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[ CAS No. 89-82-7 ] {[proInfo.proName]}

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Chemical Structure| 89-82-7
Chemical Structure| 89-82-7
Structure of 89-82-7 * Storage: {[proInfo.prStorage]}
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Product Details of [ 89-82-7 ]

CAS No. :89-82-7 MDL No. :MFCD00063000
Formula : C10H16O Boiling Point : -
Linear Structure Formula :- InChI Key :NZGWDASTMWDZIW-MRVPVSSYSA-N
M.W : 152.23 Pubchem ID :442495
Synonyms :
(+)-Pulegone;NSC 15334;D-Pulegone;(R)-(+)-Pulegone

Calculated chemistry of [ 89-82-7 ]

Physicochemical Properties

Num. heavy atoms : 11
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.7
Num. rotatable bonds : 0
Num. H-bond acceptors : 1.0
Num. H-bond donors : 0.0
Molar Refractivity : 47.8
TPSA : 17.07 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.04 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.32
Log Po/w (XLOGP3) : 3.08
Log Po/w (WLOGP) : 2.71
Log Po/w (MLOGP) : 2.2
Log Po/w (SILICOS-IT) : 2.76
Consensus Log Po/w : 2.61

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -2.72
Solubility : 0.287 mg/ml ; 0.00189 mol/l
Class : Soluble
Log S (Ali) : -3.11
Solubility : 0.119 mg/ml ; 0.000784 mol/l
Class : Soluble
Log S (SILICOS-IT) : -2.38
Solubility : 0.635 mg/ml ; 0.00417 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.75

Safety of [ 89-82-7 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P501-P273-P201-P264-P280-P308+P313 UN#:N/A
Hazard Statements:H302-H351-H412 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 89-82-7 ]

* 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.

  • Downstream synthetic route of [ 89-82-7 ]

[ 89-82-7 ] Synthesis Path-Downstream   1~85

  • 2
  • [ 89-82-7 ]
  • [ 13368-65-5 ]
YieldReaction ConditionsOperation in experiment
90% With sulfuric acid; cetylpyridinium chloride In water at 80℃; for 15h; 4.2 (R)-3-methylcyclohexanone Practical (R)-(+)-pulegone (250g, 1.64mol, 92% from ABCR, [α]D20+22.3° neat) was added dropwise at 80°C to a well stirred solution of sulfuric acid (552g, 5.63mol), water (1.2L) and cetylpyridinium chloride (5.0g, 14.7mmol) in a 3L double-jacketed vessel equipped with an overhead stirrer. After 15h, the reaction mixture was cooled to 25°C and phases were separated. The organic phase was washed with brine (20mL) and neutralized with NaHCO3. After drying with MgSO4, the crude brownish oil (184g) was purified by distillation under reduced pressure (52°C, 5.6mbar) providing a colorless liquid (110g, 96% purity by GC). Additional 43g were obtained from the aqueous phase (via steam distillation) increasing the overall yield to 90%. [α]D20+12.1° (neat), lit.39+12.7° (neat). Enantiomeric purity >99% (according to GC on a HYDRODEX-γ-TBDAc column, 100°C isotherm, RT: 6.7min for R and 6.3min for S). 1H NMR (400MHz, Chloroform-d) δ ppm 2.40-2.29 (m, 2H), 2.22 (dddd, J=14.1, 12.4, 6.2, 1.4Hz, 1H), 2.08-2.00 (m, 1H), 1.97 (dd, J=13.4, 1.3Hz, 1H), 1.94-1.80 (m, 2H), 1.65 (dtdd, J=13.5, 12.1, 4.8, 3.5Hz, 1H), 1.32 (dddd, J=13.3, 12.0, 10.4, 3.6Hz, 1H), 1.00 (d, J=6.3Hz, 3H).
83% With hydrogenchloride In water at 125℃; for 8h;
70% With hydrogenchloride; water for 8h; Reflux;
62% With hydrogenchloride In water
With water at 250℃;
With hydrogenchloride
With hydrogenchloride Heating;
With hydrogenchloride
With hydrogenchloride In water for 5h; Reflux; 35.1 Example 35 3N Hydrochloric acid (25 ml) was added to (+)-pulegone (5.00 g), the reaction mixture was refluxed with heating for 5 hours and water and diethyl ether were added to the reaction mixture. The organic layer was washed with saturated brine, dried over sodium sulfate and the solvent was evaporated under reduced pressure to obtain (R)-3-methylcyclohexanone.
With hydrogenchloride; water In diethyl ether for 5h; Reflux; 35.1 (1) 3N Hydrochloric acid (25 ml) was added to (+)-pulegone (5.00 g), the reaction mixture was refluxed with heating for 5 hours and water and diethyl ether were added to the reaction mixture. The organic layer was washed with saturated brine, dried over sodium sulfate and the solvent was evaporated under reduced pressure to obtain (R)-3-methylcyclohexanone.

Reference: [1]Riss, Bernard; Garreau, Marion; Fricero, Prisca; Podsiadly, Patricia; Berton, Nicolas; Buchter, Sophie [Tetrahedron, 2017, vol. 73, # 23, p. 3202 - 3212]
[2]Nannini, Leonardo J.; Nemat, Suren J.; Carreira, Erick M. [Angewandte Chemie - International Edition, 2018, vol. 57, # 3, p. 823 - 826][Angew. Chem., 2018, vol. 130, # 3, p. 831 - 834,4]
[3]Location in patent: body text Santos Pisoni, Diego dos; Sobieski da Costa, Jessé; Gamba, Douglas; Petzhold, Cesar Liberato; César de Amorim Borges, Antonio; Ceschi, Marco Antonio; Lunardi, Paula; Saraiva Gonçalves, Carlos Alberto [European Journal of Medicinal Chemistry, 2010, vol. 45, # 2, p. 526 - 535]
[4]Ishii, Shingo; Zhao, Shikai; Helquist, Paul [Journal of the American Chemical Society, 2000, vol. 122, # 24, p. 5897 - 5898]
[5]Adams et al. [Journal of the American Chemical Society, 1942, vol. 64, p. 2087]
[6]Schaefer,J.P. et al. [Journal of Organic Chemistry, 1968, vol. 33, # 7, p. 2647 - 2655]
[7]Anand, Devinder K.; Hargreaves, Michael K.; Khan, Mohsin A. [Zeitschrift fur Naturforschung, Teil B: Anorganische Chemie, Organische Chemie, 1981, vol. 36, # 8, p. 978 - 988]
[8]Mori, Kenji; Takechi, Shozo [Tetrahedron, 1985, vol. 41, # 15, p. 3049 - 3062]
[9]Current Patent Assignee: SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem); Sumitomo Pharma (in: Sumitomo Chemical) - EP2277861, 2011, A1 Location in patent: Page/Page column 24
[10]Current Patent Assignee: SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem); Sumitomo Pharma (in: Sumitomo Chemical) - US2012/28937, 2012, A1 Location in patent: Page/Page column 21
  • 3
  • [ 89-82-7 ]
  • [ 18951-85-4 ]
YieldReaction ConditionsOperation in experiment
98%
81% Stage #1: pulegone With hydrogenchloride at 0℃; for 2h; Stage #2: With sodium hydroxide at 20℃; for 2h; R)-3,7-Dimethyloct-6-enoic acid (5): Dry HCl gas was passed through (R)-(+)-pulegone (2.1mL, 13.15 mmol) at low temperature for 2 h and then without isolating the intermediate pulegone hydrochloride, the reaction mixure was allowed to keep at room temperature and the reaction was quenched by simple addition of 5% dilute NaOH. After 2 h, the resulting salt was again treated with 5N HCl (till pH = 4) to release the compound. Then extracted with EtOAc (2 x 50 mL) and washed the extracts with water (50 mL) and brine (50 mL). Finally, organic extracts were concentrated and passed through flash column chromatography to afford the R-(+)-citronellic acid 5 (1.8 g, in 81% yield) as a colourless oil. Rf = 0.4 (silica gel, 30% EtOAc in petroleum ether). [α]D25 = +17.6 (c = 2.0, CHCl3); 1H NMR (300 MHz, CDCl3): 5.04 (1H, t, J = 7.0 Hz), 2.36 (1H, dd, J = 12.0, 6.0 Hz), 2.10 (1H, dd, J = 12.0, 8.0 Hz), 2.01-1.82 (3H, m), 1.62 (3H, s), 1.58 (3H, s), 1.39 (1H, m), 1.22 (1H, m), 0.97 (3H, d, J = 7.0 Hz); 13C NMR (75 MHz, CDCl3): 179.9, 131.8, 124.1, 41.1, 41.0, 29.8, 25.2, 25.0, 19.9, 19.8; EIMS: m/z 171 [M + H]+, Anal. Cald. for C10H18O2: C, 70.55; H, 10.66. Found: C, 70.51; H, 10.69.
80%
74.8% With hydrogenchloride at -30 - 20℃; for 15h; 2a.1 Step-1: Synthesis of (R)-3, 7-dimethyloct-6-enoic acid: In a 5 L three neck round bottom flask, (K)-pulegone (150.0 g, 986.84 mmol) was purged with HCl gas for 3h at -30°C. The reaction mixture was transferred to re-sealable reaction tube and mixture allowed to stand at RT for 12 h. The mixture was treated with NaOH solution (4N, 3L) and resulting mixture was stirred at RT for further 12 h. Upon completion of reaction (monitored by TLC), the reaction mixture was diluted with water (1000 mL) and washed with diethyl ether (3 x 1000 mL). The aqueous layer was acidified (pH 4) with dilute HC1 before extracting with diethyl ether (3 x 1000 mL). The combined organic layer was dried over anhydrous Na2S04 and concentrated under reduced pressure to get the title compound (125 g, 74.8 %). 1H NMR (300 MHz, DMSO-d6): δ 12.01 (s, 1H), 5.07 (t, J = 6.9 Hz, 1H), 2.22 (dd, J = 15.0, 6.0 Hz, 1H), 2.03-1.78 (m, 4H), 1.64 (s, 3H), 1.56 (s, 3H), 1.36-1.17 (m, 2H), 0.88 (d, J = 6.6 Hz, 3H).
74.8% Stage #1: pulegone With hydrogenchloride at -30 - 20℃; for 15h; Stage #2: With sodium hydroxide In water at 20℃; for 12h; 2A.1 Synthesis of (3R)-3,7-dimethyloct-6-enoic acid In a 5 L three neck round bottom flask, (K)-pulegone (150.0 g, 986.84 mmol) was purged with HCl gas for 3 h at -30°C. The reaction mixture was transferred to re-sealable reaction tube and mixture allowed to stand at RT for 12 h. The mixture was treated with NaOH solution (4 N, 3 L) and resulting mixture was stirred at RT for further 12 h. Upon completion of reaction (TLC), the reaction mixture was diluted with water (1 L) and washed with diethyl ether (3 x 1 L). The aqueous layer was acidified (pH 4) with dilute HCl before extracting with diethyl ether (3 x 1 L). The combined organic layer was dried over anhydrous Na2S04 and concentrated under reduced pressure to get the title compound (125 g, 74.8%). (0246) 1H NMR (300 MHz, DMSO-d6): δ 12.01 (s, 1H), 5.07 (t, J = 6.9 Hz, 1H), 2.22 (dd, J = 15.0, 6.0 Hz, 1H), 2.03- 1.78 (m, 4H), 1.64 (s, 3H), 1.56 (s, 3H), 1.36- 1.17 (m, 2H), 0.88 (d, J = 6.6 Hz, 3H).
74.8% With hydrogenchloride at -30 - 20℃; for 15h; Sealed tube;
61%
49% Stage #1: pulegone With hydrogenchloride at 0 - 22℃; for 15.5h; Inert atmosphere; Stage #2: With potassium hydroxide In water at 22℃; for 3h; Inert atmosphere;
45% With hydrogenchloride; potassium hydroxide for 2h; Ambient temperature;
With hydrogenchloride und anschliessend mit wss.Kalilauge;
With hydrogenchloride; sodium hydroxide 1.) -5 deg C; 2.) rt; Yield given. Multistep reaction;
With hydrogenchloride; potassium hydroxide 2) room temp., 3 h; Yield given. Multistep reaction;
(i) HCl, (ii) aq. NaOH; Multistep reaction;
With hydrogenchloride; sodium hydroxide 1a) -10 deg C, 1 h, 1b) r.t., overnight, 2a) H2O, 10 to 15 deg C, to r.t., overnight; Yield given. Multistep reaction;
With hydrogenchloride
Multi-step reaction with 2 steps 1: hydrogenchloride / 0 °C 2: water; sodium hydroxide / 20 °C
Stage #1: pulegone With hydrogenchloride In 1,4-dioxane at 30℃; Stage #2: With potassium hydroxide In 1,4-dioxane at 20℃; for 3h; 1.2 Step 2 Preparation of (R)-(+)-3,7-dimethyl-6-octenoic acid Dissolve (R)-(+)-5-methyl-2-(prop-2-ylidene)cyclohexanone (50.0g, 328.4mmol) in 4mol/L hydrogen chloride 1,4-dioxane solution (164.2mL, 656.8mmol), stirred overnight at 30 °C, after the reaction, the reaction system was added dropwise to 2mol/L potassium hydroxide solution (350.0mL), and stirred at room temperature for 3h, then 2.5 The pH of the reaction system was adjusted by mol/L dilute hydrochloric acid to 1, the aqueous phase was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and concentrated to obtain the title compound.

Reference: [1]Fujisawa, Tamotsu; Sato, Toshio; Kawara, Tatsuo; Ohashi, Kazuo [Tetrahedron Letters, 1981, vol. 22, # 48, p. 4823 - 4826]
[2]Kumar, Jayprakash Narayan; Das, Biswanath [Synlett, 2014, vol. 25, # 6, p. 863 - 865]
[3]Kikukawa, Tadashi; Imaida, Motomasa; Tai, Akira [Bulletin of the Chemical Society of Japan, 1984, vol. 57, # 7, p. 1954 - 1960]
[4]Current Patent Assignee: ASTELLAS PHARMA INC.; SALK INST FOR BIOLOGICAL STUDIES THE; SALK INSTITUTE FOR BIOLOGICAL STUDIES - WO2017/62468, 2017, A1 Location in patent: Page/Page column 33-34
[5]Current Patent Assignee: ASTELLAS PHARMA INC. - WO2017/180818, 2017, A1 Location in patent: Page/Page column 27-28
[6]Lagu, Bharat; Kluge, Arthur F.; Tozzo, Effie; Fredenburg, Ross; Bell, Eric L.; Goddeeris, Matthew M.; Dwyer, Peter; Basinski, Andrew; Senaiar, Ramesh S.; Jaleel, Mahaboobi; Tiwari, Nirbhay Kumar; Panigrahi, Sunil K.; Krishnamurthy, Narasimha Rao; Takahashi, Taisuke; Patane, Michael A. [ACS Medicinal Chemistry Letters, 2018, vol. 9, # 9, p. 935 - 940]
[7]Clasby, Martin C.; Craig, Donald; Marsh, Andrew [Angewandte Chemie, 1993, vol. 105, # 10, p. 1495 - 1497]
[8]Heretsch, Philipp; Rabe, Sebastian; Giannis, Athanasslos [Organic Letters, 2009, vol. 11, # 23, p. 5410 - 5412]
[9]Raederstorff, Daniel; Shu, Arthur Y.L.; Thompson, Janice E.; Djerassi, Carl [Journal of Organic Chemistry, 1987, vol. 52, # 12, p. 2337 - 2346]
[10]Plesek [Collection of Czechoslovak Chemical Communications, 1957, vol. 22, p. 644]
[11]White, James D.; Jayasinghe, Lalith R. [Tetrahedron Letters, 1988, vol. 29, # 18, p. 2139 - 2142]
[12]Thijs, L.; Stokkingreef, E. H. M.; Lemmens, J. M.; Zwanenburg, B. [Tetrahedron, 1985, vol. 41, # 14, p. 2949 - 2956]
[13]Cook,C.E.; Tallent,C.R. [Journal of Heterocyclic Chemistry, 1969, vol. 6, p. 203 - 206] Naoshima, Yoshinobu; Hayashi, Daijiro; Ochi, Masato [Agricultural and Biological Chemistry, 1988, vol. 52, # 6, p. 1605 - 1606]
[14]Overberger,C.G.; Kaye,H. [Journal of the American Chemical Society, 1967, vol. 89, # 22, p. 5640 - 5645] Overberger,C.G.; Weise,J.K. [Journal of the American Chemical Society, 1968, vol. 90, # 13, p. 3525 - 3532] Ciardelli,F.; Pino,P. [Gazzetta Chimica Italiana, 1965, vol. 95, p. 1201 - 1211]
[15]White, James D.; Amedio, John C.; Gut, Samuel; Ohira, Susumu; Jayasinghe, Lalith R. [Journal of Organic Chemistry, 1992, vol. 57, # 8, p. 2270 - 2284]
[16]Kikukawa, Tadashi; Imaida, Motomasa; Tai, Akira [Chemistry Letters, 1982, p. 1799 - 1802]
[17]Bartelt, Robert J.; Zilkowski, Bruce W.; Cosse, Allard A.; Schnupf, Udo; Vermillion, Karl; Momany, Frank A. [Journal of Natural Products, 2011, vol. 74, # 4, p. 585 - 595]
[18]Current Patent Assignee: NANJING SANHOME INVESTMENT GROUP CO LTD - CN113527335, 2021, A Location in patent: Paragraph 0095; 0100-0102
  • 4
  • [ 89-82-7 ]
  • [ 623-82-5 ]
YieldReaction ConditionsOperation in experiment
92% With ruthenium trichloride; sodium periodate In tetrachloromethane; acetonitrile for 5h;
92% With ruthenium trichloride; sodium periodate
91% With ruthenium trichloride; Oxone; sodium hydrogencarbonate In water; acetonitrile at 20℃; for 1.6h;
84% With Oxone; sodium hydrogencarbonate; ruthenium In water; acetonitrile at 20℃; for 3h;
67% With Oxone; osmium(VIII) oxide; sodium hydrogencarbonate In N,N-dimethyl-formamide; <i>tert</i>-butyl alcohol at 20℃; for 3h;
67% With sodium periodate In water; ethyl acetate; acetonitrile at 0℃; for 8h;
With permanganate(VII) ion
With potassium permanganate
With ozone; acetic acid In water; ethyl acetate at 0℃; Inert atmosphere;

