Home Cart 0 Sign in  
X

[ CAS No. 24623-65-2 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
3d Animation Molecule Structure of 24623-65-2
Chemical Structure| 24623-65-2
Chemical Structure| 24623-65-2
Structure of 24623-65-2 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 24623-65-2 ]

Related Doc. of [ 24623-65-2 ]

Alternatived Products of [ 24623-65-2 ]

Product Details of [ 24623-65-2 ]

CAS No. :24623-65-2 MDL No. :MFCD00778877
Formula : C11H14O2 Boiling Point : -
Linear Structure Formula :- InChI Key :ROILLNJICXGZQQ-UHFFFAOYSA-N
M.W :178.23 Pubchem ID :3678675
Synonyms :

Calculated chemistry of [ 24623-65-2 ]

Physicochemical Properties

Num. heavy atoms : 13
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.36
Num. rotatable bonds : 2
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 53.12
TPSA : 37.3 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.08 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.14
Log Po/w (XLOGP3) : 3.25
Log Po/w (WLOGP) : 2.5
Log Po/w (MLOGP) : 2.03
Log Po/w (SILICOS-IT) : 2.69
Consensus Log Po/w : 2.52

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -3.2
Solubility : 0.112 mg/ml ; 0.000628 mol/l
Class : Soluble
Log S (Ali) : -3.71
Solubility : 0.035 mg/ml ; 0.000196 mol/l
Class : Soluble
Log S (SILICOS-IT) : -2.98
Solubility : 0.187 mg/ml ; 0.00105 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.18

Safety of [ 24623-65-2 ]

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 [ 24623-65-2 ]

* 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 [ 24623-65-2 ]
  • Downstream synthetic route of [ 24623-65-2 ]

