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Chemical Structure| 591-50-4 Chemical Structure| 591-50-4

Structure of Iodobenzene
CAS No.: 591-50-4

Chemical Structure| 591-50-4

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Deborah Sam Ogulu ;

Abstract: Organic synthesis is a critical process in the creation of small molecule pharmaceuticals and agrochemicals. However, most methods for synthesizing these small molecules rely on toxic organic solvents as the reaction medium which account for approximately 80% of pharmaceutical waste. Moreover, many catalytic reactions require expensive endangered precious metals like palladium and costly metals. This dissertation presents research that aims to develop sustainable, eco-friendly reaction conditions to address these issues. Chapter 1 provides an overview of green and sustainable chemistry and chemistry in water. It explains what sustainability entails and the drive towards greener synthetic methods. Also included is the introduction to the concept of chemistry in water, the different types of roles of water in chemistry, and the development of micellar catalysis – including its evolution, applications, current challenges, and future directions. Chapter 2 discusses the development of a ligand-free bimetallic nanocatalyst for the hydrogenation of unsaturated enones. This ligand-free nanocatalyst was prepared from nickel and ppm loading of palladium and was stabilized by harnessing the structural features of the amphiphile, PS-750-M. The physical properties of the nanoparticles were evaluated and thoroughly characterized using different analytical techniques like HRTEM, XPS, and TGA. Chapter 3 describes the application of a copper catalyst in the hydroboration of unsymmetrical internal alkynes with high regioselectivity under aqueous micellar conditions. The methodology was amenable to internal alkynes with diverse functional groups and provides a unique route to access β selective alkenyl boronates. Chapter 4 showcases the development of a protocol towards coupling of aryl boronic acids and primary amines under aqueous micellar conditions using an inexpensive nickel catalyst and oxygen balloon. The developed methodology provides another way to access amines under more sustainable reaction conditions. Chapter 5 describes the use of ppm palladium and copper catalysts immobilized on silica for the catalytic dehydration of amides to nitriles. The protocol employs acetonitrile as the additive and the reaction is performed using aqueous PS-750-M as the reaction medium.

Purchased from AmBeed: ; ;

Guo, Sheng ; Wu, Yifan ; Luo, Shao-Xiong Lennon ; Swager, Timothy M. ;

Abstract: Heterogenous catalysts with confined nanoporous catalytic sites are shown to have high activity and size selectivity. A solution-processable nanoporous organic polymer (1-BPy-Pd) catalyst displays high catalytic performance (TON > 200K) in the heterogeneous Suzuki–Miyaura coupling (SMC) reaction and can be used for the preparation of the intermediates in the synthesis of pharmaceutical agents. In comparison to the homogeneous catalyst analogue (2,2′-BPy)PdCl2, the heterogenous system offers size-dependent catalytic activity when bulkier substrates are used. Furthermore, the catalyst can be used to create catalytic impellers that simplify its use and recovery. We found that this system also works for applications in heterogenous Heck and nitroarenes reduction reactions. The metal-binding nanoporous polymer reported here represents a versatile platform for size-selective heterogeneous and recyclable catalysts.

Keywords: nanoporous organic polymer ; heterogeneous catalyst ; Suzuki−Miyaura coupling reaction ; size-selective reaction ; catalyst processing

Alternative Products

Product Details of [ 591-50-4 ]

CAS No. :591-50-4
Formula : C6H5I
M.W : 204.01
SMILES Code : IC1=CC=CC=C1
MDL No. :MFCD00001029
InChI Key :SNHMUERNLJLMHN-UHFFFAOYSA-N
Pubchem ID :11575

Safety of [ 591-50-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 591-50-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 7
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 39.16
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

0.0 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.97
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

3.25
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

2.29
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

3.21
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

2.94
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.73

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-3.79
Solubility 0.0333 mg/ml ; 0.000163 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.92
Solubility 0.243 mg/ml ; 0.00119 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-3.35
Solubility 0.0907 mg/ml ; 0.000445 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

Low
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

Yes
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

Yes
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

Yes
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.24 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

1.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

2.14

Application In Synthesis of [ 591-50-4 ]

* 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 [ 591-50-4 ]
  • Downstream synthetic route of [ 591-50-4 ]