  • 5
  • [ 89-82-7 ]
  • [ 22472-80-6 ]
YieldReaction ConditionsOperation in experiment
98% With potassium <i>tert</i>-butylate; hydrogen; Trimethylenediamine In isopropyl alcohol at 30℃; for 18h;
98% With potassium <i>tert</i>-butylate; hydrogen In isopropyl alcohol at 30℃; for 18h; Autoclave; optical yield given as %de;
94% With sodium tetrahydroborate In methanol at 0℃; for 1h; stereoselective reaction;
93% With (R)-((4,4’-bi-1,3-benzodioxole)-5,5’-diyl)bis(bis(3,5-di-t-butyl-4-methoxyphenyl))phosphine; diethoxymethylsilane; copper(II) acetate monohydrate In diethyl ether at -25℃; for 5h; Inert atmosphere; optical yield given as %de; diastereoselective reaction;
92% With sodium tetrahydroborate In methanol; ethanol; water at 0 - 20℃; Inert atmosphere;
89% With LiPyrrBH3 In tetrahydrofuran at 25℃; for 3h;
87% With sodium tetrahydroborate In methanol at 0 - 20℃;
85% With potassium hydroxide; hydrogen; Trimethylenediamine In isopropyl alcohol at 25℃; for 3h;
75% With diisopropoxytitanium(III) tetrahydroborate In dichloromethane at -20℃; for 0.333333h;
With ethanol; sodium
With lithium aluminium tetrahydride In diethyl ether Heating;
With lithium aluminium tetrahydride
With sodium tetrahydroborate; cerium(III) chloride
With sodium tetrahydroborate In methanol; ethanol; water at 20℃; for 2h;
12 mg With NaBHn In methanol for 2.5h; Ambient temperature;
With sodium tetrahydroborate In methanol; ethanol; water at 20℃; for 2h;

Reference: [1]Current Patent Assignee: TAKASAGO INTERNATIONAL CORPORATION - US6342644, 2002, B1 Location in patent: Example 13
[2]Location in patent: experimental part Ohshima, Takashi; Tadaoka, Hiroshi; Hori, Kiyoto; Sayo, Noboru; Mashima, Kazushi [Chemistry - A European Journal, 2008, vol. 14, # 7, p. 2060 - 2066]
[3]Gonda, Tímea; Szakonyi, Zsolt; Csámpai, Antal; Haukka, Matti; Fülöp, Ferenc [Tetrahedron Asymmetry, 2016, vol. 27, # 11-12, p. 480 - 486]
[4]Moser, Ralph; Boskovia, Zarko V.; Crowe, Christopher S.; Lipshutz, Bruce H. [Journal of the American Chemical Society, 2010, vol. 132, # 23, p. 7852 - 7853]
[5]Plummer, Christopher M.; Gericke, Robert; Kraft, Philip; Raynor, Aaron; Froese, Jordan; Hudlick, Tom; Rook, Trevor J.; Jones, Oliver A. H.; Hügel, Helmut M. [European Journal of Organic Chemistry, 2015, vol. 2015, # 3, p. 486 - 495]
[6]Fisher, Gary B.; Fuller, Joseph C.; Harrison, John; Alvarez, Salvador G.; Burkhardt, Elizabeth R.; et al. [Journal of Organic Chemistry, 1994, vol. 59, # 21, p. 6378 - 6385]
[7]Lee; Ji; Lee; Lee [Journal of Organic Chemistry, 1996, vol. 61, # 7, p. 2542 - 2543]
[8]Current Patent Assignee: TAKASAGO INTERNATIONAL CORPORATION - US6342644, 2002, B1 Location in patent: Example 8
[9]Ravikumar, K. S.; Baskaran, Sundarababu; Chandrasekaran, Srinivasan [Journal of Organic Chemistry, 1993, vol. 58, # 22, p. 5981 - 5982]
[10]Macbeth; Shannon [Journal of the Chemical Society, 1952, p. 4748,4751] Bonichon [Bulletin de l'Institut du pin, 1934, p. 1,3]
[11]Eschinasi,E.H. [Journal of Organic Chemistry, 1970, vol. 35, p. 2010 - 2012]
[12]Schulte-Elte,K.H. et al. [Helvetica Chimica Acta, 1971, vol. 54, p. 1870 - 1880] Tagaki,W.; Mitsui,T. [Journal of Organic Chemistry, 1960, vol. 25, p. 1476 - 1479]
[13]Wovkulich, P. M.; Shankaran, K.; Kiegiel, J.; Uskokovic, M. R. [Journal of Organic Chemistry, 1993, vol. 58, # 4, p. 832 - 839]
[14]Dams, Iwona; Bialonska, Agata; Ciunik, Zbigniew; Wawrzenczyk, Czeslaw [Journal of Agricultural and Food Chemistry, 2004, vol. 52, # 6, p. 1630 - 1634]
[15]Kubo, Masayoshi; Sasaki, Hiroshi; Endo, Tohru; Taguchi, Heihachiro; Yosioka, Itiro [Chemical and pharmaceutical bulletin, 1986, vol. 34, # 8, p. 3097 - 3101]
[16]Dams, Iwona; Bialonska, Agata; Ciunik, Zbigniew; Wawrzenczyk, Czeslaw [European Journal of Organic Chemistry, 2004, # 12, p. 2662 - 2668]
  • 6
  • [ 89-82-7 ]
  • [ 22472-80-6 ]
  • [ 22472-79-3 ]
YieldReaction ConditionsOperation in experiment
69% With (S)-(+)-5,5’-bis[di(3,5-di-tert-butyl-4-methoxyphenyl)phosphino]-4,4’-bi-1,3-benzodioxole; diethoxymethylsilane; copper(II) acetate monohydrate In diethyl ether at -25℃; for 5h; Inert atmosphere; optical yield given as %de; diastereoselective reaction;
With lithium aluminium tetrahydride; diethyl ether
With lithium aluminium tetrahydride; diethyl ether Reinigung ueber das 3.5-Dinitro-benzoyl-Derivat;
With potassium hydroxide; hydrogen In isopropyl alcohol at 28℃; for 16h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
150 mg With sodium tetrahydroborate; cerium(III) chloride In methanol for 0.0833333h; Yields of byproduct given;
1: 69 % Chromat. 2: 31 % Chromat. With sodium tetrahydroborate In methanol effect of CeCl3 present;
With roots of Manihot dulcis In water at 20℃; for 72h; Title compound not separated from byproducts.;
With hydrogen; Trimethylenediamine at 25℃; for 15h;
With hydrogen; Trimethylenediamine at 25℃; for 17h;
With hydrogen; ethylenediamine at 25℃; for 17h;
With hydrogen; ethylenediamine at 25℃; for 15h;
62 % de With sodium tetrahydroborate; erbium(III) triflate In 2-methyltetrahydrofuran at 20℃; for 0.0833333h; Green chemistry; Overall yield = > 99 %Chromat.; regioselective reaction; 9 4.2 General procedure for the stereoselective reduction of α,β-unsaturated carbonyl compounds General procedure: To a suspension of α,β-unsaturated carbonyl compound (2.0 mmol) and Er(OTf)3 (0.1 mmol) in 2-MeTHF (3 mL) an equimolar quantity of NaBH4 (2.0 mmol) was added. The reaction mixture was stirred at room temperature and monitored by GC/MS until consumption of starting material. The crude reaction mixture was quenched with H2O (3 mL), the organic phase was dried on dry Na2SO4 and the solvent was evaporated under reduced pressure. The desired product was obtained pure after work-up.

Reference: [1]Moser, Ralph; Boskovia, Zarko V.; Crowe, Christopher S.; Lipshutz, Bruce H. [Journal of the American Chemical Society, 2010, vol. 132, # 23, p. 7852 - 7853]
[2]Tagaki,W.; Mitsui,T. [Journal of Organic Chemistry, 1960, vol. 25, p. 1476 - 1479] Macbeth; Shannon [Journal of the Chemical Society, 1952, p. 4748,4751]
[3]Macbeth; Shannon [Journal of the Chemical Society, 1952, p. 4748,4751]
[4]Ohkuma, Takeshi; Ikehira, Hideyuki; Ikariya, Takao; Noyori, Ryoji [Synlett, 1997, # SPEC. ISS., p. 467 - 468]
[5]Gemal, Andre L.; Luche, Jean-Louis [Journal of the American Chemical Society, 1981, vol. 103, # 18, p. 5454 - 5459]
[6]Gemal, Andre L.; Luche, Jean-Louis [Journal of the American Chemical Society, 1981, vol. 103, # 18, p. 5454 - 5459]
[7]Machado, Luciana L.; Souza, Joao Sammy N.; de Mattos, Marcos Carlos; Sakata, Solange K.; Cordell, Geoffrey A.; Lemos, Telma L.G. [Phytochemistry, 2006, vol. 67, # 15, p. 1637 - 1643]
[8]Current Patent Assignee: TAKASAGO INTERNATIONAL CORPORATION - US6342644, 2002, B1 Location in patent: Example 9
[9]Current Patent Assignee: TAKASAGO INTERNATIONAL CORPORATION - US6342644, 2002, B1 Location in patent: Example 10
[10]Current Patent Assignee: TAKASAGO INTERNATIONAL CORPORATION - US6342644, 2002, B1 Location in patent: Example 11
[11]Current Patent Assignee: TAKASAGO INTERNATIONAL CORPORATION - US6342644, 2002, B1 Location in patent: Example 12
[12]Nardi, Monica; Sindona, Giovanni; Costanzo, Paola; Oliverio, Manuela; Procopio, Antonio [Tetrahedron, 2015, vol. 71, # 7, p. 1132 - 1135]
  • 7
  • [ 89-82-7 ]
  • [ 89-80-5 ]
  • [ 1196-31-2 ]
YieldReaction ConditionsOperation in experiment
1: 37% 2: 31% With glucose dehydrogenase; D-glucose; Nicotiana tabacum double-bond reductase; nicotinamide adenine dinucleotide phosphate In aq. phosphate buffer; ethanol at 30℃; for 4h; Sealed tube; Enzymatic reaction; Overall yield = 68 %;
With titanium tetrachloride; magnesium; <i>tert</i>-butyl alcohol In tetrahydrofuran for 48h; Ambient temperature; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With ethanol; nickel Hydrogenation;
With triethylsilane In benzene at 70℃; for 48h; Yield given;
With hydrogen; benzyltriphenylphosphonium chloride In water; benzene for 720h; Ambient temperature; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With triethylsilane; hydrogen fluoride In water; benzene at 70℃; for 48h; hydrosilylation with various silanes and catalysts;
With NADPH; Triton X-100 In phosphate buffer at 35℃;
With N,N,N,N,N,N-hexamethylphosphoric triamide; trichlorosilane In dichloromethane at 0 - 20℃; for 20h; Inert atmosphere;
2 % de With leukotriene B<SUB>4</SUB> 12-hydroxydehydrogenase from Rattus norvegicus, rat; NADPH In aq. buffer at 30℃; for 24h; Enzymatic reaction; stereoselective reaction;
25 % de With D-glucose; glucose dehydrogenase (GDH; 10U); holo-(flavin free double bond reductase from Nicotiana tabacum); nicotinamide adenine dinucleotide phosphate In aq. phosphate buffer at 30℃; for 24h; Enzymatic reaction; Overall yield = 61 %; diastereoselective reaction;
29 % de With hydrogen; palladium dichloride; tetrabutylammonium L-prolinate In isopropyl alcohol at 20℃; for 18h; Schlenk technique; Inert atmosphere; enantioselective reaction;
40 % de With tetrabutylphosphonium prolinate; hydrogen; palladium dichloride at 20℃; for 18h; Schlenk technique; Inert atmosphere; Green chemistry; diastereoselective reaction;
With glucose dehydrogenase; D-glucose; Mentha piperita pulegone reductase Q6WAU0; nicotinamide adenine dinucleotide phosphate In aq. buffer at 30℃; for 24h; Enzymatic reaction;
With nickel; ammonium chloride; cucurbit[5]uril In water for 24h; Electrochemical reaction; General procedure: The presence of cucurbit[5]uril toward the electrochemicalreduction of isophorone was evaluated. For this purpose,10 mL of an aqueous solution of isophorone (2.6 mmol L-1)in 0.2 mol L-1 NH4Clwas prepared. The resulting solutionwas stirred for 24 h and added to the electrochemicalsystem. Different dispersions of cucurbit[5]uril rangingfrom 0.614 to 1.32 mmol L-1 were prepared directly in0.2 mol L-1 of NH4Cl.The cyclic voltammetry experimentsof the cucurbit[5]uril dispersions in presence of isophorone(2.6 mmol L-1) were conducted as mentioned before.
With 10% Pd/C; hydrogen In dichloromethane at 20℃; for 2h; Overall yield = 99 percent; Overall yield = 475 mg; ENTRY 8. Reduction of (R)-(+)-pulegone to (-)-trans-menthone and (+)-cis-isomenthone. A mixture of (R)-(+)-pulegone (472 mg, 3.10 mmol) and 10% palladium on carbon (160 mg) in DCM (30 mL) was vigorously stirred under hydrogen for 2 h.

