, nesting, foraging, resting, over

wintering, migration

- No protected area or sensitive species

within 15 km from the proposed

project site.

4 Inland, coastal, marine or underground

waters

-

5 State, National boundaries

- N.A.

6 Routes or facilities used by the public for

access to recreation or other tourist,

pilgrim areas

- N.A.

7 Defense installations - N.A.

8 Densely populated or built-up area Kim 15 Km away from project site

9 Area occupied by sensitive man-made land

uses Hospitals, schools, places of worship,

community facilities)

- N.A.

10 Areas containing important, high quality or

scarce resources (ground water resources,

surface resources, forestry, agriculture,

fisheries, tourism, minerals)

- N.A.

11 Areas already subjected to pollution

environmental damage. (those where

existing legal environmental standards are

exceeded)or

- N.A.

12 Are as susceptible to natural hazard which

could cause the project to present

environmental problems (earthquake s,

subsidence ,landslides, flooding erosion, or

extreme or adverse climatic conditions)

- N.A.

IV). Proposed Terms of Reference for EIA studies: For detail please refer Annexure – X

11

I hereby given undertaking that the data and information given in the application and enclosures

are true to the best of my knowledge and belief and I am aware that if any part of the data and

information submitted is found to be false or misleading at any stage, the project will be rejected

and clearance given, if any to the project will be revoked at our risk and cost.

Date: Feb. 6, 2017

Place: Surat

For VASOYA INDUSTRIES P. LTD.

Rajeshbhai. S. Vasoya

(Director)

NOTE:

1. The projects involving clearance under Coastal Regulation Zone Notification, 1991 shall submit

with the application a C.R.Z. map duly demarcated by one of the authorized agencies, showing

the project activities, w. r. t. C.R.Z. (at the stage of TOR) and the recommendations of the State

Coastal Zone Management Authority (at the stage of EC). Simultaneous action shall also be taken

to obtain the requisite clearance under the provisions of the C.R.Z. Notification, 1991 for the

activities to be located in the CRZ.

2. The projects to be located within 10 km of the National Parks, Sanctuaries, Biosphere

Reserves, Migratory Corridors of Wild Animals, the project proponent shall submit the map duly

authenticated by Chief Wildlife Warden showing these features vis-à-vis the project location and

the recommendations or comments of the Chief Wildlife Warden thereon (at the stage of EC).

3. All correspondence with the Ministry of Environment & Forests including submission of

application for TOR/Environmental Clearance, subsequent clarifications, as may be required from

time to time, participation in the EAC Meeting on behalf of the project proponent shall be made

by the authorized signatory only. The authorized signatory should also submit a document in

support of his claim of being an authorized signatory for the specific project.

12

LIST OF ANNEXURES

SR. NO. NAME OF ANNEXURE

I List of products with their production capacity

II Layout Map of the Plant

III Brief Manufacturing Process Description with Chemical and Mass Balance

IV Details of Water Consumption Wastewater Generation

V Effluent Treatment Scheme

VI Details of Hazardous /Solid Waste Generation, Handling and Disposal

VII Details of Air pollution Control System (Stack & Vent)

VIII Details of Hazardous Chemicals Storage & Handling

IX Socio-economic Impacts

X Proposed Terms of Reference for EIA studies

13

ANNEXURE – 1

LIST OF PRODUCTS WITH THEIR PRODUCTION CAPACITY

Sr.

No.

NAME OF PRODUCTS DRUG TYPE PROPOSED

QUANTITY

(MT/Month)

Group-A (APIs)

1 Eslicarbazepine Acetate Anti -Epiletic

10

2 Oxcarbazepine Anti -Epiletic

3 Dapoxetine Hydrochloride Anti- Depressant

4 Dobutamine Hydrochloride Cardiac Drug

5 Edaravone Anti Oxidant

6 Flupirtine Maleate Anti Parkinsonian Agent

7 Topiramate Anti- Convulsant

8 Levosulpirride Antagonist

9 Metaxalone Muscle Relaxant

10 Metoprolol Succinate Anti Hypertensive

11 Modafinil Cns Stimulant

12 Dexmethylphenidate Cns Stimulant

13 Quetiapine Fumarate Anti Psychotic

14 Carbamazepine Epilepsy

15 Rivaroxaban Anticoangulant

16 Betahistine dihydrochloride Anti-vertigo

17 Flurbiprofen Anti Inflammatory

18 Aripiperazole Bipolar Disorder

Group-B (API Intermediates)

19 N-(2-methyl-5-nitrophenyl)guanidine Nitrate

15

20 3-dimethylamino-l-pyridin-3-ylpropenone

21 (2-methyl-5-nitrophenyl)-(4-pyridin-3-ylpyrimidin-2-yl)amine

22 1-(2-(2-Hydroxyethoxy)ethyl piperazine (HEEP)

23 3-(Dimethylamino)propiophenone hydrochloride

24 N,N-Dimethyl-3-phenyl-3-hydroxypropylamine

25 N,N-Dimethyl-3-(2-methylphenoxy)-3-phenylpropylamine oxalate

26 3-Dimethylamino-1-(2-thienyl)-1-propanone hydrochloride

27 N,N-Dimethyl-3-hydroxy-3-(2-thienyl)-1-propylamide

28 N,N-Dimethyl-3-(1-naphthoxy)-3-(2-thienyl)-1-propylamine

oxalate

29 10-Methoxy Iminostilbene

Total 25

14

LIST OF RAW MATERIALS

SR. NO. Name of Raw Materials CAPACITY (MT/MONTH)

