Annexures - Welcome to Environmentenvironmentclearance.nic.in/writereaddata/Online/TOR/20_May_2017... · Annexures 1 List of Products ... further reacts with Stage-3 product in presence

Annexures

1 List of Products & By-Products Annexure-I

2 Manufacturing Process Description Annexure-II

3 Water Requirement Details Annexure-III

4 Waste Water Details Annexure-IV

5 Hazardous waste / Solid Waste Details Annexure-V

6 Stack Emission Details Annexure-VI

7 Process Emission Details Annexure-VII

8 List of Raw Materials Annexure-VIII

9 Consolidated Statement- Pollution Details Annexure-IX

10 Site Plan Attached

Annexure- I

LIST OF PRODUCTS

S. No Product Name Production capacity

MT/Month

1 Albendazole 10.00

2 Biopenem 5.00

3 Carvedilol 5.00

4 Ciprofloxacin 10.00

5 Closantel Sodium 10.00

6 Dorapenem 5.00

7 Enrofloxacin 10.00

8 Gabapentin 5.00

9 Glucosamine HCl 5.00

10 Imipenem 5.00

11 Lamivudine 10.00

12 Lansoprazole 5.00

13 Meropenem 5.00

14 Nevirapine 10.00

15 Niclosamide 10.00

16 Omeprazole 5.00

17 Rafoxanide 10.00

18 Terbinafine HCl 5.00

19 Triclabendazole 10.00

20 Zudovudine 10.00

Total (Worst combination of any 10products at any given point of time)

100.00

LIST OF BY-PRODUCTS

S. No

Name of the Product

Name of the By-Product

Quantity In Kg/Day

1 Biapenem 1-Methyl-4-nitro benzene 66.67

2 Ciprofloxacin Piperazine HCl 114.65

Ammonium acetate 71.33

3 Dorepenem Para Nitro Toluene 56.00

4 Enrofloxacin n-Ethyl piperazine 139.76

5 Glucosamine Poly glucosamine compound 81.33

6

Lamivudine

Trimethyl Silanol 142.00

Trimethyl Chloro Silane 175.80

L-Menthol 236.59

7 Meropenem TEA HCl 63.33

8 Zidovudine TEA HCl 348.00

Trityl alcohol 326.97

Annexure- II

ALBENDAZOLE

Process Description

Stage-1

Ortho Nitro phenyl amine reacts with Ammonium thiocyanate in presence of Methanol to

give Stage-1 product.

Stage-2

Stage-1 product reacts with n-Propyl bromide to give Stage-2 product.

Stage-3

Stage-2 product reacts with Sodium Hydrosulphide in presence of Methanol to give

Stage-3 product.

Stage-4

Cyanamide reacts with Methylchloroformate to give Methyl-N-cyano carbamate.this

further reacts with Stage-3 product in presence of Acetone to give Albendazole.

ALBENDAZOLE

Route of Synthesis:

Stage-1

NO2

NH2

2-Nitro-phenylamine

C6H6N2O2

138.12

+

Ammonium thiocyanate

2 NH4SCN

2X76.12=152.24

+ Cl2

70.19

Methanol

NO2

NH2

NCS

2-Nitro-4-thiocyanato-phenylamine

C7H5N3O2S

195.20

+ HSCN

59.09

+ 2 NH4Cl

Ammonium chloride

106.98

Stage-2

NO2

NH2

NCS

2-Nitro-4-thiocyanato-phenylamine

C7H5N3O2S

195.20

+

n-Propyl bromide

CH3

Br

C3H7Br

122.99

NO2

NH2

SH3C

2-Nitro-4-propylsulfanyl-phenylamine

C9H12N2O2S

212.27

+

+ NaOH

Sodium Hydroxide

40.00

+ H2O

18.00

NaBr

Sodium Bromide

102.89

+ CO2

44.00

+ NH3

Ammonia gas

17.03

Stage-3

NO2

NH2

SH3C

2-Nitro-4-propylsulfanyl-phenylamine

C9H12N2O2S

212.27

+ 2NaSH

Sodium Hydrosulphide

2X56.06=112.12

+ H2O

18.00

NH2

NH2

SH3C

4-Propylsulfanyl-benzene-1,2-diamine

C9H14N2S

182.29

+ Na2S2O3

158.11

+ H2

Sodium dithionate 2.00

Stage-4

Step-A

NC NH2

Ctanamide

42.04

+

Methylchloroformate

O

OClCH3

C2H3ClO2

94.50

+ NaOH

Sodium hydroxide

40.00

CNNH

O

O

CH3

Methyl-N-cyano carbamide

C3H4N2O2

100.08

+NaCl

Sodium chloride

58.44

+ H2O

18.00

Acetone

Step-B

CNNH

O

O

CH3

Methyl-N-cyano carbamide

C3H4N2O2

100.08

NH2

NH2

S

CH3

4-Propylsulfanyl-benzene-1,2-diamine

+

C9H14N2S

182.29

S

CH3

N

HN

NHCOOCH3

Albendazole

C12H15N3O2S

265.33

+NH3

Ammonia gas

17.03

ALBENDAZOLE

Flow Chart

Stage-1

Stage-2

Stage-3

Stage-4

ALBENDAZOLE

Ortho Nitro phenyl amine Ammonium thiocyanate Methanol

Methanol Rec

Stage-1 n-Propyl bromideSodium Hydroxide

Sodium BromideEffluent water

Stage-2Sodium HydrosulphideMethanol

Methanol Rec

Stage-3Methyl chloroformateMethyl-N-cyano carbamateAcetone

Acetone Rec

ALBENDAZOLE

Material Balance

Material Balance of Albendazole

Stage-1 Batch Size: 500.00Kgs

Name of the input Quantity in Kg

Name of the out put Quantity in Kg

O-Nitro aniline 270.00 Stage-1 375.00

Ammonium thio cyanate 298.00 Methanol Recovery 475.00

Chlorine gas 138.00 Methanol Loss 10.00

Methanol 500.00 Effluent water 1834.63

Water 1500.00 (Water-1500,Ammonium chloride-209.12,Thiocyanic acid-115.51,Methanol-10)

Organic Residue 11.37

Process residue – 6.37

Distillation residue – 5 (Methanol -5)

Total 2706.00 Total 2706.00





Stage-1 375.00 Stage-2 405.00

n-Propyl bromide 237.00 n-Propanol Recovery 475.00

Sodium hydroxide solution (50%) 77.00 n-Propanol Loss 15.00

n-Propanol 500.00 Effluent water 1672.66

Water 1500.00 (Water-1465, Sodium bromide-197.66,n-Propanol-10)

0

Process Emissions 117.23

(Carbon dioxide-84.52, Ammonia-32.71)

0


Process residue – 4.11

Total 2689.00 Total 2689.00





Stage-2 405.00 Stage-3 345.00

Methanol 600.00 Methanol Recovery 570.00

Sodium hydrosulphide 214.00 Methanol Loss 12.00

Water 1500.00 Effluent water 1776.66

(Water-1465,Sodium dithionate-301.66,Methanol-10)


(Hydrogen-3.81)

Organic residue 11.53

Process residue –3.53

Distillation residue – 8 (Methanol -8)

Total 2719.00 Total 2719.00





Stage-3 345.00 Albendazole 500.00

Methyl chloroformate 182.00 Acetone Recovery 760.00

Cyanamide 81.00 Acetone Loss 16.00

Sodium hydroxide solution (50%) 77.00 Methanol Recovery 570.00

EDTA 1.00 Methanol Loss 12.00

Acetone 800.00 Effluent water 2136.55

Methanol 600.00 (Water-2000,Generated water-34.65,Sodium chloride-112.55, Methanol-10, Acetone- 14)

Water 2000.00 Process Emissions 32.23

(Ammonia-32.23)


Process residue-41.22 Distillation residue - 18 (Methanol-8, Acetone - 10)

Total 4086.00 Total 4086.00

BIAPENEM

Process Description

Stage-1:

Stage-A:

3-(Diphenoxy-phosphorylox)-6-(1-hydroxy-ethyl)-4-methyl-7-oxo-1-azbicyclo[3.2.0]hept-

2-ene-2-carboxylic acid 4-nitro-benzyl ester reacts with 6-Mercapto-6,7-dihydro-5H-

pyrazolo[1,2] [1,2,4] triazol-4-ylium in presence of Sodium hydroxide and Acetonitrile to

give Stage-A Product.

Stage-B:

Stage-A Product undergoes Hydrogenation with Hydrogen gas in presence of Pd/c and

Acetonitrile, THF, n-Heptane, Ethyl Acetate to give Biapenem.

BIAPENEM

Route of Synthesis:

Stage-1

Step-A

NO

OO

NO2

H3C

OH

P OPh

OPh

OCH3

O

HH

+N

N+

NHS

6-Mercapto-6,7-dihydro-5H-pyrazolo[1,2-a][1,2,4]

triazol-4-yliumC5H8N3S

142.2

+ NaOH

40.0

HO P OPh

OPh

O

+

Phosphoric acid diphenyl ester

C12H11O4P

250.19

+ HCl

+ NaCl

58.44

36.5

+ H2O

18.02

N

OO

NO2

H3C

OH CH3

O

HH

N

N+

NS

6-[6-(1-Hydroxy-ethyl)-4-methyl-2-(4-nitro-benzyloxycarbonyl)-7-oxo-1-aza-bicyclo[3.2.0]hept-2-en-3-ylsulfanyl]-6,7-dihydro-5H-pyrazolo

[1,2-a][1,2,4]triazol-4-ylium

C22H24N5O6S

486.52

3-(Diphenoxy-phosphoryloxy)-6-(1-hydroxy-ethyl)-4-methyl-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-

carboxylic acid 4-nitro-benzyl esterC29H27N2O10P

594.51

Step-B

N

OOH

CH3

NO2

H3C

OH CH3

O

HH

N

N+

NS

C15H19N4O4S

351.4

+

1-Methyl-4-nitro-benzene

C7H7NO2

137.14

Biapenem

N

OO

NO2

H3C

OH CH3

O

HH

N

N+

NS

+ H2

2.00

Pd/C

6-[6-(1-Hydroxy-ethyl)-4-methyl-2-(4-nitro-benzyloxycarbonyl)-7-oxo-1-aza-bicyclo[3.2.0]hept-2-en-3-ylsulfanyl]-6,7-dihydro-5H-pyrazolo

[1,2-a][1,2,4]triazol-4-ylium

C22H24N5O6S

486.52

BIAPENEM

Flow Chart:

Methyl Vinyl PhosphatePyrazole triazolium chlorideAcetonitrileTHF Palladium Carbonn-HeptaneHydrogen gasHydrochloric AcidNaOHEthyl Acetate

Acetonitrile RecoveryTHF Recoveryn-Heptane RecoveryEthyl Acetate Recovery

Stage-1

Biapenem

BIAPENEM

Material Balance:

Material balance of Biapenem Stage-1

Batch Size:250Kg



3-(Diphenoxy-phosphorylox)-6-(1-hydroxy-ethyl)-4-methyl-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester

450.00 Biapenem Sodium 250.00

6-Mercapto-6,7-dihydro-5H-pyrazolo[1,2] [1,2,4] triazol-4-ylium

107.00 Acetonitrile Recovery 275.00

Acetonitrile 300.00 Acetonitrile Loss 25.00

THF 600.00 THF Recovery 570.00

Hydrogen 2.00 THF Loss 12.00

Palladium Carbon 10.00 n-Heptane Recovery 380.00

n-Heptane 400.00 n-Heptane Loss 8.00

Hydrochloric Acid 28.00 Ethyl Acetate Recovery 475.00

Sodium hydroxide 30.00 Ethyl Acetate Loss 10.00

Ethyl Acetate 500.00 Effluent Water 1272.60

DM Water 1000.00 (Water-1000,gen.Water-13.60,Diphenyl phosphoric acid sodium-189,Sodium chloride-44,Ethyl acetate-8,THF-10, n-Heptane-8)

0

Palladium Carbon Reuse 10.00

Byproduct (1-Methyl-4-nitro-benzene)

100.00


(Process Residue-20.40 Distillation Residue-19.00 (Ethyl acetate-7,THF-8, n-Heptane-4)

Total 3427.00 Total 3427.00

CARVEDILOL

Process Description:

Stage-1

9H-carbazol -4-ol reacts with (chloromethyl) oxirane in presence of Tetrahydrofuran to

give Stage-1 product

Stage-2

Stage-1 compound undergoes condensation with 2-(2-methoxyphenoxy) ethylamine in

presence of Ethyl acetate to give Carvedilol product.

CARVEDILOL

Route of synthesis:

Stage-1

NH

OH

9H-Carbazol-4-ol

C12H9NO

183.21

+

(Chloromethyl)oxirane

OCl

C3H5ClO

92.52

THFNH

O O

4-Oxiranylmethoxy-9H-carbazole

C15H13NO2

239.27

HCl

36.46

+

Stage-2

NH

O O

4-Oxiranylmethoxy-9H-carbazole

C15H13NO2

239.27

+

2-(2-methoxyphenoxy)ethylamine

NH2

OO

C9H13NO2

167.21

Ethyl acetate

NH

O NH

OH

O

H3CO

Carvedilol

C24H26N2O4

406.47

CARVEDILOL

Flow Chart:

4(Oxiranyl methoxy)-9H-Carbazole(2-methoxyphenoxy)ethylamineEthyl acetateMethanol

Stage-2Ethyl acetate RecMethanol Rec

CARVEDILOL

Stage-19H-Carbazol-4-ol(Chloromethyl) oxiraneTetrahydrofuran

Tetrahydrofuran Rec

CARVEDILOL

Material Balance:

Material balance of Carvedilol Stage-1

Batch Size:250.0 0Kg Name of the input Quantity

in Kg Name of the out put Quantity

In Kg 9H-Carbazol-4-ol 121.00 Stage-1 152.00 (Chloromethyl) oxirane 60.50 Tetrahydrofuran Recovery 428.00 Tetrahydrofuran 450.00 Tetrahydrofuran loss 10.00 Toluene 500.00 Toluene Recovery 475.00 Sodium sulfate 125.00 Toluene Loss 15.00

Water 100.00 Inorganic waste 125.00 (Sodium sulfate) 0 Effluent water 111.00

(Water-100,THF-6,Toluene-5) 0 Process Emission 23.88 (Hydrogen chloride – 23.88) 0 Organic residue 16.62 Process residue-5.62

Distillation residue-11 (THF-6,Toluene-5)

Total 1356.50 Total 1356.50

Material balance of Carvedilol Stage-2

Batch Size:250.0 0Kg Name of the input Quantity

in Kg Name of the out put Quantity

In Kg Stage-1 152.00 Carvedilol 250.00 (2-methoxyphenoxy)ethylamine 106.06 Ethyl acetate Recovery 475.00 Ethyl acetate 500.00 Ethyl acetate Loss 10.00 Sodium chloride(washing) 50.00 Effluent water 560.00 Activated carbon 20.00 (Water-500,

Sodium chloride-50, Ethyl acetate-10)

0

Sodium sulfate 125.00 Spent Carbon 20.00 Water 500.00 Inorganic waste 0 (Sodium sulfate) 125.00


Process residue-8.06 Distillation Residue-5 (Ethyl acetate-5)

Total 1453.06 Total 1453.06

CIPROFLOXACIN HYDROCHLORIDE

Process Description

Stage-1

2, 4-Dichloro 5-Fluoro Acetophenone reacts with Dimethyl carbonate, Sodium Hydride

Dimethyl Formamide and Cyclo propyl Amine in presence of Toluene to give Stage-1

product.

Stage-2

Stage-1 reacts with Sodium Hydroxide and Hydrochloric acid in presence of Toluene to

give Stage-2 product

Stage-3

Stage-2 reacts with Piperazine in presence of n-Butanol to give Stage-3 product.

Stage-4

Stage-3 reacts with Acetic acid and Ammonium Hydroxide to give Stage-4 product.

Stage-5

Stage-4 reacts with Hydrochloric acid in presence of Methanol to give Ciprofloxacin

Hydrochloride product.