Reference: [1]Cheallaigh, Aisling Ní; Mansell, David J.; Toogood, Helen S.; Tait, Shirley; Lygidakis, Antonios; Scrutton, Nigel S.; Gardiner, John M. [Journal of Natural Products, 2018, vol. 81, # 7, p. 1546 - 1552]
[2]Pons, Jean-Marc; Santelli, Maurice [Tetrahedron Letters, 1986, vol. 27, # 35, p. 4153 - 4156]
[3]Naves [Helvetica Chimica Acta, 1942, vol. 25, p. 732,738][Helvetica Chimica Acta, 1943, vol. 26, p. 162,171]
[4]Schmidt, Thomas [Tetrahedron Letters, 1994, vol. 35, # 21, p. 3513 - 3516]
[5]Reger, Daniel L.; Habib, M. M.; Fauth, D. J. [Journal of Organic Chemistry, 1980, vol. 45, # 19, p. 3860 - 3865]
[6]Schmidt, Thomas [Tetrahedron Letters, 1994, vol. 35, # 21, p. 3513 - 3516]
[7]Matsushima, Akihito; Sato, Yuya; Otsuka, Miki; Watanabe, Takayoshi; Yamamoto, Hiroaki; Hirata, Toshifumi [Bioorganic Chemistry, 2008, vol. 36, # 1, p. 23 - 28]
[8]Sugiura, Masaharu; Sato, Norimasa; Kotani, Shunsuke; Nakajima, Makoto [Chemical Communications, 2008, # 36, p. 4309 - 4311]
[9]Durchschein, Katharina; Wallner, Silvia; MacHeroux, Peter; Schwab, Wilfried; Winkler, Thorsten; Kreis, Wolfgang; Faber, Kurt [European Journal of Organic Chemistry, 2012, # 26, p. 4963 - 4968]
[10]Mansell, David J.; Toogood, Helen S.; Waller, John; Hughes, John M.X.; Levy, Colin W.; Gardiner, John M.; Scrutton, Nigel S. [ACS Catalysis, 2013, vol. 3, # 3, p. 370 - 379]
[11]Ferlin, Nadege; Courty, Matthieu; Van Nhien, Albert Nguyen; Gatard, Sylvain; Pour, Milan; Quilty, Brid; Ghavre, Mukund; Haiss, Annette; Kuemmerer, Klaus; Gathergood, Nicholas; Bouquillon, Sandrine [RSC Advances, 2013, vol. 3, # 48, p. 26241 - 26251]
[12]Hayouni, Safa; Robert, Anthony; Ferlin, Nadège; Amri, Hassen; Bouquillon, Sandrine [RSC Advances, 2016, vol. 6, # 114, p. 113583 - 113595]
[13]Currin, Andrew; Dunstan, Mark S.; Johannissen, Linus O.; Hollywood, Katherine A.; Vinaixa, Maria; Jervis, Adrian J.; Swainston, Neil; Rattray, Nicholas J. W.; Gardiner, John M.; Kell, Douglas B.; Takano, Eriko; Toogood, Helen S.; Scrutton, Nigel S. [ACS Catalysis, 2018, vol. 8, # 3, p. 2012 - 2020]
[14]Sales, Ayrlane; de Oliveira e Castro, Isabela Andrade; de Menezes, Frederico Duarte; Selva, Thiago Matheus Guimarães; Vilar, Márcio [Journal of Inclusion Phenomena and Macrocyclic Chemistry, 2019, vol. 95, # 3-4, p. 295 - 305]
[15]Mason, David J.; Timofeyenko, Yegor G.; Jagadish, Bhumasamudram; Mash, Eugene A. [Synthetic Communications, 2022, vol. 52, # 18, p. 1825 - 1833]
  • 8
  • [ 89-82-7 ]
  • [ 7712-68-7 ]
YieldReaction ConditionsOperation in experiment
(i) Br2, AcOH, (ii) NaOEt; Multistep reaction;
Multi-step reaction with 2 steps 1: bromine; acetic acid / 0 °C / Inert atmosphere 2: potassium hydroxide / water / Reflux; Inert atmosphere
Stage #1: pulegone With bromine; sodium hydrogencarbonate In diethyl ether at 0℃; for 0.5h; Inert atmosphere; Stage #2: With sodium ethanolate In diethyl ether; ethanol at 50℃; for 1h; Inert atmosphere; Stage #3: With water; potassium hydroxide In ethanol at 100℃; for 18h; Inert atmosphere;
  • 9
  • [ 89-82-7 ]
  • [ 762-72-1 ]
  • (2R,5R)-2-(1',1'-dimethyl-3'-butenyl)-5-methyl-cyclohexanone [ No CAS ]
  • (2S,5R)-2-(1',1'-dimethyl-3'-butenyl)-5-methyl-cyclohexanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
31% With titanium tetrachloride In dichloromethane at -78 - 0℃; for 0.666667h;
(i) TiCl4, CH2Cl2, (ii) /BRN= 906755/, (iii) (hydrolysis); Multistep reaction;
Stage #1: pulegone With titanium tetrachloride In dichloromethane at -78℃; for 0.25h; Stage #2: allyl-trimethyl-silane In dichloromethane at -78 - 0℃; for 0.416667h; Stage #3: With triethylamine In methanol; dichloromethane at 0℃; for 0.0833333h;
  • 10
  • [ 67-56-1 ]
  • [ 89-82-7 ]
  • [ 138286-50-7 ]
YieldReaction ConditionsOperation in experiment
80% With rose bengal In dichloromethane for 14h; Irradiation;
  • 11
  • [ 4894-61-5 ]
  • [ 89-82-7 ]
  • [ 117712-89-7 ]
YieldReaction ConditionsOperation in experiment
60% With titanium tetrachloride; magnesium In tetrahydrofuran at 20℃; for 48h;
  • 12
  • [ 75-24-1 ]
  • [ 89-82-7 ]
  • [ 56782-80-0 ]
  • [ 56816-94-5 ]
YieldReaction ConditionsOperation in experiment
81% Stage #1: trimethylaluminum; pulegone With chloro-trimethyl-silane; copper(I) bromide In tetrahydrofuran; n-heptane at 0 - 20℃; Stage #2: With potassium hydroxide In ethanol; water for 3h; Reflux;
With chloro-trimethyl-silane; copper(I) bromide In tetrahydrofuran; hexane for 4h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With copper(I) bromide In tetrahydrofuran; hexane for 0.5h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With copper(I) bromide In tetrahydrofuran; toluene at 0 - 20℃; for 5h; Inert atmosphere; Overall yield = 56 %; Overall yield = 95 mg;

  • 13
  • [ 89-82-7 ]
  • [ 24400-84-8 ]
  • (R)-1,1,8-Trimethyl-3-triisopropylsilanyl-spiro[4.5]decan-6-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
97% With titanium tetrachloride In dichloromethane at -78 - -20℃;
  • 14
  • [ 89-82-7 ]
  • [ 308358-04-5 ]
YieldReaction ConditionsOperation in experiment
100% With dihydrogen peroxide; potassium hydroxide In methanol; water at 20℃; for 4h;
96% With lithium hydroxide; dihydrogen peroxide
95% With dihydrogen peroxide; lithium hydroxide In methanol; water for 4h; (6R)-2,2,6-Trimethyl-1-oxaspiro[2.5]octan-4-one (34): Toa mixture of (R)-pulegone 33 (15.22 g, 100 mmol) and aqH2O2 (30%, 56.7 mL, 500 mmol) in methanol (300 mL)cooled at 15 °C was added aq LiOH (0.5 M, 20 mL) in adropwise manner over a period of 15 mins. Stirring wascontinued for 4 h at 20 °C. The reaction mixture was thenpoured into brine solution (150 mL) and the aq layer wasextracted with ethyl acetate (2 x 250 mL). The combinedorganic layers were washed with water (100 mL), brine(100 mL) and dried over Na2SO4. The solvent was evaporatedunder reduced pressure to furnish the crude compoundwhich was purified by column chromatography on silica gel(EtOAc/hexane, 0.5:9.5) to afford the epoxide 34 as a 1:1mixture of diasteromers (15.96 g, 95.0 mmol) in 95% yieldas an oil. TLC Rf: 0.2 (ethyl acetate:hexane, 1:9). IR (KBr):2958, 2872, 1721, 1116, 1032, 881, 605 cm-1; 1H NMR(500 MHz, CDCl3) δ 2.57 (m, 1H), 2.41-2.36 (m, 3H),2.19-2.12 (m, 1H), 2.04-1.93 (m, 5H), 1.79-1.68 (m, 2H),1.45-1.39 (m, 8H), 1.18 (s, 3H), 1.17 (s, 3H), 1.04 (d, J =6.3 Hz, 3H), 1.02 (d, J = 7.1 Hz, 3H); 13C NMR (100 MHz,CDCl3) δ 207.2, 206.1, 69.9, 69.8, 63.0, 62.9, 51.0, 49.2,33.7, 32.6, 30.3, 29.8, 29.6, 25.9, 21.7, 19.6, 19.4, 19.3,19.0, 18.6. MS (ESI): m/z 191 [M+Na]+. HRMS (ESI):calcd for C20H16O2Na: 191.1048; found: 191.1049
94% With lithium hydroxide; dihydrogen peroxide In methanol at 30℃;
94% With lithium hydroxide In methanol at 25℃; for 8h;
93% With dihydrogen peroxide; sodium dodecyl-sulfate; benzonitrile In methanol at 60℃; for 48h;
90% With lithium hydroxide monohydrate; dihydrogen peroxide In methanol; water at 21℃; for 6h;
74% With alkaline H2O2 In tetrahydrofuran
With dihydrogen peroxide; potassium hydroxide In methanol; water
With water; lithium hydroxide In methanol at 23℃; Inert atmosphere;
With lithium hydroxide monohydrate; dihydrogen peroxide In methanol; water at 20℃; for 6h;
With dihydrogen peroxide Inert atmosphere;

Reference: [1]Ishida, Hiroaki; Kimura, Shinya; Kogure, Noriyuki; Kitajima, Mariko; Takayama, Hiromitsu [Organic and Biomolecular Chemistry, 2015, vol. 13, # 28, p. 7762 - 7771]
[2]Location in patent: scheme or table Kozak, Jennifer A.; Dake, Gregory R. [Angewandte Chemie - International Edition, 2008, vol. 47, # 22, p. 4221 - 4223]
[3]Karella, Satish; Raghavan, Sadagopan [Journal of Chemical Sciences, 2020, vol. 132, # 1]
[4]Mutti, Stephane; Daubie, Christophe; Decalogne, Francois; Fournier, Robert; Rossi, Pierre [Tetrahedron Letters, 1996, vol. 37, # 18, p. 3125 - 3128]
[5]Chen, Yuzhong; Evarts Jr., Jerry B.; Torres, Eduardo; Fuchs, Philip L. [Organic Letters, 2002, vol. 4, # 21, p. 3571 - 3574]
[6]Yamaguchi, Kazuya; Mori, Kohsuke; Mizugaki, Tomoo; Ebitani, Kohki; Kaneda, Kiyotomi [Journal of Organic Chemistry, 2000, vol. 65, # 21, p. 6897 - 6903]
[7]Haley, Hannah M. S.; Payer, Stefan E.; Papidocha, Sven M.; Clemens, Simon; Nyenhuis, Jonathan; Sarpong, Richmond [Journal of the American Chemical Society, 2021, vol. 143, # 12, p. 4732 - 4740]
[8]Avery; Chong; Jennings-White [Journal of the American Chemical Society, 1992, vol. 114, # 3, p. 974 - 979]
[9]Location in patent: scheme or table Ding, Rui; Lu, Yunyu; Yao, Hequan; Sun, Bingfeng; Lin, Guoqiang [Science China Chemistry, 2012, vol. 55, # 6, p. 1097 - 1100]
[10]Yuan, Changxia; Chang, Chih-Tsung; Siegel, Dionicio [Journal of Organic Chemistry, 2013, vol. 78, # 11, p. 5647 - 5668]
[11]Meng, Lingxing [Journal of Organic Chemistry, 2016, vol. 81, # 17, p. 7784 - 7789]
[12]Zeng, Xin; Jia, Zhuqing; Qiu, Fayang G. [Tetrahedron Letters, 2020, vol. 61, # 41]
  • 15
  • [ 89-82-7 ]
  • [ 117773-78-1 ]
YieldReaction ConditionsOperation in experiment
98% With hydrogen In ethanol at 20℃; for 2h; chemoselective reaction;
96% With hydrogen In ethanol at 20℃; for 2h; chemoselective reaction; 2.6. General procedure for the hydrogenation of different unsaturated compounds General procedure: In a typical reaction, 0.015 g of catalyst and 2 mmol of the reactant were taken in 10 mL of ethanol under hydrogen atmosphere. The reaction was monitored by thin-layer chromatography (TLC). After complete disappearance of the starting material, the catalyst was separated by simple filtration and the solvent was removed under reduced pressure to obtain the pure product.
91% With ethanol; lithium In tetrahydrofuran at 0℃; for 8h;
90% With hexacarbonyl molybdenum; phenylsilane In tetrahydrofuran for 3h; Heating;
70% With titanium tetrachloride; magnesium; <i>tert</i>-butyl alcohol In tetrahydrofuran at 20℃; for 3h;
90 % Chromat. With diphenylsilane In chloroform for 6h; Ambient temperature;
With aluminium tris(2,6-diphenylphenoxide); n-butyllithium; diisobutylaluminium hydride 1) toluene, -78 deg C; 2) toluene, THF, hexane, -78 deg C, 15 min; Yield given. Multistep reaction;
Multi-step reaction with 2 steps 1: Bu3SnH, di-tert-butyl peroxide / toluene / 12 h / Heating 2: aq. NaOH / toluene; acetone
95 %Chromat. With C135H237N27O45Si9; hydrogen In water at 25℃; for 50h; General procedure for hydrogenation reactions with PtNPs General procedure: PtNPs were freshly prepared in a Schlenk flask in an aqueous solution (1.2.10-3 M in Pt), and 100 equiv of the substrate were added. The Schlenk flask was filled with H2 and the solution was allowed to stir at 25 °C. After respectively, for the isophorone and the (R)-(+)-pulegone, 26 and 50 h, the mixture is analyzed by gas chromatography (injector temperature, 250 °C; split injection mode; carrier gas, nitrogen at 1 mL min-1; initial oven temperature, 60 °C, 1 min; rate, 10 °C min-1; final temperature, 250 °C, 2 min; detector, 300 °C; solvent, diethyl ether). The retention times were found to be approx. 8 min for the isophorone and 7 min for the corresponding hydrogenated product. refText
With hydrogen In ethanol at 20℃; for 5h; chemoselective reaction;
With palladium on activated charcoal; hydrogen In ethyl acetate at 20℃; General procedure: Authentic standards for each reduction product by stirring ethyl acetate solutions under an atmosphere of H2 in the presence of Pd/C. Reactions were stirred at room temp until GC/MS indicated complete consumption of starting materials, the solvent was removed by rotary evaporation.
With hydrogen In water at 25℃; for 16h; chemoselective reaction;
With hydrogen In water at 20℃; for 48h; Schlenk technique; Inert atmosphere;

Reference: [1]Kantam, Mannepalli Lakshmi; Kishore, Ramineni; Yadav, Jagjit; Sudhakar, Medak; Venugopal, Akula [Advanced Synthesis and Catalysis, 2012, vol. 354, # 4, p. 663 - 669]
[2]Lakshmi, Kantam M.; Parsharamulu; Manorama [Journal of Molecular Catalysis A: Chemical, 2012, vol. 365, p. 115 - 119]
[3]Alonso, Francisco; Osante, Iñaki; Yus, Miguel [Synlett, 2006, # 18, p. 3017 - 3020]
[4]Keinan, Ehud; Perez, Daniel [Journal of Organic Chemistry, 1987, vol. 52, # 12, p. 2576 - 2580]
[5]Pons, Jean-Marc; Santelli, Maurice [Journal of Organic Chemistry, 1989, vol. 54, # 4, p. 877 - 884]
[6]Keinan, Ehud; Greenspoon, Noam [Tetrahedron Letters, 1985, vol. 26, # 10, p. 1353 - 1356]
[7]Saito, Susumu; Yamamoto, Hisashi [Journal of Organic Chemistry, 1996, vol. 61, # 9, p. 2928 - 2929]
[8]Hays, David S.; Scholl, Matthias; Fu, Gregory C. [Journal of Organic Chemistry, 1996, vol. 61, # 19, p. 6751 - 6752]
[9]Location in patent: experimental part Gatard, Sylvain; Liang, Liyuan; Salmon, Lionel; Ruiz, Jaime; Astruc, Didier; Bouquillon, Sandrine [Tetrahedron Letters, 2011, vol. 52, # 16, p. 1842 - 1846]
[10]Location in patent: scheme or table Hagiwara, Hisahiro; Nakamura, Tomomi; Hoshi, Takashi; Suzuki, Toshio [Green Chemistry, 2011, vol. 13, # 5, p. 1133 - 1137]
[11]Patterson-Orazem, Athéna; Sullivan, Bradford; Stewart, Jon D. [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 20, p. 5628 - 5632]
[12]Ferry, Angélique; Schaepe, Kira; Tegeder, Patricia; Richter, Christian; Chepiga, Kathryn M.; Ravoo, Bart Jan; Glorius, Frank [ACS Catalysis, 2015, vol. 5, # 9, p. 5414 - 5420]
[13]Menot, Bérengère; Salmon, Lionel; Bouquillon, Sandrine [European Journal of Inorganic Chemistry, 2015, vol. 2015, # 27, p. 4518 - 4523]
  • 16
  • [ 89-82-7 ]
  • [ 22472-79-3 ]
YieldReaction ConditionsOperation in experiment
89% With lithium pyrrolidinoborohydride In tetrahydrofuran at 25℃; for 1h;
  • 17
  • [ 89-82-7 ]
  • 4-chloroisopulegone [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With calcium hypochlorite In dichloromethane; water
With calcium hypochlorite; Methamphetamin In dichloromethane; water for 3h;
  • 18
  • [ 1826-67-1 ]
  • [ 89-82-7 ]
  • [ 83648-88-8 ]
YieldReaction ConditionsOperation in experiment
80% With copper(I) bromide In tetrahydrofuran at -20℃;
  • 19
  • [ 1826-67-1 ]
  • [ 89-82-7 ]
  • [ 83648-88-8 ]
  • [ 83648-89-9 ]
YieldReaction ConditionsOperation in experiment
With copper(l) iodide In tetrahydrofuran at -30℃; for 1h; Yield given. Yields of byproduct given;
Stage #1: vinyl magnesium bromide With copper(l) iodide In tetrahydrofuran at -40℃; for 0.25h; Inert atmosphere; Schlenk technique; Stage #2: pulegone In tetrahydrofuran at -40 - 20℃; Inert atmosphere; Schlenk technique; Overall yield = 83 percent; Overall yield = 1.49 g;
  • 20
  • [ 89-82-7 ]
  • [ 100-53-8 ]
  • [ 898541-20-3 ]
YieldReaction ConditionsOperation in experiment
90% With sodium hydroxide In tetrahydrofuran for 2h; Heating;
90% With sodium hydroxide In tetrahydrofuran for 2h; Heating;
90% With sodium hydroxide In tetrahydrofuran; water for 2h; Inert atmosphere; Reflux;
86% In dichloromethane at 20℃; for 0.166667h;
85% With sodium hydroxide In tetrahydrofuran for 18h; Heating;