1. Eslicarbazepine Acetate

Oxcarbazepine 0.1667

Ruthenium catalyst 0.0167

MDC 1.1667

DMF 0.3333

Formic acid 0.1667

Triethylamine 0.2167

NaHco3 0.0167

Acetone 0.8333

DMAP 0.0083

Acetyl chloride 0.1000

2. Oxcarbazepine

10-Methoxy Iminostilbene 3.0000

Sodium Cyanate 1.4400

MDC 12.0000

Acetic Acid 9.0000

Conc. Hydrochloric acid 4.5000

Methanol 18.0000

Methanol ( washing ) 3.0000

hYflow super cell 0.1500

Activated carbon 0.0600

3. Dapoxetine Hydrochloride

Dapoxetine hydrochloride stage-1 0.1724

Caustic lye 0.3845

Ethyl acetate 1.2069

10% Sodium chloride solution 0.1724

Sodium sulphate 0.0172

IPA HCl 0.2586

4. Dobutamine Hydrochloride

Dobutamine -1 0.1786

Glacial acetic acid 0.5714

Hydrobromic acid 0.8321

Hydrochloric acid 0.1071

Isopropyl alcohol 1.4482

Norrit cap charcoal 0.0179

15

Hyflo 0.0071

5. Edaravone

Methanol 0.3808

Phenyl Hydrazine Hcl 0.0962

Methane Sulfonic Acid 0.0029

Methylacetoacetate 0.0923

Cyclohexane 0.5769

Sodium Chloride 0.0712

Methylene Dichloride 0.5077

Sodium Bicarbonate 0.0096

Activated Carbon 0.0019

Hyflow super cell 0.0010

IPA 0.1923

6.Flupirtine Maleate

2-Amino-6-chloro-3-nitropyridine 0.5556

Pottasium carbonate 0.5111

4-Flouro benzylamine 0.4222

Raney Nickel 0.0833

Hydrazine hydrate 0.7778

Isobutanol 4.4444

Ethylchloroformate 0.4167

Maleic acid 0.5500

7.Topiramate

D-Fructose Pyranuse 0.5682

Acetone 3.3409

Sulphuric acid( C.P. Grade ) 0.6307

Sodium Hydroxide Lye 1.3636


Toluene 2.9205

Hexane 1.3011


Sulfuryl Chloride 0.4716


Sodium chloride 0.1307

Sodium hydroxide lye 0.1307

MDC 1.1761

Acetic acid 0.1307

Eno carbon 0.0341

16

8.Levosulpiride

Methyl 5-(aminosulfonyl)2-methoxy benzoate 0.1786

2-(s)-(Amino methyl)-1-Ethyl pyrrolidine 0.1000

Methanol 1.9643

Hydrochloric acid C.P Grade 0.0893

Ammonia Liquor 0.2554

9.Metaxalone

Dimethylformamide 0.3615

3,5-Dimethylphenol 0.3846

Triglycidyl isocynurate 0.3462

KOH Flakes 0.0077

Methanol 3.0769

Eno-acticromos carbon 0.0077

10.Metoprolol Succinate

4-Methoxy ethyl Phenol 0.3448

Epichlorohydrin 0.3138

TBAB 0.0034

Sodium hydroxide lye 0.3586


Mono Isopropyl Amine 0.2931

succinic acid 0.1310

Acetone 2.1069

Hyflow supercel 0.0034


11.Modafinil

Diphenylmethyl sulfanyl acetamide 2.2222

Acetic acid 6.6667

hydrogen peroxide 1.2000

Methanol 22.2222

12.Dexmethylphenidate

Dl-threo Ritalinic acid 0.0244

Dibenzoyl tarteric acid 0.0444

Methanol 0.6341

Toluene 0.0488

CP HCl 0.0122

Acetone 0.0732

Thionyl chloride 0.0122

Sodium hdroxide 0.0034

17

MDC 0.0976

IPA 0.0610

IPA Hcl 0.0068

13.Quetiapine Fumarate

2-Amino diphenyle sulfide 1.4388

Sodium Hydroxide flakes 0.4173

Toluene 8.6331

Phenyl chloroformate 1.6403


Polyphosphoric acid 11.5108

Acetone 4.5036

N,N-Dimethyl aniline 0.8345

Phosphorous oxychloride 0.6763


Sodium sulphate 0.2014

Toluene 11.5108

Triethanolamine 0.8345

Hydroxy ethoxyrthyl piparazine 0.8345

Sodium bicarbonate 0.2878

1N HCL 0.2878

Hyflosupercel 0.0719

Methanol 17.2662

Fumaric acid 0.5180

14.Carbamazepine

Iminostilbenecarbonyl chloride 2.4390


Ammonia Hydroxide(25%) 3.4146

Acetone 12.1951

Hyflo super cell 0.1220


15.Rivaroxaban

4-(4-Aminophenyl)morpholin-3-one 0.0100

2-[(2s)-oxiran-2-ylmethyl]-1H-isoindol-1,3(2H)-dione 0.0137

IPA 0.1400

N,N-carbonyldiimidazole 0.0100

DMAP 0.0002

Toluene 0.1200

40% Methylamine solution 0.0160

18

Methanol 0.1500

CP Hcl 0.0200

MDC 0.0500

5-chlorothiophene-2-carbonylchloride 0.0094

Pottasium carbonate 0.0126

16.Betahistine dihydrochloride

2-vinyl pyridine 0.0313

Methylamine hydrochloride 0.0400

Chloroform 0.1563

sodium hydroxide 0.0225

Acetic acid 0.0031

IPA 0.1250

IPA HCl(20%) 0.0688

17. Flurbiprofen

sodium salt of Flurbiprofen 0.1429

Toluene 0.2857

Hydrochloric acid 9CP grade) 0.1429



Hydflosupercel 0.0071

Petrolium ether 0.5714

18.Aripiperazole

7-Hydroxy-3,4-dihydroQuinoline 0.0741

1-Bromo-4-chloro Butane 0.4444

Sodium Hydroxide 0.0244

n-Propanol 0.3704

Cyclohexane 0.1481

Triethylamine 0.0593

DCPP Hcl 0.0593

Methanol 0.0370

Intermediates

19. 3 Dimethylamino -1-Pyridin-3-ylpropenone

3-Acetyl Pyridine 0.0909

Dimethylformamide dimethylacetal 0.1164

Toluene 0.1636

Hexane 0.0709

20. N-(2- methyl -5-nitrophenyl) Guanidine Hydrochloride

19

2-Methyl 5- Nitroaniline 0.0510

Hydrochlorid acid-CP Grade 0.0352

Cynamide L-500 solution 0.0423

Liqour ammonia 0.0372

Acetonitrile 0.1592

21. (2- methyl -5- nitrophenyl)-(4- pyridine-3-ylpyrimidin -2- yl)amine

Dimethylformamide 0.5186

3-dimethylamino-l-pyridin-3-ylpropenone 0.1379

N-(2-methyl-5-nitrophenyl)guanidine Nitrate 0.1669


Hexane 0.3586

22. 1-(2-(2-Hydroxyethoxy)ethyl piperazine (H.E.E.P)

Piperazine 1.5000

2-chloroethoxyethanol 1.2750

CP HCl 0.7500

Methanol 7.5000

Caustic lye 3.0000

23. 3-(Dimethylamino)propiophenone hydrochloride

Acetophenone 0.2276

IPA 0.5234

Dimethyl amine HCl 0.1821

Paraformaldehyde 0.0683

CP Grade HCl 0.0228

Acetone 0.3641

Acetone for washing 0.0910

24. N,N-Dimethyl-3- phenyl -3- hydroxyl propylamine

Methanol 0.2800

3-(Dimethylamino)propiophenone hydrochloride 0.4000

Sodium Hydroxide Flakes 0.0800

Sodium Borohydride 0.0400

Purified water +CP HCl (1:1) 0.6520

Caustic Lye sol.+ Purified Water (1:1) 0.4000

MDC 2.6600

Sodium Sulphate 0.0800

Hexane 0.7880

25. N,N –Dimethyl-3- (2- methyl phenoxy )-3- phenylpropylamine oxalate

Dimethylsulphoxide 0.7538

N,N-Dimethyl-3-phenyl-3-hydroxypropylamine 0.2513

Pottasium t-Butoxide 0.2186

20

2-flouro Toluene 0.2161

CP HCl+Purified water(1:1) 0.3769

Hexane 0.5025

Purified water+ NaOH (W/V) (1:1) 0.3769

Ethyl Acetate 1.7889


Oxalic Acid 0.1784

Acetone 0.3970

26. 3-Dimethylamino-1-(2-thienyl)-1-Propanone hydrochloride

2-Acetyl thiophene 0.0694

IPA 0.1625

Dimethyl amine HCl 0.0569

Paraformaldehyde 0.0208

CP HCl 0.0083

Acetone 0.1389

27. N,N- Dimethyl-3-hydroxy-3- (2- thienyl)-1- propylamide

Methanol 0.0933

3-Dimethylamino-1-(2-thienyl)-1-propanone

hydrochloride

0.1333

Sodium Hydroxide Flakes 0.0267

Sodium Borohydride 0.0133

Purified water +CP HCl (1:1) 0.2173

Caustic Lye sol.+ Purified Water (1:1) 0.1333

28. N,N- Dimethyl-3- (1- naphthoxy)-3- (2-thienyl)-1- propylamine oxalate

Dimethylsulphoxide 0.7538

N,N-Dimethyl-3-phenyl-3-hydroxypropylamine 0.2513

Pottasium t-Butoxide 0.2186

2-flouro Naphthalene 0.2161

CP HCl+Purified water(1:1) 0.3769

Hexane 0.5025

Purified water+ NaOH (W/V) (1:1) 0.3769



Oxalic Acid 0.1784

Acetone 0.3970

29. 10-Methoxy Iminostilbene

Iminostilbene carbonyl chloride 11.2500

Acetic acid 33.7500

Bromine 33.7500

21

Toluene 90.0000

Methyl chloroformate 16.8750

22

ANNEXURE – 2

PLANT LAYOUT

23

ANNEXURE – 3

MANUFACTURING ACTIVITIES

• Organic Synthetic Product

1) ESLICARBAMAZEPINE ACETATE:

Manufacturing Process:

Stage-1:

Oxcarbazepine React with solution of formic acid and triethylamine in presence of (s,s)-

TsDpen-Ru(p-cymene)cl at Reflux temperature to give eslicarbazepine.

Stage-F

Eslicarbazepine react with Acetyl chloride anhydride in the presence of Dimethylamino

pyridine catalyst to form Eslicarbazepine acetate-Final .

CHEMICAL REACTION:

N

O

ONH2

Oxcarbazepine

Molecular Formula = C15H12N2O2

Formula Weight = 252.26798

N

ONH2

OH



N

ONH2

O

O

CH3

Molecular Formula = C17

H16

N2O

3


Eslicarbazepine Final

Eslicarbazepine

N

ONH2

OH



Eslicarbazepine

DMAP

Acetyl chloride

Formic acid

Triethyl amine

24

Flow Diagram:

Oxcarbazepine

Ruthenium catalyst

MDC

Methanol

Formic acid

Triethylamine

NaHCO3 Solution

Reaction Mixture

Residue of Stage-1

Acetone

DMAP

Acetyl chloride

Process water

Reaction mixture

Water for washing

wet cakeDrying

Final packing

REACTOR

Distillation

REACTOR

Centrifuge

25

Mass Balance:

Input Ton Output Ton

OXCARBAZEPINE 1.67 Air Waste 0.08

Ruthenium catalyst 0.17 Aqueous waste 10.00

MDC 11.67 Distilled residue 2.50

DMF 3.33 Product 1.00

Formic acid 1.67 MDC Recovery 11.08

Triethylamine 2.17 MDC Loss 0.58

NaHCO3 0.17 DMF Recovery 3.20

Acetone 8.33 DMF Loss 0.13

DMAP 0.08 Acetone Recovery 8.08

Acetyl chloride 1.00 Acetone loss 0.25

Process Water 6.67

Total 36.92 Total 36.92

2. OXCARBAMAZEPIN:

MANUFACTURING PROCESS:

stage – 1

10-methoxy iminostillbene (OXC – 3) will get carbamylation in presence of sodium cyanate

followed by acitic acid further hydrolyzed by using Hydrochloric acid.

Stage - F

Oxcarbazepine final stage involves purification in Methanol .

CHEMICL REACTION:

NH

O

CH3

N

O

NH2O

MF:C15H14N2O2

FW:254.28

Oxcarbazepine stage-Crude

10-methoxy iminostilbene

Molecular Formula: C15H15NOFormula Weight: 225.2857

N

O

NH2O

MF:C15H14N2O2

FW:254.28

Oxcarbazepine stage-Crude

Sodium cyanate

ClH

N

O

NH2O

oxcarbazepine

Molecular Formula: C15H14N2O2

Formula Weight: 254.28386

CH3 OH

26

Flow Diagram:

10-Methoxy Iminostilbene

Sodium Cyanate

MDC

Acetic Acid

Conc. Hydrochloric acid

Reaction Mixture

Methanol

Methanol ( washing )

Wet cake

Reactor

Distillation

Drying (FBD)

Mass Balance:

Input ton Output ton

10- Methoxy Iminostilbene 1 Air waste 0.05

Sodium Cyanate 0.5 Aqueous waste 5.5

MDC 4 Distillation residue 0.48

Acetic acid 3 Product 1

Conc. Hydrochloric acid 1.5 Spent carbon+hyflow 0.07

Methanol 6 MDC Recovery 3.8

Methanol (washing) 1 MDC Loss 0.2

hYflow super cell 0.05 Methanol Recovery 5.76

Activated carbon 0.02 Methanol loss 0.24


3. DAPOXETINE HYDROCHLORIDE:


Stage-1:

N, N-dimethyl-3-(naphthalen-1-yloxy)-1-phenylpropan-1-amine hydrochloride react with D-

tartaric acid and undergoes resolution of form Dapoxetine hydrochloride stage-1.

Stage-Final:

Dapoxetine hydrochloride stage-1 under goes hydrolysis in the presence of Sodium hydroxide to

form Dapoxetine hydrochloride final.

27

CHEMICAL REACTION:

N

CH3

CH3

O

ClH

N,N-dimethyl-3-(naphthalen-1-yloxy)-1-phenylpropan-1-amine hydrochloride

Molecular Formula: C21H24ClNO


Sodium hydroxideWater/Ethyl acetate

D-Tartaric acid

N

CH3

CH3

O

OHOH

O

O OH

OH

Molecular Formula: C25H29NO7


N

CH3

CH3

O

ClH



Dapoxetine hydrochloride Final

Sodium hydroxideIPA. HCl

CH2

CH2

N

CH3

CH3

O

OHOH

O

O OH

OH



DPH stage-1

DPH stage-1

Flow Diagram:

28

Process waterDapoxetine hydrochloride stage-1Ethyl acetateCaustic lyeEthyl acetateCombined product (Ethyl acetate layer)Process water10% Sodium chloride solutionSodium sulphate

Reaction MixtureWashing with Ethyl acetate

Product enriched filtrateIsopropyl alcohol + HClEthyl acetateEthyl acetate

Reaction MixtureEthyl acetate

Wet Cake

FINAL PACKINGDAPOXETIN

HYDROCHLORIDE FINAL

REACTOR

FILTRATION BAG FILTER

orMICRON FILTER

REACTOR

CENTRIFUGE

DRYINGTRAY DRYER

SIFTING

MULTIMILL

29

Mass Balance:


Dapoxetine Hydrochloride stage-1 1.47 Air Waste 0.07

Process water 6.04 Aqueous waste 7.06

sodium hydroxide 1.65 spent sodium sulphate 0.15

Ethyl acetate 10.29 Distillation residue 1.18

Sodium chloride 0.15 Product 1.00

Sodium sulphate 0.15 Ethyl Acetate Recovery 9.78

IPA HCl 2.21 Ethyl acetate loss 0.51

IPA HCl Recovery 2.12

IPA HCl Loss 0.09


4.DOBUTAMINE HYDROCHLORIDE:


Dobutamine -1 subsequent demethylation in presence of Hydrobromic acid and hydrochloric

acid to gives dobutamine hydrochloride.

