Home Cart 0 Sign in  
X

[ CAS No. 16588-16-2 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
3d Animation Molecule Structure of 16588-16-2
Chemical Structure| 16588-16-2
Chemical Structure| 16588-16-2
Structure of 16588-16-2 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 16588-16-2 ]

Related Doc. of [ 16588-16-2 ]

Alternatived Products of [ 16588-16-2 ]
Product Citations

Product Details of [ 16588-16-2 ]

CAS No. :16588-16-2 MDL No. :MFCD00219621
Formula : C9H8ClNO4 Boiling Point : -
Linear Structure Formula :- InChI Key :BLNLZRQIUGDTAO-UHFFFAOYSA-N
M.W : 229.62 Pubchem ID :1268247
Synonyms :

Calculated chemistry of [ 16588-16-2 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 15
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.22
Num. rotatable bonds : 4
Num. H-bond acceptors : 4.0
Num. H-bond donors : 0.0
Molar Refractivity : 56.36
TPSA : 72.12 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.8 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.93
Log Po/w (XLOGP3) : 2.68
Log Po/w (WLOGP) : 2.42
Log Po/w (MLOGP) : 1.73
Log Po/w (SILICOS-IT) : 0.57
Consensus Log Po/w : 1.87

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -2.98
Solubility : 0.238 mg/ml ; 0.00104 mol/l
Class : Soluble
Log S (Ali) : -3.85
Solubility : 0.0327 mg/ml ; 0.000142 mol/l
Class : Soluble
Log S (SILICOS-IT) : -2.88
Solubility : 0.301 mg/ml ; 0.00131 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 2.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.0

Safety of [ 16588-16-2 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 16588-16-2 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Upstream synthesis route of [ 16588-16-2 ]
  • Downstream synthetic route of [ 16588-16-2 ]