  • 21
  • [ 89-82-7 ]
  • [ 74-88-4 ]
  • [ 501369-28-4 ]
YieldReaction ConditionsOperation in experiment
70% With lithium chloride; lithium diisopropyl amide
With lithium diisopropyl amide 1.) THF, -78 deg C, 1 h, 2.) -78 deg C, 1 h; 0 deg C, 1 h; Yield given. Multistep reaction;
Stage #1: pulegone With lithium diisopropyl amide In tetrahydrofuran; hexane at -78℃; for 1h; Stage #2: methyl iodide In tetrahydrofuran; hexane at -78 - 0℃; for 2h;
  • 22
  • [ 89-82-7 ]
  • [ 22472-80-6 ]
  • [ 20549-46-6 ]
  • [ 22472-79-3 ]
YieldReaction ConditionsOperation in experiment
9.7% With potassium hydroxide; hydrogen In isopropyl alcohol at 28℃; Yields of byproduct given;
  • 23
  • [ 89-82-7 ]
  • oxime (5R)-5-methyl-2-(propan-2-ylidene)cyclohexanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
96% With pyridine; hydroxylamine hydrochloride In ethanol Reflux; General procedure for ketone oximation General procedure: 50 mL of ethanol, 5 mL of pyridine, 6.50 mmol ketone and 60 mmol hydroxylamine hydrochloride were added into a 100 mL round-bottom flask. The reaction was monitored with thin layer chromatography. After the complete reaction of the substrates, 300 mL of distilled water was added to the mixture. The beaker was placed in the refrigerator to accelerate product crystallization. The crystals were filtered under reduced pressure. The crude product was sufficiently pure for use in the next stage of the reaction and microbiological assays.
78% With hydroxylamine hydrochloride; sodium acetate In methanol; water at 60℃;
  • 24
  • [ 89-82-7 ]
  • 5-(R)-2-<1-<2H3>methyl<2,2,2-2H3>ethylidene>-5-methyl<6,6-2H2>cyclohexanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
98% With d(4)-methanol; prenyl bromide at 28℃; for 16h;
With deuteromethanol; water-d2; sodium for 1.5h; Heating;
190 mg With deuteromethanol; water-d2; sodium for 1.5h; Heating;
  • 25
  • [ 89-82-7 ]
  • [ 407619-25-4 ]
  • [ 407619-28-7 ]
YieldReaction ConditionsOperation in experiment
95% With sodium hydroxide In tetrahydrofuran at 20℃;
95% With sodium hydroxide In tetrahydrofuran at 20℃;
95% With sodium hydroxide at 20℃; for 24h;
  • 26
  • [ 89-82-7 ]
  • [ 75-05-8 ]
  • 2-[(5S)-1-hydroxy-5-methyl-2-(methylethylidene)cyclohexyl]acetonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
89% With n-butyllithium In tetrahydrofuran at -78 - 20℃; for 2h;
  • 27
  • [ 89-82-7 ]
  • [ 74-86-2 ]
  • [ 639839-74-0 ]
YieldReaction ConditionsOperation in experiment
91% Stage #1: acetylene With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Stage #2: pulegone In tetrahydrofuran at -78℃; for 1h;
Stage #1: acetylene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: pulegone In tetrahydrofuran; hexane at -78 - 20℃; Further stages.;
  • 28
  • [ 2769-71-3 ]
  • [ 89-82-7 ]
  • (R)-2,6-dimethyl-N-(4,5,6,7-tetrahydro-3,3,6-trimethyl-2(3H)-benzofuranylidene)-benzenamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% With gallium(III) trichloride In toluene at 60℃; for 18h;
  • 29
  • [ 66-71-7 ]
  • [ 89-82-7 ]
  • 2-[1-methyl-1-[(4R)-4-methyl-2-oxocyclohexyl]ethyl]-1,2,3,4-tetrahydrophenanthroline [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% Stage #1: 1,10-Phenanthroline With samarium diiodide In tetrahydrofuran at 25℃; for 0.0833333h; Stage #2: pulegone In tetrahydrofuran at 25℃; for 12h;
50% With samarium diiodide In tetrahydrofuran at 25℃; for 12h;
  • 30
  • [ 89-82-7 ]
  • [ 95849-63-1 ]
  • 2-[1-(4-methoxy-phenyl)-1-methyl-ethyl]-5-methyl-cyclohexanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% Stage #1: 1-(4-(butyltellanyl)phenyl)ethan-1-one With dilithium methyl(2-thienyl)cyanocuprate In tetrahydrofuran at 20℃; Stage #2: pulegone With boron trifluoride diethyl etherate In tetrahydrofuran at -78℃; for 0.666667h;
  • 31
  • [ 89-82-7 ]
  • [ 456-64-4 ]
  • 3-methyl-6-(1-methylethylidene)cyclohexen-1-yl trifluoromethanesulfonate [ No CAS ]
  • 32
  • [ 89-82-7 ]
  • [ 75-08-1 ]
  • (R)-2-(1-Ethylsulfanyl-1-methyl-ethyl)-5-methyl-cyclohexanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% With borax In water at 20℃; for 3h;
80% In dichloromethane at 20℃; for 0.166667h;
  • 33
  • [ 89-82-7 ]
  • [ 863725-39-7 ]
YieldReaction ConditionsOperation in experiment
With bromine; sodium hydrogencarbonate In diethyl ether at 0℃; for 0.5h; 2; 1.4; 3.1 (R)-(+)-Pulegone (76.12 g, 0.5 mmol), anhydrous NaHCO3 (12.5 g) and anhydrous ether (500 mL) were added to a 1 L round-bottom flask. The reaction mixture was cooled with an ice-bath under nitrogen. Bromine (25.62 mL, 0.5 mmol) was added dropwise over 30 minutes. The mixture was filtered and carefully added to NaOEt (21%, 412 mL, 1.11 mmol) in an ice-cooled bath. The mixture was stirred at room temperature overnight, and then 5% HCl (1 L) and ether (300 mL) were added. The aqueous phase was extracted with ether (2 X 300 mL). The combined organic phase was washed with water, dried and concentrated. The residue was added to a warmed solution of semicarbazide hydrochloride (37.5 g) and NaOAc (37.5 g) in water (300 mL). Then boiling ethanol (300 mL) was added to give a clear solution. The mixture was refluxed for 2.5 hours and then stirred at room temperature overnight. The mixture was treated with water (1 L) and ether (300 mL). The aqueous phase was extracted with ether (2 X 300 mL). The combined organic phase was washed with water, dried and concentrated. The residue was purified by vacuum distillation (73-76 C at 0.8 mm Hg) to give (2R)-ethyl 2-methyl-5-(propan-2-ylidene)cyclopentanecarboxylate (63 g, 64%). 1H NMR (CDCl3, 400 MHz) d 4.13 (m, 2H), 3.38 (d, J = 16 Hz, 0.5H), 2.93 (m, 0.5H), 2.50-2.17 (m, 2H), 1.98 (m, IH), 1.76 (m, IH), 1.23 (m, 6H), 1.05 (m, 6H).
With bromine; sodium hydrogencarbonate In diethyl ether for 0.5h; Cooling with ice; 1.3 Step 3: (R)-(+)-Pulegone (76.12 g, 0.5 mmol), anhydrous NaHCO3 (12.5 g) and anhydrous ether (500 mL) were added to a 1 L round-bottom flask. The reaction mixture was cooled with an ice-bath under nitrogen. Bromine (25.62 mL, 0.5 mmol) was added dropwise over about 30 minutes. The mixture was filtered and added to NaOEt (21%, 412 mL, 1.11 mmol) in an ice-cooled bath. The mixture was stirred at about room temperature overnight, and then 5% HCl (1 L) and ether (300 mL) were added. The aqueous phase was extracted with ether (2 X 300 mL). The combined organic phase was washed with water, dried and concentrated. The residue was added to a warmed solution of semicarbazide hydrochloride (37.5 g) and NaOAc (37.5 g) in water (300 mL). Then boiling ethanol (300 mL) was added to give a clear solution. The mixture was refluxed for 2.5 hours and then stirred at about room temperature overnight. The mixture was treated with water (1 L) and ether (300 mL). The aqueous phase was extracted with ether (2 X 300 mL). The combined organic phase was washed with water, dried and concentrated. The residue was purified by vacuum distillation (73-760C at 0.8 mm Hg) to give (2R)-ethyl 2-methyl-5-(propan-2- ylidene)cyclopentanecarboxylate (63 g, 64%). 1H NMR (CDCl3, 400 MHz) δ 4.13 (m, 2H), 3.38 (d, J = 16 Hz, 0.5H), 2.93 (m, 0.5H), 2.50-2.17 (m, 2H), 1.98 (m, IH), 1.76 (m, IH), 1.23 (m, 6H), 1.05 (m, 6H).
With bromine; sodium hydrogencarbonate In diethyl ether for 0.5h; Inert atmosphere; Cooling with ice; 1.1 Example 1Preparation of (S)-3-amino-2-(4-chlorophenyl)-l-(,4-((5RJR -7-hvdroxy-5-methyl-6J- dihydro-5H-cyclopentardlpyrimidin-4-yl)piperazin- 1 -vOpropan- 1 -one dihvdrochloride Step 1 : To a 1 L round-bottom flask were added (R)-(+)-Pulegone (76.12 g, 0.5 mmol), anhydrous NaHC03 (12.5 g) and anhydrous ether (500 mL). The reaction mixture was cooled with ice-bath under nitrogen. The bromine (25.62 mL, 0.5 mmol) was added dropwise over 30 minutes. The mixture was filtered and carefully added to NaOEt (21%, 412 mL, 1.11 mmol) in an ice-cooled bath. The mixture was stirred at room temperature overnight and then 1 L of 5% HC1 and 300 mL of ether were added. The aqueous phase was extracted with ether (2 x 300 mL). The combined organic phase was washed with water, dried and concentrated. The residue was added to a warmed solution of semicarbazide hydrochloride (37.5 g) and NaOAc (37.5 g) in water (300 mL), and then boiling ethanol (300 mL) was added to give a clear solution. The mixture was refluxed for 2.5 hours and then stirred at room temperature overnight. The mixture was treated with 1 L of water and 300 mL of ether. The aqueous phase was extracted with ether (2 x 300 mL). The combined organic phase was washed with water, dried and concentrated. The residue was purified by vacuum distillation (73-76°C at 0.8 mm Hg) to give (2R)-ethyl 2-methyl-5-(propan-2- ylidene)cyclopentanecarboxylate (63 g, 64%). 1H NMR (CDC13, 400 MHz) δ 4.13 (m, 2H), 3.38 (d, J = 16 Hz, 0.5H), 2.93 (m, 0.5H), 2.50-2.17 (m, 2H), 1.98 (m, 1H), 1.76 (m, 1H), 1.23 (m, 6H), 1.05 (m, 6H).
With bromine; sodium hydrogencarbonate In diethyl ether at 0℃; for 0.5h; 1.1 Example 1; 2-(4-chlorophenyl)-3-(isopropylamino)-l-(4-((R)-5-methyl-6,7-dihydro-5H- cyclopenta[d]pyrimidin-4-yl)piperazin- 1 -yPpropan- 1 -one dihvdrochloride; [00273] Step 1: To a 1 L round-bottom flask were added (R)-(+)-Pulegone (76.12 g, 0.5 mmol), anhydrous NaHCO3 (12.5 g) and anhydrous ether (500 mL). The reaction mixture was cooled with ice-bath under nitrogen. The bromine (25.62 mL, 0.5 mmol) was added dropwise over 30 minutes. The mixture was filtered and carefully added to NaOEt (21%, 412 mL, 1.11 mmol) in an ice-cooled bath. The mixture was stirred at room temperature overnight and then 1 L of 5% HCl and 300 mL of ether were added. The aqueous phase was extracted with ether (2 x 300 mL). The combined organic phase was washed with water, dried and concentrated. The residue was added to a warmed solution of semicarbazide hydrochloride (37.5 g) and NaOAc (37.5 g) in water (300 mL), and then boiling ethanol (300 mL) was added to give a clear solution. The mixture was refluxed for 2.5 hours and then stirred at room temperature overnight. The mixture was treated with 1 L of water and 300 mL of ether. The aqueous phase was extracted with ether (2 x 300 mL). The combined organic phase was washed with water, dried and concentrated. The residue was purified by vacuum distillation (73-76 °C at 0.8 mm Hg) to give (2R)-ethyl 2-methyl-5-(propan-2- ylidene)cyclopentanecarboxylate (63 g, 64%). 1H NMR (CDCl3, 400 MHz) δ 4.13 (m, 2H), 3.38 (d, J = 16 Hz, 0.5H), 2.93 (m, 0.5H), 2.50-2.17 (m, 2H), 1.98 (m, IH), 1.76 (m, IH), 1.23 (m, 6H), 1.05 (m, 6H).
With bromine In acetic acid at 5 - 15℃; for 1h; 4.25.1. (R)-pulegone dibromide (55) Bromine (19 mL, 370 mmol) was added dropwise over 30 min to a stirred and ice-cooled solution of 54 (54.2 g, 357 mmol) in glacial AcOH (75 mL) at 5-15 °C. The mixture was stirred for 30 min after the addition of Br2, poured into ice-water, and extracted with pentane. The pentane solution was washed with water, NaHCO3 solution and brine, dried (MgSO4), and filtered to give a pentane solution of 55.