CHEMICAL REACTION:

H3CO

H3CO NH

CH3

OCH3

HCl

Molecular Formula = C21H30ClNO3


OH

OH NH

CH3

OH

HCl



Dobutamine-crude

NH

CH3

OHOH

OH HCl

NH

CH3

OHOH

OH HCl

Dobutamine-Final

IPA

ClH

BrH



Dobutamine-crude



Dobutamine -1

30

Flow Diagram: Glacial acetic acid

Hydrobromic acid

Dobutamine -1

Hydrochloric acid

Process water

Wet cake

Purification

Isopropyl alcohol

Purified water

Hydrochloric acid

DBN-Crude

Sodium metabisulphite

Isopropyl alcohol

Isopropyl alcohol

Purified water

DBN-wet cake

Norrit cap charcoal

Hyflo

Hydrochloric acid

Isopropyl alcohol

Wet cakeDrying (TD)

Reactor

Drying (TD)

Reactor

Purification

Mass Balance:


Dobutamine -1 1.79 Air Waste 0.09

Glacial acetic acid 5.71 Aqueous Waste 18.66

Hydrobromic acid 8.32 spent carbon+ hyflow 0.25

Hydrochloric acid 1.07 Iso Propyl Alchol Recovery 13.75

Process water 4.29 ISO Propyl Alchol Loss 0.73

Isopropyl alchol 14.48 distillation residue 1.43

Norrit Cap Charcoal 0.18 Product 1.00

Hyflo 0.07


31

5. EDARAVONE:


Phenyl Hydrazine reacts with Methyl acetoacetate and undergoes condensation reaction

followed by Cyclization reaction to form Edaravone.

CHEMICAL REACTION:

NHNH2

+ CH3 O

CH3

O O

NN

OH

O


Formula Weight: 176.17202Molecular Formula: C5H8O3


Molecular Formula: C6H8N2


Flow Diagram

32

Methanol

Phenyl Hydrazine Hcl

Methane Sulfonic Acid

Methylacetoacetate

Cyclohexane

Sodium Chloride

Methylene Dichloride

Sodium Bicarbonate

Process Water

Activated Carbon

Reaction Mixture

Wash with MDC

Reaction Mixture

Cyclohexane

Reaqction Mixture

washing for cyclohexane

Wet cake

PURIFICATION

3.5 time in L Isopropyl

Alcohol (each lot) (wet dry

of Edaravone cude)

Edaravone HCl crude

Activated Carbon (each lot)

Reaction Mixture

Hyflow super cell (each lot)

Washing with IPA

Reaction Mixture

Washing IPA

Wet Cake

REACTOR

SPARKLER

FILTER

MICRON FILTER

REACTOR

CENTRIFUGE

DRYING TRY

DRYER

GLASS ASEMBLY

SPARKLER

FILTER

CENTRIFUGATI

ON

DRYING TRY

DRYER

Mass Balance:


Methanol 7.62 Air waste 0.10

Phenyl Hydrazine HCl 1.92 Aqueous Waste 8.75

Methane Sulfonic Acid 0.06 Methanol Recovery 7.62

Methylacetoacetate 1.85 Methanol Loss 0.38

Cyclohexane 11.54 Cyclohexane Recovery 11.08

Sodium Chloride 1.42 Cyclohexane Loss 0.46

Methylene Dichloride 10.15 Mehylene Dichloride Recovery 9.87

Sodium Bicarbonate 0.19 Methylene Dichloride Loss 0.29

Process Water 3.65 IPA Recovery 3.77

Activated Carbon 0.04 IPA Loss 0.08

Hyflow super cell 0.02 Distillation residue 0.38

IPA 3.85 spent carbon+hyflow 0.06

Product 1.00

Total 42.31

42.31

33

6. FLUPIRTINE MALEATE:


Stage-1

ACNP react with 4-FBA in presence of basic medium to form ANFP.

Stage-2

ANFP reduction with hydrazine hydrate to form diamine to react ethylchloroformate to

Form flupirtine hydrochloride.

Stage-3

Flupirtine hydrochloride react with maleic acid in presence base to form flupirtine maleate

CHEMICAL REACTION:

NO

O

NH2Cl

Molecular Formula: C6H5ClN2O2


+

NH2

F

Molecular Formula: C7H8FN


Naco3

NH

F

NH2

N

O

O

Molecular Formula: C13H12FN3O2


NH

F

NH2

N

O

O



+Cl O CH3

O

Molecular Formula: C3H5ClO2


NH2 NH2NH

F

NH2

NH

O

CH3

O

ClH

Molecular Formula: C16H19ClFN3O2


NH

F

NH2

NH

O

CH3

O

ClH

Molecular Formula: C16

H19

ClFN3O

2


+ OH

OH

O

O

Molecular Formula: C4H4O4


TEA NH

F

NH2

NH

O

CH3

O

OH

OH

O

O



34

Flow Diagram:

2-Amino-6-chloro-3-nitropyridine

Process water

Pottasium carbonate

4-Flouro benzylamine

Process water

Wet cake

Stage-1

Raney Nickel

Hydrazine hydrate

Isobutanol

Reaction mass

Ethylchloroformate

Process water

Maleic acid

Isobutanol

Wet cake

Centrifuge

Dryer

Reactor

Centrifuge

Dryer

Reactor

Sparkler filter

Reactor

Mass Balance:


2- Amino 6- chloro -3- nitropyridine 0.56 Air waste 0.06

Process water 9.44 Spent catalyst 0.08

Potassium carbonate 0.51 Aqueous waste 11.11

4- Flouro Benzylamine 0.42 Isobutanol Recovery 4.22

Raney Nickel 0.08 ISOBUTANOL Loss 0.22

Hydrazine Hydrate 0.78 distillation residue 0.51

Isobutanol 4.44 Product 1.00

Ethylchloroformate 0.42

Maleic acid 0.55


35

5.Topiramate: TOPIRAMATE CRUDE:


Step-I: Bis-acetonide formation

1 mole D-(-)-Fructose reacts with 2 mole Acetone in the presence of 1 mole Sulfuric acid which

gives 1 mole of this Step-I with the by-product 3 mole Water and 1 mole Sulphur trioxide (gas).

Step-Final

1 mole Step-I reacts with 1 mole Sulfuryl chloride and then 1 mole Ammonia (gas) in the

solvent media which gives 1 mole of this Step-Final (Topiramate) with the by-product 2

mole Hydrochloric aci

CHEMICAL REACTION:

O

OH

OH

OH

OH

OH

H2SO4

CH3 CH3

O

2+

MF:C6H12O6

FW:180.15

MF:C3H6O

Acetone

FW:2X58.08 (116.16)

D-(-)-Fructose

Sulfuric acid

MF:H2SO4

FW:98

CH3

CH3

O

O

O

O

O

OH

CH3

CH3

MF:C12H20O6

FW:260.28

2,3,4,5-Bis-O-(1-Methyl-ethylidene)-

B-D-Fructopyranose

3 H2O

Water

MF:H2O

FW:3X18 (54)

SO3

+

+ +

Sulfur trioxide (gas)

MF: SO3

FW: 80.07

SO2Cl

2

Sulfuryl chloride

MF:SO2Cl

2

FW:134.97

NH3(gas)

Ammonia(gas)

MF:NH3

FW:17.03

+

CH3

CH3

O

O

O

O

O

CH3

CH3

O

SOO

NH2

MF:C12

H21

NO8S

FW:339.36

Topiramate, Stage-Crude

2HCl

Hydrochloric acid

MF:HClFW:2X36.5 (73)

CH3

CH3

O

O

O

O

O

OH

CH3

CH3

MF:C12

H20

O6

FW:260.28

2,3,4,5-Bis-O-(1-Methyl-ethylidene)-

B-D-Fructopyranose

+

+

36

Flow Diagram stage-1:

Acetone

Sulphuric acid( C.P. Grade )

D-Fructose PyranuseSodium Hydroxide Lye

Reaction mass

Toluene for washing

Product enriched organic layer

Purified water

Product enriched organic layerHexane

Isopropyl alcohol

Reaction mass

Hexane for Washing

Toluene

Wet cake

Slurry of Activated Carbon in toluene

Toluene for Washing

Product enriched Filtrate

Hexane

Isopropyl alcohol

Reaction mass

Hexane for Washing

Wet cake

Distillation

Neutch filter

Drying ( ND )

Reaction

Neutch filter

Distillation

Neutch filter

Dissolution &

Charcoliazation

Mass Balance stage-1:


D- Fructose Pyranuse 1.1 Air Waste 0.1

Acetone 6.5 Aqueous Waste 4.4

Sulpheric acid (C.P. Grade) 1.2 Acetone Recovery 6.2

Sodium Hydroxide Lye 2.7 Acetone Loss 0.3

Activated Carbon 0.0 Toluene Recovery 5.5

Toluene 5.7 Toluene Loss 0.2

Process Water 1.2 Hexane Recovery 2.5

Hexane 2.5 Hexane loss 0.1

Isopropyl Alchol 0.5 Isopropyl Alchol Recovery 0.5

0.0 Isopropyl Alchol Loss 0.0

0.0 Distillation residue 0.6

0.0 spent carbon 0.1

0.0 Product 1.0


37

Flow Diagram Stage-final Ethyl acetate

Sulfuryl Chloride

2,3:4,5-bis-O-(1-methylethylidene)-3-D-fructopyranose

Pyridine

Purified Water


Sodium chloride solution in purified water


Ethyl acetate

Ammonia gas purging

Eno carbon

Ethyl acetate for Washing

Product enriched Filtrate + Washing ML

Purified water

Sodium Hydroxide Solution in Purified water

Reaction mass

MDC for Washing

Reaction massAcetic acid

Reaction mass

Process water for Washing

Wet cakeDrying ( FBD )

Centrifuge

Reactor

Distillation ,

Ammonolysis &

Chacolisation

Distillation & pH

Adjustment

Reactor

pH Adjustment

Mass Balance Stage-final:


2,3:4,5-bis- o-(1- methylethylidene)-3 -d- fructopyranose 1.02 Air Waste 0.05

Sulfuryl Chloride 0.85 Ethyl Acetate Recovery 11.05

Ethyl Acetate 11.63 Ethyl Acetate Loss 0.58

Purified Water 15.48 MDC Recovery 2.03

Sodium Chloride 0.23 MDC Loss 0.08

Sodium Hydroxide lye 0.23 Aqueous waste 17.00

MDC 2.11 Carbon waste 0.06

Acetic acid 0.23 Product 1.00

Eno Carbon 0.06


38

8. LEVOSULPIRIDE:


Methyl-5-(amino sulphonyl)-2-methoxy benzoate react with 2-(S)-(Aminomethyl)-1-ethyl

Pyrrolidine in the presence of Methanol to form Levosulpiride.