[ 16588-16-2 ] Synthesis Path-Upstream   1~8

  • 1
  • [ 96-99-1 ]
  • [ 16588-16-2 ]
YieldReaction ConditionsOperation in experiment
97% With sulfuric acid In ethanol Step 1
Production of Ethyl 4-chloro-3-nitrobenzoate
4-Chloro-3-nitrobenzoic acid (300 g) was dissolved in ethyl alcohol (1500 ml) and concentrated sulfuric acid (100 ml) was added with ice-cooling.
The mixture was refluxed under: heating for 7 hr.
The reaction mixture was poured into ice-cold water and the precipitated crystals were collected by filtration to give the title compound (332 g, yield 97percent).
1H-NMR (300 MHz, CDCl3): 8.50 (1H, d, J=2.1 Hz), 8.16 (1H, dd, J=8.4, 2.1 Hz), 7.63 (1H, d, J=8.4 Hz), 4.43 (2H, q, J=7.5 Hz), 1.42 (3H, t, J=7.5 Hz).
86%
Stage #1: With potassium carbonate In DMF (N,N-dimethyl-formamide) for 0.5 h;
Stage #2: at 50℃; for 4 h; Heating / reflux
To a solution of 4-chloro-3-nitrobenzoic acid (20.0 g, 99.2 mmol) in N,N-dimethylformamide (400 mL) was added potassium carbonate (35.0 g, 254 mmol, 2.6 eqiv). After 30 min, ethyl iodide (18.6 g, 119 mmol, 1.2 eqiv) was added and the reaction mixture was heated at 50 C for 4 h. Water (3 L) was added and the mixture was extracted with diethyl ether (2 x 500 mL). The organic extracts were combined, washed with brine (1 L), dried over anhydrous sodium sulfate and concentrated on vacuum rotary evaporator. The residue was crystallized from hexanes to provide 19.7 g (86percent) of the ester. 1H NMR (500 MHz, CDCl3) delta; 8.51 (d, 1H), 8.17 (dd, 1H), 7.65 (d, 1H), 4.43 (q, 2H), 1.42 (t, 3H)
Reference: [1] Patent: US2003/50320, 2003, A1,
[2] Patent: WO2004/29050, 2004, A1, . Location in patent: Page 105;106
[3] Synthetic Communications, 2002, vol. 32, # 11, p. 1703 - 1707
[4] Patent: US6204264, 2001, B1,
  • 2
  • [ 75-03-6 ]
  • [ 96-99-1 ]
  • [ 16588-16-2 ]
YieldReaction ConditionsOperation in experiment
100% With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 3 h; Step O
To potassium carbonate (103 g) was added DMF (1 L), and a solution of 3-nitro-4-chlorobenzoic acid (125 g) in DMF (500 ml) was added thereto under ice-cooling.
Ethyl iodide (116 g) was added thereto and the resulting mixture was stirred at 60°C for 3 hours.
The reaction solution was added to a 1N aqueous hydrochloric acid solution and the crystals precipitated were collected by filtration, washed with a 1N aqueous hydrochloric acid solution and water and then dried under reduced pressure to obtain ethyl 4-chloro-3-nitrobenzoate quantitatively.
1H-NMR (CDCl3) δ
1.42(t,J=7.1Hz,3H), 4.43(q,J=7.1Hz,2H), 7.65 (d,J=8.4Hz,1H), 8.17(dd,J=8.4,2.0Hz,1H), 8.52(d,J=2.0 Hz, 1H).
86%
Stage #1: With potassium carbonate In DMF (N,N-dimethyl-formamide) for 0.5 h;
Stage #2: at 50℃; for 4 h;
Aldehyde preparation: To a solution of 4-chloro-3-nitrobeznoic acid (20 g, 99.2 mmol, 1.0 eq) in dimethylformamide (400 mL) was added potassium carbonate (35 g, 254 mmol, 2.55 eq). The mixture was stirred 30 min and ethyl iodide (18.6 g, 119 mmol, 1.20 eq) was added. The reaction mixture was stirred at 50 [°C] for 4h. Water (3 L) was added and the mixture was extracted with diethyl ether (2 x 500 mL). The organic extracts were combined, washed with brine (1 L), dried over anhydrous sodium sulfate and concentrated. The residue was crystallized from hexanes to provide 19.7 g (86percent) of the ester. Data [: IH] NMR (500 MHz, CDC13) [8] 8.51 (d, 1H), 8.17 (dd, 1H), 7.65 (d, 1H), 4.43 (q, 2H), 1.42 (t, 3H). Sulfur (1.60 g, 49.9 mmol, 0.58 eq) was dissolved in a solution of sodium sulfide [NONAHYDRATE] (12.0 g, 50.0 mmol, 0.58 eq) in water (60 [ML).] This solution was combined with a solution of ethyl 4-chloro-3-nitrobenzoate (19.6 g, 85.4 mmol, 1.00 eq) in ethanol (100 mL). The resulting mixture was heated at reflux for 3 h. The hot reaction mixture was poured into water (600 mL) and stirred for 15 min. The product was