Route of Synthesis:

Stage-1:

Step-A

Cl

Cl

F

O CH3

2,4Dichloro 5-Fluoro Acetophenone

C8H5Cl2FO

207.03

Dimethyl Carbonate

O

OO

CH3

H3C+

C3H6O3

90.08

+ NaH

Sodium Hydride

24.00

+

Acetic acid

H3C OH

O

C2H4O2

60.05

Toluene

Cl

Cl

F

OCOOCH3

3-(2,4-Dichloro-5-fluoro-phenyl)-3-oxo-propionic acid methyl ester

C10H7Cl2FO3

265.07

+ CH3OH

Methanol

32.04

+

Sodium Acetate

CH3COONa

82.03

+ H2

Hydrogen gas

2.00

Step-B

NaH

Sodium Hydride

24.00

Toluene

Cl

Cl

F

OCOOCH3

3-(2,4-Dichloro-5-fluoro-phenyl)-3-oxo-propionic acid methyl ester

C10H7Cl2FO3

265.07

+

Dimethyl Formamide

O N

CH3

CH3

73.09

+

Dimethyl Sulfate

S

O

O

OO

CH3

H3C+

126.13

Cl

Cl

F

OCOOCH3

HC

NH3C CH3

Dimethyl Amine Acrylate

C13H12Cl2FNO3

320.14

Sodium Methyl Sulfate

+ NaCH3SO4

134.09

+ CH3OH

Methanol

32.04

+ H2

Hydroges gas

2.00

Step-C

Cl

Cl

F

OCOOCH3

HC

NH3C CH3

Dimethyl Amine Acrylate

C13H12Cl2FNO3

320.14

NH2

Cyclopropylamine

C3H7N

57.09

Cl

Cl

F

OCOOCH3

HC

HN

Toluene

3-Cyclopropylamino-2-(2,4-dichloro-5-fluoro-benzoyl)-acrylic acid methyl ester

C14H12Cl2FNO3

332.15

Dimethyl Amine

HN

CH3H3C+

C2H7N

45.08

Stage-2:

Step-A

Cl

Cl

F

OCOOCH3

HC

HN

3-Cyclopropylamino-2-(2,4-dichloro-5-fluoro-benzoyl)-acrylic acid

methyl esterC14H12Cl2FNO3

332.15

+ NaOH

Sodium Hydroxide

40.00

Toluene

N

O

COOCH3

+ NaCl

Sodium Chloride

58.44

Cl

F

7-Chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid

methyl esterC14H11ClFNO3

295.69

+ H2O

18.00

Step-B

NaOH

Sodium Hydroxide

40.00

N

O

COOCH3

Cl

F

C14H11ClFNO3

295.69

+

N

O

COONa

Cl

F

Methyl ester of Fluoroquinolonic Acid

Sodium salt of Fluoroquinolonic Acid

C13H8ClFNNaO3

303.65

Water

+ CH3OH

32.04

Step-C

N

O

COONa

Cl

F

Sodium salt of Fluoroquinolonic Acid

C13H8ClFNNaO3

303.65

+ HCl

Hydrochloric acid

36.5

N

O

COOH

Cl

F

Q-Acid

C13H9ClFNO3

281.67

+ NaCl

Sodium Chloride

58.44

Stage-3:

N

O

COOH

Cl

F

Q-Acid

C13H9ClFNO3

281.67

Piperazine

NH

HN+

N

O

COOH

N

F

HN

n-Butanol

C4H10N2

2X86.14=172.28

Ciprobase (Tech)

C17H18FN3O3

331.34

+

2

NH

HN

HCl

Piperazine Hydrochloride

C4H11ClN2

122.64

Stage-4:

N

O

COOH

N

F

HN

Ciprobase (Tech)

C17H18FN3O3

331.34

+ CH3COOH

Acetic acid

60.05

+ NH4OH

Ammonium Hydroxide

35.05

N

O

COOH

N

F

HN

Ciprobase (Pure)

C17H18FN3O3

331.34

+ CH3COONH4

Ammonium Acetate

77.08

+ H2O

18.00

Stage-5:

N

O

COOH

N

F

HN

Ciprobase (Pure)

C17H18FN3O3

331.34

+ HCl

Hydrochloric acid

36.5

N

O

COOH

N

F

HN

HCl

(Ciprofloxacin Hydrochloride)

C17H19ClFN3O3

367.80

1-Cyclopropyl-6-fluoro-4-oxo-7-piperazin-1-yl-1,4-dihydro-quinoline-3-carboxylic acid; HCl


Flow Chart:

Stage-1

Stage-2

Stage-3

Stage-4

Stage-5

AcetophenoneDimethyl carbonateDMFToluene

Toluene RecDMF Rec

Stage-1TolueneC.S.FlakesHydrochloric acid(36%)

Toluene Rec

Stage-2Piperazinen-Butanol n-Butanol Rec

Stage-3Acetic acidAmmonia solution(20%)

Acetic acid Rec

Stage-4Hydrochloric acid(36%)Methanol Methanol Rec



Material Balance:

Material Balance of Ciprofloxacin HCl




Acetophenone 300.00 Stage-1 472.00

Dimethyl carbonate 131.00 Toluene Recovery 760.00

Sodium hydride 70.00 Toluene Loss 39.00

DMF 105.00 Effluent water 1968.37

Toluene 800.00 (Water-1500,Sodium acetate-118.86,Sodium Methyl sulphate-192.22, Methanol-92.94, Dimethyl amine-64.35)

DMSO 181.00 Process Emission 2.86

Acetic Acid 87.00 (Hydrogen – 2.86)

Cyclopropyl amine 82.00 Organic Residue 13.77

Water 1500.00 Process residue-12.77, Distillation residue-1 (Toluene-1)

Total 3256.00 Total 3256.00

Material Balance of Ciprofloxacin HCl




Stage-1 472.00 Q-Acid 395.00

Toluene 500.00 Toluene Recovery 475.00

C.S.Flakes 125.00 Toluene Loss 23.00

Hydrochloric acid 52.00 Effluent water 2237.86

Water 2000.00 (Water-2000,Generated water-25.57,Sodium chloride-166, Methanol-45.29,Toluene-1)


Process residue-17.14, Distillation residue-1 (Toluene-1)

Total 3149.00 Total 3149.00

Material Balance of Ciprofloxacin Hydrochloride




Stage-2 395.00 Stage-3 460.00

Piperazine 242.00 n-Butanol Recovery 270.00

n-Butanol 300.00 n-Butanol Loss 28.00


(Water-2000,n-Butanol-1)

By-Product 171.98

(Piperazine HCl-171.98)


Process residue-5.02,

Distillation residue-1 n-Butanol-1)

Total 2937.00 Total 2937.00


Stage-4 Batch Size: 500.0 Kgs



Stage-3 460.00 Stage-4 455.00

Acetic acid 84.00 Effluent water 1524.36

Ammonia Hydroxide 49.00 (Water-1500,Generated water-24.98)

Activated carbon 3.00 Spent carbon 3.00

Water 1500.00 By-Product 107.00

(Ammonium acetate-107)


Process residue-6.64

Total 2096.00 Total 2096.00





Stage-4 455.00 Ciprofloxacin Hydrochloride (Pure)

500.00

Hydrochloric acid (36%) 51.00 Methanol Recovery 949.00

Methanol 1000.00 Methanol Loss 48.00


(Water-2000, Methanol-2)


Process residue-6, Distillation residue-1 (Methanol-1)

Total 3506.00 Total 3506.00

CLOSANTEL SODIUM


Stage-1:

4-Chloro -1-methy -2-nitro –benzene undergoes condensation with Para chloro benzyl cyanide in presence of Sodium sulfide, Sodium bicarbonate, Toluene and water to give Stage -1 product. Stage – 2 Stage -1 product undergoes condensation with 2-Hydroxy 3, 5-diido benzoic acid in

presence of PCl3 and Toluene to give Closental Sodium

CLOSANTEL SODIUM

Route of Synthesis:

Stage-1

Cl

CH2-CN

Para Chloro Benzyl Cyanide

C8H6ClN

151.59

+ Na2S

78.04

+ NaHCO3

84.01

+

H2N

H3C

Cl

Cl

N

(4-Amino-2-chloro-5-methyl-phenyl)-(4-chloro-phenyl)-acetonitrile

(Closantel Amine Intermediate)

C15H12Cl2N2

291.18

+ NaHSO4

120.06

+ Na2CO3

105.99

Toluene

2 H2O

36.02

+ 2H2

4.03

H3C

NO2

Cl

4-Chloro-1-methyl-2-nitro-benzene

C7H6ClNO2

171.58

+

Stage-2

H2N

H3C

Cl

Cl

N

(4-Amino-2-chloro-5-methyl-phenyl)-(4-chloro-phenyl)-acetonitrile

(Amino compound)

C15H12Cl2N2

291.18

+

I

OH

COOH

I

2-Hydroxy-3,5-diiodo-benzoic acid

C7H4I2O3

389.91

+ PCl3

137.33

Toluene

HN

H3C

Cl

Cl

N

ONa

I

I

O

C22H13Cl2I2N2O2Na

Closantel Sodium Sodium phosphite

P

ONa

ONa

NaO+

147.94

+

+

4 NaOH

4X40=160.0

685.06

3X36.5=109.5

3 HCl + 2 H2O

2X18.02=36.04

CLOSANTEL SODIUM

Flow Chart

Stage-1

4-Chloro -1-methy -2-nitro -benzenePara Chloro Benzyl CyanideMethanolSodium sulfideSodium bicarbonatePotassium hydroxideToluene

Stage-2

Stage-12-hydroxy -3,5-diiodo-benzoic acidPhosphorus trichlorideSodium HydroxideToluene Methanol

Methanol RecToluene RecEffluent water

Methanol RecToluene RecEffluent water

CLOSANTEL SODIUM

CLOSANTEL SODIUM

Material Balance

Material balance of Closantel Sodium Stage-1

Batch Size:500Kg



4-Chloro -1-methy -2-nitro -benzene 134.00 Stage-1 220.00

Para Chloro Benzyl Cyanide 118.00 Methanol Recovery 475.00

Methanol 500.00 Methanol loss 10.00

Sodium sulfide 60.80 Toluene Recovery 475.00

Sodium bicarbonate 65.50 Toluene loss 10.00

Toluene 500.00 Effluent water 2158.06

Water 2000.00 (Water-1971.95, Sodium bisulfate-93.53,Sodium carbonate-82.58, Methanol-5,Toluene-5)

Process Emission 4.15

(Hydrogen – 4.15)


Process residue-6.09, Distillation Residue-20 (Methanol-10,Toluene-10)

Total 3378.30 Total 3378.30

Material balance of Closantel Sodium Stage-2

Batch Size:500Kg



Stage-1 220.00 Closantel Sodium 500.00

2-hydroxy -3,5-diiodo-benzoic acid 294.00 Methanol Recovery 475.00

Phosphorus trichloride 104.00 Methanol loss 10.00

Sodium Hydroxide 120.50 Toluene Recovery 760.00

Toluene 800.00 Toluene loss 16.00


Activated carbon 5.00 (Water-3000, Generated water-27.11,Sodium phosphite-111.33, Methanol-5, Toluene-16)

Hyflow 3.00 Process Emission 84.13

Water 3000.00 (Hydrogen chloride – 84.13)

Spent carbon & Hyflow 8.00


Process residue-15.93, Distillation Residue-18 (Methanol-10,Toluene-8)

Total 5046.50 Total 5046.50

DOREPENEM


Stage-1:

Methyl Vinyl Phosphate reacts with Mercapto pyrrolidine side chain, Sodium hydroxide

in presence of N-Ethyl diisopropyl amine as a Solvent of DMF. After PH adjustment with

Hydrochloric Acid get Stage-1.

Stage-2:

Protected Dorepenem Reacts with Hydrogen gas in presence of Palladium carbon as a

Catalyst.After Filtration get Dorepenem Product and get 4-Nitro benzyl alcohol By

product.

DOREPENEM

Route of Synthesis:

Stage-1

O

O

N

NO2

O

H3C

OHH H CH3

O P

O

OPh

OPh

C29H27N2O10P

594.51

+

ON

HN

SH

O

NO2

C13H18N4O6S2

390.44

O

O

N

NO2

O

H3C

OH

H HCH3

S NH

HN

C22H29N5O8S2

555.62

HO P

O

OPh

OPh


+

C12H11O4P

250.19

+

+ NaCl58.44

+

S OO

NH2

(2S,3S)-1-p-nitrobenzyloxycarbonyl -2-sulfamylaminomethyl-4-

mercaptopyrrolidone

S OO

NH2

6-(1-Hydroxy-ethyl)-4-methyl-3-(5-methylaminomethyl-pyrrolidin-3-ylsulfanyl)

-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester;

N- Ethyldiisopropylamine

N

+

C8H19N

129.24

+ NaOH

40.00

+ 2 HCl

72.92

N

. HCl

N- Ethyldiisopropylamine Hydrochloride

C8H20ClN

165.70

O

O

NO2

H

C8H7NO4

181.15

Formic acid 4-nitro-benzyl ester

3-(Diphenoxy-phosphoryloxy)-6-(1-hydroxy-ethyl)-4-methyl-7-oxo-1-aza-

bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester

0.5 O2

16.00

+

Stage-2

O

O

N

NO2

O

H3C

OHH H CH3

S NH

HN

C22H29N5O8S2

555.62

S OO

NH2

6-(1-Hydroxy-ethyl)-4-methyl-3-(5-methylaminomethyl-pyrrolidin-3-ylsulfanyl)

-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester;

Pd/C, THF,Acetonitrile

CH3

NO2

OH

O

NO

H3C

OHH H CH3

S NH

HN

S OO

NH2

Dorepenem

C15H24N4O6S2

420.50

+ H2

2.00

+

Para nitro toluene

C7H7NO2

137.14

DOREPENEM

Flow Chart:

Stage-1

Methyl vinyl phosphate

Mercapto pyrrolidine

N-Ethyl diisopropyl amine

Reactor

Sodium hydroxide

Acetonitrile

DMF

Water

Hydrochloric AcidWorkup

Rec. Acetonitrile

Rec.DMF

Stage-1

Stage-2

Stage-1

Acetonitrile

Tetrahydrofuran

Reactor

Palladium carbon

Water

Sodium hydroxide

FiltrationHCl Rec.Actonitrile/THF

Rec. Pd/c

Dorepenem

DOREPENEM

Material Balance:

Material balance of Dorepenem Stage-1

Batch Size:250Kg



3-(Diphenoxy-phosphoryloxy)-6-(1-hydroxy-ethyl)-4-methyl-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester

365.00 Stage-1 340.00

(2S,3S)-1-p-nitrobenzyloxycarbonyl-2-sulfamylaminomethyl-4-mercaptopyrrolidone



N-Ethyl Diispropyl Amine 82.00 DMF Recovery 285.00

DMF 300.00 DMF Loss 6.00

Sodium Hydroxide 46.00 Effluent Water 919.00

Hydrochloric acid 42.00 (Water-500, DMF-4, Sodium Chloride-36, n-DIPEA HCl-104,Acetonitrile-4,

Diphenyl phosphoric acid-157,Formic acid 4-nitro-benzylester-114)

Water 500.00 Process emission 10.00

(Oxygen)


Process Residue-20, Distillation Residue-10 (DMF-5,Acetonitrile-5)

Total 1881.00 Total 1881.00

Material balance of Dorepenem Stage-2

Batch Size:250Kg



Stage-1 340.00 Dorepenem 250.00

Palladium Carbon 20.00 Acetonitrile Recovery 289.00

Hydrogen 2.00 Acetonitrile Loss 6.00

Acetonitrile 300.00 THF Recovery 289.00

Tetrahydrofuran 300.00 THF Loss 6.00

Acivated carbon 10.00 Effluent water 500.00

Water 500.00 (Water-500) 0

Palladium Carbon Recovery 20.00

Spent carbon 10.00

By- Product 84.00

(Para Nitro toluene-84) 0


Process Residue-8, Distillation Residue-10 (THF-5, Acetonitrile-5)

Total 1472.00 Total 1472.00

ENROFLOXACIN


Stage-1

7-Chloro-1-cyclopropyl-6-fluoro-4-oxo-1, 4-dihydro-quinoline-3-carboxylic acid (Q.Acid)

reacts with n-Ethyl Piperazine in presence of n-Butanol to give Enrofloxacin .