CHEMICAL REACTION:

S NH2O

O

OCH3

O

O

CH3

Molecular Formula = C9H11NO5S


+N

CH3

NH2

H

Molecular Formula = C7H16N2


S NH2O

O

OCH3

O

N

CH3

NHH

Molecular Formula = C15H23N3O4S


Methyl-5-(amino sulfonyl) 2-(S)-(AMinomethyl)-1-ethyl pyrrolidine-2-methoxy benzoate

Levosulpiride

Flow Diagram

Methyl 5-(aminosulfonyl)2-methoxy benzoate

2-(s)-(Amino methyl)-1-Ethyl pyrrolidine

Methanol

Process Water

Hydrochloric acid C.P Grade

Reaction Mixture

Process Water for Washing

Charged Product enriched Filtrate

Ammonia Liquor

Reaction Mixture

Process Water for Washing

Wet Cake

Purification

Methanol

Levosulpiride Crude dry material

Activated Carbon

Reaction Mixture

Methanol for washing

MICRON FILTER

Charged Product enriched Filtrate

Reaction Mixture

Methanol for Washing

Wet Cake

IF REQUIRED MILLING

: MULTIMILL :

IF REQUIRED SIFTING :

SIFTER:

IF REQUIRED

MICRON ISATION:

AIR JET MIL

FINAL PACKING OF

LEVOSULPIRIDE

STAGE-FINAL

DRYING:

VACUUM TRAY

DRYER:

CENTRIFUGATION :

CENTRIFUGE:

NUTSCHE FILTER

Reactor

REACTOR

CENTRIFUGATION:

CENTRIFUGE:

DRYING:

VACUUM TRAY

DRYER:

REACTOR

SPARKLER FILTER

REACTOR

39

Mass Balance:


Methyl 5-(aminosulfonyl)2- methoxy benzoate 0.89 Air Waste 0.04

2-(S)- (Amino methyl)-1- Ethyl Pyrrolidine 0.50 Aqueous Waste 3.41

Methanol 9.82 Methanol Recovery 9.33

Process Water 1.79 Methanol Loss 0.49

Hydrochloric acid C.P Grade 0.45 Distillation residue 0.45

Ammonia Liquor 1.28 Product 1.00


9. METAXOLONE:


Stage-1

Charge DMF, 3,5-Dimethyl phenol, TGIC & potassium hydroxide flakes in to reactor, stir and heat the

content, check TLC after reaction completion then charge purified water in to reactor, stir the content

and centrifuge then dry.

Stage-Final

Charge methanol, Process water & metaxalone stage-1in to reactor, stir & heat the content, Sparkler filter,

stir & cool the content, centrifuge, wash the wet cake with with methanol. Dry the product in a FBD till

LOD complies.

CHEMICAL REACTION:

CH3

CH3

OH

MF:C8H10O

FW:122.16

3,5-dimethylphenol

+N

N

N

O

OO

O

O

O



O

NH

O

O

CH3

CH3



40

FLOW DIAGRAM

Dimethylformamide

3,5-Dimethylphenol

Triglycidyl isocynurate

KOH Flakes

Purified water

Reaction Mixture

Purified water for wash

Methanol+Purified water

MTX stage-final wet cake

Reaction Mixture


for washing

Purification

Methanol

MTX-Final Dry Material

Eno-acticromos carbon

Methanol for wash

Filtered ML

Purified water


for washing

CENTRIFUGATIO

N

CENTRIFUGATIO

N

DRYING

NAUTA DRYER

REACTOR

SPARKLER

FILTER

REACTOR

REACTOR

CENTRIFUGATIO

N

REACTOR

SIFTING

MICRONISATION

METAXALONE

STAGE-FINAL

PACKING

DRYING

NAUTA DRYER

MILLING

MASS BALANCE :


Dimethylformamide 0.72 Air Waste 0.08

3,5- Dimethylphenol 0.77 Aqueous Waste 4.82

Triglycidyl isocynurate 0.69 Methanol Recovery 5.85

KOH Flakes 0.02 Methanol Loss 0.31

Purified Water 3.85 distillation residue 0.15

Methanol 6.15 Spent carbon 0.02

Eno- acticromos carbon 0.02 Product 1.00


41

10. METOPROLOL SUCCINATE:


Stage: 1

4-methoxyethylphenol react with epichlorohydrine in presence of sodium hydroxide and water afer

completion of reaction organic layer react with monoisopropylamine in presence of isopropyl alcohol to

give metoprolol stage-1

Stage: Final

Metoprolol Succinate stage-1 Distilled out IPA.charged Acetone & activated carbon in to reactor, stir &

heat the content. Filter through sparkler followed by micron. Transfer the filtrate in to another

reactor,add Succinic acid solution, stir & cool the content, centrifuge the reaction mixture, wash wet cake

with Acetone.

CHEMICAL REACTION:

Metoprolol succinate, Stage-Final

OH

O CH3

O

Cl

4-(2-methoxy ethyl) phenolMF:C9H12O2

FW:152.1

Epichlorohydrin

MF:C3H5ClO

FW:92.5

Metoprolol Base

MF:C30H50N2O6

FW:2X267.3(534.6)

COOH

COOH

Succinic acid

MF:C4H6O4

FW:118.0

O

O CH3

NH

CH3

CH3OH

2

COOH

COOH

Metoprolol succinate

FW:652.8

MF:C34H56N2O10

O

O CH3

NH

CH3

CH3OH

2

CH3

CH3

NH2

Diethyl amine

MF:C3H9N

FW:59.1

Metoprolol Base

MF:C15H25NO3

FW:267.3

O

O CH3

NH

CH3

CH3OH

HCl

Hydrochloric acid

FW:36.5

MF: HCl

+ +

+

+

42

FLOW DIAGRAM

Epichlorohydrin

4-Methoxy ethyl Phenol

TBAB

Purified water

Sodium hydroxide lye

Isopropyl alcohol

Mono Isopropyl Amine

MPS crude Epoxide

Acetone

Hyflow supercel

Activated Carbon

Hot Acetone for SF wash

Filtrate ML

Succinic acid solution

Reaction Mixture

Acetone for wash

Wet Cake

MILLING

SIFTING

MICRONISATIO

N

MICRON

FILTER

REACTOR

CENTRIFUGATI

ON

WET CAKE

DRYING

NAUTA DRYER

A/D-201/301

SPARKLER

FILTER

REACTOR

MPS-EPOXIDE

REACTOR

METOPROLOL

SUCCINATE

FINAL

PACKING

(625 Kg)

43

MASS BALANCE :


4- Methoxy ethyl Phenol 0.69 Air Waste 0.03

Epichlorohydrin 0.63 Aqueous Waste 5.17

TBAB 0.01 Isopropyl Alchol Recovery 0.34

Purifed water 3.45 Isopropyl Alchol Loss 0.02

Sodium Hydroxide lye 0.72 Acetone Recovery 4.05

Isopropyl alcohol 0.36 Acetone Loss 0.17

Mono Isopropyl Amine 0.59 Distillation residue 0.14

Succinic acid 0.26 Spent carbon+hyflow 0.02

Acetone 4.21 product 1.00

Hyflow supercel 0.01



11. MODAFINIL:


Stage-I

Diphenylmethyl sulfanyl acetamide react with hydrogen peroxide in presence acidic medium to

give modafinil crude.

Stage-Final

Modafinil purify in methanol to modafinil final.

CHEMICAL REACTION:

H2O2

S

NH2

O

O

S

NH2

O

2-[(diphenylmethyl)sulfanyl]acetamide

Molecular Formula: C15H15NOS


CH3

O

OH

2-[(diphenylmethyl)sulfinyl]acetamide

Molecular Formula: C15H15NO2S


S

NH2

O

O



S

NH2

O

O



Modafinil

CH3 OH

44

FLOW DIAGRAM:

Diphenylmethyl sulfanyl acetamide

Acetic acid

hydrogen peroxide

process water

Total reaction mass

Purified water for washing

Cooling

Reaction mass

Process water

Purification

Modafinil crude wet cake

Methanol

Methanol for washing

Wet cake

Micron Filter

Centrifuge

Drying

Reactor

Neustch Filter

Reactor

Reactor

Centrifuge

MASS BALANCE:


Diphenylmethyl sulfanyl

acetamide 1.11 Air Waste 0.06

Acetic acid 3.33 Aqueous waste 10.33

Hydrogen Peroxide 0.60 Methanol Recovery 10.56

Process Water 6.57 Methanol Loss 0.56

Methanol 11.11 distillation residue 0.22

0.00 Product 1.00


45

12. DEXMETHYLPHENIDATE HYDROCHLORIDE:


Stage-1

DL- threo ritalinic acid react with Dibenzyl tartaric acid to form D-threo salt of ritalinic acid.

Stage-2

D-threo salt of ritalinic acid react with HCl to form d-threo ritalinic acid.

Stage-3

d-threo ritalinic acid react with thionyl chloride and methanol to form dexmethylphenidate

hydrochloride.