isolated by filtration and recrystallized from ethanol to provide 16.45 g (77percent) of the disulfide. Data: [APOS;H NMR] (500 MHz, CDC13) [5] 8.96 (d, 1H), 8.19 (dd, 1H), 7.88 (d, 1H), 4.43 (q, 2H), 1.41 (t, 3H). A mixture of diethyl 4,4'-dithiobis (3-nitrobenzoate) (11.2 g, 24.75 mmol, 1.00 eq) and zinc granules (15.0 g, 234 mmol, 9.47 eq) in formic acid (600 mL) was heated to reflux for 48 h. The mixture was cooled to room temperature and concentrated to dryness on vacuum rotary evaporator. The residue was partitioned between ethyl acetate (500 mL) and saturated aqueous sodium bicarbonate (500 mL). The organic layer was separated, dried over anhydrous sodium sulfate and concentrated on vacuum rotary evaporator. The residue was purified by chromatography on neutral Alumina (1/0 to 0/1 hexanes/dichloromethane) to provide 5.30 g (51percent) of the benzthiazole ester. Data: 1H NMR (500 MHz, [CDC13)] [8] [9. 08 (S, 1H),] 8.83 (d, 1H), 8.14 (dd, 1H), 8.02 (d, 1H), 4.45 (q, 2H), 1.44 (t, 3H); MS [(EI)] m/z 208 [(M++1).] Diisobutylaluminum hydride (1.0 M in dichloromethane, 6.0 mL, 6 mmol, 1.05 eq) was added over 15 min to a solution of the ester (1.18 g, 5.70 mmol) in dichloromethane (40 mL) [AT-35] [°C.] The reaction mixture was allowed to warm to rt and was maintained overnight. Analysis of the reaction progress by thin layer chromatography revealed the presence of starting material. The reaction mixture was cooled to [0 °C] and was treated with additional diisobutylaluminum hydride (6.0 mL, 6 mmol). After 4 h at rt, the reaction was quenched by the addition of water (10 mL) and the slurry was poured onto 5percent sodium hydroxide and dichloromethane (200 mL) and maintained for 30 min with vigorous stirring. The organic layer was separated, washed with brine, dried (sodium sulfate), and concentrated. The residue was dissolved in dichloromethane (100 mL) and was treated with manganese [(IV)] oxide (3.0 g) and powdered [4A] seives (3.0 g). The reaction mixture was filtered through Celite (100 mL dichloromethane rinse) after 14 h and the filtrate was extracted with 0.6 N aqueous sodium hydrogen sulite (2 x 150 mL). The combined aqueous layers were back-extracted with dichloromethane [(50] mL), were made basic (pH 11) by the addition of 50percent sodium hydroxide, and were extracted with ethyl acetate (2 x 100 mL). The ethyl acetate layers were dried (sodium sulfate) and concentrated to provide 268 mg (29percent) of the aldehyde as a tan solid. Data [: IHNMR (CDCL3) 6] 10.18 (s, 1H), 9.13 (s, [1H),] 8.61 (d, J= 1.0, 1H), 8.11 (d, J= 8.0, 1H), 8.01 (dd, J= 8.5, 1.5, 1H).
86%
Stage #1: With potassium carbonate In DMF (N,N-dimethyl-formamide) for 0.5 h;
Stage #2: at 50℃; for 4 h;
To a solution of 4-chloro-3-nitrobenzoic acid (99.2 mmol) in N, N-dimethylformamide (400 mL) was added potassium carbonate (254 mmol). After 30 min, ethyl iodide (119 mmol) was added and the reaction mixture was heated at 50 °C for 4 h. Water (3 L) was added and the mixture was extracted with diethyl ether (2 x 500 mL). The organic extracts were combined, washed with brine (1 L), dried over anhydrous sodium sulfate and concentrated. The residue was crystallized from hexanes, thus providing the ester in 86percent yield.'H NMR (500 MHz, CDC13) 8 8. 51 (d, 1H), 8.17 (dd, 1H), 7.65 (d, 1H), 4.43 (q, 2H), 1.42 (t, 3H). Sulfur (49.91 mmol) was dissolved in a solution of sodium sulfide nonahydrate (49.96 mmol) in water (60 mL). This solution was combined with a solution of ethyl 4-chloro- 3-nitrobenzoate (85.36 mmol) in ethanol (100 mL) and the resulting mixture was heated at reflux for 3 h. The hot reaction mixture was poured into water (600 mL) and maintained for 15 min. The product was isolated by filtration and recrystallized from ethanol, thus providing the disulfide in 77percent yield. 