ENROFLOXACIN

Route of Synthesis:

Stage-1:

7-Chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid

N

O

OH

O

F

Cl

+2

N-Ethyl piperazine

N NH

n-Burtanol

Enrofloaxcin

N

O

HO

O

F

N

N+

N-Ethyl piperazine

N NH HCl

C13H9ClFNO3

C6H14N2

C6H15ClN2

359.40 150.69

281.67

228.4

C19H22FN3O3

.

ENROFLOXACIN

Flow Chart:

Stage-1

Quinoline-3- Carboxylic acidn-Ethyl PiperazineSodium HydroxideHydrochloric Acid n-Butanol

N-Butanol Rec

ENROFLOXACIN

ENROFLOXACIN

Material Balance:

Material Balance of Enrofloxacin Stage-1

Batch Size:500Kg



Quinoline-3- Carboxylic acid 405.00 Enrofloxacin 500.00

n-Ethyl Piperazine 328.00 n-Butanol Recovery 950.00

Sodium Hydroxide 11.65 n-Butanol Loss 50.00

Hydrochloric Acid 10.62 Effluent water 5034.49

n-Butanol 1000.00 (Water-5000, Sodium acetate-23.87, Hydrochloric acid-10.62)

Acetic acid 17.46 By-product 209.64

Activated Carbon 12.00 (n-Ethyl Piperazine-209.64)

Water 5000.00 Spent carbon 12.00


Process residue - 28.60

Total 6784.73 Total 6784.73

GABAPENTIN


Stage-1

(1-caramoylmethyl-cyclohexyl)-acetic acid reacts with sodium hypochlorite in presence

of MDC to give Stage-1 product.

Stage-2

Stage-1 compound reacts with Hydrochloric acid in presence of water to give Stage-2

product.

Stage-3

Stage-2 compound reacts with sodium hydroxide in presence of Activated carbon and

water to give Gabapentin.

GABAPENTIN

Route of Synthesis:

Stage-1

+ NaOCl

Sodium hypochlorite

74.44

HN

O

MDC

C9H15NO

153.22

+ NaCl

58.44

+ CO2

44.01

+ H2O

18.02

C10H17NO3

199.25

O

OH

O

NH2

(1-Carbamoylmethyl-cyclohexyl)-acetic acid

2-Aza-spiro[4.5]decan-3-one

Stage-2

HN

O

C9H15NO

153.22

+ HCl

Hydrochloric acid36.46

O

HO

NH2

H

Cl

C9H18ClNO2

207.70

+ H2O

18.022-Aza-spiro[4.5]decan-3-one (1-Aminomethyl-cyclohexyl)-acetic acid; hydrochloride

Stage-3

O

HO

NH2

H

Cl

C9H18ClNO2

207.70

+ NaOH

Sodium Hydroxide

40.0

Water

O

HO

NH2

GabapentinC9H17NO2

171.24

+ NaCl + H2O

58.44 18.02(1-Aminomethyl-cyclohexyl)-acetic

acid; hydrochloride

GABAPENTIN

Flow Chart:

Stage-1Hydrochloric acid

Stage-2Sodium HydroxideActivated Carbon

GABAPENTIN

Effluent water

Effluent water

MDC RecEffluent waterStage-1

Stage-2

Stage-3

(1-Carbamoylmethyl-cyclohexyl)-acetic acidSodium HypochloriteMethylene Dichloride

GABAPENTIN

Material Balance:

Material Balance of Gabapentin Stage-1

Batch Size: 250.00Kg



(1-Carbamoylmethyl-cyclohexyl)-acetic acid

318.00 Stage-1 237.00

Sodium Hypochlorite 118.00 MDC Recovery 475.00

Methylene Dichloride 500.00 MDC Loss 15.00

Water 500.00 Effluent Water 621.00

(Water-500, generated water-28. Sodium Chloride-93)

0


(Carbon Dioxide) 0


Process residue-8 Distillation residue - 10 (MDC-10)

0

Total 1436.00 Total 1436.00


Batch Size:250.00Kg



Stage-1 237.00 Stage-2 312.00

Hydrochloric acid 57.00 Effluent Water 472.10

Water 500.00 (Water-472.10)



Total 794.00 Total 794.00


Batch Size:250.00Kg



Stage-2 312.00 Gabapentin 250.00


Activated Carbon 8.00 (Water-600,Generated water-27.12,Sodiumchloride-87.90)

Water 600.00 Spent Carbon 8.00




GLUCOSAMINE HYDROCHLORIDE

Process Description

Stage-1

Chitin undergoes deacetylation with Hydrochloric acid in presence of Methanol to give

Glucosamine Hydrochloride.


Route of Synthesis

Chitin (Pure)

C26H45N3O16

OO

H O

NHCOCH3H

CH2OH

H

O

OO

H

NHCOCH3H

CH2OH

H

H NHCOCH3

CH2OH

H

O

n

HOHOH HH

HHOH

655.65

O

HO

OH

OH

OH

NH2

HCl

+ HCl

Hydrochloric acid

36.5

Methanol

Glucosamine Hydrochloride

C6H14ClNO5

215.63

OO

H O

NHCOCH3H

CH2OH

H

O

H NHCOCH3

CH2OH

H

O HOHOH HH

+ 2 H2O

2X18=36.0

Byproduct

+

C18H32N2O11

452.45

+ CH3COOH

Acetic acid

C2H4O2

60.05

n


Reaction Scheme

Stage-1

Stage-1 Product

MAINTENANCE

DECANTING -ACID

ML’S ML’S EFFLUENT

WASHINGS

Glucosamine

Hydrochloride

Water

RECYCLING TANK

Chitin

HCl


Material Balance

Material Balance of Glucosamine Hydrochloride

Stage-1

Batch Size:250.0Kg’s

Name of the input Quantity

in Kg

Name of the out put Quantity

In Kg

Chitin 375.00 Glucosamine Hydrochloride 250.00

Hydrochloric acid 20.00 Methanol Recovery 760.00



(Water-1179.5,Acetic acid-

34,Methanol-12)

0

By-Product 122.00

(poly glucosamine

compound)

0


Process residue-9.5,

Distillation residue-12

(Methanol-12)

Total 2395.00 Total 2395.00

IMIPENEM


Stage-1:

Bi cyclic ketone Acetophenone reacts with amino ethane thiol in presence of Di

isopropyl amine, Acetonitrile and MDC, After PH adjustment with Hydrochloric Acid get

Stage-1.

Stage-2:

Stage -1 reacts with Formamidine in presence of Para toluene sulfonyl chloride .After

filtration get Stage-2

Stage-3:

Stage-2 reacts with Hydrogenation, Palladium carbon as a catalyst, Ethyl acetate using

as a solvent. After Filtration get Imipenem Product

IMIPENEM

Route of synthesis:

Stage-1

NO

H3C

H H

O

NO2

O

OH

O

+

+

6-(1-Hydroxy-ethyl)-3,7-dioxo-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid

4-nitro-benzyl esterC16H16N2O7

348.31

2-Amino-ethanethiol

NH2HS

C2H7NS

77.15

Diisopropyl-amine

NO

H3C

H H

O

NO2

O

OH

SNH2

3-(2-Amino-ethylsulfanyl)-6-(1-hydroxy-ethyl)-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid

4-nitro-benzyl ester

C18H21N3O6S

407.44

H2O

18.02

Stage-2

NO

H3C

H H

O

NO2

O

OH

SNH2

3-(2-Amino-ethylsulfanyl)-6-(1-hydroxy-ethyl)-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid

4-nitro-benzyl esterC18H21N3O6S

407.44

C2H5NO

59.07

NO

H3C

H H

O

NO2

O

OH

SNH

NH

SO2Cl

H3C

C7H7ClO2S

190.65

+

+

+

NaOH

+

Formimidic acid methyl ester

O NHH3C

Para Toluene Sulfonyl chloride

40.00

3-(2-Formimidoylamino-ethylsulfanyl)-6-(1-hydroxy-ethyl)-7-oxo-1-aza-bicyclo

[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester

C19H22N4O6S

434.47

Para Toluene Sulfonic acid

SO

OOH

C7H8O3S

172.20

+ NaCl

58.44

+ CH3OH

32.04

Acetonitrile

Stage-3

NO

H3C

H H

O

NO2

O

OH

SNH

NH

+

3-(2-Formimidoylamino-ethylsulfanyl)-6-(1-hydroxy-ethyl)-7-oxo-1-aza-bicyclo

[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester

C19H22N4O6S

434.47

H2

2.02

Pd/C, Ethyl acetate

NO

H3C

H H

OHO

OH

SNH

NH

IMIPENEM

C12H17N3O4S

299.35

CH3

NO2

Para Nitro Toluene

C7H7NO2

137.14

+

IMIPENEM

Flow Chart:

Stage-1

Bi cyclic ketone Acetophenone

Amino ethane thiol

Di isopropyl Amine

Acetone

MDC

Reactor

Hydrochloric Acid

Water

Rec.MDC/AcetoneWorkup

Di isopropyl amine HCl

Stage-1

Stage-2

Stage-1

Formamidine

PTSC

Acetonitrile

EthylacetateReactor

Hydrochloric acid

Activated Carbon

Sodium hydroxide Water

FiltrationRec.Acetonitrile/Ethylacetate

Spent Carbon

Stage-2

Stage-3

Stage-2

Palladium CarbonMethanol

Ethyl Acetate

Reactor

Hexane

WaterFiltration

Rec.Ethyl acetate/Methanol

Rec.Palladium carbon

Imipenem

IMIPENEM

Material Balance:

Material balance of Imipenem Stage-1

Batch Size:250Kg



6-(1-Hydroxy-ethyl)-3,7-dioxo-1-aza-bicyclo[3.2.0]heptanes-2-carboxylic acid 4-nitro-benzyl ester

318.00 Stage-1 361.00

2-Amine -ethanethiol 70.00 Acetonitrile Recovery 570.00

Di-Isopropyl Amine 500.00 Acetonitrile Loss 24.00

Acetonitrile 600.00 MDC Recovery 285.00

MDC 300.00 MDC Loss 12.00

DM Water 1000.00 Di-Isopropyl Amine Recovery 475.00

Di-Isopropyl Amine loss 20.00

Effluent Water 1016.00

(Water-1000, Generated Water-16)


Process residue-11 Distillation residue-14 ( Acetonitrile-6, MDC-3, Di-Isopropyl Amine-5)

Total 2788.00 Total 2788.00

Material Balance of Imipenem

Stage-2

Batch Size:250Kg


in Kg


in Kg

Stage-1 361.00 Stage-2 374.00

Formimidic acid methyl ester 52.00 Acetonitrile Recovery 333.00

Para toluene sulfonyl chloride 170.00 Acetonitrile Loss 14.00

Sodium Hydroxide 35.00 Ethyl Acetate Recovery 665.00

Acetonitrile 350.00 Ethyl Acetate Loss 28.00

Ethyl Acetate 700.00 Effluent Water 1031.00

Activated Carbon 5.00 (Water-800,Sodium Chloride-51,

Methanol-28,Para Toluene

sulfonic acid-152)

Water 800.00 Spent Carbon 5.00


Process residue-13

Distillation Residue-10

(Acetonitrile-3, Ethyl acetate-7,

Total 2473.00 Total 2473.00

Material Balance of Imipenem

Stage-3

Batch Size:250Kg


in Kg


in Kg

Stage-2 374.00 Imipenem 250.00

Palladium Carbon 5.00 Ethyl Acetate Recovery 760.00

Ethyl Acetate 800.00 Ethyl Acetate Loss 32.00

Hydrogen 2.00 Methanol Recovery 380.00


n- Hexane 400.00 n-Hexane Recovery 390.00

Activated carbon 20.00 n-Hexane Loss 8.00

Water 750.00 Effluent Water 876.00

(Water-750, Methanol-8, Para

Nitro Toluene – 118)

Spent carbon 20.00

Spent Palladium Carbon 5.00


Process residue-8


(Ethyl acetate-8, Methanol-4, n-

Hexane-2)

Total 2751.00 Total 2751.00

LAMIVUDINE

Process Description

Stage – 1

Step-A

L (-) Menthol is reacts with glyoxylic acid in presence of sulphuric acid and

cyclohexane to give Step-A Product.

Step-B

Step-A Product reacts with Sodium bisulphite in presence of water to give Step-B

Product.

Step-C

Step-B Product reacts with Formaldehyde in presence of water and Toluene to give

Stage-1 Product.

Stage – 2

.Stage-1 Product reacts with 1, 4, Dithiane-2, 5-diol in presence of Acetic acid and

Toluene to give Stage-2 Product.

Stage – 3

Step-A

Stage-2 Product reacts with Thionyl chloride in presence of MDC to give Step-A

Product.

Step-B

Cytosine reacts with Hexamethyl disilazane in presence of Methane sulfonic acid to

give Step-B Product.

Step-C

Step-A Product reacts with Step-B in presence of TEA to give Step-C Product.

Step-D

Step-C Product undergoes hydrolysis with water in presence of n-Hexane to give

Step-D Product.

Step-E

Step-D Product undergoes Purification in Ethyl acetate to give Cyclohexyl ester

Tech Product.

Stage-4

Step-A

Stage-3 Product reacts with Sodium borohydride in presence of Toluene and IPA to

give Step-A Product.

Step-B

Step-A Product undergoes purification in Methanol and IPA to give Lamivudine.

LAMIVUDINE

Route of synthesis:

Stage-1

Step-A

CH3

H3C CH3

OH

Glyoxalic acid

O

O

OH

CH3

H3C CH3

O C

O

CH

OH

OH

+H2SO4

L-Menthol

C10H20O

156.27

C2H2O3

74.04

L-Menthyl glyoxilate

C12H22O4

230.31

Step-B

CH3

H3C CH3

O C

O

CH

OH

OH


C12H22O4

230.31

+ NaHSO3

Sodium bisulphite

104.06

Water

CH3

H3C CH3

O C

O

CH

SO3Na

OH

Sodiumbisulphite aduct

C12H21NaO6S

316.35

+ H2O

18.0

Step-C

CH3

H3C CH3

O C

O

CH

SO3Na

OH

Sodiumbisulphite aduct

C12H21NaO6S

316.35

+ HCHO

Formaldehyde

30.03

+ H2O

18.0

CH3

H3C CH3

O C

O

CH

OH

OH


C12H22O4

230.3

+

Formaldehyde bisulphite

-OS O

HNa+

O

16.0

O2

CH3O3SNa

118.09

Stage-2

CH3

H3C CH3

O C

O

CH

OH

OH


C12H22O4

2X230.3=460.6

S

SHO

OH

CH3

H3C CH3

O C

O

S

OOH

2

+

1,4-Dithiane-2,5-diol

C4H8O2S2

152.24

Acetic acid

Toluene

2

5-Hydroxy-1,3-oxathiolane-2-arboxylic acid(1R,2S,5R)menthyl ester

C14H24O4S

2X288.4=576.8

+ 2H2O

36.0

Stage-3

(Step-A)