  • 34
  • [ 89-82-7 ]
  • [ 501369-29-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: 70 percent / LDA; LiCl 2.1: 75 percent / KOH / Heating 3.1: diisopropyl amine; n-butyllithium; triethylamine / chlorotrimethylsilane / tetrahydrofuran; petroleum ether / -78 - 0 °C 3.2: bromine / tetrahydrofuran; petroleum ether / 2 h / -78 °C
  • 35
  • [ 89-82-7 ]
  • C10H16O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: 70 percent / LDA; LiCl 2.1: 75 percent / KOH / Heating 3.1: diisopropyl amine; n-butyllithium; triethylamine / chlorotrimethylsilane / tetrahydrofuran; petroleum ether / -78 - 0 °C 3.2: bromine / tetrahydrofuran; petroleum ether / 2 h / -78 °C 4.1: 5.0 g / lithium carbonate; lithium bromide / dimethylformamide / 4 h / 100 - 105 °C 5.1: diisopropyl amine; n-butyllithium / diethyl ether; petroleum ether / 0.58 h / -78 °C 5.2: diethyl ether; petroleum ether / 1 h / -78 °C
  • 36
  • [ 89-82-7 ]
  • C13H22O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: 70 percent / LDA; LiCl 2.1: 75 percent / KOH / Heating 3.1: diisopropyl amine; n-butyllithium; triethylamine / chlorotrimethylsilane / tetrahydrofuran; petroleum ether / -78 - 0 °C 3.2: bromine / tetrahydrofuran; petroleum ether / 2 h / -78 °C 4.1: 5.0 g / lithium carbonate; lithium bromide / dimethylformamide / 4 h / 100 - 105 °C 5.1: diisopropyl amine; n-butyllithium / diethyl ether; petroleum ether / 0.58 h / -78 °C 5.2: diethyl ether; petroleum ether / 1 h / -78 °C 6.1: 378 mg / triethylamine; methanesulfonyl chloride / CH2Cl2 / 4 h / 20 °C 7.1: lithium chloride / tetrahydrofuran / 2 h / 20 °C 7.2: n-butyllithium / tetrahydrofuran; petroleum ether / 0.08 h / -78 °C 7.3: 70 percent / tetrahydrofuran; petroleum ether / 0.5 h / -78 °C
  • 37
  • [ 89-82-7 ]
  • C13H21BrO4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 12 steps 1.1: 70 percent / LDA; LiCl 2.1: 75 percent / KOH / Heating 3.1: diisopropyl amine; n-butyllithium; triethylamine / chlorotrimethylsilane / tetrahydrofuran; petroleum ether / -78 - 0 °C 3.2: bromine / tetrahydrofuran; petroleum ether / 2 h / -78 °C 4.1: 5.0 g / lithium carbonate; lithium bromide / dimethylformamide / 4 h / 100 - 105 °C 5.1: diisopropyl amine; n-butyllithium / diethyl ether; petroleum ether / 0.58 h / -78 °C 5.2: diethyl ether; petroleum ether / 1 h / -78 °C 6.1: 378 mg / triethylamine; methanesulfonyl chloride / CH2Cl2 / 4 h / 20 °C 7.1: lithium chloride / tetrahydrofuran / 2 h / 20 °C 7.2: n-butyllithium / tetrahydrofuran; petroleum ether / 0.08 h / -78 °C 7.3: 70 percent / tetrahydrofuran; petroleum ether / 0.5 h / -78 °C 8.1: 91 percent / PCC / CH2Cl2 / 48 h / 20 °C 9.1: cerium trichloride; sodium borohydride / methanol / 0.5 h / 0 °C 10.1: 173 mg / mCPBA / CH2Cl2 / 1 h / 0 °C 11.1: 86 percent / Dess-Martin periodonane; sodium bicarbonate / CH2Cl2 / 1 h / 20 °C 12.1: magnesium bromide diethyl etherate / CH2Cl2 / 12 h / -78 °C
  • 38
  • [ 89-82-7 ]
  • [ 501369-33-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 13 steps 1.1: 70 percent / LDA; LiCl 2.1: 75 percent / KOH / Heating 3.1: diisopropyl amine; n-butyllithium; triethylamine / chlorotrimethylsilane / tetrahydrofuran; petroleum ether / -78 - 0 °C 3.2: bromine / tetrahydrofuran; petroleum ether / 2 h / -78 °C 4.1: 5.0 g / lithium carbonate; lithium bromide / dimethylformamide / 4 h / 100 - 105 °C 5.1: diisopropyl amine; n-butyllithium / diethyl ether; petroleum ether / 0.58 h / -78 °C 5.2: diethyl ether; petroleum ether / 1 h / -78 °C 6.1: 378 mg / triethylamine; methanesulfonyl chloride / CH2Cl2 / 4 h / 20 °C 7.1: lithium chloride / tetrahydrofuran / 2 h / 20 °C 7.2: n-butyllithium / tetrahydrofuran; petroleum ether / 0.08 h / -78 °C 7.3: 70 percent / tetrahydrofuran; petroleum ether / 0.5 h / -78 °C 8.1: 91 percent / PCC / CH2Cl2 / 48 h / 20 °C 9.1: cerium trichloride; sodium borohydride / methanol / 0.5 h / 0 °C 10.1: 173 mg / mCPBA / CH2Cl2 / 1 h / 0 °C 11.1: 86 percent / Dess-Martin periodonane; sodium bicarbonate / CH2Cl2 / 1 h / 20 °C 12.1: magnesium bromide diethyl etherate / CH2Cl2 / 12 h / -78 °C 13.1: 1.0 g / pyridine; trifluoroacetic anhydride; triethylamine / CH2Cl2 / 3.5 h / 0 - 20 °C
  • 39
  • [ 89-82-7 ]
  • [ 501369-15-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: 70 percent / LDA; LiCl 2.1: 75 percent / KOH / Heating 3.1: diisopropyl amine; n-butyllithium; triethylamine / chlorotrimethylsilane / tetrahydrofuran; petroleum ether / -78 - 0 °C 3.2: bromine / tetrahydrofuran; petroleum ether / 2 h / -78 °C 4.1: 5.0 g / lithium carbonate; lithium bromide / dimethylformamide / 4 h / 100 - 105 °C
Multi-step reaction with 2 steps 1.1: lithium diisopropyl amide / tetrahydrofuran / 2 h / -78 - 0 °C / Inert atmosphere 1.2: 72 h / Inert atmosphere; Reflux 2.1: lithium diisopropyl amide; bromine; chloro-trimethyl-silane / tetrahydrofuran / 4 h / -78 °C / Inert atmosphere 2.2: 4 h / 100 °C / Inert atmosphere
  • 40
  • [ 89-82-7 ]
  • [ 501369-16-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: 70 percent / LDA; LiCl 2.1: 75 percent / KOH / Heating 3.1: diisopropyl amine; n-butyllithium; triethylamine / chlorotrimethylsilane / tetrahydrofuran; petroleum ether / -78 - 0 °C 3.2: bromine / tetrahydrofuran; petroleum ether / 2 h / -78 °C 4.1: 5.0 g / lithium carbonate; lithium bromide / dimethylformamide / 4 h / 100 - 105 °C 5.1: diisopropyl amine; n-butyllithium / diethyl ether; petroleum ether / 0.58 h / -78 °C 5.2: diethyl ether; petroleum ether / 1 h / -78 °C 6.1: 378 mg / triethylamine; methanesulfonyl chloride / CH2Cl2 / 4 h / 20 °C
Multi-step reaction with 3 steps 1.1: lithium diisopropyl amide / tetrahydrofuran / 2 h / -78 - 0 °C / Inert atmosphere 1.2: 72 h / Inert atmosphere; Reflux 2.1: lithium diisopropyl amide; bromine; chloro-trimethyl-silane / tetrahydrofuran / 4 h / -78 °C / Inert atmosphere 2.2: 4 h / 100 °C / Inert atmosphere 3.1: lithium diisopropyl amide / diethyl ether / 2 h / -78 °C / Inert atmosphere 3.2: 4 h / 20 °C / Inert atmosphere
  • 41
  • [ 89-82-7 ]
  • [ 101693-93-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 94 percent / 30percent H2O2; LiOH / methanol / 8 h / 25 °C 2: 84 percent / tetrahydrofuran / 18 h / Heating
Multi-step reaction with 2 steps 1: 94 percent / 30percent H2O2, LiOH / methanol / 30 °C 2: 73 percent / tAmONa / various solvent(s) / 5 h / Heating
Multi-step reaction with 2 steps 1: 74 percent / alkaline H2O2 / tetrahydrofuran 2: 1.) NaH / 1.) THF, RT, 30 min, 2.) THF, reflux, 24 h
Multi-step reaction with 2 steps 1: lithium hydroxide; water / methanol / 23 °C / Inert atmosphere 2: sodium hydride / tetrahydrofuran / 66 °C / Inert atmosphere
Multi-step reaction with 2 steps 1: potassium hydroxide; dihydrogen peroxide / methanol; water / 4 h / 20 °C 2: sodium hydride / tetrahydrofuran / 21 h / Reflux
Multi-step reaction with 2 steps 1: dihydrogen peroxide / Inert atmosphere 2: sodium hydride / tetrahydrofuran / Inert atmosphere
Multi-step reaction with 2 steps 1.1: dihydrogen peroxide; lithium hydroxide / water; methanol / 4 h 2.1: sodium hydride / tetrahydrofuran; mineral oil 2.2: 24 h / Reflux
Multi-step reaction with 2 steps 1.1: lithium hydroxide monohydrate; dihydrogen peroxide / methanol; water / 6 h / 21 °C 2.1: sodium / tetrahydrofuran / 21 °C / Inert atmosphere 2.2: 7 h / 85 °C / Inert atmosphere

  • 42
  • [ 89-82-7 ]
  • [ 88154-77-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 94 percent / 30percent H2O2; LiOH / methanol / 8 h / 25 °C 2: 84 percent / tetrahydrofuran / 18 h / Heating 3: 90 percent / mCPBA / CH2Cl2 / 2 h / -30 °C
Multi-step reaction with 3 steps 1: 94 percent / 30percent H2O2, LiOH / methanol / 30 °C 2: 73 percent / tAmONa / various solvent(s) / 5 h / Heating 3: sodium perborate / acetic acid / 40 °C
Multi-step reaction with 3 steps 1: 74 percent / alkaline H2O2 / tetrahydrofuran 2: 1.) NaH / 1.) THF, RT, 30 min, 2.) THF, reflux, 24 h 3: 95 percent / m-CPBA / CH2Cl2 / -78 °C
Multi-step reaction with 3 steps 1: dihydrogen peroxide / Inert atmosphere 2: sodium hydride / tetrahydrofuran / Inert atmosphere 3: 3-chloro-benzenecarboperoxoic acid / dichloromethane / -78 °C / Inert atmosphere
Multi-step reaction with 3 steps 1.1: dihydrogen peroxide; lithium hydroxide / water; methanol / 4 h 2.1: sodium hydride / tetrahydrofuran; mineral oil 2.2: 24 h / Reflux 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h
Multi-step reaction with 3 steps 1.1: lithium hydroxide monohydrate; dihydrogen peroxide / methanol; water / 6 h / 21 °C 2.1: sodium / tetrahydrofuran / 21 °C / Inert atmosphere 2.2: 7 h / 85 °C / Inert atmosphere 3.1: sodium perborate tetrahydrate; acetic acid / 0.75 h / 40 °C / Inert atmosphere

  • 43
  • [ 89-82-7 ]
  • [ 15466-88-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: 62 percent / HCl / H2O 2.1: 30 percent / Br2 / H2O / 20 °C 3.1: ehtylene glycol; p-toluenesulfonic acid / benzene / 6 h 3.2: 70 percent / NaOH / methanol / 72 h
Multi-step reaction with 4 steps 1: 94 percent / 30percent H2O2, LiOH / methanol / 30 °C 2: 73 percent / tAmONa / various solvent(s) / 5 h / Heating 3: sodium perborate / acetic acid / 40 °C 4: CaCO3 / 80 °C
Multi-step reaction with 3 steps 1: sulfuric acid; cetylpyridinium chloride / water / 15 h / 80 °C 2: acetic acid; bromine / water / 5 - 18 °C 3: magnesium oxide / 1-methyl-pyrrolidin-2-one / 0.83 h / 110 °C
Multi-step reaction with 4 steps 1: dihydrogen peroxide / Inert atmosphere 2: sodium hydride / tetrahydrofuran / Inert atmosphere 3: 3-chloro-benzenecarboperoxoic acid / dichloromethane / -78 °C / Inert atmosphere 4: calcium carbonate / tetrachloromethane / Reflux; Inert atmosphere
Multi-step reaction with 4 steps 1.1: dihydrogen peroxide; lithium hydroxide / water; methanol / 4 h 2.1: sodium hydride / tetrahydrofuran; mineral oil 2.2: 24 h / Reflux 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h 4.1: calcium carbonate / tetrachloromethane / 24 h / Reflux

  • 44
  • [ 89-82-7 ]
  • [ 17957-94-7 ]
YieldReaction ConditionsOperation in experiment
75% With iodine; dimethyl sulfoxide at 60℃; for 6.5h;
Multi-step reaction with 2 steps 1: 75 percent / "70percent" calcium hypochlorite / H2O; CH2Cl2 2: 84 percent / aluminum chloride / CH2Cl2 / 4 h / 0 °C
Multi-step reaction with 2 steps 1: 76 percent / Cu / methanol; CH2Cl2 / 17 h / Irradiation 2: 90 percent / Zn, CH3COOH / 0.03 h / 40 °C
With P450 microsomes at 30℃; for 1h; Enzymatic reaction;

  • 45
  • [ 89-82-7 ]
  • [ 15815-65-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: NaOCMe2Et 2: H2 / Pd-C / ethanol
Multi-step reaction with 2 steps 1: (methylation) 2: H2 / Pd-C
Multi-step reaction with 2 steps 1: (i) NaOCMe2Et, benzene, (ii) /BRN= 969135/ 2: H2 / Pd-C / ethanol
Multi-step reaction with 2 steps 1: diethyl ether; sodium <i>tert</i>-pentylate; benzene 2: H2 / Pd-C / ethanol

  • 46
  • [ 89-82-7 ]
  • [ 80845-89-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: (i) NaOCMe2Et, benzene, (ii) /BRN= 969135/ 2: H2 / Pd-C / diethyl ether
Multi-step reaction with 3 steps 1: diethyl ether; sodium <i>tert</i>-pentylate; benzene 2: H2 / Pd-C / diethyl ether
  • 47
  • [ 89-82-7 ]
  • [ 43128-39-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: (i) NaOCMe2Et, benzene, (ii) /BRN= 969135/ 2: H2 / Pd-C / diethyl ether
Multi-step reaction with 2 steps 1: diethyl ether; sodium <i>tert</i>-pentylate; benzene 2: H2 / Pd-C / diethyl ether
  • 48
  • [ 491-09-8 ]
  • [ 6091-52-7 ]
  • [ 89-82-7 ]
  • cis-5-methyl-2-(1-methylethyl)cyclohexanone [ No CAS ]
  • trans-5-methyl-2-(1-methylethyl)cyclohexanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
With cyclohexyl(triphenyl)phosphonium bromide; hydrogen In tetrahydrofuran at 50℃; for 18h;
With N-benzyl-N,N,N-triethylammonium chloride; hydrogen In tetrahydrofuran at 50℃; for 18h;
With cyclohexyl(triphenyl)phosphonium bromide; hydrogen In acetone at 50℃; for 18h;
With cyclohexyl(triphenyl)phosphonium bromide; hydrogen In tetrahydrofuran at 50℃; for 18h;
With cyclohexyl(triphenyl)phosphonium bromide; hydrogen In tetrahydrofuran at 50℃; for 18h;
With cyclohexyl(triphenyl)phosphonium bromide; hydrogen In tetrahydrofuran at 50℃; for 18h;