1H NMR (500 MHz, CDC13) 8 8.96 (d, 1H), 8.19 (dd, 1H), 7.88 (d, 1H), 4.43 (q, 2H), 1.41 (t, 3H). A mixture of diethyl 4,4'-dithiobis (3-nitrobenzoate) (24.8 mmol) and zinc granules (234 mmol) in formic acid (600 mL) was heated to reflux for 48 h. The mixture was allowed to cool to room temperature and concentrated to dryness. The residue was partitioned between ethyl acetate (500 mL) and saturated aqueous sodium bicarbonate (500 mL). The organic layer was separated, dried over anhydrous sodium sulfate and concentrated. The residue was chromatographed on neutral Alumina (1/1 to 0/1 hexanes/dichloromethane), thus providing the thiazole in 51percent yields NMR (500 MHz, CDCl3) 5 9. 08 (s, 1H), 8.83 (d, 1H), 8.14 (dd, 1H), 8.02 (d, 1H), 4.45 (q, 2H), 1.44 (t, 3H); MS (EI) nilz 208 (M++1). To a solution of ethyl 1, 3-benzothiazole-5-carboxylate (25.6 mmol) in a mixture of methanol (150 mL), tetrahydrofuran (40 mL) and water (5 mL) was added a 50percent aqueous solution of sodium hydroxide (10 mL). The mixture was maintained at rt for 18 h and was concentrated. The residue was partitioned between water (300 mL) and diethyl ether (200 mL) and the organic layer was removed. Concentrated hydrochloric acid was added to the aqueous layer to adjust the pH to 4 and the mixture was extracted with ethyl acetate (3 x 300 mL). The combined extracts were washed with brine (200 mL), dried over anhydrous sodium sulfate, and concentrated thus providing the acid in 94percent yield.
Reference: [1] Patent: EP1726587, 2006, A1, . Location in patent: Page/Page column 47
[2] Patent: WO2004/19943, 2004, A1, . Location in patent: Page/Page column 78; 79
[3] Patent: WO2005/92890, 2005, A2, . Location in patent: Page/Page column 70-71
  • 3
  • [ 64-17-5 ]
  • [ 96-99-1 ]
  • [ 16588-16-2 ]
YieldReaction ConditionsOperation in experiment
96% for 2.25 h; Heating / reflux 4-Chloro-3-nitrobenzoic acid (100.0 g, 0.496 mole) was suspended in EtOH (250 mL) and thionyl chloride (54 mL, 0.74 mole) was added drop-wise over 15 min. The mixture was then reflux for 2 h. After cooling to ambient temperature, volatiles were removed under reduced pressure and the residue was co-evaporated twice with EtOH (2.x.250 mL). The residue was crystallized from hot EtOH to give the desired ethyl ester as light yellow needles (109.8 g, 96percent yield).
Reference: [1] Archiv der Pharmazie, 2004, vol. 337, # 5, p. 259 - 270
[2] Patent: US2003/236251, 2003, A1, . Location in patent: Page 16; 19
[3] Heterocyclic Communications, 2001, vol. 7, # 5, p. 455 - 460
[4] Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 5, p. 1587 - 1597
[5] Patent: WO2005/12288, 2005, A1, . Location in patent: Page/Page column 87; 126
[6] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 22, p. 5315 - 5320
[7] RSC Advances, 2016, vol. 6, # 10, p. 8303 - 8316
[8] Indian Journal of Heterocyclic Chemistry, 2018, vol. 28, # 3, p. 415 - 422
  • 4
  • [ 14719-83-6 ]
  • [ 64-17-5 ]
  • [ 16588-16-2 ]
Reference: [1] Synthetic Communications, 2002, vol. 32, # 11, p. 1703 - 1707
  • 5
  • [ 64-17-5 ]
  • [ 38818-50-7 ]
  • [ 16588-16-2 ]
Reference: [1] Justus Liebigs Annalen der Chemie, 1884, vol. 222, p. 183
  • 6
  • [ 16588-16-2 ]
  • [ 74-89-5 ]
  • [ 71254-71-2 ]
Reference: [1] RSC Advances, 2016, vol. 6, # 10, p. 8303 - 8316
[2] Indian Journal of Heterocyclic Chemistry, 2018, vol. 28, # 3, p. 415 - 422
  • 7
  • [ 16588-16-2 ]
  • [ 367-80-6 ]
Reference: [1] Patent: US2891074, 1954, ,
[2] Patent: DE1018042, 1953, ,
  • 8
  • [ 16588-16-2 ]
  • [ 347174-05-4 ]
Reference: [1] Synthesis, 2003, # 11, p. 1683 - 1692
[2] Journal of the American Chemical Society, 2014, vol. 136, # 12, p. 4551 - 4556
[3] Patent: WO2015/84749, 2015, A1,
[4] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 22, p. 5315 - 5320
[5] Patent: WO2005/121132, 2005, A1,
Recommend Products
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 16588-16-2 ]