CH3

H3C CH3

O C

O

S

OOH

5-Hydroxy-1,3-oxathiolane-2-carboxylic acid(1R,2S,5R)menthyl ester

C14H24O4S

288.4

+ SOCl2

Thionyl cloride

118.97

CH3

H3C CH3

O C

O

S

OCl

5-Chloro-[1,3]oxathiolane-2-carboxylic acid-2-isopropyl-5-

methyl-cyclohexyl ester

C14H23ClO3S

306.85

+ HCl + SO2

36.5 64.06

Step-B

N

NH

NH2

O

Cytosine

C4H5N3O

111.10

+

Hexamethyl disilazane

Si

N HSi

H3C

CH3

CH3

H3CCH3

CH3

C6H19NSi2

161.39

CH3SO3H N

N

NH

O

Si(CH3)3

Si(CH3)3

Bis trimethylsilyl cytosine

C10H21N3OSi2

255.46

+ NH3

Ammonia

17.03

Step-C

N

N

NH

O

Si(CH3)3

Si(CH3)3

Bis trimethylsilyl cytosine

C10H21N3OSi2

255.46

CH3

H3C CH3

O C

O

S

OCl

5-Chloro-[1,3]oxathiolane-2-carboxylic acid2-isopropyl-5-methyl-cyclohexyl ester

C14H23ClO3S

306.85

+

CH3

H3C CH3

O CO

S

O

N

N

NH

O

Si(CH3)3

Silyl cyclohexyl ester

C21H35N3O4SSi

453.67

+(CH3)3SiCl

Trimethyl chlorosilane

108.64

Step-D

CH3

H3C CH3

O C

O

S

O

N

N

NH

O

Si(CH3)3

Silyl cyclohexyl ester

C21H35N3O4SSi

453.67

+ H2O

18.0

CH3

H3C CH3

O C

O

S

O

N

N

NH2

O

C18H27N3O4S

381.49

+(CH3)3SiOH

Trimethyl silanol

90.60

(2R-Cis)-5-(4-amino-1,2-dihydro-2-oxo-1-pyrimidinyl1,3-oxathiolane-2-carboxylic acid(2S,5R)-Methylester

(CYCLOHEXYL ESTER TECH)

Step-E

CH3

H3C CH3

O C

O

S

O

N

N

NH2

O

C18H27N3O4S

381.49



CH3

H3C CH3

O C

O

S

O

N

N

NH2

O

C18H27N3O4S

381.49



Ethylacetate

Stage-4

CH3

H3C CH3

O C

O

S

O

N

N

NH2

O

C18H27N3O4S

381.49

CH3

H3C CH3

OH

S

O

N

N

NH2

O

HO

+

Lamivudine (Crude)

+

229.26

L-Menthol

C10H20O

156.27

K2HPO4

+ NaBH4

37.83

+

C8H11N3O3S

HCl

Hydrochloric acidSodium boro hydride(2R-Cis)-5-(4-amino-1,2-dihydro-2-oxo-1-pyrimidinyl-1,3-oxathiolane-2-

carboxylic acid(2S,5R)-Methylester

Toluene

36.5

NaCl

Sodium chloride

58.44

+ 3 H2O

+ H3BO3

Boric acid

61.83

3X18.02=54.06

+ 2 H2

4.03

Stage-5

S

O

N

N

NH2

O

HO

Lamivudine (Crude)

229.26

C8H11N3O3S

Methanol,IPA

S

O

N

N

NH2

O

HO

Lamivudine Pure)

229.26

C8H11N3O3S

LAMIVUDINE

Flow-chart:

L(-) MentholGlyoxylic Acid (50%)Sulphuric AcidSodium Carbonate Sodium BisulphiteFormaldehyde Cyclohexane

Stage - 1Acetic acid2,5-Dithiane-1,4-diolHyflow Triethylaminen-Hexane Toluene

Toluene + Acetic Acid Recoveryn-Hexane Recovery

Stage- 2Thionyl chlorideHexamethyldisilazane cytosineToluenen-HexaneEthyl AcetateMethylene dichloride

MDC Recoveryn-Hexane RecoveryEthyl acetate RecoveryToluene Recovery

Stage-1

Stage-2

Stage-3

Cyclohexane RecoveryEffluent water

Stage -3Dipotassium hydrogen ortho phosphateSodium BorohydrideActivated CarbonConc. HClTolueneMethanolIso propyl alcohol

Toluene RecoveryIsopropyl alcohol RecoveryMethanol Recovery

Stage-4

Lamivudine

LAMIVUDINE

Material Balance:

Material balance of Lamivudine Stage-1 Batch size : 500kg

Name of the input Quantity In kg

Name of the out put Quantity In kg

L(-) Menthol 443.00 Stage-1 595.00

Glyoxylic Acid (50%) 420.00 Cyclohexane Recovery 598.00

Sulphuric Acid 3.00 Cyclohexane Loss 12.00

Sodium Carbonate 15.00 Effluent water 1039.51

Sodium Bisulphite 286.00 (Water-752.05, Generated water-49.45, Sodium carbonate-15, Cyclo hexane-10, Sulfuric acid-3, Water from Glyoxylic acid-210)

Formaldehyde 80.00 Process emission 42.62

Cyclohexane 630.00 (Oxygen)

Water 800.00 Organic residue 389.87

Process Residue-379.87 (Formaldehyde bi sulphate-314.64) Distillation residue-10 (Cyclo hexane-10)

Total 2677.00 Total 2677.00

Material balance of Lamivudine

Stage-2 Batch size : 500kg



Stage - 1 595.00 Stage- 2 722.00

Acetic acid 18.00 Toluene + Acetic Acid Recovery 683.00

2,5-Dithiane-1,4-diol 196.50

Toluene Loss 14.00

Hyflow 5.00 n-Hexane Recovery 218.00

Triethylamine 3.00 n-Hexane Loss 4.00

n-Hexane 230.00 Generated Water 46.50

Toluene 700.00 Spent Hyflow 5.00


Process residue-26 (Triethylamine-3) Distillation Residue-29 (n- Hexane-8, Toluene-21)

Total 1747.50 Total 1747.50




Stage- 2 722.00 Stage-3 867.00

Thionyl chloride 298.00 MDC Recovery 950.00

Methane Sulphonic Acid 2.00 MDC loss 30.00

Hexamethyldisilazane 404.00 Triethylamine Recovery 209.00

cytosine 279.00 Triethylamine Loss 4.00

Toluene 388.00 n-Hexane Recovery 190.00

Triethylamine 220.00 n-Hexane Loss 4.00

n-Hexane 200.00 Ethyl acetate Recovery 142.00

Ethyl Acetate 150.00 Ethyl acetate Loss 3.00

Methylene dichloride 1000.00 Toluene Recovery 368.00

Water 1000.00 Toluene Loss 7.00

By Products 476.70

(trimethyl silanol-213,

Tri methyl chloro silane-263.7)

Effluent water 972.69

(water -957.69 , Methane sulfonic acid-2, TEA-3, n-Hexane-3, Toluene-5,Ethyl acetate-2)

Process emission 294.47

(Hydrogen chloride-91.36, Sulphur dioxide-160.5, Ammonia-42.61)


Process Residue-107.14 Distillation Residue-38 ( MDC-20, Ethyl acetate-3, n-Hexane-3, Toluene-8, Triethylamine-4)

Total 4663.00 Total 4663.00


Stage -3 867.00 Stage-4 505.00

Sodium Borohydride 86.00 Toluene Recovery 190.00

Activated Carbon 8.00 Toluene Loss 4.00

Conc. HCl 83.00 Isopropyl alcohol Recovery 570.00

Toluene 200.0 Isopropyl alcohol Loss 12.00


Iso propyl alcohol 600.00 Methanol Loss 16.00

Water 1500.0 By-product 354.88

(L-Menthol – 354.88)

Spent Carbon 8.00


(Water-1377, Boric acid-140.43, Sodium chloride-132.72, Toluene-3,IPA-9, Methanol-12)


(Hydrogen)


Process Residue-16.82, Distillation Residue-24 (IPA-9, Toluene-3, Methanol-12)

Total 4144.00 Total 4144.00


Stage -4 505.00 Lamivudine 500.00


IPA 50.00 Methanol Loss 16.00

IPA Recovery 48.00

IPA Loss 2.00


Process residue -5.00 Distillation residue- 4 (Methanol-4)


LANSOPRAZOLE

Process Description

Stage-1

2, 3-Lutidine reacts with Hydrogen Peroxide and Nitric Acid in Presence of Acetic acid

to give stage-1 product.

Stage-2

Stage-1 Product reacts with 2, 2, 2- trifluoroehtanol and Acetic Anhydride in presence of

Potassium Carbonate to give stage-2 product.

Stage-3

Stage-2 product undergoes chlorination with Thionyl Chloride inpresence of Toluene to

give stage-3 product.

Stage-4

Stage-3 product undergoes condensation with 2-Mercapto benzimidazole in presence of

Sodium Hydroxide to give stage-4 product.

Stage-5

Stage-4 product undergoes oxidation with Hydrogen peroxide in presence of IPA to give

Lansoprazole.

LANSOPRAZOLE

Route of Synthesis:

Stage-1

N

CH3

CH3

2,3-Lutidine

107.15

+ H2O2

34.00

+ HNO3

63.00

N

NO2

CH3

CH3

O + 2

4-Nitro-2,3-Dimethyl pyridine-N-Oxide

168.15

H2O

C7H9N

C7H8N2O3

36.04

Stage-2

N

NO2

CH3

CH3

O

+

4-Nitro-2,3-Dimethyl pyridine-N-Oxide

168.00

CF3CH2OH + K2CO3 + (CH3CO)2O + NaoH + HCl

Trifluoro ethanol

Potassium carbonate

Acetic anhydride

Sodium hydroxide

Hydrogen chloride

100 138 102 40 36.5

N

OCH2CF3

CH3

CH2OH

. HCl

2-Hydroxy methyl-3-methyl pyridine hydrochloride

257.5

+ KHCO3

Potassium bicarbonate

100

+ KNO2

Potassium nitrite

85

+ CH3COONa

Sodium acetate

82

+ CH3COOH

Acetic acid

60

C7H8N2O3

C9H11ClF3NO2

Stage-3

N

OCH2CF3

CH3

CH2OH

. HCl

2-Hydroxy methyl-3-methyl pyridine hydrochloride

257.5

+ SOCl2

Thionyl chloride

119

N

OCH2CF3

CH3

CH2Cl

. HCl

2-Chloromethyl-3-methyl pyridine hydrochloride

276

+ SO2

64

+ HCl

36.5

C9H11ClF3NO2

C9H10Cl2F3NO

Stage-4

N

OCH2CF3

CH3

CH2Cl

. HCl

2-Chloromethyl-3-methyl pyridine hydrochloride

276

+N

HN

HS + 2 NaoH

2-Mercapto benzimidazole

Sodium hydroxide

2x40=80.0

150

N

OCH2CF3

CH3

CH2 S

N

HN

2[4-(2,2,2-Tri fluoro ethoxy)-3-methylpyridinyl]methyl thio]-1H-Benzimidazole

+ 2 NaCl

Sodium chloride

2x58.5=117.0

+ 2H2O

Water

36.0

C9H10Cl2F3NO C7H6N2S

C16H14F3N3OS

353.0

Stage-5

N

OCH2CF3

CH3

CH2 S

N

HN

2[4-(2,2,2-Tri fluoro ethoxy)-3-methylpyridinyl]methyl thio]-1H-Benzimidazole

353

+ H2O2

Hydrogen peroxide

34

N

OCH2CF3

CH3

CH2 S

N

HN

O

Lansoprazole

369

+ H2O

Water

18

C16H14F3N3OS

C16H14F3N3O2S

LANSOPRAZOLE

Flow Chart:

Stage - 1

Stage - 2

2,3-LutidineAcetic AcidHydrogen Peroxide Sulfuric AcidNitric Acid

Generated water

Stage-1Sodium HydroxidePotassium CarbonateTri Fluoro EthanolToluene

Potassium nitritePotassium bicarbonateSodium acetateToluene Recovery

Stage-2Methylene DichlorideTolueneThionyl Chloride

Sulphur dioxiodeHydrogen chlorideToluene Recovery

Stage - 3

Stage-3Sodium Hydroxide2-Mercapto Benzimidazole

Generated waterSodium chloride

Stage - 4

Stage - 5

Stage-4Isopropyl AlcoholHydrogen Peroxide ChloroformAcetoneAcetic Acid

Generated waterIsopropyl alcohol RecoveryAcetone Recovery

Lansoprazole

LANSOPRAZOLE

MATERIAL BALANCE:

Material Balance of Lansoprazole

Stage-1

Batch Size:250Kg


in Kg


in Kg

2,3-Lutidine 84.00 Stage-1 128.00

Hydrogen Peroxide (50%) 30.00 Spent Sulfuric Acid 50.00

Sulfuric Acid 50.00 Effluent water 534.00

Nitric Acid 49.00 (Water-500, gen.water-28,water from

hydrogen peroxide-6)

0

Water 500.00 Organic Residue 1.00



Stage-2

Batch Size:250Kg


in Kg


in Kg

Stage-1 128.00 Stage-2 190.00

Sodium Hydroxide 30.00 MIBK Recovery 124.00

Potassium Carbonate 105.00 MIBK Loss 3.00

Tri Fluoro Ethanol 76.00 Toluene Recovery 214.00

MIBK 130.00 Toluene Loss 5.00

Acetic Anhydride 77.00 Effluent Water 610.00

TEBAC 1.00 (Water-500, Sodium Acetate-62,

Acetic Acid-45,Toluene-3)

Toluene 225.00 Inorganic solid waste 140.00

Hydrogen Chloride Gas 27.00 (Potassium Nitrite-64, Potassium

Bicarbonate-76)

Activated Carbon 3.00 Spent Carbon 3.00


Process Residue-7


(MIBK-3,Toluene-3)

Total 1302.00 Total 1302.00


Stage-3

Batch Size:250Kg


in Kg


in Kg

Stage-2 190.00 Stage-3 198.00

Methylene Dichloride 200.00 Toluene Recovery 238.00

Toluene 250.00 Toluene Loss 5.00

Thionyl Chloride 88.00 Methylene Dichloride Recovery 190.00

Methylene Dichloride Loss 4.00


(Sulfur Dioxide-47,Hydrogen

Chloride-27)


Process residue-6


(Toluene-7, MDC-6)



Stage-4

Batch Size:250Kg


in Kg


in Kg

Stage-3 198.00 Stage-4 246.00


2-Mercapto Benzimidazole 107.00 (Water-540, gen.Water-25,Sodium

Chloride-84)


Process Residue-7



Stage-5

Batch Size:250Kg


in Kg


in Kg

Stage-4 246.00 Lansoprazole Pharma 250.00

Isopropyl Alcohol 250.00 Isopropyl Alcohol Recovery 238.00

Hydrogen Peroxide (50%) 30.00 Isopropyl Alcohol Loss 5.00

Catalyst 1.00 Chloroform Recovery 384.00

Chloroform 400.00 Chloroform Loss 12.00

Acetone 150.00 Acetone Recovery 143.00

Water 400.00 Acetone Loss 3.00


(Water-400, gen.Water-12,Water

from Hydrogen Peroxide-10,

Acetone-2,IPA-4)

Catalyst Reuse 1.00


Process residue-4


(IPA-3, Chloroform-4,Acetone-2)

Total 1477.00 Total 1477.00

MEROPENEM


Stage-1:

Methyl Vinyl Phosphate reacts with Mercapto side chain and Sodium hydroxide as a

solvent of Acetonitrile and MDC.After PH Adjustment with Hydrochloric acid get Stage-

1.

Stage-2:

Stage-1reacted with Hydrogen gas Palladium carbon As a Catalyst .Ethyl acetate as a

solvent using this reaction. After Filtration get Meropenem tech and finally get 4-nitro

toluene by product.