[ 591-50-4 ] Synthesis Path-Upstream   1~13

  • 1
  • [ 1126-09-6 ]
  • [ 591-50-4 ]
  • [ 94201-40-8 ]
References: [1] Patent: US2006/116368, 2006, A1, . Location in patent: Page/Page column 56; 57.
  • 2
  • [ 591-50-4 ]
  • [ 95-68-1 ]
  • [ 25078-04-0 ]
References: [1] Organic Letters, 2007, vol. 9, # 17, p. 3397 - 3399.
[2] Advanced Synthesis and Catalysis, 2008, vol. 350, # 3, p. 395 - 398.
  • 3
  • [ 591-50-4 ]
  • [ 127-19-5 ]
  • [ 95-68-1 ]
  • [ 25078-04-0 ]
  • [ 2050-43-3 ]
References: [1] ChemCatChem, 2018, vol. 10, # 17, p. 3907 - 3913.
  • 4
  • [ 591-50-4 ]
  • [ 68-12-2 ]
  • [ 95-68-1 ]
  • [ 60397-77-5 ]
  • [ 25078-04-0 ]
References: [1] ChemCatChem, 2018, vol. 10, # 17, p. 3907 - 3913.
  • 5
  • [ 591-50-4 ]
  • [ 1033783-02-6 ]
  • [ 17755-10-1 ]
References: [1] Organic Letters, 2013, vol. 15, # 5, p. 984 - 987.
  • 6
  • [ 591-50-4 ]
  • [ 17755-10-1 ]
References: [1] Tetrahedron, 2017, vol. 73, # 26, p. 3591 - 3595.
  • 7
  • [ 591-50-4 ]
  • [ 79-03-8 ]
  • [ 31970-26-0 ]
YieldReaction ConditionsOperation in experiment
38% With aluminum (III) chloride In carbon disulfide at 5 - 10℃; for 24 h; Inert atmosphere Iodobenzene (10Og, 0.49 mol) was taken in a dry 1 L 3 neck flask equipped with a N2 inlet and to it 200 ml of CS2 was added. The contents were cooled to 0-50C and then AICI3 (80 g, 0.6 moles) and subsequently propionyl chloride (60 g, 0.64 mol) were added while keeping the temperature (internal) at 5-100C. The contents were stirred for 24 hrs.The reaction mixture was poured into a 5 liter plastic beaker containing 1 L of 10percent HCI + 1 Kg of crushed ice. The resultant slurry was extracted with 1 L of ethyl acetate. The organic layer was separated and washed with 2x500 ml of water and 500 ml of brine. The organic layer was dried over sodium sulphate and concentrated at 400C to give 4'-iodopropiophenone (48 g, 38percent).1H NMR (500 MHz, CDCI3-d) 7.82 (d, 2H), 7.67 (d, J = 8.30 Hz, 2H), 2.96 (q, J = 7.00 Hz, 2H), 1.22 (t, J = 7.32 Hz, 3H)
References: [1] Patent: WO2010/104488, 2010, A1, . Location in patent: Page/Page column 62.
[2] Yakugaku Zasshi, 1936, vol. 56, p. 690,696; dtsch. Ref. S. 163, 166[3] Chemisches Zentralblatt, 1937, vol. 108, # I, p. 2584.
[4] Chemische Berichte, 1941, vol. 74, p. 321,324.
  • 8
  • [ 591-50-4 ]
  • [ 27913-58-2 ]
References: [1] Journal of the American Chemical Society, 1948, vol. 70, p. 3177.
[2] Journal of the American Chemical Society, 1942, vol. 64, p. 1436,1438.
  • 9
  • [ 591-50-4 ]
  • [ 99-92-3 ]
  • [ 23600-83-1 ]
YieldReaction ConditionsOperation in experiment
53.4% With copper; potassium carbonate In <i>N</i>-methyl-acetamide 368.1
1-(4-anilinophenyl)ethanone
4-amino-acetophenone (4.87 g; 36.0 mmol) is dissolved in dimethylformamide (75 ml).
15 g (0.108 mol) of potassium carbonate (previously dried at 170° C. under an argon atmosphere), 7.236 g (36.0 mmol) of iodobenzene, 0.4 g of copper in powder form and a catalytic quantity of copper iodide are added.
The reaction mixture is taken to reflux for 12 hours.
After leaving the reaction medium to return to ambient temperature, it is filtered on celite and poured into ice-cold water.
After extraction with ethyl acetate, the organic phase is washed with water before being dried over magnesium sulphate, filtered and concentrated under vacuum.
The product obtained is purified by crystallization from heptane in order to produce a yellow solid with a yield of 53.4percent.
Melting point: 105° C.
References: [1] Organometallics, 2012, vol. 31, # 21, p. 7336 - 7338.
[2] Patent: US2004/132788, 2004, A1, .
[3] Patent: US2005/38087, 2005, A1, .
  • 10
  • [ 591-50-4 ]
  • [ 12775-96-1 ]
  • [ 99-92-3 ]
  • [ 23600-83-1 ]
YieldReaction ConditionsOperation in experiment
53.4% With potassium carbonate In <i>N</i>-methyl-acetamide 335.1
1-(4-anilinophenyl)ethanone
4-amino-acetophenone (4.87 g; 36.0 mmol) is dissolved in dimethylformamide (75 ml).
15 g (0.108 mol) of potassium carbonate (previously dried at 170° C. under an argon atmosphere), 7.236 g (36.0 mmol) of iodobenzene, 0.4 g of copper powder and a catalytic quantity of copper iodide are added.
The reaction mixture is taken to reflux for 12 hours.
After leaving the reaction medium to return to ambient temperature, the latter is filtered on celite and poured into ice-cooled water.