CHEMICAL REACTION:

NH

OHO

NH

OHO

H

H O

O

OH

O

OH

O

O

O(+)Dibenzo d-tartaric acid


Formula Weight: 219.27958Molecular Formula: C31H31NO10


NH

OHO

H

H O

O

OH

O

OH

O

O

O



ClH

NH

OHO

H

H ClH

Molecular Formula: C13H18ClNO2


NH

OHO

H

H ClH



SOCl2

NH

OO

H

H

CH3

Na OHClH



46

FLOW DIAGRAM: Dl-threo Ritalinic acid

Dibenzoyl tarteric acid

Methanol

Process water

Process water

wet cake

Toluene

Process water

CP HCl

Acetone

Acetone

Wet cake

methanol

Thionyl chloride

Process water

Sodium hdroxide

MDC

MDC mass

IPA

IPA Hcl

IPA

Wet cake

Centrifuge

Dryer

Reactor

Centrifuge

Reactor

Centrifuge

Reactor

Reactor

Distillation

MASS BALANCE:


Dl-threo Ritalinic acid 2.44 Air waste 0.24

Dibenzoyl tarteric acid 4.44 Aqueous waste 16.17


Process water 7.56 Methanol Loss 3.17

Toluene 4.88 Toluene Recovery 4.68

CP HCl 1.22 Toluene Loss 0.20

Acetone 7.32 Acetone Recovery 7.10

Thionyl chloride 1.22 Acetone Loss 0.22

Sodium hydroxide 0.34 MDC Recovery 9.56

MDC 9.76 MDC Loss 0.20

IPA 6.10 IPA Recovery 6.05

IPA HCl 0.68 IPA Loss 0.05

Distillation residue 0.49

Product 1.00


47

13. QUETIAPINE FUMARATE:


Quetiapine stage-1 & 2

2-Amino dimethyl sulfide reacts with phenylchloro formate to give carbamate product which

cyclize in the presence of phosphoric acid to give quetiapine stage 1 & 2.

Quetiapine stage-F

Quetiapinefumarate stage – 2 reacts with N,N-Dimethyl aniline in presence of phosphorous

oxychloride will further reacts with 1-hydroxy ethoxy ethyl piperazine using triethanolamine as

catalyst in toluene as media.

Finally product will be isolated by distillation of toluene and addition of Methanol and fumaric

acid solution to form Quetiapine fumarate.

CHEMICAL REACTION:

NH2

S

O

O

Cl

NH

S

O

Molecular Formula = C12H11NS


2-(phenylsulfanyl)aniline

Formula Weight:156.57

Molecular Formula:C7H5ClO2

Phenyl chloroformate

OH

HCl


Molecular Formula = C13H9NOS

Quetiapine stage-1 & 2


Molecular Formula:C6H6O

Phenol Hydrochloric acid

Formula Weight:36.5

Molecular Formula:HCl

+

+ +

FW= 2x227.28(454.56)

Molecular Formula = C13H9NOSQuetiapine stage-1 & 2

COOH

HOOC

FW:2x174.24(348.48)

Molecular Formula:C8H18N2O2

2-[2-(piperazin-1-yl)ethoxy]ethanol Fumeric acid

Formula Weight:116.07Molecular Formula:C4H4O4

N

S

N

N

OOH

COOH

HOOC

2

Molecular Formula = C46H54N6O8S2


Quetiapine Fumerate Final

++

PO

Cl

Cl

Cl

Molecular Formula:Cl3OPphosphoric trichloride


H2O

Water

Formula Weight:18

Molecular Formula:H2O

PO

OH

OH

OH 3HCl

Hydrochloric acid

Formula Weight:109.5Molecular Formula:H3Cl3

phosphoric acid

Formula Weight:98

Molecular Formula:H3O4P

+ +

++

NH

S

O

2N

NH

OOH

2

48

FLOW DIAGRAM - 1

2-Amino diphenyle sulfide

Sodium Hydroxide flakes

Process water

Toluene

Phenyl chloroformate

Hydrochloric acid

Purified water

Product enriched Toluene layer

Purified water

Product enriched Toluene layer

Polyphosphoric acid

Purified water

Purified water for washing

Wet cake of

Dibenzo[b,f][1,4]Thiazepin-

11(10H)-One

Purified water

Acetone

Acetone for washing

Wet cakeDrying (FBD )

Reactor

Reactor

Reactor

Reactor

Centrifuge

MASS BALANCE :


2- Amino diphenyle sulfide 1.11 Air Waste 0.06

Sodium Hydroxide flakes 0.32 Aqueous waste 19.99

Process water 7.80 Toluene Recovery 6.33


Phenyl chloroformate 1.27 Acetone Recovery 3.33

Hydrochloric acid 0.66 Acetone Loss 0.14

Polyphospheric acid 8.89 distillation residue 0.33

Acetone 3.48 Product 1.00


49

FLOW DIAGRAM – F

Dibenzo[b,f][1,4]Thiazepin-11(10H)-One

N,N-Dimethyl aniline

Phosphorous oxychloride

Hydrochloric acid

Sodium sulphate

Process water

Toluene

Triethanolamine

Hydroxy ethoxyrthyl piparazine

Sodium bicarbonate

1N HCL

Hyflosupercel

Methanol

Fumaric acid

Wet cake

Reactor

Reactor

Reactor

Centrifuge

Drying (FBD )

MASS BALANCE :


Dibenzo [b,f] [1,4] Thiazepin -11(1 OH)- ONE 0.6 Air Waste 0.03

N,N- Dimethyl ANILINE 0.4 Aqueous waste 8.42

Phosphorous oxychloride 0.3 Toluene Recovery 4.90

Hydrochloric acid 0.5 Toluene Loss 0.26

Sodium Sulphate 0.1 Methanol Recovery 7.43

Process water 6.5 Methanol Loss 0.31

Toluene 5.2 distillation residue 0.19

Triethanolamine 0.4 Spent hyflow 0.03

Hydroxy ethoxyrthyl piparazine 0.4 Product 1.00

Sodium bicarbonate 0.1

1 N HCl 0.1

Hyflosupercel 0.0

Methanol 7.7

Fumaric acid 0.2


50

14. CARBAMAZEPIN:


Stage: Final

Iminostilbene carbonylchloride react with ammonium hydroxide to give carbamazepine

crude purify in Acetone and water to give final product

CHEMICAL REACTION:

OCl


Molecular Formula: C16H15ClO

Iminostilbene carbonyl chloride


Molecular Formula: NH4OH

Aq. ammonia

ONH2


Molecular Formula: C16H17NO

Carbamezapine, Stage-Final

HCl

Hydrochloric acid

Molecular Formula: HCl


NH4OH

H2O

Water

MF:H2O

FW:18

+

++

FLOW DIAGRAM:

Ethyl acetate

Iminostilbenecarbonyl chlorideAmmonia Hydroxide(25%)

AcetoneHyflo

Water

Activated carbon

Acetone (wash)

Filtrate

Acetone

Acetone (wash)

Wet cakeDrying (FBD)

Reactor

Addition,

Filtration

(Sparkler+Micron)

Centrifuge

51

MASS BALANCE :


Iminostilbenecarbonyl chloride 1.22 Air Waste 0.06

Ethyl acetate 6.52 Aqueous waste 2.84

Ammonia Hydroxide (25%) 1.71 Ethyl acetate Recovery 6.20

Acetone 6.10 Ethyl acetate Loss 0.33

Hyflo super cell 0.06 Acetone Recovery 5.85

Process Water 1.22 Acetone Loss 0.24

Activated Carbon 0.06 Distillation residue 0.24

Spent carbon + hyflow 0.12

Product 1.00


15. RIVAROXABAN:


Stage-1

4-(4-Aminophenyl)morpholine-3-one react with 2-[(2s)-oxiran-2-ylmethyl]-1H-isoindole-1,3(2H)-

indole to form BAN stage-1.

Stage-2

BAN stage-1 react with N,N-carbonyldiimidazole in presence of DMAP to form BAN stage-2.

Stage-3

BAN Stage-2 raect with Aq.methyl amine solution to form BAN stage-3.

Stage-Final

BAN stage-3 react with 5-chlorothiophene-2-carbonylchloride in presence of Pottasium carbonate to

form Rivaroxaban final.

CHEMICAL REACTION:

N

OO

NH2


H12

N2O

2


+ N

O

OO


H9NO

3


N

OO

NH

N

OH

O O


H21

N3O

5


IPA

N

OO

NH

N

OH

O O



+ NN N N

O

Molecular Formula: C7H6N4O


N

O O

N

O

O

O

O



N

O O

N

O

O

O

O



N

O O

N

ONH2O

ClH


H18

ClN3O

4


CH3 NH2

52

FLOW DIAGRAM:

4-(4-Aminophenyl)morpholin-3-one

2-[(2s)-oxiran-2-ylmethyl]

-1H-isoindol-1,3(2H)-dione

IPA

Process water

IPA

Wetcake

N,N-carbonyldiimidazole

DMAP

Toluene

process water

Process water

Wet cake

40% Methylamine solution

Methanol

CP Hcl

Process water

Process water

Wet cake

MDC

5-chlorothiophene-2-carbonylchloride

Pottasium carbonate

process water

Methanol

Wet cake

Reactor

Centrifuge

Centrifuge

Centrifuge

Reactor

Reactor

Reactor

Centrifuge

Dryer

MASS BALANCE:


4-(4- Aminophenyl)morpholin-3-one 1 Air waste 0.1

2-[(2s)- oxiran -2-ylmethyl] -1H -ISOINDOL- 1,3 (2H)-

dione 1.37 Aqueous waste 11.8

IPA 14 IPA Recovery 13.3

Process water 4 IPA Loss 0.7

N,N-Carbonyldiimidazole 1 Toluene Recovery 11.52

DMAP 0.02 Toluene Loss 0.48

Toluene 12 Methanol Recovery 14.55

40% Methylamine solution 1.6 Methanol Loss 0.45

Methanol 15 MDC Recovery 4.9

CP HCl 2 MDC Loss 0.1

MDC 5 distillation residue 0.29

5- Chlorothiphene- 2- carbonylchloride 0.94 Product 1

Potassium Carbonate 1.26


53

16. BETAHISTINE DIHYDROCLORIDE:


Stage-1

2-vinyl pyridine react with methylamine hydrochloride in presence of acetic acid to form

betahistidine Base isolated by high vacuum distillation.

Stage-2

Betahistidine Base react with IPA Hcl to form Betahistidine dihydrochloride.