MEROPENEM

Route of Synthesis:

Stage-1

O

O

N

NO2

O

H3C

OHH H CH3

O PO

OPhOPh

3-(Diphenoxy-phosphoryloxy)-6-(1-hydroxy-ethyl)-4-methyl-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-

carboxylic acid 4-nitro-benzyl esterC29H27N2O10P

594.51

+

ON

OMe2N

SH

O

NO2

2-Dimethylcarbamoyl-4-mercapto-pyrrolidine-1-carboxylic acid

4-nitro-benzyl ester

C15H19N3O5S

353.39

+

Triethylamine

N

C6H15N

101.19

NaOH

40.00

+ 2 HCl

72.92

O

O

N

NO2

O

H3C

OHH H CH3

S

+

O

N

OMe2N

O NO2

3-[5-Dimethylcarbamoyl-1-(4-nitro-benzyloxycarbonyl)-pyrrolidin-

3-ylsulfanyl]-6-(1-hydroxy-ethyl)-4-methyl-7-oxo-1-aza-bicyclo[3.2.0]

hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester

C32H35N5O11S

697.71

HO P

O

OPh

OPh


+

C12H11O4P

250.19

+ (C6H14)NH HCl

137.65

+ NaCl

58.44

+ H2O

18.02Triethyl amine Hydrochloride

Stage-2

O

O

N

NO2

O

H3C

OHH H CH3

S

O

N

O

Me2N

O NO2

3-[5-Dimethylcarbamoyl-1-(4-nitro-benzyloxycarbonyl)-pyrrolidin-3-yl

sulfonyl]-6-(1-hydroxy-ethyl)-4-methyl-7-oxo-1-aza-bicyclo[3.2.0]

hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester

C32H35N5O11S

697.71

Ethyl acetate,Pd/C

OH

O

NO

H3C

OHH H CH3

S NH

O

Me2N CH3

NO2

O

O NO2H

1-Methyl-4-nitro-benzene

Meropenem

C17H25N3O5S

383.46

+

C8H7NO4

181.15

+

C7H7NO2

137.14

Formic acid 4-nitro-benzyl ester

+ 2 H2

4.03

MEROPENEM

Flow Chart:

Stage-1

Methyl vinyl phosphate

Mercapto side chain

Triethyl amine Sodium hydroxide

Acetonitrile

MDCReactor

Water

Hydrochloric Acid Rec. MDC

Rec. Acetonitrile

Stage-1

Workup

Stage-2

Stage-1Ethyl Acetate

Isopropyl Alcohol

Reactor

n-Hexane

Hexane

Water

Palladium carbon

FiltrationRec.Ethyl Acetate

Rec.Palladium carbon

Meropenem

Rec.Isopropyl Alcohol

4-Nitro toluene

MEROPENEM

Material Balance:

Material balance of Meropenem Stage-1

Batch Size:250Kg



3-(Diphenoxy-phosphoryloxy)-6- (1-hydroxy-ethyl)-4-methyl-7-oxo- 1-aza-bicyclo[3.2.0]hept-2-ene-2- carboxylic acid 4-nitro-benzyl ester

430.00 Stage-1 469.00

2-Dimethylcarbamoyl-4-mercapto- pyrrolidine-1-carboxylic acid 4-nitro-benzyl ester



Triethylamine 70.00 MDC Recovery 570.00

MDC 600.00 MDC Loss 30.00

Sodium Hydroxide 50.00 Byproduct (TEA HCl- 95) 95.00


(Water-800, gen.water-12,Sodium chloride-40, Diphenyl phosphoric acid-173)

0


Process residue-6

Total 2795.00 Total 2795.00

Material balance of Meropenem

Stage-2

Batch Size:250Kg


in Kg


in Kg

Stage-1 469.00 Meropenem 250.00

10% Palladium Carbon 5.00 Ethyl Acetate Recovery 970.00

Hydrogen 3.000 Ethyl Acetate Loss 30.00

Ethyl Acetate 1000.00 Isopropyl Alcohol Recovery 670.00

Isopropyl Alcohol 700.00 Isopropyl Alcohol Loss 25.00

Hexane 350.00 n-Hexane Recovery 335.00

Water 950.00 n-Hexane Loss 15.00


(Water-950,Isopropyl Alcohol-5)

10% Palladium Carbon Reuse 5.00


Process Residue-7.99

Distillation Residue-214.10

(Formic acid 4-Nitro-benzyl

ester-122,1-Methyl-4-Nitro-

benzene-92)

Total 3477.00 Total 3477.00

NEVIRAPINE

Description:

Stage – 1

Nevirapine amide reacts with calcium oxide and cyclopropylamine in presence of o-

xylene to give stage-1 product.

Stage – 2

Stage-1 product undergoes reduction with Sodium hydride in presence of Diglyme,

Acetic Acid and O–xylene to give Nevirapine Crude.

Stage – 3

Nevirapine crude undergoes purification in methanol and Carbon to give Nevirapine.

NEVIRAPINE

Route of synthesis:

Stage -1:

N Cl HN

HN

N

OCH3

N Cl Cl

HN

N

OCH3

C12H9Cl2N3O

282.12

+

Cyclo propyl amine

H2N O-Xylene

Nevirapine Penultimate

C3H7N

57.09

C15H15ClN4O

302.75

+ HCl

36.5

CaO

2-Chloro-N-(2-chloro-4-methyl-pyridin-3-yl)-

nicotinamide

Stage – 2:

N ClHN

HN

N

OCH3

Nevirapine Penultimate

C15H15ClN4O

302.75

+ NaH

Sodium hydride

24.00

N

HN

N

OCH3

N

Nevirapine (Crude)

C15H14N4O

266.30

O-Xylene

Acetic acid

+ NaCl + H2

58.44 2.00

Stage – 3:

N

HN

N

OCH3

N

Nevirapine (Crude)

C15H14N4O

266.29

Methanol

CarbonN

HN

N

OCH3

N

Nevirapine (Pure)

C15H14N4O

266.29

NEVIRAPINE

Flow chart:

Stage-1

Stage-2

Stage-3

2-Chloro-N-(2-Chloro-4-Methyl-3-Pyridinyl)-3-Pyridine CarboxamideCalcium oxideOrtho xyleneCyclopropylamine

Stage-1Ortho xyleneSodium hydroxideDiglymeCyclohexane

Ortho xylene Rec

Ortho xylene RecDiglyme Rec

Stage-2Methanol Methanol Rec

NEVIRAPINE

NEVIRAPINE

Material Balance:

Material Balance of Nevirapine Stage-1

Batch Size: 500Kg



2-Chloro-N-(2-Chloro-4-Methyl-3-Pyridinyl)-3-Pyridine Carboxamide

570.00 Stage-1 593.00

Calcium oxide 25.50 Ortho-Xylene Recovery 1140.00

Ortho-Xylene 1200.00 Ortho-Xylene Loss 24.00

Cyclo propyl amine 115.50 Effluent Water 4025.50

DM Water 4000.00 (Water-4000, Calcium oxide-25.5)

0


(Hydrogen chloride-73.71) 0


Process Residue-18.79 Distillation Residue-36 (Xylene-36)

Total 5911.00 Total 5911.00

Material Balance of Nevirapine Stage-2

Batch Size: 500Kg



Stage-1 593.00 Stage-2 505.00

Ortho-Xylene 800.00 Ortho-Xylene Recovery 760.00

Sodium Hydride 47.00 Ortho-Xylene Loss 16.00

Hyflow 5.00 Cyclohexane Recovery 380.00

Activated Carbon 15.00 Cyclohexane Loss 8.00

Cyclohexane 400.00 Effluent Water 3630.25

Acetic acid 10.00 (Water-3500,Acetic Acid-10, Sodium Chloride-114.25, Cyclohexane-6)

DM Water 3500.00 Spent Carbon & Hyflow 20.00


(Hydrogen – 3.91)


Process Residue-16.84, Distillation Residue-30 (Xylene-24,Cyclo hexane-6)

Total 5370.00 Total 5370.00

Material Balance of Nevirapine

Stage-3 Batch Size: 500Kg



Stage-2 505.00 Nevirapine 500.00


Activated Carbon 20.00 Methanol Loss 18.00

Hyflow 8.00 Spent Carbon & Hyflow 28.00


Process Residue-5, Distillation Residue-27 (Methanol-27)

Total 1433.00 Total 1433.00

NICLOSAMIDE


Stage-1:

5 Chloro salicylic acid undergoes chlorination with Thionyl chloride in presence of Mono

chloro benzene to give Stage -1 product

Stage-2:

Stage -1 product undergoes condensation with 2-Chloro 4-nitro aniline in presence of

Mono chloro benzene to give Niclosamide

NICLOSAMIDE

Route of Synthesis:

Stage-1

Cl

OH

COOH

5-Chloro Salicylic Acid

C7H5ClO3

172.57

+ SOCl2

118.97

Cl

OH

COCl

5-Chloro-2-hydroxy-benzoyl chloride

C7H4Cl2O2

191.01

+ SO2

64.06

+ HCl

36.46

MCB

Stage-2

Cl

OH

COCl

5-Chloro-2-hydroxy-benzoyl chloride

C7H4Cl2O2

191.01

+

H2N

Cl

NO2

2-Chloro-4-nitro-phenylamine

C6H5ClN2O2

172.57

MCB

Cl

OH

HN

Cl

NO2

O

Niclosamide

C13H8Cl2N2O4

327.12

+ HCl

36.46

NICLOSAMIDE

Flow Chart

Stage-1

Stage-2

NICLOSAMIDE

5-Chloro Salicylic AcidThionyl chlorideMono Chloro Benzene

Mono Chloro Benzene RecEffluent water

Stage-12-Chloro 4-Nitro anilineMono Chloro Benzene

Mono Chloro Benzene RecEffluent water

NICLOSAMIDE

Material Balance:

Material balance of Niclosamide Stage-1

Batch Size:500Kg



5-Chloro Salicylic Acid 282.00 Stage-1 302.00

Thionyl chloride 194.00 Mono Chloro Benzene Recovery

475.00

Mono Chloro Benzene 500.00 Mono Chloro Benzene loss 10.00


(Water-2000)


(Sulfur dioxide-104.42, Hydrogen chloride-59.43)


Process Residue-10.15, Distillation Residue-15 (Mono chloro benzene-15)

Total 2976.00 Total 2976.00

Material balance of Niclosamide Stage-2

Batch Size:500Kg



Stage-1 302.00 Niclosamide 500.00

2-Chloro 4-Nitro aniline 272.00 Mono Chloro Benzene Recovery

570.00

Mono Chloro Benzene 600.00 Mono Chloro Benzene loss 12.00

water 3000.00 Effluent water 3000.00

(Water-3000)


(Hydrogen chloride-57.45)


Process Residue-16.55 Distillation Residue-18 (Mono Chloro benzene-18)

Total 4174.00 4174.00

OMEPRAZOLE

Process Description

Stage-1

3, 5-Lutidine undergoes oxidation with Hydrogen peroxide and then Nitration with Nitric

acid in presence of Acetic acid to give stage-1 product.

Stage-2

Stage-1 product reacts with Sodium methoxide and Dimethyl sulphate in presence of

sodium hydroxide and Methanol to give satge-2 product.

Stage-3

Stage-2 product undergoes chlorination with Thionyl chloride in presence of Sodium

hydroxide and Toluene to give stage-3 product.

Stage-4

Stage-3 product undergoes condensation with 2-Mercapto-5-methoxy benzimidazole in

presence of sodium hydroxide and Toluene to give stage-5 product.

Stage-5

Stage-4 product undergoes reduction with hydrogen peroxide in presence of Methanol

to give Omeprazole.

OMEPRAZOLE

Route of Synthesis:

Stage-1

N

3,5-Lutidine

C7H9N

107.15

+ H2O2

Hydrogen peroxide

34.01

+ HNO3

Nitric acid

63.01

N

NO2

3,5-Dimethyl-4-nitro-pyridine N-Oxide

O

C7H8N2O3

168.15

Acetic acid+ 2H2O

2X18=36.0

Stage-2

N+

NO2

3,5-Dimethyl-4-nitro-pyridine N-Oxide

O-

C7H8N2O3

168.15

+ CH3ONa

Sodium methoxide

54.02

+ 2NaOH

Sodium hydroxide

2X40=80.0

+ (CH3)2SO4

Dimethyl sulfate

126.13

Methanol

N

O

+ NaNO2

69.0

+ Na2SO4

142.04

+ CH3OH

32.0

C9H13NO2

167.21

OH

(4-methoxy-3,5-dimethylpyridin-2-yl)methanol

+ H2O

18.0

Stage-3

+ SOCl2

Thionyl chloride

118.97

+ NaOH

Sodium hydroxide

40.0

Toluene

C9H12ClNO

185.65

H2O + SO2

18.0 64.06

N

O

C9H13NO2

167.21

OH

(4-methoxy-3,5-dimethylpyridin-2-

yl)methanol

N

O

Cl

2-(chloromethyl)-4-methoxy-3,5-dimethylpyridine

+NaCl

58.4

Stage-4

2-Mercapto-5-methoxy benzimidazole

N

HN

O

HS+

C8H8N2OS

180.23

+ NaOH

Sodium Hydroxide

40.0

Toluene

N

NH

O

S

N

CH3

H3C OCH3

5-Methoxy-2-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethylsulfanyl)-1H-benzoimidazole

C17H19N3O2S

329.42

+ NaCl

58.5

+ H2O

18.0

C9H12ClNO

185.65

N

O

Cl

2-(chloromethyl)-4-methoxy-3,5-dimethylpyridine

Stage-5:

N

NH

O

S

N

CH3

H3C OCH3

5-Methoxy-2-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethylsulfanyl)-1H-benzoimidazole

C17H19N3O2S

329.42

+ H2O2

Hydrogen peroxide

34.01

Methanol

HN

N

S

O

N

O

O

Omeprazole

C17H19N3O3S

345.42

+ H2O

18.0

OMEPRAZOLE

Flow Chart:

Stage-1

3,5-LutidineHydrogen peroxideNitric acidAcetic acid

Acetic acid Rec

Stage-2

Stage-1MethanolSodium hydroxideDimethyl sulfateToluene

Sodium NitriteToluene Rec

Stage-3Stage-3Thionyl chlorideToluene

Sulphur dioxideHydrogen chlorideToluene Rec

Stage-4

Stage-42-Mercapto-5-methoxybenzimidazoleSodium hydroxideToluene

Toluene RecSodium chloride

Stage-5Stage-5Hydrogen peroxideMethanolAcetone

Methanol RecAcetone Rec

OMEPRAZOLE

OMEPRAZOLE

Material Balance:

Material balance of Omeprazole Stage-1

Batch Size:250Kg



3,5-Lutidine 89.00 Stage-1 136.00

Hydrogen Peroxide 28.00 Effluent Water 280.00

Nitric acid 52.00 (Water-200, gen.water-30, Acetic acid-25, sulphuric acid-25)

Sulphuric acid 25.00 Organic Residue 3.00

Acetic acid 25.00 Process residue-3

Water 200.00



Batch Size:250Kg



Stage-1 136.00 Stage-2 132.00

Sodium methoxide 44.00 Methanol Recovery 475.00

Sodium hydroxide 65.00 Methanol Loss 10.00

Dimethyl sulphate 102.00 Effluent Water 846.00

Methanol 500.00 (Water-750, gen.water-14, Methanol-26, Sodium nitrate-56)

Water 750.00 Inorganic Solid Waste 115.00

(Sodium Sulphate-115.00)


Process residue-4 Distillation Residue-15 (Methanol-15)

Total 1597.00 Total 1597.00


Batch Size:250Kg



Stage-2 132.00 Stage-3 142.00

Thionyl Chloride 93.00 Toluene Recovery 475.00

Sodium hydroxide 31.00 Toluene Loss 10.00


Water 500.00 (Water-500, gen.water-14, Sodium chloride-45, Toluene-5)

0


(Sulphur dioxide - 50) 0

Organic residue- 15.00

Process residue-5 Distillation Residue-10 (Toluene-10)

Total 1256.00 Total 1256.00


Batch Size:250 Kg



Stage-3 142.00 Stage-4 245.00

2-Mercapto-5-methoxy Benzimidazole

138.00 Toluene Recovery 475.00

Sodium chloride 30.00 Toluene Loss 10.00

Toluene 500.00 Effluent Water 464.00

Water 400.00 (Water-400, Generated water-14 Sodium Chloride - 45, Toluene-5)


Process residue-6 Distillation residue-10 (toluene-10)

Total 1210.00 Total 1210.00

Material balance of Omeprazole Stage-5:Pharma

Batch Size:250 Kg



Stage-4 245.00 Omeprazole 250.00

Hydrogen peroxide 25.00 Methanol Recovery 238.00



Acetone Loss 5.00

Generated Water 13.00


Process residue-7 Distillation residue-14 (methanol-7, Acetone-7)


RAFOXANIDE


Stage-1:

Iodine is reacts with Chlorine in presence of dilute HCl to give Iodine mono chloride

[Step - A] and further it is reacts with Salicylic acid to stage-1 product.