  • 49
  • [ 89-82-7 ]
  • [ 34352-05-1 ]
  • [ 34349-25-2 ]
YieldReaction ConditionsOperation in experiment
With hydrogen sulfide In dichloromethane for 3h; 7 Synthesis of (1R)-mercaptomenthone from d-pulegone Synthesis of (1R)-mercaptomenthone from d-pulegone A reactor equipped with a thermometer and a gas-introducing tube was charged with the d-pulegone (3 g, 23 mmol) obtained in Synthesis Example 5 and methylene chloride (30 ml), anhydrous aluminum chloride (612 mg, 0.2 equivalent) was added thereto, and then hydrogen sulfide gas was blown through the gas-introducing tube for 3 hours. After completion of the reaction, a portion of the reaction mixture was taken out, and the conversion ratio was measured by a gas chromatography to find that it was 100%. After releasing the remaining hydrogen sulfide from the reaction mixture by nitrogen, a crude product was obtained in the usual way by dilute hydrochloric acid treatment, washing with water and concentration. By distilling the thus obtained crude product under a reduced pressure (95° C./600 Pa), 3 g (yield 70%) of the title compound was obtained with a purity of 96%.
  • 50
  • [ 7786-67-6 ]
  • [ 89-82-7 ]
YieldReaction ConditionsOperation in experiment
90% With hydrogen;(R)-((4,4?-bi-1,3-benzodioxole)-5,5?-diyl)bis(bis(3,5-di-t-butyl-4-methoxyphenyl))phosphine; [Rh(cyclooctadiene)2](PF6); [1,1'-(butane-1,4-diyl)bis(triphenylphosphonium)] dibromide; In ethyl acetate; at 50℃; under 22502.3 Torr; for 20h;Product distribution / selectivity; A 500 ml capacity autoclave was charged with 150 g (1 mol) of piperitenone, 18.6 mg (0.04 mmol) of [Rh(cod)2]PF6, 47.2 mg (0.04 mmol) of (S)-DIBM-SEGPHOS, 14.8 mg (0.02 mmol) of BrPPh3(CH2)4PPh3Br and 7.5 ml of ethyl acetate, and the reaction was carried out at 50 C. for 20 hours under a hydrogen pressure of 3 MPa. After completion of the reaction, hydrogen was purged, and the reaction solution was concentrated and distilled under a reduced pressure to obtain 136.8 g of d-pulegone (yield 90%).
87% copper-zinc-aluminum catalyst; at 150℃; for 8h;Product distribution / selectivity; A 50 g portion of the l-<strong>[7786-67-6]isopulegol</strong> obtained in (1) was stirred at 150 C. for 8 hours in the coexistence of 200 mg of a copper-zinc-aluminum catalyst to carry out isomerization of the double bond together with dehydrogenation reaction, thereby obtaining 43 g of d-pulegone (yield 87%).
  • 51
  • oxone [ No CAS ]
  • Os(VIII) [ No CAS ]
  • [ 89-82-7 ]
  • [ 81177-02-8 ]
YieldReaction ConditionsOperation in experiment
67% With hydrogenchloride; sodium hydrogencarbonate; sodium sulfate In ethyl acetate; N,N-dimethyl-formamide; <i>tert</i>-butyl alcohol 29 EXAMPLE 29 EXAMPLE 29 This example shows the oxidation of (+)-pulegone using Condition B. (+)-Pulegone (500 mg) was dissolved in DMF (25 mL), and OsO4 (0.41 mL, 2.5% in tBuOH) was added and stirred for 5 min. A solid mixture of OXONE (8.06 g) and NaHCO3 (1.10 g) was added in one portion and the reaction had a final volume (30 mL). The reaction was stirred at room temperature for 3 hours or until the solution becomes colorless. This usually marks the completion of the reaction which was verified by TLC or GC. Na2SO3 (3.0 g) was added, to reduce the remaining Os(VIII), and stirred for an additional hour or until solution became dark brown/black. EtOAc was added to extract the products and 1N HCl was used to dissolve the salts. The organic extract was washed with 1N HCl (100 mL*3) and brine (100 mL), dried over Na2SO4, and the solvent was removed under reduced pressure to obtain the crude product. 3R-Methyladipic acid was obtained in 67% yield after purification by silica gel column chromatography.
  • 52
  • BrPPh3(CH2)4PPh3Br [ No CAS ]
  • [ 491-09-8 ]
  • [ 89-82-7 ]
YieldReaction ConditionsOperation in experiment
90% In ethyl acetate 7 Synthesis of Pulegone EXAMPLE 7 Synthesis of Pulegone A 500 ml capacity autoclave was charged with 150 g (1 mol) of piperitenone, 18.6 mg (0.04 mmol) of [Rh(cod)2]PF6, 47.2 mg (0.04 mmol) of (S)-DTBM-SEGPHOS, 14.8 mg (0.02 mmol) of BrPPh3(CH2)4PPh3Br and 7.5 ml of ethyl acetate, and the reaction was carried out at 50° C. for 20 hours under a hydrogen pressure of 3 Mpa. After completion of the reaction, hydrogen was purged, the reaction solution was concentrated and then distillation was carried out under a reduced pressure to obtain 136.8 g of pulegol. The yield was 90%.
  • 53
  • [ 89-82-7 ]
  • (3R)-3-methyl-6-(1-methylethyl)cyclohexanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
62% With isopropyl alcohol In tetrahydrofuran at 76℃; for 1h;
  • 54
  • [ 89-82-7 ]
  • [ 1576-35-8 ]
  • [ 122407-23-2 ]
YieldReaction ConditionsOperation in experiment
92% With hydrogenchloride In ethanol at 0℃; for 2h;
  • 55
  • [ 491-09-8 ]
  • [ 6091-52-7 ]
  • [ 89-82-7 ]
  • [ 10458-14-7 ]
YieldReaction ConditionsOperation in experiment
With bis[(4S)-[4,4'-bi-1,3-benzodioxole]-5,5'-diyilbis[diphenylphosphine-κ-P]di-μ-chlorodirhodium]; hydrogen In dichloromethane at 50℃; for 18h; Autoclave;
  • 56
  • [ 89-82-7 ]
  • [ 20752-34-5 ]
  • [ 2216-51-5 ]
  • [ 2216-52-6 ]
YieldReaction ConditionsOperation in experiment
73% Stage #1: pulegone With potassium <i>tert</i>-butylate; hydrogen In isopropyl alcohol at 30℃; for 18h; Autoclave; Stage #2: With hydrogen In methanol at 50℃; for 18h; Autoclave; optical yield given as %ee;
  • 57
  • [ 358-23-6 ]
  • [ 89-82-7 ]
  • [ 24850-33-7 ]
  • [ 1010821-07-4 ]
YieldReaction ConditionsOperation in experiment
68% With 2,6-di-tert-butyl-pyridine In dichloromethane; acetonitrile at 0℃; Molecular sieve; Inert atmosphere;
  • 58
  • [ 89-82-7 ]
  • [ 288-36-8 ]
  • [ 1104001-68-4 ]
  • 59
  • [ 89-82-7 ]
  • [ 141-52-6 ]
  • [ 623935-92-2 ]
YieldReaction ConditionsOperation in experiment
66% Stage #1: pulegone With bromine; sodium hydrogencarbonate In diethyl ether Cooling with ice; Inert atmosphere; Stage #2: sodium ethanolate at 20℃; Cooling with ice; Stage #3: With semicarbazide hydrochloride; sodium acetate In ethanol; water for 3h; Reflux; 19.1 (1) Ethyl (2R)-2-methyl-5-(prop-2-ylidene)cyclopentacarboxylate (Intermediate 19-A): To a 500mL round bottom flask was added (R) - (+) - pulegone (7.61g, 50mmol),Anhydrous NaHCO3 (1.25g, 15mmol) and anhydrous ether (50mL). The reaction mixture was cooled with an ice bath under nitrogen.Liquid bromine (2.6 mL, 50 mmol) was added dropwise. The mixture was filtered and carefully added to NaOEt (21%, 42 mL, 110 mmol) in an ice bath. The mixture was stirred at room temperature overnight, and then 100 mL of 5% HCl and 30 mL of ether were added. The aqueous phase was extracted with ether (2×30 mL), the combined organic phases were washed with water, dried and concentrated. Semicarbazide hydrochloride (3.75 g, 34 mmol), NaOAc (37.5 g, 46 mmol), ethanol (40 mL) and water (40 mL) were added, and the mixture was heated to reflux for 3 hours, and then stirred at room temperature overnight. The mixture was treated with 100 mL of water and 30 mL of ether. The aqueous phase was extracted with ether (2x30 mL). The combined organic phase was washed with water, dried over anhydrous sodium sulfate and concentrated. The residue was purified by distillation under reduced pressure (at 0.8mm Hg 73-76°C) to give ethyl (2R)-2-methyl-5-(prop-2-ylidene)cyclopentacarboxylate (6.5g, 66% ).
64% Stage #1: pulegone With bromine; sodium hydrogencarbonate In diethyl ether Cooling with ice; Inert atmosphere; Stage #2: sodium ethanolate In diethyl ether at 20℃; Cooling with ice; Stage #3: With semicarbazide hydrochloride; sodium acetate In ethanol; water at 20℃; Reflux; 3.1 (R)-(+)-Pulegone (76.12 g, 0.5 mmol), anhydrous NaHCO3 (12.5 g) and anhydrous ether (500 mL) were added to a 1 L round-bottom flask. The reaction mixture02121.014WO1 / 105-13-PRV / P4157R1 49 was cooled with an ice-bath under nitrogen. Bromine (25.62 niL, 0.5 mmol) was added dropwise over 30 minutes. The mixture was filtered and carefully added to NaOEt (21%, 412 mL, 1.11 mmol) in an ice-cooled bath. The mixture was stirred at room temperature overnight, and then 5% HCl (1 L) and ether (300 mL) were added. The aqueous phase was extracted with ether (2 X 300 mL). The combined organic phase was washed with water, dried and concentrated. The residue was added to a warmed solution of semicarbazide hydrochloride (37.5 g) and NaOAc (37.5 g) in water (300 mL). Then boiling ethanol (300 mL) was added to give a clear solution. The mixture was refluxed for 2.5 hours and then stirred at room temperature overnight. The mixture was treated with water (1 L) and ether (300 mL). The aqueous phase was extracted with ether (2 X 300 mL). The combined organic phase was washed with water, dried and concentrated. The residue was purified by vacuum distillation (73-76°C at 0.8 mm Hg) to give (2R)-ethyl 2-methyl-5-(propan-2- ylidene)cyclopentanecarboxylate (63 g, 64%). 1H NMR (CDCl3, 400 MHz) δ 4.13 (m, 2H), 3.38 (d, J = 16 Hz, 0.5H), 2.93 (m, 0.5H), 2.50-2.17 (m, 2H), 1.98 (m, IH), 1.76 (m, IH), 1.23 (m, 6H), 1.05 (m, 6H).
64% Stage #1: pulegone With bromine; sodium hydrogencarbonate In diethyl ether at 0℃; for 1.5h; Stage #2: sodium ethanolate In diethyl ether; ethanol at 0 - 40℃; Stage #3: With semicarbazide hydrochloride; sodium acetate In water
  • 60
  • [ 626-03-9 ]
  • [ 89-82-7 ]
  • 6,6,9-trimethyl-7,8,9,10-tetrahydro-6H-isochromeno[3,4-b]pyridin-1-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
With piperidine; pyridine; In ethanol; at 130℃; for 1h;Microwave irradiation; Example 8; 6,6,9-Trimethyl-7,8,9,10-tetrahydro-6H-isochromeno[3,4-b]pyridin-1-ol (8)-Pyridine-2,4-diol (4, 100 mg, 0.9 mmol) was added to 3 mL of absolute ethanol in a 10 mL microwave reaction vessel. To this was also added 66 muL of pyridine and 3 muL of piperidine followed by 0.46 g (3 mmol) of (R)-(+)-pulegone. The reaction vessel was then sealed and irradiated at 300 watts to 130 C. for 1 hour. The solvent was then removed by rotary evaporation and the product purified by flash chromatography using a methanol/methylene chloride gradient to yield a light yellow solid. MS: (ESI, Neg) m/z 244.9 (M-1).
  • 61
  • [ 37595-74-7 ]
  • [ 89-82-7 ]
  • [ 1310340-07-8 ]
YieldReaction ConditionsOperation in experiment
99% With lithium hexamethyldisilazane In tetrahydrofuran at -78 - 20℃; Inert atmosphere;
89% Stage #1: pulegone With n-butyllithium; diisopropylamine In tetrahydrofuran at -78℃; for 2h; Inert atmosphere; Stage #2: N,N-phenylbistrifluoromethane-sulfonimide In tetrahydrofuran Inert atmosphere; 4.2. General procedure for the triflation of carbonyl compounds (GP-A) General procedure: A solution of i-Pr2NH (1.1 equiv) in dry THF (1 M) was cooled at -78 °C and n-BuLi (1.1 equiv) was added dropwise under an argon atmosphere. The reaction mixture was stirred for 10 min at the same temperature, then for 30 min at 0 °C, and recooled to -78 °C. A solution of a carbonyl compound (1 equiv) in THF (1 M) was added and the reaction mixture was stirred for 2 h at the same temperature. PhNTf2 (1.5 equiv) was added to the reaction mixture, which was then allowed to warm to room temperature in a water bath overnight. The solution was evaporated in vacuo, then the residue was purified by flash column chromatography on silica gel to give the vinyl triflate.
Stage #1: pulegone With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.583333h; Inert atmosphere; Stage #2: N,N-phenylbistrifluoromethane-sulfonimide In tetrahydrofuran at -78 - 24℃; for 2.66667h; Inert atmosphere;
  • 62
  • [ 89-82-7 ]
  • [ 100-58-3 ]
  • [ 205057-17-6 ]
YieldReaction ConditionsOperation in experiment
93% Stage #1: phenylmagnesium bromide With copper(I) bromide In diethyl ether at -20℃; for 0.5h; Inert atmosphere; Stage #2: pulegone In diethyl ether at -20℃; for 16.25h; Inert atmosphere; Stage #3: With hydrogenchloride In diethyl ether; water at 0℃; 4.7.1. (1R,2S,5R)-2-(2'-Phenylpropan-2'-yl)-5-methylcyclohexanol 6 Step 1: PhMgBr (3.0 M in Et2O, 26.4 mL, 78.8 mmol) was added dropwise to a stirred solution of copper(I) bromide (1.12 g, 7.82 mmol) in Et2O (20 mL) at -20 °C. After 30 min, a solution of (R)-(+)-pulegone (10.0 g, 65.7 mmol) in Et2O (13 mL) was added over a period of 15 min and the resultant mixture was stirred at -20 °C for 16 h. The reaction mixture was then added to 2.0 M aq HCl (80 mL) at 0 °C and the aqueous layer was saturated with NH4Cl and extracted with Et2O (3×80 mL). The combined organic extracts were washed with satd aq NaHCO3 (80 mL) and brine (80 mL), then dried and concentrated in vacuo to give a yellow oil (14.0 g, 93%).
Stage #1: phenylmagnesium bromide With copper(l) iodide In tetrahydrofuran at -20℃; for 1.5h; Inert atmosphere; Schlenk technique; Stage #2: pulegone In tetrahydrofuran at 20℃; for 18h; Inert atmosphere; Schlenk technique; Stage #3: With hydrogenchloride In tetrahydrofuran; water Inert atmosphere; Schlenk technique;