CHEMICAL REACTION:

NCH3

+ CH3 NH2 ClH

NNH

CH3

Molecular Formula: C7H9N


Molecular Formula: CH6ClN




NNH

CH3



IPA HCl

NNH

CH3

ClH

Molecular Formula: C8H14Cl2N2

Formula Weight: 209

2

FLOW DIAGRAM :

2-vinyl pyridine

Methylamine hydrochloride

process water

Chloroform

sodium hydroxide

Acetic acid

Reaction mixture

Stage-1

IPA

IPA HCl

IPA

Wet cake

Reactor

Distillation

Reactor

Centrifuge

Dryer

54

MASS BALANCE:

17. FLURBIPROFEN:


Stage-Final

Sodium salt of flurbiprofen breaking by using HCl to form flurbiprofen final.

CHEMICAL REACTION:

CH3

F

O

O

Na

CH3

F

O

OH

Molecular Formula: C15H13FO2


ClH

Molecular Formula: C15H12FNaO2


FLOW DIAGRAM:

Process water

sodium salt of Flurbiprofen

Toluene

Hydrochloric acid 9CP grade)

Ethyl acetate

Activated carbon

Hydflosupercel

Product Layer

Ethyl acetate for washing

Filtrate ML

Distilation

Petrolium ether

Reaction Mixture

Petroleum ether washing

Wet Cake Drying

Vacuum tray dryer

Reactor

Sparkler filter

Reactor

Centrifugation

Input TON Output TON

2- vinyl pyridine 0.63 Air Waste 0.03

Methylamine hydrochloride 0.80 Aqueous waste 2.22

process water 0.31 Chloroform Recovery 2.97

Chloroform 3.13 Chloroform Loss 0.16

Sodium hydroxide 0.45 IPA Recovery 2.40

Acetic Acid 0.06 IPA Loss 0.10

IPA 2.50 Distillation residue 0.38

IPA HCl(20%) 1.38 Product 1.00


55

MASS BALANCE:


Process water 4.29 Air Waste 0.07

Sodium salt of Flurbiprofen 1.43 Aqueous waste 7.46

Toluene 2.86 Toluene Recovery 2.71

Hydrochloric acid 9CP grade) 1.43 Toluene Loss 0.14

Ethyl acetate 7.14 Ethyl acetate Recovery 6.86

Activated carbon 0.14 Ethyl acetate Loss 0.29

Hydflosupercel 0.07 Petrolum Ether Recovery 5.54

Petrolum ether 5.71 Petrolum Ether Loss 0.17


spent carbon+hyflow 0.21

product 1.00


18. ARIPIPERAZOLE:


Stage-1

7-HDQ react with 1-bromo-4-chlorobutane to form 7-(4-chlorobutoxy)-3,4-dihydroquinoline-2-one.

Stage-2

Stage-1 react with DCCPP hydrochloride in presence of TEA and TBAB to form Aripiperazole crude.

Stage-Final

Aripiperazole crude purify by usingAcetonitrile and isobutanol to form pure Aripiperazole.

CHEMICAL REACTION:

56

NH

O OH

+

Cl

Br

Na OH

NH

O OCl



Molecular Formula: C4H8BrCl




NH

O OCl



+N

NH

Cl

Cl

ClH

Molecular Formula: C10H13Cl3N2


TEA

NH

O

O

N

N

Cl

Cl

Molecular Formula: C23H29Cl2N3O2


NH

O

O

N

N

Cl

Cl

NH

O

O

N

N

Cl

Cl





Purification

FLOW DIAGRAM:

7-Hydroxy-3,4-dihydroQuinoline

1-Bromo-4-chloro Butane

Sodium Hydroxide

n-Propanol

Cyclohexane

Process water

Wet cake

Process water

Triethylamine

DCPP Hcl

Methanol

Process water

Wet cake Dryer

Reactor

Centrifuge

Reactor

Centrifuge

MASS BALANCE:

57


7- Hydroxy -3,4- dihydroQuinoline 0.74 Air Waste 0.06

1- Bromo -4- Chloro Butane 4.44 Aqueous waste 10.22

Sodium Hydroxide 0.24 1- Bromo -4- Chloro Butane

Recovery 4.22

n- Propanol 3.70 1- Bromo -4- Chloro Butane

Loss 0.22

Cyclohexane 1.48 n-Propanol Recovery 3.56

Process water 9.26 n-Propanol Loss 0.15

Triethylamine 0.59 Cyclohexane Recovery 1.44

DCPP HCl 0.59 Cyclohexane Loss 0.04


Methanol Loss 0.01

distillation residue 0.15

Product 1.00


GROUP B-(API INTERMEDIATE PRODUCTS)

19. 3-dimethylamino-l-pyridin-3-ylpropenone:


Stage-1:

3-Acetyl pyridine reacts with Dimethyl formamide dimethyl acetal to form 3-dimethylamino-

l-pyridin-3-ylpropenone.

CHEMICAL REACTION: N

CH3

O

Molecular Formula = C7H7NO


+

NCH3 CH3

OO

CH3 CH3

Molecular Formula = C5H13NO2


N

O

NCH3CH3

Molecular Formula = C10H12N2O


58

Flow Diagram

3-Acetyl Pyridine

Dimethylformamide dimethylacetal

Toluene

Reaction Mixture

Washing with Toluene (chilled)

Washing with Hexane

Wet Cake

Final Packing

DRYING

TRAY DRYER

REACTOR

CENTRIFUGATION

IN

CENTRIFUGE

Mass Balance:


3-Acetyl Pyridine 0.91 Air Waste 0.05

Dimethylformamide dimethylacetal 1.16 Toluene Recovery 1.57


Hexane 0.71 Hexane Recovery 0.69

Hexane Loss 0.02


Product 1.00


20. N-(2-methyl-5-nitrophenyl) guanidine Hydrochloride:

2-Methyl-5-nitro aniline reacts with Cyanamide solution in the presence of Hydrochloric acid

to form N-(2-methyl-5-nitrophenyl) guanidine hydrochloride.

CHEMICAL REACTION:

NH2

CH3

N+

O-

O

+ NH2 CN

NH

CH3

N+

O-

O

NH

NH2


Formula Weight = 152.15062 Molecular Formula = CH2N2

Formula Weight = 42.03998 Molecular Formula = C8H10N4O2


FLOW DIAGRAM:

59

Purified water

2-Methyl 5- Nitroaniline

Hydrochlorid acid-CP Grade

Cynamide L-500 solution

Hydrochlorid acid-CP Grade

Liqour ammonia

Reaction Mixture

Water Washing

Acetonitrile

Imatinib mesylate-2 wet cake

Reaction Mixture

Wash the Wet cake with Acetonitrile

Wet cake

FINAL PACKING

REACTOR

CENTRIFUGE

REACTOR

CENTRIFUGE

DRYING:

VACUUM TRAY

DRYER

MASS BALANCE:


Purified Water 3.93 Air waste 0.10

2 -Methyl 5- Nitroaniline 1.02 Aqueous waste 5.96

Hydrochlorid Acid -CP Grade 0.70 Acetonitrile recovery 3.02

Cynamide L- 500 Solution 0.85 Acetonitrile Loss 0.16

LIQUOR ammonia 0.74 distillation residue 0.20

Acetonitrile 3.18 Product 1.00


21. (2-methyl-5-nitrophenyl)-(4-pyridin-3-ylpyrimidin-2-yl)amine:

3-dimethylamino-l-pyridin-3-ylpropenone and N-(2-methyl-5-nitrophenyl)guanidine

Hydrochloride undergoes condensation and cyclization reaction to form (2-methyl-5-

nitrophenyl)-(4-pyridin-3-ylpyrimidin-2-yl)amine.

CHEMICAL REACTION:

N

O

NCH3CH3

Molecular Formula = C10H12N2O


+

NH

CH3

N+

O-

O

NH

NH2



N

N

NH

CH3

N+

O-

ON



60

FLOW DIAGRAM:

Dimethylformamide

3-dimethylamino-l-pyridin-3-ylpropenone

N-(2-methyl-5-nitrophenyl)guanidine Nitrate

Isopropyl alcohol

Reaction Mixture

Washing with chilled IPA

Washing with chilled Hexane

Wet Cake

REACTOR

CENTRIFUGATION

DRYING

FLUIDBED DRYER

FINAL PACKING

(2-methyl-5-

nitrophenyl)-(4-

pyridin-3-ylpyrimidin-

2-yl)amine

MASS BALANCE:

22. 1-Hydroxyethoxyethyl piperazine:

Piperazine reacts with 2-chloroethoxy ethanol in presence of water and methanol to form 1-

hydroxyethoxyethylpiperazine isolated by Distillation.

REACTION SCHEME:

NH

NH

+O

Cl OHN

NH

OOH



Molecular Formula: C4H9ClO2





Dimethylformamide 2.59 Air waste 0.14

3- Dimethylamino -I-pyridin -3-Ylpropenone 0.69 DMF Recovery 2.46

N-(2-methyl- 5-nitrophenyl)GUANIDINE Nitrate 0.83 DMF Loss 0.13

Isopropyl alcohol 9.19 Iso propyl alcohol recovery 8.83

Hexane 1.79 Iso propyl alcohol Loss 0.37

Hexane Recovery 1.74

Hexane Loss 0.06

distillation residue 0.39

Product 1.00


61

FLOW DIAGRAM:

Piperazine

2-chloroethoxyethanol

Process water

CP HCl

Methanol

Caustic lye

Reaction mass

Reactor

Distillation

Highvaccum

Distillation

Final Packing

Mass Balance:


Piperazine 1 Air Waste 0.05

2- chloroethoxyethanol 0.85 spent NaCL salt 0.9

Process water 1.5 Methanol Recovery 4.75

CP HCl 0.5 Methanol Loss 0.25

Methanol 5 Distillation Residue 3.9

Caustic lye 2 Product 1


23. 3-(Dimethylamino)propiophenone hydrochloride:

Acetophenone React with dimethylamine hydrochloride in presence of peraformaldeyde

and HCl to give 3-(Dimethylamino)propiophenone hydrochloride.

CHEMICAL REACTION:

CH3O

+CH3

NH

CH3

ClH

O

NCH3 CH3

O

H

H

ClH

Molecular Formula: C8H8O


Molecular Formula: C2H8ClN


ClH



62

FLOW DIAGRAM:

Acetophenone

IPA

Dimethyl amine HCl

Paraformaldehyde

CP Grade HCl

Acetone

Acetone for washing

Wetcake

Reaction &

Filtration

DRYING

MASS BALANCE:


Acetophenone 0.67 Air Waste 0.07


Dimethyl amine HCl 0.53 IPA Loss 0.07

Paraformaldehyde 0.20 Acetone Recovery 1.03

CP Grade HCl 0.07 Acetone Loss 0.04

Acetone 1.07 Distillation residue 0.67

Acetone for washing 0.27 Product 1.00


24. N,N-Dimethyl-3-phenyl-3-hydroxypropylamine:

Hydrolysis of 3-(Dimethylamino)propiophenone hydrochloride by using sodium borohydride

to give N,N-Dimethyl-3-phenyl-3-hydroxypropylamine.