Stage-2:

3, 4 Dichloro nitro benzene undergoes condensation with Para Chloro Phenol in

presence of Potassium Hydroxide to give Stage-2 product.

Stage-3:

Stage-2 product undergoes reduction with Iron dust in presence of HCl to give Stage -3

product

Stage-4:

Stage-3 product undergoes condensation with stage-1 product in presence of Toluene

and Potassium trichloride to give stage-4product.

Stage-5:

Stage-4 product undergoes purification in presence of acetone to give Refoxanide.

RAFOXANIDE

Route of Synthesis:

Stage-1:

Step-A

I2

253.81

+ Cl2

70.91

324.72

Iodine monochloride

I Cl2

Step-B

OH

COOH

Salicylic acid

C7H6O3

138.12 324.72

Iodine monochloride

I Cl2+

OH

COOHI

I

3,5 Di Iodo Salicylic acid(DISA)

C7H4I2O3

389.91

+ 2 HCl

72.92

Stage-2

C6H3Cl2NO2

192.00

+O2N

Cl

Cl

1,2-Dichloro-4-nitro-benzene

HO

Cl

4-Chloro-phenol

C6H5ClO

128.56

+ KOH

56.11

O2N

O

Cl Cl

2-Chloro-1-(4-chloro-phenoxy)-4-nitro-benzene

C12H7Cl2NO3

284.09

+ KCl

74.55

+ H2O

18.02

Stage-3

O2N

O

Cl Cl

2-Chloro-1-(4-chloro-phenoxy)-4-nitro-benzene

C12H7Cl2NO3

284.09

+ Fe

55.84

HCl

H2N

O

Cl Cl

3-Chloro-4-(4-chloro-phenoxy)-phenylamine

254.11

C12H9Cl2NO

+ +

H2O

FeO

71.84

+

O2

32.00

18.02

Stage-4

H2N

O

Cl Cl

3-Chloro-4-(4-chloro-phenoxy)-phenylamine

254.11

C12H9Cl2NO

OH

COOHI

I

2-Hydroxy-3,5-diiodo-benzoic acid

C7H4I2O3

389.91

(Stage-1)

+

(Stage-3)

PCl3+

137.33

OH

CI

I

NH

O

Cl Cl

O

N-[3-Chloro-4-(4-chloro-phenoxy)-phenyl]-2-hydroxy-3,5-diiodo-benzamide

626.01

C19H11Cl2I2NO3

+ H3PO3

82.00

+

2 H2O+

36.03

3 HCl

109.38

Stage-5

OH

CI

I

NH

O

Cl Cl

O

N-[3-Chloro-4-(4-chloro-phenoxy)-phenyl]-2-hydroxy-3,5-diiodo-benzamide

626.01

C19H11Cl2I2NO3

OH

CI

I

NH

O

Cl Cl

O

Refoxanide

626.01

C19H11Cl2I2NO3

Acetone,Acetic acid

RAFOXANIDE

Flow Chart

Stage-1

Stage-2

Stage-3

Stage-4

Stage-5

RAFOXANIDE

Iodine Chlorine gasSalicylic acidMDC

1,2 -Di chloro -4-nitro-benzene4-chloro -phenolPotassium hydroxide Methanol MDC

Stage-2Iron powder Hydrochloric acidToluene

Stage-1Stage-3Phosphorus trichlorideToluene

Stage-4Acetone Acetic acid

MDC RecEffluent water

Methanol RecMDC RecEffluent water

Toluene RecEffluent water

Toluene RecEffluent water

Acetone RecEffluent water

RAFOXANIDE

Material Balance:

Material balance of Rafoxanide Stage-1

Batch Size:500Kg



Iodine 210.00 Stage-1 325.00

Chlorine gas 60.00 MDC Recovery 475.00

Salicylic acid 119.00 MDC loss 10.00

MDC 500.00 Effluent water 1000.00

Water 1000.00 (Water-1000)


(Hydrogen chloride – 62.66)


Process Residue-1.34, Distillation Residue-15 (MDC -15)

Total 1889.00 Total 1889.00


Batch Size:500Kg



1,2 –Di chloro -4-nitro-benzene 171.00 Stage-2 245.00

4-chloro -phenol 115.00 Methanol recovery 475.00

Potassium hydroxide 50.00 Methanol loss 10.00

Methanol 500.00 MDC Recovery 475.00

MDC 500.00 MDC loss 10.00


(water-1500, Methanol -9, Potassium chloride-66.28, Generated water-16.02)


Process Residue -8.7, Distillation Residue-21 (Methanol-6, MDC-15)

Total 2836.00 Total 2836.00


Batch Size:500Kg



Stage-2 245.00 Stage-3 212.00

Iron powder 48.00 Toluene recovery 760.00

Hydrochloric acid 10.00 Toluene loss 16.00


Water 1500.00 (water- 1484.51, Toluene-10)

Spent Iron(II) oxide 61.78


(Oxygen)


Process Residue -17.19, Distillation Residue-14 (Toluene-14)

Total 2603.00 Total 2603.00


Batch Size:500Kg



Stage-1 325.00 Stage-4 505.00

Stage-3 212.00 Toluene Recovery 665.00

Phosphorus trichloride 115.00 Toluene loss 14.00


Water 1500.00 (Water-1470.03, Toluene-10, Phosphorous acid-68.19)

0


(Hydrogen chloride) 0


Process residue-17.79, Distillation Residue-11 (Toluene -11)

Total 2852.00 Total 2852.00


Batch Size:500Kg



Stage-4 505.00 Rafoxanide 500.00


Acetic acid 20.00 Acetone loss 10.00

Activated carbon 5.00 Effluent water 1027.00

Hyflow 3.00 (Water-1000, Acetic acid-20, Acetone-7)

Water 1000.00 Spent Carbon & Hyflow 8.00

Organic Residue 13

Process Residue-5 Distillation Residue-8 (Acetone-8)

Total 2033.00 Total 2033.00

TERBINAFINE HYDROCHLORIDE

Process Description

Stage-1

1-Chloromethyl-naphthalene reacts with Methyl amine in presence of to give Stage-1

product.

Stage-2

Stage-1 product reacts with 1-chloro-6, 6-Dimethyl Hept-2-ene-4-Yne in presence of

Toluene to give Stage-2 product.

Stage-3

Stage-2 product reacts with Hydrochloric acid in presence of Isopropyl alcohol to give

Terbinafine Hydrochloride.


Route of Synthesis

Stage-1

Cl

1-Chloromethyl-naphthalene

C11H9Cl

176.64

+

Methyl amine

H2N CH3

31.06

Toluene

NH3C CH3

Dimethyl-naphthalen-1-yl-amine

C12H13N

171.24

+ HCl

Hydrochloric acid

36.5

Stage-2

Toluene

NH3C CH3

Dimethyl-naphthalen-1-yl-amine

C12H13N

171.24

1-Chloro-6,6-Dimethyl Hept-2-ene-4-yne

H3C

H3CCH3

Cl

C9H13Cl

156.65

+

N

CH3H3C

CH3

CH3

Terbinafine

C21H25N

291.43

+ KCl

+ 1/2K2CO3

Potassium carbonate

69.10

74.55

+ 1/2CO2

22.0

+ 1/2H2O

9.0

Stage-3

N

CH3H3C

CH3

CH3

Terbinafine

C21H25N

291.43

+ HCl

Hydrochloric acid

36.5

IPA

N

CH3H3C

CH3

CH3

H

Cl

Terbinafine Hydrochloride

C21H26ClN

327.89


Flow Chart

Stage-1

Stage-2

Stage-3


1-Chloromethyl-naphthalene Methyl amine Toluene

Toluene Rec

Toluene Rec

Stage-11-chloro-6, 6-Dimethyl Hept-2-ene-4-YneToluene

Stage-2Hydrochloric acidIsopropyl alcohol

Isopropyl alcohol Rec


Material Balance:

Material Balance of Terbinafine Hydrochloride

Stage-1

Batch Size: 250.0Kgs


in Kg


in Kg

Napthyl methyl chloride 140.00 Stage-1 135.00

Mono methyl amine 25.00 Toluene Recovery 284.00


MDC 500.00 MDC Recovery 475.00

Water 450.00 MDC Loss 25.00


(Water-450, Toluene-1)





Total 1415.00 Total 1415.00


Stage-2

Batch Size: 250.0Kgs


in Kg


in Kg

Stage-1 135.00 Stage-2 225.00

Chloro methyl heptane 124.00 Toluene Recovery 284.00


Potassium carbonate 55.00 Effluent water 866.86

Water 800.00 (Water-800,Potassium chloride-58.77,

Generated water-7.09,Toluene-1)


(Carbon dioxide – 17.34)



Total 1414.00 Total 1414.00


Stage-3

Batch Size: 250 Kgs


in Kg


in Kg

Stage-2 225.00 Terbinafine Hydrochloride 250.00

IPA 600.00 IPA Recovery 570.00

Hydrochloric acid 30.00 IPA Loss 30.00


Process residue-5.0


TRICLABENDAZOLE


Stage-1:

3, 4, Dichloro aniline undergoes Acetylation with Acetic anhydride in presence of acetic

acid to give Acetamide further it is reacts with Nitric acid and potassium hydroxide to

give stage-1 product

Stage-2:

Stage-1 product reacts with 2, 3, Dichloro Phenol in presence of DMSO to give Stage-2

product

Stage-3:

Stage-2 product undergoes reduction with Hydrogen in presence of Methanol and

Raney nickel to give Stage-3 product

Stage-4:

Stage-3 product reacts with carbon disulfide and sodium hydroxide in presence of

Methanol to give Stage- 4 product

Stage-5:

Stage-4 product reacts with Dimethyl sulphate in presence of methanol and Sodium

hydroxide to give Triclabendazole.

TRICLABENDAZOLE

Route of Synthesis

Stage-1

Step-A

Cl

Cl

NH2

3,4-Dichloro-phenylamine

C6H5Cl2N

162.02

+ (CH3CO)2O

Acetic anhydride

102.09

Cl

Cl

NHCOCH3

N-(3,4-Dichloro-phenyl)-acetamide

C8H7Cl2NO

204.05

+ CH3COOH

60.05

Acetic acid

Step-B

Cl

Cl

NHCOCH3

N-(3,4-Dichloro-phenyl)-acetamide

C8H7Cl2NO

204.05

+ HNO3

Nitric acid

Cl

Cl

NHCOCH3

NO2

N-(4,5-Dichloro-2-nitro-phenyl)-acetamide

C8H6Cl2N2O3

249.05

+ H2O

18.02

63.01

Step-C

Cl

Cl

NHCOCH3

NO2

N-(4,5-Dichloro-2-nitro-phenyl)-acetamide

C8H6Cl2N2O3

249.05

+ KOH

Cl

Cl

NH2

NO2

+ CH3COOK

98.14

Potassium acetate4,5-Dichloro-2-nitro-phenylamine

C6H4Cl2N2O2

207.01

56.11

Stage-2

Cl

Cl

NH2

NO2

4,5-Dichloro-2-nitro-phenylamine

C6H4Cl2N2O2

207.01

+

Cl

Cl

OH

2,3-Dichloro-phenol

C6H4Cl2O

163

NH2

NO2

O

Cl

Cl

Cl

4-Chloro-5-(2,3-dichloro-phenoxy)-2-nitro-phenylamine

C12H7Cl3N2O3

333.55

+ HCl

36.5

Stage-3

NH2

NO2

O

Cl

Cl

Cl

4-Chloro-5-(2,3-dichloro-phenoxy)-2-nitro-phenylamine

C12H7Cl3N2O3

333.55

+ H2

2.00

Raney Nickel

NH2

NH2

O

Cl

Cl

Cl

4-Chloro-5-(2,3-dichloro-phenoxy)-benzene-

1,2-diamineC12H9Cl3N2O

303.57

+ O2

32.0

Stage-4

NH2

NH2

O

Cl

Cl

Cl

4-Chloro-5-(2,3-dichloro-phenoxy)-benzene-

1,2-diamine

C12H9Cl3N2O

303.57

+ CS2

76.14

Carbon disulfide

O

Cl

Cl

Cl

N

HN

C13H7Cl3N2OS345.63

SH

5-Chloro-6-(2,3-dichloro-phenoxy)-1H-benzoimidazole-2-thiol

2 NaOH+

79.99

Na2S+

78.04

2 H2O+

36.03

Stage-5

O

Cl

Cl

Cl

N

HN

C13H7Cl3N2OS345.63

SH

5-Chloro-6-(2,3-dichloro-phenoxy)-1H-benzoimidazole-2-thiol

Di methyl sulphate

S

O

O

O

H3COOCH3

+

O

Cl

Cl

Cl

N

HN

S

Triclabendazole

C14H9Cl3N2OS

359.66

142.13

C2H6O5S

+ 2 NaOH

80.00

Na2S+

78.04

CH3OH+

32.04

+ 3 O2

96.00

H2+

2.02

TRICLABENDAZOLE

Flow Chart

Stage-1

Stage-2

Stage-3

Stage-4

Stage-5

TRICLABENDAZOLE

3,4-Di chloro-phenyl amineAcetic anhydrideNitric acidPotassium hydroxide

Stage-12,3-Di chloro -phenolToluene Methanol

Stage-2Hydrogen Raney nickel Methanol

Stage-3Carbon di sulfideSodium hydroxideMethanol Ethyl acetate

Stage-4Di methyl sulphateSodium hydroxideMethanol

Effluent water

Toluene RecMethanol RecEffluent water

Methanol Rec

Methanol RecEthyl acetateEffluent water

Methanol RecEffluent water

TRICLABENDAZOLE

Material Balance:

Material balance of Triclabendazole

Stage-1 Batch Size:500Kg



3,4-Di chloro-phenyl amine 283.00 Stage-1 328.00

Acetic anhydride 179.00 Effluent water 1795.33

Nitric acid 107.00 (Water-1500, Acetic acid-104.67, Potassium acetate-160.31, generated water-30.35)

Potassium hydroxide 92.00 Organic residue 37.67

Water 1500.00 Process Residue-37.67

Total 2161.00 Total 2161.00





Stage-1 328.00 Stage-2 511.00

2,3-Di chloro -phenol 258.00 Methanol recovery 665.00

Toluene 500.00 Methanol loss 14.00

Methanol 700.00 Toluene recovery 475.00

Water 1500.00 Toluene loss 10.00

Effluent water 1516

(Water-1500, Toluene -7, Methanol-9)




Process Residue-17.36 Distillation bottom Residue-20 (Methanol-12, Toluene-8,)

Total 3286.00 Total 3286.00





Stage-2 511.00 Stage-3 450.00

Hydrogen 3.05 Methanol Recovery 760.00

Raney nickel 10.00 Methanol Loss 16.00


Water 1500.00 (Water-1500,Methanol-12)

Spent Raney nickel 10.00


(Oxygen – 48.90)


Process Residue-15.15, Distillation Residue-12 (Methanol-12)

Total 2824.05 Total 2824.05





Stage-3 450.00 Stage-4 496.00

Carbon di sulfide 113.00 Methanol Recovery 760.00


Methanol 800.00 Ethyl acetate recovery 475.00

Ethyl acetate 500.00 Ethyl acetate loss 10.00


(Water-1500,Methanol-12, Di sodium sulfide-115.45, generated water-53.30)


Process Residue-18.25, Distillation residue-27 ( Methanol-12, Ethyl acetate-15)

Total 3483.00 Total 3483.00





Stage-4 496.00 Triclabendazole 500.00

Di methyl sulphate 204.00 Methanol Recovery 760.00



Water 1500.00 (Water-1500,Methanol-45.95, Di sodium sulfide-111.85)


(Oxygen-137.58, Hydrogen-2.89)


Process residue-28.73, Distillation Residue-12 (Methanol-12)

Total 3115.00 Total 3115.00

ZIDOVUDINE

Process Description

Stage-1

Step-A

Thymidine reacts with Trityl chloride in presence of TEA and 1, 4-Dioxane to give

Step-A Product

Step-B

Step-A compound reacts with Methane sulfonyl chloride in presence of TEA and

Toluene to give Step-B Product.