Aryls

Chemical Structure| 36138-28-0

[ 36138-28-0 ]

Methyl 3-chloro-5-nitrobenzoate

Similarity: 0.90

Chemical Structure| 14719-83-6

[ 14719-83-6 ]

Methyl 4-chloro-3-nitrobenzate

Similarity: 0.87

Chemical Structure| 51282-49-6

[ 51282-49-6 ]

Methyl 5-chloro-2-nitrobenzoate

Similarity: 0.85

Chemical Structure| 53553-14-3

[ 53553-14-3 ]

Methyl 2-chloro-3-nitrobenzoate

Similarity: 0.83

Chemical Structure| 2516-96-3

[ 2516-96-3 ]

2-Chloro-5-nitrobenzoic acid

Similarity: 0.83

Chlorides

Chemical Structure| 36138-28-0

[ 36138-28-0 ]

Methyl 3-chloro-5-nitrobenzoate

Similarity: 0.90

Chemical Structure| 14719-83-6

[ 14719-83-6 ]

Methyl 4-chloro-3-nitrobenzate

Similarity: 0.87

Chemical Structure| 51282-49-6

[ 51282-49-6 ]

Methyl 5-chloro-2-nitrobenzoate

Similarity: 0.85

Chemical Structure| 53553-14-3

[ 53553-14-3 ]

Methyl 2-chloro-3-nitrobenzoate

Similarity: 0.83

Chemical Structure| 2516-96-3

[ 2516-96-3 ]

2-Chloro-5-nitrobenzoic acid

Similarity: 0.83

Esters

Chemical Structure| 36138-28-0

[ 36138-28-0 ]

Methyl 3-chloro-5-nitrobenzoate

Similarity: 0.90

Chemical Structure| 14719-83-6

[ 14719-83-6 ]

Methyl 4-chloro-3-nitrobenzate

Similarity: 0.87

Chemical Structure| 51282-49-6

[ 51282-49-6 ]

Methyl 5-chloro-2-nitrobenzoate

Similarity: 0.85

Chemical Structure| 53553-14-3

[ 53553-14-3 ]

Methyl 2-chloro-3-nitrobenzoate

Similarity: 0.83

Chemical Structure| 143269-74-3

[ 143269-74-3 ]

Hexadecyl 3-amino-4-chlorobenzoate

Similarity: 0.81

Nitroes

Chemical Structure| 36138-28-0

[ 36138-28-0 ]

Methyl 3-chloro-5-nitrobenzoate

Similarity: 0.90

Chemical Structure| 14719-83-6

[ 14719-83-6 ]

Methyl 4-chloro-3-nitrobenzate

Similarity: 0.87

Chemical Structure| 51282-49-6

[ 51282-49-6 ]

Methyl 5-chloro-2-nitrobenzoate

Similarity: 0.85

Chemical Structure| 53553-14-3

[ 53553-14-3 ]

Methyl 2-chloro-3-nitrobenzoate

Similarity: 0.83

Chemical Structure| 2516-96-3

[ 2516-96-3 ]

2-Chloro-5-nitrobenzoic acid

Similarity: 0.83