CHEMICAL REACTION:

O

NCH3 CH3

+ OH2

OH

NCH3 CH3


H16

ClNO

Na OH

NaBH4


H17

NO


63

FLOW DIAGRAM:

Methanol

3-(Dimethylamino)propiophenone hydrochloride

Purified water

Sodium Hydroxide Flakes

Sodium Borohydride

Purified water +CP HCl (1:1)

Caustic Lye sol.+ Purified Water (1:1)

MDC

MDC Product Layer

Sodium Sulphate

MDC

MDC Product Layer

Hexane

Reaction Mixture

Wet cake

REACTOR

REACTOR

REACTOR

NEUTCH

FILTER

DRYING

MASS BALANCE:


Methanol 0.93 Air Waste 0.40

3-(Dimethylamino )propiophenone hydrochloride 1.33 Aqueous Waste 9.44

Purified water 8.41 Methanol Recovery 0.89

Sodium Hydroxide Flakes 0.27 Methanol Loss 0.05

Sodium Borohydride 0.13 MDC Recovery 8.51

Purified water +CP HCl (1:1) 1.09 MDC Loss 0.35

Caustic Lye sol. + Purified Water (1;1) 0.00 Hexane Recovery 2.55

MDC 8.87 Hexane Loss 0.08

Sodium Sulphate 0.27 Distillation residue 0.27

Hexane 2.63 Spent sodium sulphate 0.40

Product 1


25. N,N-Dimethyl-3-(2-methylphenoxy)-3-phenylpropylamine oxalate:

N,N-Dimethyl-3-phenyl-3-hydroxypropylamine react with2-flouro toluene in presence

strong Base to produce N,N-Dimethyl-3-phenyl-3-hydroxypropylamine Base further react

with oxalic acid to give N,N-Dimethyl-3-(2-methylphenoxy)-3-phenylpropylamine oxalate

64

CHEMICAL REACTION:

OH

NCH3 CH3



+

CH3

F

Molecular Formula: C7H7F


O

NCH3 CH3

CH3

O OH

OH O

O OH

OH O



FLOW DIAGRAM:

Dimethylsulphoxide

N,N-Dimethyl-3-phenyl-3-hydroxypropylamine

Pottasium t-Butoxide

2-flouro Toluene

Purified water

CP HCl+Purified water(1:1)

Hexane

Product Layer

Purified water+ NaOH (W/V) (1:1)

Ethyl Acetate

Purified water

Product Layer

Purified Water

Ethyl Acetate

Oxalic Acid

Reaction Mixture

Ethyl Acetate for Washing

Acetone for Washing

Wet cake

REACTOR

B/R-303/204/401/

402/419/304

REACTOR

B/R-303/204/401/

402/419/304

REACTOR

B/R-303/204/401/

402/419/304

CENTRIFUGE

B/C-201/401/403/

404/407

DRYING

MASS BALANCE:


Dimethylsulphoxide 1.51 Air Waste 0.05

N,N -Dimethyl-3-Phenyl -3- hydroxypropylamine 0.50 Hexane Recovery 0.95

Potassium t-Butoxide 0.44 Hexane Loss 0.05

65

2- flouro Toluene 0.43 Ethyl Acetate Recovery 5.15

Purified Water 5.28 Ethyl Acetate Loss 0.21

CP HCl + Purified Water (1:1) 0.38 Acetone Recovery 0.770151

Hexane 1.01 Acetone Loss 0.023819

Purified water + NaOH (W/V) (1:1) 0.38 Distillation residue 0.155779

Ethyl Acetate 5.37 Aqueous waste 8.06

Oxalic Acid 0.36 Product 1

Acetone 0.79


26. 3-Dimethylamino-1-(2-thienyl)-1-propanone hydrochloride:

2-Acetyl thiophene React with dimethylamine hydrochloride in presence of

peraformaldeyde and HCl to give 3-Dimethylamino-1-(2-thienyl)-1-propanone

hydrochloride.

CHEMICAL REACTION:

+

CH3NH

CH3

ClHO

H

H

ClH

Molecular Formula: C2H8ClN


ClHS CH3

O

Molecular Formula: C6H6OS


O

NCH3 CH3

S

Molecular Formula: C9H14ClNOS


FLOW DIAGRAM:

2-Acetyl thiophene

IPA

Dimethyl amine HCl

Paraformaldehyde

CP HCl

Acetone

Acetone for washing

Wetcake

Reaction &

Filtration

DRYING

MASS BALANCE:


2-Acetyl thiophene 0.68 Air Waste 0.07


66

Dimethyl amine HCl 0.56 IPA Loss 0.08

Paraformaledhyde 0.20 Acetone Recovery 1.31

CP HCl 0.08 Acetone Loss 0.05

Acetone 1.36 Distillation residue 0.48

Product 1.0

Total 4.5 Total 4.5

27. N,N-Dimethyl-3-hydroxy-3-(2-thienyl)-1-propylamide:

Hydrolysis of 3-Dimethylamino-1-(2-thienyl)-1-propanone hydrochloride by using sodium

borohydride to give N,N-Dimethyl-3-hydroxy-3-(2-thienyl)-1-propylamide.

CHEMICAL REACTION:

+ OH2

Na OH

NaBH4

ClH

O

NCH3 CH3

S

Molecular Formula: C9H14ClNOS


OH

NCH3 CH3

S



FLOW DIAGRAM:

Methanol

3-Dimethylamino-1-(2-thienyl)-1-propanone hydrochloride

Purified water

Sodium Hydroxide Flakes

Sodium Borohydride

Purified water +CP HCl (1:1)

Caustic Lye sol.+ Purified Water (1:1)

Sodium chloride

Reaction Mixture

Process water

Wet cake

REACTOR

NEUTCH

FILTER

DRYING

67

MASS BALANCE:


Methanol 0.93 Air Waste 0.40

3-Dimethylamino-1-(2- thienyl)-1- Propanone

Hydrochloride 1.33

Aqueous waste 9.07

Purified Water 6.97 Methanol Recovery 0.89

Sodium Hydroxide Flakes 0.27 Methanol Loss 0.047

Sodium Borohydride 0.13 Product 1

Purified water + CP HCl(1:1) 1.09

Caustic Lye sol. + Purified Water (1:1) 0.67


28. N, N-Dimethyl-3-(1-naphthoxy)-3-(2-thienyl)-1-propylamine oxalate:

N,N-Dimethyl-3-hydroxy-3-(2-thienyl)-1-propylamide react with1-flouro naphthalene in

presence strong Base to produce N,N-Dimethyl-3-(1-naphthoxy)-3-(2-thienyl)-1-propylamine

Base further react with oxalic acid to give N,N-Dimethyl-3-(1-naphthoxy)-3-(2-thienyl)-1-

propylamine oxalate.

CHEMICAL REACTION:

+

O OH

OH O

OH

NCH3 CH3

S



F


H7F


O

NCH3 CH3

S

O OH

OH O


H23

NO5S


FLOW DIAGRAM:

Dimethylsulphoxide

N,N-Dimethyl-3-phenyl-3-hydroxypropylamine

Pottasium t-Butoxide

2-flouro Naphthalene

Purified water

CP HCl+Purified water(1:1)

Hexane

Product Layer

Purified water+ NaOH (W/V) (1:1)

Ethyl Acetate

Purified water

Product Layer

Purified Water

Ethyl Acetate

Oxalic Acid

Reaction Mixture

Ethyl Acetate for Washing

Acetone for Washing

Wet cake

REACTOR

B/R-303/204/401/

402/419/304

REACTOR

B/R-303/204/401/

402/419/304

REACTOR

B/R-303/204/401/

402/419/304

CENTRIFUGE

B/C-201/401/403/

404/407

DRYING

68

MASS BALANCE:


Dimethyl sulphoxide 1.51 Air Waste 0.05

N,N- Dimethyl-3-Phenyl -3- hydroxypropylamine 0.50 Hexane recovery 0.95

Potassium t- Butoxide 0.44 Hexane loss 0.05

2- flouro Naphthalene 0.43 Ethyl Acetate recovery 5.18

Purified water 5.28 Ethyl Acetate loss 0.22

CP HCl 0.38 Acetone recovery 0.77

Hexane 1.01 Acetone loss 0.03

NaOH 0.38 distillation residue 0.11

Ethyl Acetate 5.37 Aqueous waste 8.09

Oxalic Acid 0.36 Product 1

Acetone 0.79


29. 10-Methoxy Iminostilbene:

Iminostilbene carbonylchloride react with Bromine to give dibromo derivetives to react with

methyl chloroformate to give 10-methoxy iminostilbene.

69

CHEMICAL REACTION:

N

ClO

NCl

O

Br

Br

NH

O

CH3

NCl

O

Br

Br



Molecular Formula: C15H10Br2ClNO





Bromination

Methoxy Reaction

Toluene

Acetic acid

Molecular Formula: C15H10Br2ClNO

70

FLOW DIAGRAM:

Iminostilbene carbonyl chloride

Acetic acid

Bromine

Process water

Reaction Mixture

Toluene

Methyl chloroformate

Reaction Mixture

Toluene for washing

Wet cake

Toluene

Cooling

Raection Mixture

Toluene for washing

Wet cake

Centrifuge

Drying

Reactor

Reactor

Centrifuge

Reactor

Sparkler filter

Reactor

MASS BALANCE:


Iminostilbene carbonyl chloride 1.25 Air Waste 0.56

Acetic Acid 3.75 Bromine Recovery 2.275

Bromine 3.75 Toluene Recovery 9.60

Process water 6.25 Toluene Loss 0.40

Toluene 10 Distillation residue 1.375

Methyl chloroformate 1.9 Aqueous waste 11.69

Product 1


71

ANNEXURE – IV

WATER CONSUMPTION AND WASTEWATER GENERATION

Sr. No. Purpose of Water Water Consumption

M3/Day

Waste Water Generation

M3/Day

1. Domestic 2.0 1.6

2. Industrial

2.1 Process 20.0 18.5

2.2 Boiler 5.0 0.5

2.3 Cooling 5.0 0.5

2.4 Gardening 1.0 -

2.5 Other (Washing) 0.5 0.5

Total (Industrial) 31.5 20.0

Total (Industrial + Domestic) 33.5 21.6

Water Balance Diagram (Unit-KL/Day):

Water Consumption: 33.5 KL/Day

Domestic: 2.0

Gardening:1.0

0.1

Industrial: 31.5

1.6 KL/Day

� Septic

tank & soak

pit

Process: 20.0 Washing: 0.5 Boiler: 5.0 Cooling: 5.0

Process: 18.5 Washing: 0.5 Boiler: 0.5 Cooling: 0.5

ETP Common

MEE

Waste Water generation=

20.0 KL/Day

72

ANNEXURE - V

EFFLUENT TREATMENT PLANT

M/s. Vasoya Industries Pvt. Ltd. shall have an Effluent treatment plant consisting of primary

treatment units.