[ 24623-65-2 ] Synthesis Path-Upstream   1~13

  • 1
  • [ 50-00-0 ]
  • [ 88-18-6 ]
  • [ 24623-65-2 ]
YieldReaction ConditionsOperation in experiment
90% With triethylamine; magnesium chloride In tetrahydrofuran for 3 h; Heating / reflux To a stirred suspension of 2-tert-butylphenol (6)(4.55g, 30 mmol), magnesium chloride (5.71 g, 60 mmol) and paraformaldehyde (2.08 g, 66 mmol) in THF (120 mL) at room temperature, was added triethylamine (8.35 mL, 60 mmol) dropwise. The reaction was heated to reflux for 3 hours to give an orange suspension. The crude was extracted using EtOAc (3*50 mL). A small amount of diluted HCI can be added if a permanent emulsion is formed. The organic layers were dried over MgSO4 and the volatiles evaporated under low pressure to yield a pale yellow oil which did not need any further purification. It can become dark green on storage. Yield: 90percent. Pale yellow oil. 1H-NMR δH (CDpI3, 300 MHz): 1.44 (9H, s, 3χCH3), 6.97 (1 H, t, J = 7.5 Hz, HAT), 7.41 (1 H, dd, J = 1.5 Hz, J = 7.5 Hz, HAr), 7.54 (1 H, dd, J = 1.2 Hz, J = 7.5 Hz, HAr), 9.88 (1 H, s, CHO), 11.82 (1 H, s, OH).
90% With triethylamine; magnesium chloride In tetrahydrofuran at 20℃; Reflux To a stirred suspension of 2-terf-butylphenol (3)(4.55g, 30 mmol), magnesium chloride (5.71 g, 60 mmol) and paraformaldehyde (2.08 g, 66 mmol) in THF (120 mL) <n="29"/>at room temperature, was added triethylamine (8.35 ml_, 60 mmol) dropwise. The reaction was heated to reflux for 3 hours to give an orange suspension. This was extracted using EtOAc (3*50 mL). A small amount of diluted HCI can be added if a permanent emulsion is formed. The organic layers were dried over MgSO4 and the volatiles evaporated under low pressure to yield a pale yellow oil which did not need any further purification. It can become dark green on storage. Yield: 90percent. Pale yellow oil. 1H-NMR δH: 1.44 (9H, s, 3*CH3), 6.97 (1H, t, J = 7.5 Hz, HAr), 7.41 (1H, dd, J = 1.5 Hz, J = 7.5 Hz, HAr), 7.54 (1 H, dd, J = 1.2 Hz, J = 7.5 Hz, HAr), 9.88 (1 H, s, CHO), 11.82 (1H1 S1 OH).
85%
Stage #1: With methylmagnesium bromide In tetrahydrofuran; diethyl ether at 20℃; for 2 h;
Stage #2: With triethylamine In toluene at 88℃; for 2 h;
Stage #3: With hydrogenchloride In water
4.6.1
Synthesis of 3-tert-butyl-salicylaldehyde (1)
To 2-tert-butylphenol (50 mmol), dissolved in tetrahydrofuran (40 ml), methylmagnesium bromide (55.5 mmol, 3 M in diethyl ether) was added.
After stirring for 2 h at room temperature the gas production ended and 90percent of the solvent was removed in vacuo.
Then toluene (100 ml), triethylamine (72 mmol) and paraformaldehyde (125 mmol) were added.
The reaction mixture was stirred for 2 h at 88 °C.
After cooling down to room temperature, the yellow fluorescent solution was hydrolysed with cold hydrochloric acid (250 ml, 1 M in water).
The organic phase was removed and dried over sodium sulphate.
The solvent was evaporated and 3-tert-butylaldehyde was obtained from high vacuum distillation. Yield: 85percent.
1H NMR: 11.84 s (1H, OH), 9.72 s (1H, O=C-H), 7.43-7.47 m (1H, Ar-H), 7.25-7.29 m (1H, Ar-H), 6.86 t (1H, Ar-H), 1.38 s (9H, tBu-CH3).
13C NMR: 197.2 (O=C-H), 161.1, 138.0, 120.7 (Cq), 134.1, 132.0, 119.3 (Ar-CH), 34.8 (Cq), 29.2 (tBu-CH3). MS m/z: 178 M+ (26), 163 M - Me (100), 135 M - C3H7 (39).
74% With triethylamine; magnesium chloride In acetonitrile for 5 h; Reflux Step 1:
3-(tert-Butyl)-2-hydroxybenzaldehyde (7a)
A mixture of 2-(tert-butyl)phenol (15 g, 0.1 mol), Et3N (37 g, 374 mmol), MgCl2 (14.3 g, 0.15 mol) and paraformaldehyde (20.2 g, 674 mmol) in acetonitrile (200 mL) was heated at reflux for 5 h. TLC (PE:EA = 10:1) showed the reaction was complete.
The resulting mixture was poured into aq. HCl (2N, 200 mL) and extracted with Et2O.
The organic layer was concentrated under reduced pressure and purified by CC (PE:EA = 8:1) to give compound 7a (13 g, 74percent) as a colorless oil.
74% With triethylamine; magnesium chloride In acetonitrile for 5 h; Reflux Preparative Example P7Step 1 : 3-(terf-Butyl)-2-hvdroxybenzaldehvde (P7a) A mixture of 2-(tert-butyl)phenol (15 g, 0.1 mol), Et3N (37 g, 374 mmol), MgCI2 (14.3 g, 0.15 mol) and paraformaldehyde (20.2 g, 674 mmol) in ACN (200 mL) was heated at reflux for 5 h, cooled, poured into aq. HCI (2N, 200 mL) and extracted with Et20. The organic layer was concentrated and purified by CC (PE/EA = 8/1) to give compound P7a (13 g, 74percent) as a colorless oil.