6.321 g Stage #1: phenylmagnesium bromide With copper(I) bromide In diethyl ether at -20℃; for 0.5h; Inert atmosphere; Stage #2: pulegone In diethyl ether at -20℃; Inert atmosphere; Stage #3: With potassium hydroxide In ethanol; water for 3h; Reflux; 4.8 Preparation of bis(8-phenyl-(ℓ)-menthyl) 2,3-naphthalenedicarboxylate (1g) [69,70] To a stirred mixture of Mg (1.751g, 72.0mmol) and Et2O (15mL) was added Et2O (15mL) solution of bromobenzene (6mL, 57.0mmol) at 0°C under a N2 atmosphere, and the solution was stirred at reflux overnight. To a stirred Et2O (5mL) solution of CuBr (0.817g, 5.7mmol) was slowly added the PhMgBr solution prepared above at -20°C under a N2 atmosphere, and the solution was stirred 30min at -20°C. To the solution was added Et2O (5mL) solution of (R)-(+)-pulegone ((R)-(+)-1-methyl-4-isopropylidene-3-cyclohexanone, 4mL, 24.6mmol) at -20°C, and the solution was stirred at -20°C overnight. To the solution was added HCl aq. (2.0M, 20mL) at -20°C. Et2O and NaHCO3 aq. were added. The organic layer was separated, dried over Na2SO4, filtered, and concentrated in vacuo. To the residue were added H2O (8mL), EtOH (60mL), and KOH (7.398g, 131.8mmol), and the solution was stirred at reflux for 3h. Et2O and brine were added. Organic layer was separated, dried over Na2SO4, filtered, and concentrated in vacuo to give a residue (6.321g, 27.4mmol, a diastereomeric mixture of 5-methyl-2-(1-methyl-1-phenylethyl)cyclohexanone). (0025) A mixture of Na (2.0g, 87.0mmol) and toluene (30mL) was vigorously stirred at reflux under a N2 atmosphere until a fine suspension of Na is obtained. To the mixture was simultaneously added the above residue (6.321g, 27.4mmol) and i-PrOH (5mL). The mixture was stirred at reflux overnight. After the mixture was cooled to 0°C, H2O was slowly added until remained Na is decomposed. Et2O and brine were added. The organic layer was separated, dried over Na2SO4, filtered, and concentrated in vacuo to give a residue (4.929g, 21.2mmol, a mixture of 8-phenyl-(ℓ)-menthol and its diastereomer). (0026) To a mixture of the residue (4.929g, 21.2mmol), N,N-dimethylaniline (4mL, 31.7mmol), Et2O (10mL) was added dropwise a Et2O (10mL) solution of chloroacetyl chloride (7mL, 88.0mmol) over 1h at 0°C under a N2 atmosphere, and the mixture was stirred at reflux for 3h. CH2Cl2 and H2O were added. The organic layer was separated, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by distillation under reduced pressure followed by crystallization from EtOH to give (1R,2S,5R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexyl chloroacetate (2.097g, 6.8mmol). (0027) A mixture of (1R,2S,5R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexyl chloroacetate (2.097g, 6.8mmol), EtOH (50mL), H2O (8mL), and KOH (1.05g, 18.7mmol) was stirred at reflux for 2h. The mixture was extracted with Et2O. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was subjected to silica gel column chromatography (benzene: AcOEt=4: 1, Rf=0.90) to give 8-phenyl-(ℓ)-menthol (1.576g, 6.8mmol, 27% yield). (0028) A mixture of 2,3-naphthalenedicarboxylic acid (0.758g, 3.5mmol), SOCl2 (2.5mL, 34.5mmol), and DMF (few drops) was stirred at reflux overnight under a N2 atmosphere. Excess SOCl2 was removed by distillation. The residue (2,3-naphthalenedicarbonyl dichloride) was dried under reduced pressure. To a stirred THF (30mL) solution of 8-phenyl-(ℓ)-menthol (1.576g, 6.8mmol) and pyridine (4mL) was slowly added a THF (20mL) solution of the residue (2,3-naphthalenedicarbonyl dichloride) under a N2 atmosphere. The resulting solution was stirred at reflux overnight. The mixture was extracted with Et2O. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was subjected to silica gel column chromatography (CHCl3, Rf=0.93) followed by HPLC (GPC) to give bis(8-phenyl-(ℓ)-menthyl) 2,3-naphthalenedicarboxylate ( 1f, 1.188g, 1.9mmol, 53% yield). Colorless solid; mp 79-82°C; 1H NMR (500MHz, CDCl3) δ 0.89 (qd, J=12.4, 2.8Hz, 4H), 0.94 (d, J=6.4Hz, 6H), 1.08-1.22 (m, 4H), 1.31 (s, 6H), 1.38 (s, 6H), 1.52-1.59 (m, 2H), 1.63-1.66 (m, 2H), 2.09-2.14 (m, 2H), 2.24-2.26 (m, 2H), 5.14 (td, J=10.8, 4.3Hz, 2H), 6.86 (t, J=7.3Hz, 2H), 7.09 (t, J=7.8Hz, 4H), 7.27 (d, J=5.5Hz, 2H), 7.28 (d, J=7.3Hz, 2H), 7.59 (dd, J=6.0, 3.2Hz, 2H), 7.69 (s, 2H), 7.82 (dd, J=6.2, 3.4Hz, 2H) ppm; 13C NMR (125MHz, CDCl3) δ 22.1, 26.4, 27.2, 27.3, 31.5, 34.9, 40.2, 41.5, 50.9, 76.0, 125.0, 125.6, 128.0, 128.1, 128.8, 129.4, 129.7, 133.2, 151.5, 166.6ppm; MS (FAB) m/z (relative intensity, %) 199 (35), 217 (93), 431 (11), 645 (M++1, 13).
  • 63
  • [ 89-82-7 ]
  • [ 623935-92-2 ]
YieldReaction ConditionsOperation in experiment
75% Stage #1: pulegone With bromine; sodium hydrogencarbonate In diethyl ether at 0℃; for 4h; Stage #2: With sodium ethanolate In diethyl ether; ethanol at 0℃; Reflux;
Multi-step reaction with 2 steps 1.1: sodium hydrogencarbonate; bromine / diethyl ether / 0.5 h / Inert atmosphere; Cooling with ice 2.1: diethyl ether / 20 °C / Cooling with ice 2.3: 2.5 h / Reflux
Multi-step reaction with 2 steps 1.1: bromine; sodium hydrogencarbonate / diethyl ether / 0.5 h / 0 °C 2.1: water / 0 - 20 °C 2.2: 2.5 h / Heating / reflux
  • 64
  • Dihydroxy-styryl-boran [ No CAS ]
  • [ 89-82-7 ]
  • [ 1393832-16-0 ]
  • [ 1393832-15-9 ]
YieldReaction ConditionsOperation in experiment
With trifluoroacetic anhydride In dichloromethane at 60℃; for 18h; diastereoselective reaction; 9 General procedure: To a stirred solution of boronic acid 1 (1.25 equiv) and 2 (1.0 equiv) in anhydrous CH2Cl2 (1.6 mL/mmol 1) was added trifluoroacetic anhydride (0.3 equiv). After stirring overnight (18 h), a saturated solution of Na2CO3 was added. The layers were separated and the aqueous one was extracted with Et2O. The combined organic layers were dried over MgSO4 and concentrated in vacuo. The residue was purified by column chromatography over silica gel (hexane/CH2Cl2 25:75).
  • 66
  • [ 89-82-7 ]
  • [ 762-72-1 ]
  • C16H30OSi [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: pulegone With titanium tetrachloride In dichloromethane at -78℃; for 0.166667h; Inert atmosphere; Stage #2: allyl-trimethyl-silane In dichloromethane at -78 - 0℃; for 0.333333h; Inert atmosphere; (2S, 5R)-5-methyl-2-(2-methylpent-4-en-2-yl)cyclohexanone (8) To a solution of (+)-pulegone (5.0 g, 32.8 mmol) in CH2Cl2 was added TiCl4 (3.60 mL, 6.2 g, 32.8 mmol) at -78 °C under argon atmosphere, and the mixture was stirredfor 10 min at same temperature. Then to this solution was added dropwise the solution of allyltrimethylsilane (6.78 mL, 4.88 mg, 42.7 mmol) in CH2Cl2 (16 mL). After the reaction mixture was stirred for 10 min at -78 °C and at 0 °C for an additional 10 min, triethylamine (25 mL) and methanol (10 mL) was added, and the resulting mixture was diluted with ether and filtered. The filtrate was washed with 10% HCl, saturated NaHCO3 aqueous solution and brine, dried over MgSO4, filtered, and concentrated in vacuo to give the crude products. The crude product was used in the next reaction without further purification.
  • 67
  • [ 504-15-4 ]
  • [ 89-82-7 ]
  • [ 1620996-70-4 ]
  • [ 19825-62-8 ]
YieldReaction ConditionsOperation in experiment
1: 13% 2: 43% With Vitamin C; ytterbium(III) triflate In 1,2-dichloro-ethane at 90 - 150℃; for 2h; Microwave irradiation; regioselective reaction; 4.2 General procedure for THXs and Δ3-THCs synthesis General procedure: In a microwave hermetically sealable vial an equimolar quantity of R-(+)-pulegone or S-(-)-pulegone and resorcinol derivatives 1a-e are placed. 1,2-dichloroethane (1-4mL) was used as solvent. The catalyst is added (either α-zyrconium sulphenylphosphonate [(α-Zr(O3PCH3)1.2(O3PC6H4SO3H)0.8], sulfuric acid supported on silica gel [H2SO4-SiO2], ytterbium triflate [Yb(OTf)3], ytterbium triflate-ascorbic acid [YTACA 1:10]. The vial was sealed with its cap and a microwave irradiation (20-240min, cooling OFF/ON, 90°C-150°C, 150-350W mean irradiation depending on reaction temperatures) was applied. At the end of the programmed reaction time, the resulting mixture was filtered on a Buchner funnel in order to recover the catalyst and evaporated under vacuum. Efficient and complete separation of the major reaction product is achieved by column chromatography on silica gel, eluting with Hexane/Et2O (98:2).
  • 68
  • [ 89-82-7 ]
  • [ 108-46-3 ]
  • [ 1620996-71-5 ]
  • [ 1620996-77-1 ]
YieldReaction ConditionsOperation in experiment
1: 34% 2: 12% With Vitamin C; ytterbium(III) triflate In 1,2-dichloro-ethane at 90 - 150℃; for 2h; Microwave irradiation; regioselective reaction; 4.2 General procedure for THXs and Δ3-THCs synthesis General procedure: In a microwave hermetically sealable vial an equimolar quantity of R-(+)-pulegone or S-(-)-pulegone and resorcinol derivatives 1a-e are placed. 1,2-dichloroethane (1-4mL) was used as solvent. The catalyst is added (either α-zyrconium sulphenylphosphonate [(α-Zr(O3PCH3)1.2(O3PC6H4SO3H)0.8], sulfuric acid supported on silica gel [H2SO4-SiO2], ytterbium triflate [Yb(OTf)3], ytterbium triflate-ascorbic acid [YTACA 1:10]. The vial was sealed with its cap and a microwave irradiation (20-240min, cooling OFF/ON, 90°C-150°C, 150-350W mean irradiation depending on reaction temperatures) was applied. At the end of the programmed reaction time, the resulting mixture was filtered on a Buchner funnel in order to recover the catalyst and evaporated under vacuum. Efficient and complete separation of the major reaction product is achieved by column chromatography on silica gel, eluting with Hexane/Et2O (98:2).
  • 69
  • [ 2896-60-8 ]
  • [ 89-82-7 ]
  • [ 1620996-72-6 ]
  • [ 1620996-78-2 ]
YieldReaction ConditionsOperation in experiment
1: 50% 2: 11% With Vitamin C; ytterbium(III) triflate In 1,2-dichloro-ethane at 90 - 150℃; for 2h; Microwave irradiation; regioselective reaction; 4.2 General procedure for THXs and Δ3-THCs synthesis General procedure: In a microwave hermetically sealable vial an equimolar quantity of R-(+)-pulegone or S-(-)-pulegone and resorcinol derivatives 1a-e are placed. 1,2-dichloroethane (1-4mL) was used as solvent. The catalyst is added (either α-zyrconium sulphenylphosphonate [(α-Zr(O3PCH3)1.2(O3PC6H4SO3H)0.8], sulfuric acid supported on silica gel [H2SO4-SiO2], ytterbium triflate [Yb(OTf)3], ytterbium triflate-ascorbic acid [YTACA 1:10]. The vial was sealed with its cap and a microwave irradiation (20-240min, cooling OFF/ON, 90°C-150°C, 150-350W mean irradiation depending on reaction temperatures) was applied. At the end of the programmed reaction time, the resulting mixture was filtered on a Buchner funnel in order to recover the catalyst and evaporated under vacuum. Efficient and complete separation of the major reaction product is achieved by column chromatography on silica gel, eluting with Hexane/Et2O (98:2).
  • 70
  • [ 89-82-7 ]
  • [ 500-66-3 ]
  • [ 1620996-73-7 ]
  • [ 95720-01-7 ]
YieldReaction ConditionsOperation in experiment
1: 22% 2: 49% With Vitamin C; ytterbium(III) triflate In 1,2-dichloro-ethane at 90 - 150℃; for 2h; Microwave irradiation; regioselective reaction; 4.2 General procedure for THXs and Δ3-THCs synthesis General procedure: In a microwave hermetically sealable vial an equimolar quantity of R-(+)-pulegone or S-(-)-pulegone and resorcinol derivatives 1a-e are placed. 1,2-dichloroethane (1-4mL) was used as solvent. The catalyst is added (either α-zyrconium sulphenylphosphonate [(α-Zr(O3PCH3)1.2(O3PC6H4SO3H)0.8], sulfuric acid supported on silica gel [H2SO4-SiO2], ytterbium triflate [Yb(OTf)3], ytterbium triflate-ascorbic acid [YTACA 1:10]. The vial was sealed with its cap and a microwave irradiation (20-240min, cooling OFF/ON, 90°C-150°C, 150-350W mean irradiation depending on reaction temperatures) was applied. At the end of the programmed reaction time, the resulting mixture was filtered on a Buchner funnel in order to recover the catalyst and evaporated under vacuum. Efficient and complete separation of the major reaction product is achieved by column chromatography on silica gel, eluting with Hexane/Et2O (98:2).
  • 71
  • [ 608-25-3 ]
  • [ 89-82-7 ]
  • [ 1620996-75-9 ]
  • [ 1620996-79-3 ]
YieldReaction ConditionsOperation in experiment
1: 38% 2: 8% With Vitamin C; ytterbium(III) triflate In 1,2-dichloro-ethane at 90 - 150℃; for 2h; Microwave irradiation; regioselective reaction; 4.2 General procedure for THXs and Δ3-THCs synthesis General procedure: In a microwave hermetically sealable vial an equimolar quantity of R-(+)-pulegone or S-(-)-pulegone and resorcinol derivatives 1a-e are placed. 1,2-dichloroethane (1-4mL) was used as solvent. The catalyst is added (either α-zyrconium sulphenylphosphonate [(α-Zr(O3PCH3)1.2(O3PC6H4SO3H)0.8], sulfuric acid supported on silica gel [H2SO4-SiO2], ytterbium triflate [Yb(OTf)3], ytterbium triflate-ascorbic acid [YTACA 1:10]. The vial was sealed with its cap and a microwave irradiation (20-240min, cooling OFF/ON, 90°C-150°C, 150-350W mean irradiation depending on reaction temperatures) was applied. At the end of the programmed reaction time, the resulting mixture was filtered on a Buchner funnel in order to recover the catalyst and evaporated under vacuum. Efficient and complete separation of the major reaction product is achieved by column chromatography on silica gel, eluting with Hexane/Et2O (98:2).
  • 72
  • [ 108-86-1 ]
  • [ 89-82-7 ]
  • [ 97371-54-5 ]
  • [ 104870-79-3 ]
YieldReaction ConditionsOperation in experiment
Stage #1: bromobenzene With magnesium In diethyl ether for 0.5h; Inert atmosphere; Reflux; Stage #2: With copper(l) iodide In diethyl ether at 0℃; for 0.5h; Inert atmosphere; Stage #3: pulegone In diethyl ether at 0 - 20℃; Inert atmosphere; Overall yield = 70 %; Overall yield = 154.87 g; Optical yield = 60 %de; (1R)-8-Phenylmenthone (6a) Under argon atmosphere magnesium turnings (4.20 g, 0.173 mol) in dry Et2O (10 mL) were placed ina dried flask equipped with a dropping funnel and a condenser. The Grignard reagent was prepared bydropwise addition of bromobenzene (27.16 g, 0.173 mol) in anhyd Et2O (60 mL). Subsequently, themixture was refluxed for 30 min. Remaining Mg was removed by filtration under inert atmosphere andthe filtrate was cooled to 0 °C before CuI (2.32 g, 0.012 mol) was added and the mixture was stirredfor 30 min. At 0 °C (+)-pulegone (purity 92%, 15.00 g, 0.099 mol) in anhyd Et2O (15 mL) was addeddropwise. The reaction mixture was stirred overnight and allowed to warm up to r.t. Then H2O(20 mL) was added (caution) while cooling, followed by addition of saturated aqueous ammoniumchloride solution (80 mL) and 1 M HCl (20 mL). After extraction with MTBE (3 × 100 mL) thecombined organic fractions were washed twice with saturated aqueous Na2S2O3 and NaHCO3solutions (each 200 mL), dried over MgSO4 and concentrated under reduced pressure. Purification bydistillation in vacuum (10-3 mbar) yielded 6a (15.87 g, 0.069 mol, 70%) as a slightly yellow oil [1].Diastereomeric ratio 4:1 (NMR data cover both diastereomers)1H NMR (400 MHz, CDCl3) δ = 0.91 (d, 3J =7.1 Hz, 3H), 0.98 (d, 3J = 6.6 Hz, 3H), 1.08-1.31 (m,2H), 1.41, 1.43, 1.47 (s, 12H), 1.56-1.64 (m, 1H), 1.68-1.91 (m, 6H), 1.98-2.06 (m, 2H), 2.23-2.28 (m,2H), 2.45-2.50 (m, 1H), 2.64-2.70 (m, 2H), 7.15-7.20 (m, 2H), 7.27-7.36 (m, 8H);13C NMR (100 MHz, CDCl3) δ = 19.3, 22.3, 23.8, 24.0, 24.9, 26.5, 27.2, 29.0, 31.3, 32.2, 34.7, 36.3,39.0, 39.5, 50.3, 52.4, 59.6, 59.7, 125.5, 125.6, 125.8, 125.9, 128.0, 149.4, 149.9, 211.2, 212.0;Analytical data were consistent with literature [1].