Step-C

Step-B Product reacts with TEA in presence of Methanol to give stage-1 Product.

Stage-2

Stage-1 Product reacts with sodium azide in presence of DMSO and Ammonium

chloride to give Stage-2 Product.

Stage-3

Stage-2 Product reacts with p-Toluene sulphonic acid and Sodium hydroxide in

presence of Toluene to give Zidovudine.

ZIDOVUDINE

Route of Synthesis:

Stage-1:

Step-A

OHO

HO

N

HN

O

O

CH3

+ (C6H5)3CCl

Triethyl amine

+ C6H15N1,4-Dioxane

C O O

HO

N

HN

O

O

CH3

+

Thymidine

C10H14N2O5

242.23

Trityl chloride

278.78 101.19

Trityl thymidine

C29H28N2O5

484.54

C6H15N.HCl

Triethyl amine hydrochloride

137.69

Step-B

C O O

HO

N

HN

O

O

CH3

Trityl thymidine

C29H28N2O5

484.54

+ CH3SO2Cl + C6H15N

114.55 101.19

Toluene

C O O

O

N

HN

O

O

CH3

+

SO2CH3

C6H15N.HCl

Methanesulfonic acid 5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-2-trityloxymethyl-

tetrahydro-furan-3-yl ester137.69

C30H30N2O7S

562.63

Step-C

C O O

O

N

HN

O

O

CH3

SO2CH3

Methanesulfonic acid 5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-2-

trityloxymethyl-tetrahydro-furan-3-yl esterC30H30N2O7S

562.63

C O ON

N

O

CH3

O

Methanol

5-O-Trityl-2,3-anhydro thymidin

C29H26N2O4

466.53

+ C6H15N

101.19

+

C7H16O3S

Triethyl methane sulfonate

SO O

O

180.27

+ NH3

17.0

Stage-2:

C O ON

N

O

CH3

O

5-O-Trityl-2,3-anhydro thymidin

C29H26N2O4

466.53

+ NaN3 + NH4Cl

C O ON

HN

O

CH3

+

O

N3

NaCl + NH3

5-O-Trityl-Zidovudine

C29H27N5O4

509.56

58.5

Sodium azide

65.01

53.49

17.0

Stage-3:

C O ON

HN

O

CH3

O

N3

5-O-Trityl-Zidovudine

C29H27N5O4

509.56

+H2O Toluene

HOO

N

HN

O

CH3

O

N3

+ C OH +

Zidovudine

C10H13N5O4

267.24

Trityl alcohol

CH3

S OO

OH

p-Toulenesulfonic Acid Mono hydrate

C7H10SO4

190.22

C19H16O

260.33

+ 2 NaOH

80.0

Na2SO4

142.04

+

CH3

Toluene

92.14

H2O+

18.0

ZIDOVUDINE

Flow Chart:

?-Thymidine1,4-DioxaneTri ethyl amineTrityl chlorideTolueneMethane sulfonyl chlorideMethanol

Stage-1Sodium azideAmmonium chlorideDMSO

DMSO RecoveryEffluent water

Toluene RecoveryEthyl Acetate RecoveryMethanol Recovery

Stage-1

Stage-2

Stage-3

Stage-2TolueneMethanolPTSA MonohydrateEthyl acetateActivated CarbonHyflowSodium hydroxide

1,4-Dioxane Recovery + TEAToluene RecoveryMethanol Recovery+TEA

Zidovudine

ZIDOVUDINE

Material Balance:

Material balance of Zidovudine Stage-1

Batch Size:500.0 Kg


Name of the out put Quantity In Kg

β-Thymidine 495.00 Stage-1 880.00

1,4-Dioxane 800.00 1,4-Dioxane + TEA Recovery 779.00

Tri ethyl amine 575.00 1,4-Dioxane + TEA Loss 17.00

Trityl chloride 530.00 Toluene Recovery 285.00


Methane sulfonyl chloride 220.00 Methanol +TEA Recovery 969.00

Methanol 1000.00 Methanol + TEA Loss 21.00

Water 1000.00 Effluent water 1366

(Water-1000, Triethylmethane sulfonate-341,Toluene-5,Methanol-20)

By-Product 522.00

(Triethyl Amine Hydrochloride- 522.00)


(Ammonia -32)


Process residue-5.00 Distillation residue-38 (Toluene-4,Methanol-10, 1,4-Dioxane-24)

Total 4920.00 Total 4920.00


Batch Size:500.0 Kg



Stage-1 880.00 Stage-2 960.00

Sodium azide 125.00 DMSO Recovery 570.00

Ammonium chloride 105.00 DMSO Loss 12.00

DMSO 600.00 Effluent water 2120.00

Water 2000.00 (Water-2000,Sodium Chloride-110.0,DMSO-10)


(Ammonia)


Process residue-8, Distillation residue-8.00 ( DMSO-8)

Total 3710.00 Total 3710.00


Batch Size:500.0 Kg



Stage-2 960.00 Zidovudine 500.00

Toluene 800.00 Toluene Recovery 760.00

Methanol 800.00 Toluene Loss 16.00

PTSA Monohydrate 393.00 Ethyl Acetate Recovery 760.00

Ethyl acetate 600.00 Ethyl Acetate Loss 16.00

Activated Carbon 5.00 Methanol Recovery 570.00

Hyflow 5.00 Methanol Loss 12.00

Sodium hydroxide 151.00 Effluent water 3513.51

Water 3000.00 (Water-3000,Generated water-33.91,Sodium sulphate-267.60,Toluene-185, Methanol-14,Ethyl acetate-13)

Spent Carbon & Hyflow 10.00

By-Product 490.45

(Trityl alcohol – 490.45)


Process residue-33.04, Distillation residue- 33 (Toluene-12,Methanol-10, Ethyl acetate-11)

Total 6714.00 Total 6714.00

Annexure- III

Water Requirement

S. No Purpose Water Input In KLD

1 Process 44

2 Washings 5

3 Boiler make up 42

4 Cooling towers make up 53

5 Scrubbing system 4

6 Domestic 4

7 Gardening 5

Total 157

Annexure- IV

Waste Water Details

Unit HTDS KLD

LTDS KLD

Effluent Generation

in KLD

Treatment Method

Process 32.18 17.64 49.82 HTDS Effluent sent to stripper

followed by MEE system.

LTDS effluents treated in ETP along with MEE condensate. Treated effluent is sent to RO, RO permeate water is recycled and RO rejects taken for evaporation in MEE followed by ATFD to collect evaporation salts for disposal to TSDF.

Washings 5.00 0.00 5.00

Boiler Blow down 0.00 6.00 6.00

Cooling towers Blow down 0.00 6.00 6.00

Scrubbing system 4.00 0.00 4.00

Domestic 0.00 3.60 3.60

Total 41.18 33.24 74.42

Annexure- V

Details of Hazardous/Solid Waste Generation & Disposal

S. No Name of the Solid/ Hazardous Waste

Quantity Disposal Method

1 Organic waste (Process Residue)

657.39 Kgs/Day Sent to Cement Industries

2 Spent Carbon 90 Kgs/Day Sent to Cement Industries

3 Solvent Distillation Residue 404 Kgs/Day Sent to Cement Industries

4 Inorganic Waste 350 Kgs/Day Sent to TSDF

5 MEE Salts 3160.93 Kgs/Day Sent to TSDF

6 Organic Evaporative Liquid (from MEE Stripper)

824 Kgs/Day Sent to Cement Industry

7 ETP Sludge 300 Kgs/Day Sent to TSDF

8 Used Oils 500 Ltrs/Annum SPCB Authorized Agencies for Reprocessing/Recycling

9 Containers liners 300 No’s / Month After Detoxification sent to

outside agencies

10 Used Lead Acid Batteries 4 No’s/ Annum Send back to suppliers for buyback of New Batteries

11 Ash from boiler 9800 Kgs/Day Sent to Brick Manufacturers

Annexure- VI

Stack Emission Details for Boiler

Particulars Units 2.0 TPH Coal fired

Boiler 5.0 TPH Coal fired

Boiler

Type of Fuel -- Indian Coal Indian Coal

Coal Consumption TPD 8.00 20.00

Ash Content % 35 35

Sulphur Content % 0.8 0.8

Nitrogen Content % 1.07 1.15

No. of Stacks No 1 1

Height of stack M 30 30

Diameter of Stack M 0.60 0.60

Temperature of Flue Gas oC 95 110

Velocity of Flue Gas m/s 6.5 8.0

Particulate Matter at outlet of Bag filter (Based on 115 mg/Nm3 at outlet)

gm/sec 0.26

0.33

Sulphur dioxide emission 110 mg/Nm3

gm/sec 0.25 0.32

Oxides of Nitrogen emission 120 mg/Nm3

gm/sec 0.27 0.35

Pollution control equipment - Cyclone separator

followed by suitable pack of Bag filters

Cyclone separator followed by suitable pack of Bag filters

Table: Stack Emission Details for DG Sets

Capacity

In KVA

Emission

of SPM in

mg/Nm3

Emission

Of SO2 in

mg/Nm3

Emission

of NOx In

mg/Nm3

Stack

dia.

In m

Flue Gas

Temp. in OC

Stack

Height

in (m)

Flue gas

Velocity

In m/sec.

250 KVA 50.0 20.0 40.0 0.30 290 10 12.76

380 KVA 74.0 150.0 185.0 0.30 220 10 21.0

Annexure-VII

PROCESS EMISSION DETAILS

S.No. Name of the Gas Quantity Treatment Method

1 Carbon dioxide 117.34 Kgs/Day Dispersed into the atmosphere

2 Sulphur dioxide 241.28 Kgs/Day Scrubbed by using C.S.Lye Solution

3 Hydrogen 15.08 Kgs/Day Diffused by using Nitrogen through Flame arrestor

4 Ammonia 114.37 Kgs/Day Scrubbed by using chilled water media

5 Hydrogen chloride 439.45 Kgs/Day Scrubbed by using chilled water media

6 Oxygen 177.75 Kgs/Day Dispersed into the atmosphere

Annexure- VIII

LIST OF RAW MATERIALS

ALBENDAZOLE

S .No. Raw Material Consumption/ Batch in Kgs

Consumption/ Day in Kgs

1 O-Nitro aniline 270.00 180.00

2 Acetone 800.00 533.33

3 Ammonium thio cyanate 298.00 198.67

4 Chlorine gas 138.00 92.00

5 Cyanamide 81.00 54.00

6 EDTA 1.00 0.67

7 Methanol 1700.00 1133.33

8 Methyl chloroformate 182.00 121.33

9 n-Propanol 500.00 333.33

10 n-Propyl bromide 237.00 158.00

11 Sodium hydrosulphide 214.00 142.67

12 Sodium hydroxide solution (50%) 77.00 51.33

13 Sodium hydroxide solution (50%) 77.00 51.33

BIAPENEM



1 3-(Diphenoxy-phosphorylox)-6-(1-hydroxy-ethyl)-4-methyl-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester

450.00

300.00

2 6-Mercapto-6,7-dihydro-5H-pyrazolo[1,2] [1,2,4] triazol-4-ylium

107.00 71.33

3 Acetonitrile 300.00 200.00

4 Ethyl Acetate 500.00 333.33

5 Hydrochloric Acid 28.00 18.67

6 Hydrogen 2.00 1.33

7 n-Heptane 400.00 266.67

8 Palladium Carbon 10.00 6.67

9 Sodium hydroxide 30.00 20.00

10 THF 600.00 400.00

CARVEDILOL



1 9H-Carbazol-4-ol 121.00 80.67

2 (2-methoxyphenoxy)ethylamine

106.06 70.71

3 (Chloromethyl) oxirane 60.50 40.33

4 Activated carbon 20.00 13.33

5 Ethyl acetate 500.00 333.33

6 Sodium chloride(washing) 50.00 33.33

7 Sodium sulfate 150.00 100.00

8 Tetrahydrofuran 450.00 300.00

9 Toluene 500.00 333.33




1 Acetophenone 300.00 200.00

2 Acetic Acid 171.00 114.00


4 Ammonia Hydroxide 49.00 32.67

5 C.S.Flakes 125.00 83.33

6 Cyclopropyl amine 82.00 54.67

7 Dimethyl carbonate 131.00 87.33

8 DMF 105.00 70.00

9 DMSO 181.00 120.67

10 Hydrochloric acid 52.00 34.67

11 Hydrochloric acid (36%) 51.00 34.00

12 Methanol 1000.00 666.67

13 n-Butanol 300.00 200.00

14 Piperazine 242.00 161.33

15 Sodium hydride 70.00 46.67

16 Toluene 1600.00 1066.67

CLOSANTEL SODIUM



1 4-Chloro -1-methy -2-nitro -benzene 134.00 89.33

3 Methanol 500.00 333.33

2 Para Chloro Benzyl Cyanide 118.00 78.67

4 Sodium sulfide 60.80 40.53

5 Sodium bicarbonate 65.50 43.67

6 2-hydroxy -3,5-diiodo-benzoic acid 294.00 196.00


8 Hyflow 3.00 2.00

9 Methanol

500.00 333.33

10 Phosphorus trichloride 104.00 69.33

11 Sodium Hydroxide 120.50 80.33

12 Toluene 1300.00 866.67

DOREPENEM



1 3-(Diphenoxy-phosphoryloxy)-6-(1-hydroxy-ethyl)-4-methyl-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester

365.00

243.33

2 (2S,3S)-1-p-nitrobenzyloxycarbonyl-2-sulfamylaminomethyl-4-mercaptopyrrolidone

246.00

164.00


4 Acivated carbon 10.00 6.67

5 DMF 300.00 200.00



8 N-Ethyl Diispropyl Amine 82.00 54.67



11 Tetrahydrofuran 300.00 200.00

ENROFLOXACIN



1 Quinoline-3- Carboxylic acid

405.00 270.00

2 Acetic acid 17.46 11.64

3 Activated Carbon 12.00 8.00

4 Hydrochloric Acid 10.62 7.08

5 n-Butanol 1000.00 666.67

6 n-Ethyl Piperazine 328.00 218.67


GABAPENTIN



1 (1-Carbamoylmethyl-cyclohexyl)-acetic acid

318.00

212.00



4 Methylene Dichloride 500.00 333.33

5 Sodium Hypochlorite 118.00 78.67




1 Chitin 375.00 250.00


3 Methanol 800.00 533.33

IMIPENEM



1 6-(1-Hydroxy-ethyl)-3,7-dioxo-1-aza-bicyclo[3.2.0]heptanes-2-carboxylic acid 4-nitro-benzyl ester 318.00 212.00

2 2-Amine -ethanethiol 70.00 46.67



5 Di-Isopropyl Amine 500.00 333.33

6 Ethyl Acetate 1500.00 1000.00

7 Formimidic acid methyl ester 52.00 34.67


9 MDC 300.00 200.00

10 Methanol 400.00 266.67

11 n- Hexane 400.00 266.67


13 Para toluene sulfonyl chloride 170.00 113.33


LAMIVUDINE



1 L(-) Menthol 280.00 186.67

2 2,5-Dithiane-1,4-diol 136.00 90.67



5 Conc. HCl 83.00 55.33

6 Cyclohexane 630.00 420.00

7 cytosine 279.00 186.00


9 Formaldehyde 55.00 36.67

10 Glyoxylic Acid (50%) 266.00 177.33

11 Hexamethyldisilazane 404.00 269.33

12 Hyflow 5.00 3.33

13 IPA 50.00 33.33

14 Iso propyl alcohol 600.00 400.00

15 Methane Sulphonic Acid 2.00 1.33

16 Methanol 1200.00 800.00

17 Methylene dichloride 1000.00 666.67

18 n-Hexane 430.00 286.67

19 Sodium Bisulphite 186.00 124.00

20 Sodium Borohydride 86.00 57.33

21 Sodium Carbonate 15.00 10.00

22 Sulphuric Acid 3.00 2.00

23 Thionyl chloride 298.00 198.67

24 Toluene 1288.00 858.67

25 Triethylamine 223.00 148.67

LANSOPRAZOLE



1 2,3-Lutidine 84.00 56.00

2 2-Mercapto Benzimidazole 107.00 71.33

3 Acetic Anhydride 77.00 51.33

4 Acetone 150.00 100.00


6 Catalyst 1.00 0.67

7 Chloroform 400.00 266.67

8 Hydrogen Chloride Gas 27.00 18.00

9 Hydrogen Peroxide (50%) 30.00 20.00

10 Hydrogen Peroxide (50%) 30.00 20.00

11 Isopropyl Alcohol 250.00 166.67

12 Methylene Dichloride 200.00 133.33

13 MIBK 130.00 86.67

14 Nitric Acid 49.00 32.67

15 Potassium Carbonate 105.00 70.00


17 Sulfuric Acid 50.00 33.33

18 TEBAC 1.00 0.67

19 Thionyl Chloride 88.00 58.67

20 Toluene 475.00 316.67

21 Tri Fluoro Ethanol 76.00 50.67

MEROPENEM



1 3-(Diphenoxy-phosphoryloxy)-6- (1-hydroxy-ethyl)-4-methyl-7-oxo- 1-aza-bicyclo[3.2.0]hept-2-ene-2- carboxylic acid 4-nitro-benzyl ester 430.00 286.67