Reference: [1] Journal of Medicinal Chemistry, 2007, vol. 50, # 7, p. 1658 - 1667
[2] Advanced Synthesis and Catalysis, 2017, vol. 359, # 22, p. 3990 - 4001
[3] Patent: WO2008/132474, 2008, A1, . Location in patent: Page/Page column 31
[4] Advanced Synthesis and Catalysis, 2009, vol. 351, # 9, p. 1325 - 1332
[5] Patent: WO2009/109765, 2009, A1, . Location in patent: Page/Page column 27; 28
[6] Journal of the Chemical Society, Perkin Transactions 1, 2000, # 13, p. 2055 - 2066
[7] Tetrahedron Asymmetry, 2007, vol. 18, # 17, p. 2016 - 2020
[8] Journal of Organometallic Chemistry, 2016, vol. 820, p. 30 - 40
[9] Acta Chemica Scandinavica, 1999, vol. 53, # 4, p. 258 - 262
[10] Chemistry Letters, 1999, # 10, p. 1065 - 1066
[11] Journal of the American Chemical Society, 2001, vol. 123, # 28, p. 6847 - 6856
[12] Dalton Transactions, 2017, vol. 46, # 25, p. 8286 - 8297
[13] Inorganica Chimica Acta, 2010, vol. 363, # 6, p. 1246 - 1253
[14] Dalton Transactions, 2010, vol. 39, # 19, p. 4602 - 4611
[15] Patent: EP2511263, 2012, A1, . Location in patent: Page/Page column 28
[16] Patent: WO2012/139775, 2012, A1, . Location in patent: Page/Page column 39-40
[17] Chemical Communications, 2014, vol. 50, # 58, p. 7870 - 7873
[18] Beilstein Journal of Organic Chemistry, 2015, vol. 11, p. 1614 - 1623
[19] Dalton Transactions, 2017, vol. 46, # 29, p. 9491 - 9497
[20] Tetrahedron, 2000, vol. 56, # 17, p. 2709 - 2712
[21] Journal of Organic Chemistry, 2013, vol. 78, # 14, p. 6890 - 6910
[22] Organic Letters, 2017, vol. 19, # 20, p. 5505 - 5508
[23] Journal of Organic Chemistry, 2018,
[24] Tetrahedron Asymmetry, 1995, vol. 6, # 10, p. 2511 - 2516
[25] Journal of Organic Chemistry, 2010, vol. 75, # 22, p. 7514 - 7518
[26] Carbohydrate Research, 2007, vol. 342, # 2, p. 254 - 258
[27] Journal of Medicinal Chemistry, 1983, vol. 26, # 2, p. 121 - 125
[28] Journal of Organic Chemistry, 1993, vol. 58, # 6, p. 1515 - 1522
[29] Chemistry--A European Journal, 1996, vol. 2, # 8, p. 974 - 980
[30] Tetrahedron Asymmetry, 1997, vol. 8, # 20, p. 3481 - 3487
[31] Tetrahedron Letters, 2005, vol. 46, # 22, p. 3829 - 3830
[32] Tetrahedron Letters, 2005, vol. 46, # 32, p. 5285 - 5287
[33] Journal of the Chemical Society, Dalton Transactions, 2001, # 7, p. 991 - 995
[34] Tetrahedron, 2007, vol. 63, # 40, p. 9997 - 10002
[35] Journal of Organometallic Chemistry, 2007, vol. 692, # 26, p. 5727 - 5753
[36] New Journal of Chemistry, 2010, vol. 34, # 12, p. 2979 - 2987
[37] Tetrahedron, 2011, vol. 67, # 43, p. 8300 - 8307
[38] European Journal of Organic Chemistry, 2011, # 28, p. 5636 - 5640
[39] Dalton Transactions, 2011, vol. 40, # 39, p. 10184 - 10194
[40] Polymer, 2011, vol. 52, # 26, p. 6029 - 6036
[41] Organic Letters, 2012, vol. 14, # 12, p. 3226 - 3229
[42] European Journal of Medicinal Chemistry, 2014, vol. 75, p. 31 - 42
[43] Russian Journal of Organic Chemistry, 2014, vol. 50, # 2, p. 191 - 199[44] Zh. Org. Khim., 2014, vol. 50, # 2, p. 201 - 208,8
[45] Journal of the American Chemical Society, 2016, vol. 138, # 8, p. 2755 - 2761
[46] Polyhedron, 2016, vol. 118, p. 37 - 51
[47] Catalysis Letters, 2017, vol. 147, # 4, p. 996 - 1005
[48] Organic Letters, 2017, vol. 19, # 23, p. 6340 - 6343
[49] Organic Letters, 2018, vol. 20, # 10, p. 2880 - 2883
  • 2
  • [ 88-18-6 ]
  • [ 7732-18-5 ]
  • [ 24623-65-2 ]
YieldReaction ConditionsOperation in experiment
26% With sodium hydroxide In chloroform Reference Example 5
3-tert-Butyl-2-hydroxybenzaldehyde
A mixture of 2-tert-butylphenol (15 g, 0.010 mol), powdered NaOH (20 g,0.50 mol), H2 O (3.6 ml), and CHCl3 (100 mL) was heated at 50° C. for 1 h.
Then more powdered NaOH (12 g, 0.30 mol) was added at an increment of 2 g every 15 min.
At the end of the NaOH additions, the reaction was continued to be heated at 56° C. for 1 h.
After cooling, the reaction was acidified with HCl (12N).
The chloroform fraction was separated, dried (MgSO4), and concentrated.
The residue was loaded on a silica gel column eluted with CH2 Cl2 to give 3-tert-butyl-2-hydroxybenzaldehyde (4.6 g, 26percent) as a solid.
Reference: [1] Patent: US5942532, 1999, A,
  • 3
  • [ 474555-29-8 ]
  • [ 24623-65-2 ]
Reference: [1] Journal of Chemical Research, Miniprint, 2001, # 7, p. 743 - 757
[2] Chemistry - A European Journal, 2007, vol. 13, # 16, p. 4433 - 4451
  • 4
  • [ 88-18-6 ]
  • [ 24623-65-2 ]
Reference: [1] Patent: US4151201, 1979, A,
  • 5
  • [ 61072-60-4 ]
  • [ 24623-65-2 ]
Reference: [1] Synthesis, 1976, p. 624 - 625
  • 6
  • [ 261903-04-2 ]
  • [ 24623-65-2 ]
Reference: [1] Chemistry - A European Journal, 2007, vol. 13, # 16, p. 4433 - 4451
[2] Journal of Chemical Research, Miniprint, 2001, # 7, p. 743 - 757