First all stream of effluent from plant shall be collected in Equalization cum Neutralization

Tank (ENT), where the continuous addition and stirring of caustic solution is done to

maintain neutral pH of wastewater from Caustic Dosing Tanks (CDT) as per requirement by

gravity. Mixer is provided in ENT to keep all suspended solids in suspension and to provide

proper mixing.

Then after, neutralize wastewater shall go to Flash Mixer (FM) by pumping. Alum and

Polyelectrolyte shall be dosed from Alum Dosing Tank (ADT) and Polyelectrolyte Dosing Tank

(PEDT) respectively by gravity into FM to carry out coagulation by using a Flash Mixer.

Then after, coagulated wastewater shall be settled in Primary Tube Settler (PTS). Sludge

settles in PTS shall be sent to Sludge Drying Beds (SDBs) for dewatering. Solids from SDBs

shall be collected and stored in HWSA. Leachate from SDBs shall be sent back to ENT for

further treatment.

Clear effluent from PTS shall be collected in Primary Treated Collection Tank (PTCT) before sent

to common MEE for further treatment.

73

SIZE OF TANKS

Flow =20 KLD

Sr.N. Name of Tank Size of Tank

(L x B x LD+FB) in M

No. MOC

1 Equalization cum

Neutralization Tank (ENT-)

3.0 x 3.0 x (2.5LD +0.5

FB)

1 RCC M25+A/A Bk.

Lining

2 Flash Mixer(FM) 1.0 x 0.7 x (1.5LD +0.5

FB)

1 RCC M25/ MSPP

3 Primary Tube Settler (PTS) 1.5 x 1.0 x (2.0LD +0.5

FB)

1 RCC M25/ MSPP

4 Primary Treated Collection

Tank (PTCT)

3.0 x 3.0 x (2.5LD +0.5

FB)

1 RCC M25

5 Sludge Drying Beds (SDBs) 3 x 2 2 Brk. Masonry with PCC

Bedding and media

6 Caustic Dosing Tank 500 lit 1 HDPE

7 Alum dosing tank 500 lit 1 HDPE

8 Poly Dosing Tank 200 lit 1 HDPE

RCC M25 = REINFORCED CEMENT CONCRETE (M 25 GRADE)

PCC = PLAIN CEMENT CONCREAT

MSPP = MILD STEEL POLYPROPELYNE

HDPE = HIGH DENSITY POLYETHYLINE

EXPECTED CHARACTERISTICS OF WASTEWATER BEFORE TREATMENT

Sr.

No. Parameter

Value (mg/L)

1. pH 2-10

2. TDS 60000

3. COD 40000

4. BOD3 7000

74

Flow Diagram:

75

ANNEXURE-VI

DETAILS OF HAZARDOUS WASTE GENERATION & DISPOSAL

Sr.

No.

Name of Waste Category Total

Quantity

Treatment & Disposal

1 Spent/ Waste/ used

oil

5.1 0.1

KL/Month

Collection, Storage

Transportation & Disposal to

registered re-processor/

Refiners.

2 Process/ Distillation

residue

28.1 1.5

MT/ Month

Collection, Storage

Transportation and given for

incineration/ co-processing.

3 Spent Carbon 28.2 1.0 MT/

Month

Collection, Storage,

Transportation & co-processing

in cement industries or Disposal

to Common TSDF site of M/s.

PSWML, Panoli or M/s. BEIL,

Ankleshwar.

4 Spent Catalyst 28.3 1.0 MT/

Month

Collection, Storage,

Transportation & Disposal by co-

processing in cement industries

or to Common Incinerator site,

M/s. SEPPL or M/s. BEIL.

5 Off specification

Products

28.4 0.01 MT/

Year

6 Date Expired,

Discarded and off-

specification drugs/

medicines

28.5 0.01 MT/

Year

7 Spent Organic Solvent 28.6 5 MT/

Month

Collection, Storage

Transportation and given for

recovery or to end user.

8 Discarded Containers/

Barrels

33.3 100 nos/

Month Collection Storage,

Decontamination and given to

authorized vendors. Liners 33.3 0.2 MT/

Month

Fiber Board Drums 33.3 50 KG/

Month

76

ANNEXURE-VII

DETAILS OF AIR POLLUTION CONTROL SYSTEM

DETAILS OF FUELCONSUMPTION

SR. NO. NAME OF FUEL Proposed Quantity

1. Diesel 200 Lit/Month

2. Natural Gas/LDO 690 Sm3/Month

DETAILS OF AIR POLLUTION CONTROL SYSTEM

Working: As the contaminated fumes with particles, coming from bag filter and goes to water

scrubber. Water is sprayed from the top of the nozzle, which washes the large particle from the

contaminated fumes and settles down to the bottom.

Upper water from the bottom of the scrubber is circulating through the pump to spraying

nozzle. Solid particle is accumulating at the bottom of the scrubber which is giving to the BEIL.

77

DETAILS OF PROCESS VENT AND BOILER STACK

FLUE GAS EMISSION:

Sr.

No.

Stack

Attached to

Stack Height in

meter

APCM Parameter Expected

Pollutants

1. Boiler (1.5

MT/Hr)

15 - SPM

SO2

NOX

150 mg/Nm3

262 mg/Nm3

94 mg/Nm3

2 DG Sets (150

KVA)

8 - SPM

SO2

NOX

150 mg/Nm3

262 mg/Nm3

94 mg/Nm3

PROCESS EMISSION:

Sr.

No.

Stack

Attached to

Stack Height in

meter

APCM Parameter Expected

Pollutants

1. Reaction

Vessels (1/R-

101 2/R-202)

11 Scrubber NH3 175 mg/Nm3

2. Reaction

Vessel (3/R-

303)

11 Scrubber HCl 25 mg/Nm3

78

ANNEXURE-VIII

DETAILS OF HAZARDOUS CHEMICALS STORAGE & HANDLING

Sr.

N0.

Name of Hazardous

chemical

Type of

Storage

MOC Size Lit. for

Storage

No.

1. Acetic Acid Drum GI 200 5

2. Acetone Drum HDPE 200 5

3. Ammonia Drum HDPE 200 5

4. Ethyl acetate Drum HDPE 200 5

5. Ethyl alcohol Drum HDPE 200 5

6. Hexene Drum HDPE 200 5

7. Isopropyl alcohol Drum HDPE 200 5

8. Methyl alcohol Drum HDPE 200 5

9. Nitric acid Carboy HDPE 50 5

10. Phosphorous

oxychloride

Carboy HDPE 50 5

11. Toluene Drum SS 200 5

12. Sulphuric acid Carboy HDPE 50 5

79

ANNEXURE – IX

SOCIO - ECONOMIC IMPACTS

1) Employment Opportunities

The manpower requirement for the proposed project is being expected to generate some

permanent jobs and secondary jobs for the operation and maintenance of plant. This will increase

direct / indirect employment opportunities and ancillary business development to some extent for

the local population.

This phase is expected to create a beneficial impact on the local socio-economic environment.

2) Industries

Required raw materials and skilled and unskilled laborers will be utilized maximum from the local

area. The increasing industrial activity will boost the commercial and economical status of the

locality, to some extent.

3) Public Health

The company regularly examines, inspects and tests its emission from sources to make sure that the

emission is below the permissible limit. Hence, there will not be any significant change in the status

of sanitation and the community health of the area, as sufficient measures have been taken and

proposed under the EMP.

4) Transportation and Communication

Since the existing factory is having proper linkage for the transport and communication, the

development of this project will not cause any additional impact. In brief, as a result of the proposed

project there will be no adverse impact on sanitation, communication and community health, as

sufficient measures have been proposed to be taken under the EMP. The proposed project is not

expected to make any significant change in the existing status of the socio - economic environment

of this region.

80

ANNEXURE-X

______________________________________________________________________

PROPOSED TERMS OF REFERENCE FOR EIA STUDIES

1. Project Description

• Justification of project.

• Promoters and their back ground

• Project site location along with site map of 10 km area and site details providing various

industries, surface water bodies, forests etc.

• Project cost

• Project location and Plant layout.

• Water source and utilization including proposed water balance.

• Product spectrum (proposed products along with production capacity) and process

• List of hazardous chemicals.

• Mass balance of each product

• Storage and Transportation of raw materials and products.

2. Description of the Environment and Baseline Data Collection

• Micrometeorological data for wind speed, direction, temperature, humidity and rainfall in 10 km

area.

• Existing environmental status Vis a Vis air, water, noise, soil in 10 km area from the project site.

For SPM, RSPM, SO2, NOx.

• Ground water quality at 8 locations within 10 km.

• Complete water balance

3. Socio Economic Data

• Existing socio-economic status, land use pattern and infrastructure facilities available in the study

area were surveyed.

4. Impacts Identification And Mitigatory Measures

• Identification of impacting activities from the proposed project during construction and

operational phase.

• Impact on air and mitigation measures including green belt

• Impact on water environment and mitigation measures

• Soil pollution source and mitigation measures

• Noise generation and control.

• Solid waste quantification and disposal.

5. Environmental Management Plan

• Details of pollution control measures

• Environment management team

• Proposed schedule for environmental monitoring including post project

6. Risk Assessment

• Objectives and methodology of risk assessment

• Details on storage facilities

• Process safety, transportation, fire fighting systems, safety features and emergency capabilities to

be adopted.

• Identification of hazards

• Consequence analysis through occurrence & evaluation of incidents

• Disaster Management Plan.

81

7. Information for Control of Fugitive Emissions

8. Post Project Monitoring Plan for Air, Water, Soil and Noise.

9. Information on Rain Water Harvesting

10. Green Belt Development plan

proposed unit of apis & api intermediates in pipodara, tal: mangrol, dist: surat...

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