~ 74 % de Stage #1: bromobenzene With magnesium In diethyl ether for 1h; Inert atmosphere; Reflux; Stage #2: With copper(I) bromide In diethyl ether at -20℃; for 0.5h; Inert atmosphere; Stage #3: pulegone Overall yield = 91 %; Overall yield = 54.5 g; Further stages;
  • 73
  • [ 20469-65-2 ]
  • [ 89-82-7 ]
  • (1R,4R)-8-(3,5-dimethoxyphenyl)menthone [ No CAS ]
  • [ 322640-12-0 ]
YieldReaction ConditionsOperation in experiment
71.429 % de Stage #1: 1-bromo-3,5-dimethoxybenzene With magnesium In tetrahydrofuran for 0.5h; Inert atmosphere; Reflux; Stage #2: With copper(l) iodide In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #3: pulegone In tetrahydrofuran at 0 - 20℃; Inert atmosphere; Overall yield = 69 %; Overall yield = 5.11 g; (1R)-8-(3,5-Dimethoxyphenyl)menthone (6b) Under argon atmosphere magnesium turnings (1.12 g, 0.046 mol) in dry THF (10 mL) were placed ina dried flask equipped with a dropping funnel and a condenser. The Grignard reagent was prepared bydropwise addition of 1-bromo-3,5-dimethoxybenzene (10.00 g, 0.046 mol) in anhyd THF (60 mL).Subsequently, the mixture was refluxed for 30 min. Remaining Mg was removed by filtration underinert atmosphere and the filtrate was cooled to 0 °C before CuI (0.64 g, 0.003 mol) was added and themixture was stirred for 30 min. At 0 °C (+)-pulegone (purity 92%, 4.07 g, 0.026 mol) in anhyd THF(6 mL) was added dropwise. The reaction mixture was stirred overnight and allowed to warm up to r.t.Then H2O (20 mL) was added (caution) while cooling, followed by addition of saturated aqueousammonium chloride solution (80 mL) and 1 M HCl (20 mL). After extraction with MTBE (3 ×100 mL) the combined organic fractions were washed twice with saturated aqueous Na2S2O3 andNaHCO3 solution (each 200 mL), dried over MgSO4 and concentrated under reduced pressure. Theresidue was purified by column chromatography (eluent cyclohexane:EtOAc = 9:1) to give the product(5.11 g, 0.018 mol, 69% yield) as a viscous yellow oil [1].Diastereomeric ratio 6:1; RF(cyclohexane:EtOAc = 9:1): 0.33; (NMR data refer to major component(1R,4S)-8-(3,5-dimethoxyphenyl)menthone.1H NMR (300 MHz, CDCl3) δ = 0.97 (d, 3J =6.2 Hz, 3H), 1.22-1.28 (m, 1H), 1.37 (s, 3H), 1.39-1.41(m, 1H), 1.43 (s, 3H), 1.72-1.84 (m, 3H), 2.02 (td, 2J = 12.5 Hz, 4J =1.3 Hz, 1H), 2.26 (ddd, 2J = 12.4Hz, 3J = 4.0 Hz, 4J = 2.1 Hz, 1H), 2.63 (ddd, 2J = 12.9 Hz, 3J =4.7 Hz, 4J = 1.2 Hz, 1H), 3.79 (s, 6H),6.30 (t, 4J = 2.2 Hz, 1H), 6.49 (d, 4J = 2.2 Hz, 2H);13C NMR (75 MHz, CDCl3) δ = 21.5, 22.6, 26.0, 28.2, 33.9, 35.4, 38.6, 51.5, 54.4, 58.6, 95.8, 103.9,151.9, 159.6, 210.4;HRMS: m/z for C18H26O3 calc: 290.1882, found: 290.1887;
  • 74
  • [ 92-66-0 ]
  • [ 89-82-7 ]
  • (1R,4R)-8-(4-biphenyl)menthone [ No CAS ]
  • [ 322640-07-3 ]
YieldReaction ConditionsOperation in experiment
Stage #1: 4-bromo-1,1'-biphenyl With magnesium In tetrahydrofuran for 0.5h; Inert atmosphere; Reflux; Stage #2: With copper(l) iodide In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #3: pulegone In tetrahydrofuran at 0 - 20℃; Inert atmosphere; Overall yield = 62 %; Overall yield = 11.33 g; Optical yield = 50 %de; (1R)-8-(4-Biphenyl)menthone (6c) Under argon atmosphere magnesium turnings (2.18 g, 0.09 mol) in dry THF (11 mL) were placed in adried flask equipped with a dropping funnel and a condenser. The Grignard reagent was prepared bydropwise addition of 1-bromo-diphenyl (17.48 g, 0.075 mol) in anhyd THF (60 mL). Subsequently,the mixture was refluxed for 30 min. Remaining Mg was removed by filtration under inert atmosphereand the filtrate was cooled to 0 °C before CuI (1.00 g, 0.005 mol) was added and the mixture wasstirred for 30 min. At 0 °C (+)-pulegone (purity 92%, 9.13 g, 0.06 mol) in anhyd THF (15 mL) wasadded dropwise. The reaction mixture was stirred overnight and allowed to warm up to r.t. Then H2O(20 mL) was added (caution) while cooling, followed by addition of saturated aqueous ammoniumchloride solution (80 mL) and 1 M HCl (20 mL). After extraction with MTBE (3 × 100 mL) thecombined organic fractions were washed twice with saturated aqueous Na2S2O3 and NaHCO3 solution(each 200 mL), dried over MgSO4 and concentrated under reduced pressure. The residue was purifiedby short path distillation in vacuum (10-3 mbar) to yield 6c (11.33 g, 0.037 mol, 62%) as a highlyviscous red oil [1].Diastereomeric ratio 3:1 (NMR data cover both diastereomeres).1H NMR (300 MHz, CDCl3) δ = 0.92, 0,99 (d, 3J =7.0 Hz, 3J =6.6 Hz, 6H), 1.21-1.39 (m, 2H), 1.44,1.46, 1.50, 1.53 (s, 12H), 1.61-1.93 (m, 8H), 1.96-2.12 (m, 2H), 2.27 (ddd, 2J = 12.4 Hz, 3J = 3.9 Hz,4J = 2.0 Hz, 2H), 2.50 (ddd, 2J = 13.0 Hz, 3J = 5.7 Hz, 4J = 1.2 Hz, 2H), 2.71 (ddd, 2J = 13.1 Hz, 3J =4.6 Hz, 4J = 1.2 Hz, 2H), 7.28-7.37 (m, 2H), 7.37-7.48 (m, 8H), 7.50-7.63 (m, 8H);13C NMR (75 MHz, CDCl3) δ = 19.4, 22.5, 24.3, 25.1, 26.6, 27.2, 29.2, 31.4, 32.4, 34.9, 36.4, 39.0,39.5, 50.5, 52.5, 59.7, 126.4, 126.8, 127.1, 128.8, 138.3, 141.0, 149.2, 211.5;HRMS: m/z for C22H27O calc: 307.2062, found: 307.2064;
  • 75
  • [ 89-82-7 ]
  • [ 18162-48-6 ]
  • (R)-tert-butyldimethyl((5-methyl-2-(prop-1-en-2-yl)cyclohex-1-en-1-yl)oxy)silane [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% Stage #1: pulegone With lithium hexamethyldisilazane In tetrahydrofuran; N,N,N,N,N,N-hexamethylphosphoric triamide at -78 - 0℃; for 2.05h; Inert atmosphere; Stage #2: tert-butyldimethylsilyl chloride In tetrahydrofuran; N,N,N,N,N,N-hexamethylphosphoric triamide at -78℃; for 0.583333h; Inert atmosphere;
  • 76
  • [ 89-82-7 ]
  • [ 141-52-6 ]
  • [ 85440-74-0 ]
YieldReaction ConditionsOperation in experiment
90% Stage #1: pulegone With bromine; sodium hydrogencarbonate In diethyl ether at -10℃; for 3.25h; Inert atmosphere; Stage #2: sodium ethanolate In diethyl ether; ethanol at 55℃; for 4h; Inert atmosphere; Further stages;
  • 77
  • [ 89-82-7 ]
  • [ 75-05-8 ]
  • [ 1356999-94-4 ]
YieldReaction ConditionsOperation in experiment
56% With sulfuric acid; water at 0 - 20℃; for 18h; N-[2-(4-Methyl-2-oxocyclohexyl)propan-2-yl]acetamide (2) Pulegone (1, 2 g, 0.013 mol) was dissolved in MeCN(10 mL) at 0°C, treated dropwise with conc. H2SO4 (2 mL), stirred at room temperature for 18 h, and neutralized with coolingby aqueous NH4OH. The product was extracted with Et2O. The extract was dried over MgSO4 and evaporated. The resultingcrystals were dried in air. Yield 1.55 g (56%), mp 97-99°C. C12H21NO2. IR spectrum (KBr, , cm-1): 3293 (NH), 3088,2949, 2926, 2868, 1710 (=), 1643 (=, amide 1), 1560 (NH, amide 2), 1455, 1440, 1368, 1300, 1205, 1121, 1053, 610.1 NMR spectrum (500 MHz, DCl3, , ppm): 7.33 (1H, s, NH), 2.06 (2, m), 1.94 (3, m), 1.75 (3H, s, NHCOCH3), 1.71(2, m), 1.33 (3H, s, CH3-9), 1.17 (3H, s, CH3-10), 0.94 (3H, d, J = 7, CH3-4), 0.83 (1, m). 13C NMR spectrum(125.76 MHz, DCl3, , ppm): 210.2 (s, C-2), 168.3 (s, NHCO), 53.4 (d, -1), 53.3 (s, C-8), 51.1 (t, -3), 35.2 (d, C-4), 33.5(t, C-5), 27.4 (t, C-6), 23.3 (q, CH3), 24.5 (q, CH3), 23.2 (q, CH3), 21.8 (q, CH3).
  • 78
  • [ 89-82-7 ]
  • [ 124-41-4 ]
  • [ 92076-03-4 ]
YieldReaction ConditionsOperation in experiment
80% Stage #1: pulegone With bromine; sodium hydrogencarbonate In diethyl ether at 0℃; for 0.5h; Stage #2: sodium methylate at 0℃; for 1h; Synthesis of Table 1 Molecule Number 83 Synthesis of Table 1 Molecule Number 83 _:To a mixture of Pulegone (1 eq.) and sodium bicarbonate (0.3 eq.) in Et20 (1 M) was added bromine (1.5 eq.) over 30 minutes at 0 °C. The resulting mixture has been filtered and NaOMe has been added to this solution at 0 °C. Full conversion has been observed after 1 hour stirring. The resulting reaction mixture has been quenched by the addition of 5% HC1 solution until pH 7. After stirring for 2 more hours, the mixture has been extracted by Et20 and washed with water. The organic layer was dried over MgS04and concentrated under reduced pressure. The resulting oil was purified using a quick filtration over silica gel by eluting with a petroleum ether - Et20 mixture (8-2). Concentration of the eluent under reduced pressure resulted in the compound as an orange oil (80% yield).
  • 79
  • N-methoxy-N-methylcyanoformamide [ No CAS ]
  • [ 89-82-7 ]
  • C13H21NO3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
93% Stage #1: pulegone With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 1h; Stage #2: N-methoxy-N-methylcyanoformamide In tetrahydrofuran at -78℃; for 0.25h;
  • 80
  • [ 89-82-7 ]
  • [ 74-88-4 ]
  • [ 234078-11-6 ]
YieldReaction ConditionsOperation in experiment
88% Stage #1: pulegone; methyl iodide With lithium diisopropyl amide In tetrahydrofuran at -78 - 0℃; for 2h; Inert atmosphere; Stage #2: With hydrogenchloride In water for 72h; Inert atmosphere; Reflux;
  • 81
  • [ 107-97-1 ]
  • [ 89-82-7 ]
  • N-Methyl-7-azaisatin [ No CAS ]
  • 1-methyl-4-(4-dimethyl)pyrrole(spiro[2.3 "]-1"-methyl-1"H-pyrrolo[2,3-B]pyridine-2"-one)-spiro[3.2']-5'-methyl hexanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% With phosphotungstic acid In ethanol at 80℃; for 8h; 4 Example 4 The reaction conditions were as follows: molar molar ratio of pterophorone, 7-azatidine derivative and sarcosine were 1: 1: 1,The reaction temperature was 80 and the reaction time was 4 hours, 6 hours, 8 hours and 10 hours respectively. The results showed that the reaction time was 8 hours and the yield was the highest.
  • 82
  • [ 107-97-1 ]
  • [ 89-82-7 ]
  • [ 281192-95-8 ]
  • 1-methyl-4-(4-dimethyl)pyrrole(spiro[2.3 "]-1"-ethyl-1"H-pyrrolo[2,3-B]pyridine-2"-one)-spiro[3.2']-5'-methyl hexanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
70.9% With phosphotungstic acid In ethanol at 80℃; for 6h; 8 Example 8 (0.49 g), sarcosine (0.27 g) was added to a 100 mL flask, and about 50 mL of ethanol was added to the solution, and vialfen was added dropwise (0.3 g).The reaction was carried out under conditions catalyzed by phosphotungstic acid (0.5 g), heated to 80 ° C with a heat jacket,Placed on a magnetic stirrer and stirred for 6 hours. The reaction solution was concentrated by rotary steam and then filtered,The obtained filter cake was recrystallized by adding 50 ml of a mixed solution of ethyl acetate and petroleum ether 1: 1,A yellow crystalline powder (0.50 g) was added in a total yield of 70.9%.
  • 83
  • [ 107-97-1 ]
  • 1-acetyl-7-azatidine [ No CAS ]
  • [ 89-82-7 ]
  • 1-methyl-4-(4-dimethyl)pyrrole(spiro[2.3 "]-1"-acetyl-1"H-pyrrolo[2,3-B]pyridine-2"-one)-spiro[3.2']-5'-methyl hexanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With phosphotungstic acid In ethanol at 80℃; for 6h; 9 Example 9 Accurately weighed 1-acetyl-7-azatidine (0.53 g)Sarcosine (0.27 g) was added to a 100 mL flask,Add about 50 mL of ethanol solvent, add paproxone (0.3 g).The reaction was carried out under conditions catalyzed by phosphotungstic acid (0.5 g), heated to 80 ° C with a heat jacket,Placed on a magnetic stirrer and stirred for 6 hours. The reaction solution was concentrated by rotary steam and then filtered,The obtained filter cake was recrystallized by adding 50 ml of a mixed solution of ethyl acetate and petroleum ether 1: 1,A white crystalline powder (0.55 g) was obtained in a total yield of 75.0%.
  • 84
  • [ 107-97-1 ]
  • 1-phenyl-7-azatidine [ No CAS ]
  • [ 89-82-7 ]
  • 1-methyl-4-(4-dimethyl)pyrrole(spiro[2.3 "]-1"-phenyl-1"H-pyrrolo[2,3-B]pyridine-2"-one)-spiro[3.2']-5'-methyl hexanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
70.8% With phosphotungstic acid In ethanol at 80℃; for 6h; 10 Example 10 (0.63 g), sarcosine (0.27 g) was added to a 100 mL flask, and about 50 mL of ethanol was added to the solution, and tulipenone (0.3 g) was added dropwise.The reaction was carried out under conditions catalyzed by phosphotungstic acid (0.5 g), heated to 80 ° C with a heat jacket,Placed on a magnetic stirrer and stirred for 6 hours. The reaction solution was concentrated by rotary steam and then filtered,The obtained filter cake was recrystallized by adding 50 ml of a mixed solution of ethyl acetate and petroleum ether 1: 1,The orange-red crystalline powder (0.57 g) was added in a total yield of 70.8%.
  • 85
  • [ 107-97-1 ]
  • [ 89-82-7 ]
  • [ 281192-96-9 ]
  • 1-methyl-4-(4-dimethyl)pyrrole(spiro[2.3 "]-1"-(methylphenyl)-1"H-pyrrolo[2,3-B]pyridine-2"-one)-spiro[3.2']-5'-methyl hexanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
69.2% With phosphotungstic acid In ethanol at 80℃; for 6h; 11 Example 11 Accurately weighed 1-benzyl-7-azatidine (0.67 g),Sarcosine (0.27 g) was added to a 100 mL flask and about 50 mL of ethanol was added,Dropping puberphon (0.3 g). The reaction was carried out under conditions catalyzed by phosphotungstic acid (0.5 g)Heated to 80 ° C with a heat jacket, placed on a magnetic stirrer, stirred for 6 hours,The reaction solution was concentrated by rotary steam and then filtered,The obtained filter cake was recrystallized by adding 50 ml of a mixed solution of ethyl acetate and petroleum ether 1: 1,Dark red crystalline powder (0.58 g), the total yield of 69.2%.
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