  • 7
  • [ 61072-57-9 ]
  • [ 24623-65-2 ]
Reference: [1] Synthesis, 1976, p. 624 - 625
  • 8
  • [ 67-66-3 ]
  • [ 88-18-6 ]
  • [ 24623-65-2 ]
Reference: [1] Tetrahedron Asymmetry, 2008, vol. 19, # 15, p. 1813 - 1819
[2] Polymer, 2010, vol. 51, # 5, p. 994 - 997
  • 9
  • [ 88-18-6 ]
  • [ 24623-65-2 ]
Reference: [1] Chemistry - A European Journal, 2007, vol. 13, # 16, p. 4433 - 4451
  • 10
  • [ 72138-54-6 ]
  • [ 24623-65-2 ]
  • [ 18299-54-2 ]
Reference: [1] Journal of the American Chemical Society, 2017, vol. 139, # 17, p. 6042 - 6045
  • 11
  • [ 1342864-99-6 ]
  • [ 24623-65-2 ]
  • [ 1342865-13-7 ]
  • [ 1342865-08-0 ]
Reference: [1] European Journal of Organic Chemistry, 2011, # 28, p. 5636 - 5640
  • 12
  • [ 88-18-6 ]
  • [ 122-51-0 ]
  • [ 24623-65-2 ]
Reference: [1] Gazzetta Chimica Italiana, 1978, vol. 108, p. 79 - 84
  • 13
  • [ 24623-65-2 ]
  • [ 153759-58-1 ]
YieldReaction ConditionsOperation in experiment
73% With bromine In acetic acid at 20℃; for 3 h; Step 2:
5-Bromo-3-(tert-butyl)-2-hydroxybenzaldehyde (7b)
To a solution of compound 7a (3.0 g, 17 mmol) in AcOH (15 mL) was added Br2 (2.95 g, 18 mmol) dropwise at rt and the mixture was stirred for 3 h. TLC (PE:EA = 50:1) showed the reaction was complete.
The reaction mixture was quenched with aq. NaHSO3 (50 mL) and extracted with Et2O.
The organic layer was concentrated under reduced pressure to give crude compound 7b (3.2 g, 73percent) as white solid.
73% With bromine In acetic acid at 20℃; for 3 h; Step 2: 5-Bromo-3-(terf-butyl)-2-hvdroxybenzaldehvde (P7b)To a solution of compound P7a (3.0 g, 17 mmol) in AcOH (15 mL) was added Br2 (2.95 g, 18 mmol) dropwise at rt and the mixture was stirred for 3 h, quenched with aq. NaHS03 (50 mL) and extracted with Et20. The organic layer was concentrated to give crude compound P7b (3.2 g, 73percent) as white solid.
64% at 20℃; for 6 h; To a stirred solution of 3-tert-butylsalicylaldehyde (5.13 g, 28.8 mmol) in acetic acid (15 mL) was added a solution of bromine (1.65 mL, 32.25 mmol) in acetic acid (7.0 mL) dropwise within 20 min. The reaction mixture was stirred at room temperature for 3 h. Analytical HPLC analysis after 3 h shows the desired product -72percent and the unreacted starting material -28percent. A second batch of bromine (0.5 mL) in acetic acid (3 mL) was added and the reaction mixture was stirred at room temperature for another 3 h. Analytical HPLC analysis of the reaction mixture after 3 h (6 h total) shows the desired product -85percent and still shows the starting material -15percent. After 6 h of stirring, the reaction mixture was diluted with dichloromethane (50 mL) and the organic layer was washed with 39percent sodium bisulfite solution (1 x 10 mL), water, saturated aHC03 and brine. The organic layer was dried over anhydrous sodium sulfate, filtered and evaporated in vacuo to give the desired product as a pale yellow crystalline solid (7.2421 g). Purification by silica-gel flash chromatography on silica gel column and elution with 0-5percent ethyl acetate in n-heptane afforded the desired product as a pale yellow crystalline solid (4.792 g, 64percent yield). LC-MS analysis of the product in negative mode shows the desired product's mass: m/z 255 (79BrM+-H) and m/z 257 (81BrM+-H). GC-MS analysis of the product in CI mode (Methane) shows the desired product's mass: m/z 256 (79BrM+) and m/z 258 (81BrM+), calc'd. for CnH13Br02: 257.124. XH NMR (400 MHz, CDC13): δ 1.39 (s, 9H, t-Bu-), 7.50 (s, 1H, H-4), 7.56 (s, 1H, H-6), 9.79 (s, 1H, -CHO), 11.70 (s, 1H, -OH). 1H NMR of the isolated product was identical with that of a previously reported sample of the product (Girsch et al, 2007).
85 %Chromat. With ammonium metavanadate; perchloric acid; tetrabutylammomium bromide; dihydrogen peroxide In chloroform; water at 20℃; for 0.333333 h; General procedure: NH4VO3 (5 molpercent) and H2O2 (200 molpercent) were placed in a flask. After complete dissolution of the catalyst, TBAB (3 mmol) was added and the mixture was stirred at room temperature. Then, Et2O (10 ml) and aromatic substrate (1 mmol) were added to the mixture. Finally, by slow drip, 1 ml of 1N HClO4 solution was added. After adding the acid, the colour of the reaction changed from yellow to red due to the formation of oxomonoperoxovanadium. Conversion was followed by TLC and determined by GC. The phases were separated and the aqueous phase was extracted with CH2Cl2 (15 ml x3). The organic phases were pooled, washed with brine, dried over Na2SO4 and filtered. The solvent was removed under reduced pressure and the resulting crude product was purified by column chromatography with Hex:AcOEt.