After extraction with ethyl acetate, the organic phase is washed with water before being dried over magnesium sulphate, filtered and concentrated under vacuum.
The product obtained is purified by crystallization from heptane in order to produce a yellow solid with a yield of 53.4percent.
Melting point: 105° C.
References: [1] Patent: US2004/132788, 2004, A1, .
[2] Patent: US2005/38087, 2005, A1, .
  • 11
  • [ 591-50-4 ]
  • [ 13329-40-3 ]
  • [ 23600-83-1 ]
References: [1] Chemical Communications, 2012, vol. 48, # 51, p. 6408 - 6410.
  • 12
  • [ 591-50-4 ]
  • [ 18075-64-4 ]
References: [1] Patent: WO2017/103614, 2017, A1, .
  • 13
  • [ 591-50-4 ]
  • [ 914306-50-6 ]
YieldReaction ConditionsOperation in experiment
78% With tetrakis(triphenylphosphine) palladium(0) In toluene at 120℃; for 16 h; Inert atmosphere In the same procedure as in Synthesis Example 2, the compound 2 was prepared from a solution containing the compound 1 (28.5 g, 125 mmol), tetrahydrofuran (125ml), the n-BuLi-hexane solution (74.9 ml, mole number of n-BuLi in the solution: 125 mmol, molarity (mole number of n-BuLi/solution amount): 1.67M) and zinc chloride (28.4 g, 208 mmol) dissolved in tetrahydrofuran (208 ml). After preparing the compound 2, the compound 2 was put into a three-necked flask, to which an oil-sealed rotary pump was connected through a solvent trap that is cooled using a solvent of dry ice/acetone. The three-necked flask was heated to about 40 degrees C under reduced pressure to remove the solvent (310 ml) from the reaction system (the solvent removal step). A removal amount of the solvent herein is an amount collected by the solvent trap. Subsequently, nitrogen was put into the reaction system to return to the normal pressure. Toluene (104 ml) was put into the reaction system (toluene addition step). Next, iodobenzene (21.3g, 104 mmol) and Pd(PPh3)4 (2.89 g, 2.5 mmol) were added thereto and reacted at 120 degrees C for 16 hours under nitrogen atmosphere. [0151] A relationship of the solvent amounts in the reaction system in Synthesis Example 4 is shown in Table 1. Herein, a relationship between the total volume VA [liter] of tetrahydrofuran (i.e., the ether solvent having at most 5 carbon atoms) and the mole number Nf2 [mol] of iodobenzene is represented below according the same calculation as in Synthesis Example 3 as shown in Table 1. The relationship of the numerical formula (3) was satisfied. Further, a relationship between a volume VB [liter] of toluene (i.e., an aromatic hydrocarbon solvent having 7 carbon atoms) and a mole number Nf2 [mol] of iodobenzene is represented below as shown in Table 1. The relationship of the numerical formula (5) was satisfied. There is a possibility that n-hexane (i.e., an aliphatic hydrocarbon having 6 carbon atoms) is contained in the reaction system even after the solvent removal step in Synthesis Example 4. However, since the volume of n-hexane after the solvent removal step is less than the volume of toluene subsequently added, the relationship of the numerical formula (5) is still satisfied even in consideration of n-hexane. The same applies to Examples 3 and 4 described later. Accordingly, Synthesis Example 4 was conducted under the reaction condition of satisfying the relationships of the numerical formulae (3) and (5). [0152] After the reaction, a small amount of water was added to the sample to deactivate the reaction. The mixture was diluted with dichloromethane (300 ml). An aqueous solution of tetrasodium ethylenediaminetetraacetate dihydrate (129.9 g, 312 mmol) was added to the diluted mixture and stirred in a separating funnel. An aqueous sodium hydroxide was further added thereto to adjust an aqueous phase to pH10 or more. A dichloromethane phase was collected. The aqueous phase was extracted with dichloromethane several times. The extract was dried over anhydrous magnesium sulfate, filtrated and concentrated. The obtained product was refined by silica-gel chromatography (toluene:ethyl acetate=95:5 (volume ratio)) and was further recrystallized in a mixture solvent of hexane/ethyl acetate to obtain a white solid. The compound 4 was identified according to 1H-NMR and FD-MS. Yield: 24.7 g Yield Rate: 78percent
References: [1] Patent: EP2662365, 2013, A1, . Location in patent: Paragraph 0142; 0143; 014; 0150; 0151; 0152; 0173-0176; 0189.
 

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