2 10% Palladium Carbon 5.00 3.33

3 2-Dimethylcarbamoyl-4-mercapto- pyrrolidine-1-carboxylic acid 4-nitro-benzyl ester 245.00 163.33



6 Hexane 350.00 233.33

7 Hydrogen 3.000 2.00

8 Isopropyl Alcohol 700.00 466.67

9 MDC 600.00 400.00


11 Triethylamine 70.00 46.67

NEVIRAPINE



1 2-Chloro-N-(2-Chloro-4-Methyl-3-Pyridinyl)-3-Pyridine Carboxamide

570.00 380.00



4 Calcium oxide 25.50 17.00

5 Cyclo propyl amine 115.50 77.00

6 Cyclohexane 400.00 266.67

7 DM Water 1000.00 666.67

8 DM Water 1200.00 800.00

9 Hyflow 13.00 8.67

10 Methanol 900.00 600.00

11 Ortho-Xylene 2000.00 1333.33

12 Sodium Hydride 47.00 31.33

NICLOSAMIDE



1 5-Chloro Salicylic Acid 282.00 188.00

2 2-Chloro 4-Nitro aniline 272.00 181.33

3 Mono Chloro Benzene 1100.00 733.33

4 Thionyl chloride 194.00 129.33

OMEPRAZOLE



1 3,5-Lutidine 89.00 59.33

2 2-Mercapto-5-methoxy Benzimidazole 138.00 92.00


4 Acetone 250.00 166.67

5 Dimethyl sulphate 102.00 68.00

6 Hydrogen Peroxide 53.00 35.33

7 Methanol 750.00 500.00

8 Nitric acid 52.00 34.67

9 Sodium chloride 30.00 20.00


11 Sodium methoxide 44.00 29.33

12 Sulphuric acid 25.00 16.67

13 Thionyl Chloride 93.00 62.00

14 Toluene 1000.00 666.67

RAFOXANIDE

S .No.

Raw Material Consumption/ Batch in Kgs


1 Iodine 210.00 140.00

2 1,2 –Di chloro -4-nitro-benzene 171.00 114.00

3 4-chloro -phenol 115.00 76.67


5 Acetone 500.00 333.33


7 Chlorine gas 60.00 40.00


9 Hyflow 3.00 2.00

10 Iron powder

48.00 32.00

11 MDC 1000.00 666.67

12 Methanol 500.00 333.33

13 Phosphorus trichloride 115.00 76.67

14 Potassium hydroxide 50.00 33.33

15 Salicylic acid 119.00 79.33

16 Toluene 1500.00 1000.00




1 Napthyl methyl chloride 140.00 93.33

2 Chloro methyl heptane 124.00 82.67


4 IPA 600.00 400.00

5 MDC 500.00 333.33

6 Mono methyl amine 25.00 16.67

7 Potassium carbonate 55.00 36.67

8 Toluene 300.00 200.00

TRICLABENDAZOLE



1 3,4-Di chloro-phenyl amine 283.00 188.67

2 2,3-Di chloro -phenol 258.00 172.00

3 Acetic anhydride 179.00 119.33

4 Carbon di sulfide 113.00 75.33

5 Di methyl sulphate 204.00 136.00



8 Methanol 3100.00 2066.67

9 Nitric acid 107.00 71.33

10 Potassium hydroxide 92.00 61.33

11 Raney nickel 10.00 6.67


13 Toluene 500.00 333.33

ZIDOVUDINE



1 β-Thymidine 495.00 330.00

2 1,4-Dioxane 800.00 533.33


4 Ammonium chloride 105.00 70.00

5 DMSO 600.00 400.00


7 Hyflow 5.00 3.33

8 Methane sulfonyl chloride 220.00 146.67

9 PTSA Monohydrate 393.00 262.00

10 Sodium azide 125.00 83.33


12 Toluene 1100.00 733.33

13 Tri ethyl amine 575.00 383.33

14 Trityl chloride 530.00 353.33

11. LOSARTAN POTASSIUM

S.No. Raw Material Consumption/ Batch in Kgs


source

1. 2-Cyano-4-Methyl biphenyl (OTBN)

236.00 157.33

indigenous

2. Activated Carbon 15.00 10.00 indigenous

3. Butyl chloro formyl imidazole (BCFI)

206.00 137.33

indigenous

4. Ethyl Acetate 200.00 133.33 indigenous

5. Hydrochloric acid 83.00 55.33 indigenous

6. MDC 500.00 333.33 indigenous

7. Methanol 1700.00 1133.33 indigenous

8. Methylenedichloride 400.00 266.67 indigenous

9. N-Bromosuccinimide (NBS) 195.00 130.00 indigenous

10. Potassium hydroxide 61.00 40.67 indigenous

11. Sodium Azide 73.00 48.67 indigenous

12. Sodium hydroxide 44.00 29.33 indigenous

13. Sodium meta bisulphate 10.00 6.67 indigenous

14. Sodium nitrite 78.00 52.00 indigenous

15. TBAB 5.00 3.33 indigenous

16. TEA 30.00 20.00 indigenous

17. TEA HCl 25.00 16.67 indigenous

18. Toluene 400.00 266.67 indigenous

19. Trityl chloride 276.00 184.00 indigenous

12. NEVIRAPINE



source

1. 2-Chloro-N-(2-Chloro-4-Methyl-3-Pyridinyl)-3-Pyridine Carboxamide

541.00 360.67 indigenous

2. Acetic acid 10.00 6.67 indigenous


4. Calcium oxide 25.50 17.00 indigenous

5. Cyclo propyl amine 109.50 73.00 indigenous

6. Cyclohexane 400.00 266.67 indigenous

7. Hyflow 13.00 8.67 indigenous


9. Ortho-Xylene 2000.00 1333.33 indigenous

10. Sodium Hydride 46.00 30.67 indigenous

13. OMEPRAZOLE



source

1. 3,5-Lutidine 157.00 104.67 indigenous

2. 2-Mercapto-5-methoxy Benzimidazole

260.00 173.33

indigenous


4. Acetone 250.00 166.67 indigenous

5. Dimethyl sulphate 183.80 122.53 indigenous

6. Hydrogen Peroxide 98.60 65.73 indigenous


8. Nitric acid 92.35 61.57 indigenous

9. Sodium chloride 58.00 38.67 indigenous


11. Sodium methoxide 78.70 52.47 indigenous

12. Sulphuric acid 25.00 16.67 indigenous

13. Thionyl Chloride 172.90 115.27 indigenous


14. PANTOPRAZOLE SODIUM



source

1. Maltol 66.00 44.00 indigenous

2. 5-diFluoromethoxy-2-mercapto- benzimidazole

108.00

72.00

indigenous

3. Acetic Acid 10.00 6.67 indigenous

4. Acetic Anhydride 172.00 114.67 indigenous

5. Acetone 1000.00 666.67 indigenous


7. Ammonia 9.00 6.00 indigenous

8. Ammonium Carbonate 50.00 33.33 indigenous

9. Ammonium Chloride 25.00 16.67 indigenous

10. Ammonium hydroxide 35.50 23.67 indigenous

11. Dimethyl sulphate 33.00 22.00 indigenous

12. Hydrogen peroxide 17.00 11.33 indigenous

13. MDC 1950.00 1300.00 indigenous


15. Methylene dichloride 1300.00 866.67 indigenous

16. Phosphorous oxy chloride 26.00 17.33 indigenous

17. Potassium carbonate 36.00 24.00 indigenous


19. Sodium hypochlorite 37.00 24.67 indigenous

20. Sodium methoxide 27.00 18.00 indigenous

21. Thionyl chloride 60.00 40.00 indigenous


15. PREGABALIN



source

1. Isoveraldehyde 112.00 149.33 indigenous

2. (S)-Mandelic acid 100.00 133.33 indigenous


4. Di isopropyl amine 10.00 13.33 indigenous

5. Diethyl malonate 209.00 278.67 indigenous

6. Ethanol 900.00 1200.00 indigenous

7. Hydrogen gas 5.00 6.67 indigenous

8. IPA 1870.00 2493.33 indigenous


10. n-Hexane 180.00 240.00 indigenous

11. Potassium hydroxide 73.00 97.33 indigenous

12. Raney nickel 30.00 40.00 indigenous

13. Sodium cyanide 64.00 85.33 indigenous

14. Tetrahydrofuran 900.00 1200.00 indigenous


16. SERTRALINE HYDROCHLORIDE



source

1. Racemic Cis and Trans Sertraline

100.00 166.67

indigenous

2. Activated carbon 17.80 29.67 indigenous

3. Caustic Lye 125.00 208.33 indigenous

4. D(-) Mandelic acid 5.00 8.33 indigenous



7. IPA 4500.00 7500.00 indigenous


9. Methylene chloride 4550.00 7583.33 indigenous

17. TRAMADOL HYDROCHLORIDE



source

1. Di methyl amine 32.00 53.33 indigenous

2. Bromo Anisole 125.00 208.33 indigenous

3. Cyclohexanone 65.75 109.58 indigenous

4. Glacial Acetic acid 2.00 3.33 indigenous


6. Isopropyl Alcohol 500.00 833.33 indigenous

7. Magnesium 16.25 27.08 indigenous


9. Nitric acid 43.00 71.67 indigenous

10. p-Formaldehyde 20.11 33.52 indigenous


12. Sulfuric Acid 66.00 110.00 indigenous

13. Tetrahydrofuran 400.00 666.67 indigenous


18. ZIDOVUDINE



source

1. β-Thymidine 363.00 302.50 indigenous

2. 1,4-Dioxane 800.00 666.67 indigenous


4. Ammonium chloride 80.00 66.67 indigenous

5. DMSO 1200.00 1000.00 indigenous

6. Ethyl acetate 1300.00 1083.33 indigenous


8. Methane sulfonyl chloride 172.00 143.33 indigenous


10. PTSA Monohydrate 284.50 237.08 indigenous

11. Sodium azide 97.40 81.17 indigenous



14. Tri ethyl amine 496.00 413.33 indigenous

15. Trityl chloride 418.00 348.33 indigenous

Annexure-IX

Consolidated Statement- Pollution Details

S.No

Product Name

Productioncapaci

ty kg/ Month

Effluent in kg/day Solid waste Details in Kg/day Distillation

Residue in Kg

/Day

Emissions in Kg/day

Water Input

Water In

Effluent

Inorganics in

water

Organics in

water TDS COD HTDS LTDS Total

Effluent Organi

c

Inorgani

c

Spent carbo

n

Total solid waste

Process

Fugitive

1 Albendazole 10000.00 4333.33

4309.77 492.56 36.00 492.56

66.63

3854.99

983.33 4838.33 36.82 0.00 0.00 36.82 20.67 102.18 43.33

2 Biopenem 5000.00 666.67 675.73 155.33 17.33 155.33 25.9

7 848.40 0.00 848.40 13.60 0.00 0.00 13.60 12.67 0.00 20.00

3 Carvedilol 5000.00

400.00 400.00 33.33 14.00 33.33 53.1

9 373.33 74.00 447.33 9.12 166.

67 13.33 189.12 10.67 17.87 23.33

4 Ciprofloxacin 10000.00 6000.00

6033.42 318.05

137.72 318.05

233.69

2804.15

3685.04 6489.19 31.71 0.00 0.00 31.71 2.67 1.91 92.00

5 Closantel Sodium 10000.00 3333.33

3332.71 191.63 20.67 191.63

53.82

3545.00 0.00 3545.00 14.81 0.00

5.33 20.15 25.33 58.85 30.67

6 Dorapenem 5000.00 666.67 666.67 274.00 5.33 274.00 8.24 612.67

333.33 946.00 18.67

13.33 6.67 38.67 13.33 6.67 16.00

7 Enrofloxacin 10000.00 3333.33

3333.33 22.99 0.00 22.99 0.00

3356.33 0.00 3356.33 19.07 0.00 0.00 19.07 0.00 0.00 33.33

8 Gabapentin 5000.00 1066.67

1084.81 120.60 0.00 120.60 0.00 890.68

314.73 1205.41 17.25 0.00 5.33 22.59 6.67 46.67 10.00

9 Glucosamine HCl 5000.00 800.00 786.33 22.67 8.00 22.67

12.00 817.00 0.00 817.00 6.33 0.00 0.00 6.33 8.00 0.00 10.67

10 Imipenem 5000.00 1700.00 1710.6

7 198.67 5.33 198.67 8.00 1237.3

3 677.3

3 1914.67 21.33 0.00 16.67 38.00 25.33 0.00 97.33

11 Lamivudine 10000.00 5333.33

4893.13 335.43 31.33 335.43

82.36

3942.10

1317.79 5259.89 356.55 0.00 8.67 365.22 70.00 202.41 85.33

12 Lansoprazole 5000.00 1293.33

1347.33 127.33 6.00 127.33

12.46 839.33

641.33 1480.67 22.67

93.33 2.00 118.00 18.67 49.33 24.67

13 Meropenem 5000.00 1166.67

1174.67 142.00 3.33 142.00 8.00 683.33

636.67 1320.00 9.33 0.00 0.00 9.33 0.00 0.00 66.67

14 Nevirapine 10000.00 5000.00

5000.00 99.83 0.00 99.83

13.72

2420.17

2683.67 5103.83 27.09 0.00 13.33 40.42 62.00 51.75 44.00

15 Niclosamide 10000.00 3333.33

3333.33 0.00 0.00 0.00 0.00 0.00

3333.33 3333.33 17.80 0.00 0.00 17.80 22.00 147.53 14.67

16 Omeprazole 5000.00 1233.33

1290.00 114.00 40.67 114.00

64.70

1436.00 8.67 1444.67 16.67

76.67 0.00 93.33 32.67 33.33 26.67

17 Rafoxanide 10000.00 4333.33

4303.03 102.98 24.00 102.98

61.00

2767.00

1663.01 4430.01 33.35 0.00 12.00 45.35 46.00 120.78 46.67

18 Terbinafine HCl 5000.00 833.33 838.06 39.18 1.33 39.18 4.17 577.91

300.67 878.57 7.92 0.00 0.00 7.92 0.00 30.84 56.67

19 Triclabendazole 10000.00 5000.00

5022.23 328.19 57.30 328.19

93.56

3389.05

2018.67 5407.72 78.11 0.00 0.00 78.11 47.33 164.67 54.67

20 Zudovudine 10000.00 4000.00

4022.61 479.07

164.67 479.07

457.17

4666.34 0.00 4666.34 30.69 0.00 6.67 37.36 52.67 42.67 58.67

Total (Worst combination of any 10 products at any given point of time)

100000.00

44000.00

43583.55 2914.93

543.69

2914.93

1192.09

32181.13

17640.17 49821.31 657.39

350.00 90.00

1097.39 404.00 986.85

645.33

Annexure-X

Site Plan

Annexures - Welcome to Environmentenvironmentclearance.nic.in/writereaddata/Online/TOR/20_May_2017... · Annexures 1 List of Products ... further reacts with Stage-3 product in presence

Documents