Reference: [1] Journal of Medicinal Chemistry, 2013, vol. 56, # 20, p. 8163 - 8182
[2] Advanced Synthesis and Catalysis, 2009, vol. 351, # 9, p. 1325 - 1332
[3] Inorganic Chemistry, 2017, vol. 56, # 20, p. 12357 - 12361
[4] Chemistry - A European Journal, 2006, vol. 12, # 2, p. 576 - 583
[5] European Journal of Organic Chemistry, 2001, # 24, p. 4639 - 4649
[6] Tetrahedron Asymmetry, 2007, vol. 18, # 17, p. 2016 - 2020
[7] Chemical Communications, 2014, vol. 50, # 58, p. 7870 - 7873
[8] European Journal of Inorganic Chemistry, 2013, # 24, p. 4228 - 4233
[9] Dalton Transactions, 2017, vol. 46, # 29, p. 9491 - 9497
[10] Russian Journal of Organic Chemistry, 2014, vol. 50, # 2, p. 191 - 199[11] Zh. Org. Khim., 2014, vol. 50, # 2, p. 201 - 208,8
[12] Patent: EP2511263, 2012, A1, . Location in patent: Page/Page column 28
[13] Patent: WO2012/139775, 2012, A1, . Location in patent: Page/Page column 40
[14] Patent: WO2014/15054, 2014, A1, . Location in patent: Page/Page column 215
[15] Journal of Medicinal Chemistry, 2007, vol. 50, # 7, p. 1658 - 1667
[16] Tetrahedron, 2004, vol. 60, # 46 SPEC. ISS., p. 10461 - 10468
[17] Journal of the American Chemical Society, 2005, vol. 127, # 6, p. 1854 - 1869
[18] Chemical Communications, 2003, # 15, p. 1860 - 1861
[19] Patent: US2010/21423, 2010, A1,
[20] Patent: US2010/81658, 2010, A1, . Location in patent: Page/Page column 27-28
[21] Patent: WO2010/122082, 2010, A1, . Location in patent: Page/Page column 36
[22] Polymer, 2010, vol. 51, # 5, p. 994 - 997
[23] ChemSusChem, 2014, vol. 7, # 8, p. 2110 - 2114
[24] Tetrahedron Letters, 2016, vol. 57, # 50, p. 5644 - 5648
[25] Patent: US2010/297073, 2010, A1, . Location in patent: Page/Page column 18
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 24623-65-2 ]

Aryls

Chemical Structure| 1620-98-0

[ 1620-98-0 ]

3,5-Di-tert-butyl-4-hydroxybenzaldehyde

Similarity: 0.95

Chemical Structure| 84501-28-0

[ 84501-28-0 ]

5-(tert-Butyl)-2-hydroxyisophthalaldehyde

Similarity: 0.95

Chemical Structure| 135546-15-5

[ 135546-15-5 ]

3,5-Di-tert-butyl-2-methoxybenzaldehyde

Similarity: 0.91

Chemical Structure| 24019-66-7

[ 24019-66-7 ]

3-Allyl-2-hydroxybenzaldehyde

Similarity: 0.91

Chemical Structure| 161876-64-8

[ 161876-64-8 ]

4-Ethyl-2-hydroxybenzaldehyde

Similarity: 0.90

Aldehydes

Chemical Structure| 1620-98-0

[ 1620-98-0 ]

3,5-Di-tert-butyl-4-hydroxybenzaldehyde

Similarity: 0.95

Chemical Structure| 84501-28-0

[ 84501-28-0 ]

5-(tert-Butyl)-2-hydroxyisophthalaldehyde

Similarity: 0.95

Chemical Structure| 135546-15-5

[ 135546-15-5 ]

3,5-Di-tert-butyl-2-methoxybenzaldehyde

Similarity: 0.91

Chemical Structure| 24019-66-7

[ 24019-66-7 ]

3-Allyl-2-hydroxybenzaldehyde

Similarity: 0.91

Chemical Structure| 161876-64-8

[ 161876-64-8 ]

4-Ethyl-2-hydroxybenzaldehyde

Similarity: 0.90