Table 1. Summary of green and sustainable methods for the synthesis of isoquinoline and isoquinoline scaffoldsa.
| Sch. no. | Substrate | Product | Catalyst | Conditions | Time | Yield (upto) | Key point | Green chemistry aspects/limitations | Ref. |
|---|---|---|---|---|---|---|---|---|---|
| 1 |
|
|
Pd(PPh3)4 | HCOONa, DMF/H2O, 100 °C, MW | 30 min | 91% | Domino reaction, microwave assisted | Short time, oxidant free, scalable (6,9) | 46 |
| Limitation: DMF is toxic | |||||||||
| 2 |
|
|
Fe3O4@SiO2@Cu-MOF-74 | K3PO4, DMF, 150 °C, N2, MW | 1 h | 75% | Microwave assisted, recyclable catalyst | Reusable, broad scope (9,1) | 50 |
| Limitation: Uses DMF, excess base | |||||||||
| 3 |
|
|
[Ru(p-cymene)Cl2]2 | KPF6, PEG 400, 150 °C, MW | 10 min | 92% | Microwave assisted, Ru/PEG homogenous recyclable catalyst | Atom economy, green solvent, recyclable, scalable (2,5,9,1,6) | 52 |
| 4 |
|
|
Fe(acac)2 | TBHP, DBU, benzene, MW, 120 °C | 30 min | 91% | Oxidative cascade, microwave assisted | Benign iron catalysis, broad scope (9) | 53 |
| Limitation: Benzene is hazardous, TBHP is strong oxidant | |||||||||
| 5 |
|
|
Cul | CS2CO3, 2,2′-biimidazole, MW | 20 min | 76% | Microwave assisted, one-pot | Inexpensive catalyst, improved yields, short time (9,6) | 55 |
| 6 |
|
|
[(Rucl2 (p-cymene))2] | Cu(OAc)2, H2O NA2CO3, toulene, 100 °C | 10 min | 90% | Microwave assisted, domino C–C and C–N bond formation | Improved rates, mild conditions (6,5) | 56 |
| Limitations: Use of toluene is toxic | |||||||||
| 7 |
|
|
Nafion NR50 | HMDS, EtOH,MW 150 °C | 30 min | 95% | Microwave acidic catalyst, recyclable | Transition-metal free, better efficiency (3,9,5) | 60 |
| Limitation: HDMS is not green | |||||||||
| 8 |
|
|
— | KF, DCE, 165–185 °C, MW | 1–5 h | 87% | Microwave assisted, one-pot | Broad substrate scope, mild conditions, better yields (6, 1) | 61 |
| Limitation: DCE is hazardous solvent, high temperature | |||||||||
| 9 |
|
|
— | DBU, TBPB, 120 °C, MW | 1 h | 94% | Microwave assisted, metal free oxidative cyclization | High atom economy, high efficiency, broad substrate scope (3,2,6) | 62 |
| Limitation: TBPB is not green | |||||||||
| 10 |
|
|
— | MW, 700 W | 5 min | 96% | Microwave assisted | Improved yield, short time, simple (6,1) | 63 |
| 11 |
|
|
Cul | Cs2CO3, DMSO, 80 °C, N2, US | 2–4 h | 93% | Ultrasound assisted, one-pot, ligand-free | Mild, additive-free, efficient (1,6,9) | 66 |
| Limitations: DMSO is better than DMF, but still not ideal | |||||||||
| 12 |
|
|
— | CH3NH2, PPh3, H2O, US, rt | 1 h | 89% | Ultrasound assisted, multi-component reaction | Cataylst free, short time, green media (9,5,6) | 67 |
| 13 |
|
|
— | Oxone, EtOH, US | 10–70 min | 93% | Ultrasound assisted, high regio selectivity | Green oxidant, better yield, metal free (3,5,6) | 68 |
| 14 |
|
|
— | BSA, MeOH, reflux | 8 h | 96% | Oxidant-free, Se-isoquinoline derivative | Green solvent, mild conditions, scalable (5,6,1,3) | 71 |
| 15 |
|
|
Eosin Y | CHD, K2CO3, anh. DMF, ar, rt, green LED 535 nm | 12 h | 80% | Visble-light catalysis, N– N-centered radicals | Mild conditions, recyclable catalyst, metal-free (6,9,3) | 75 |
| Limitation: DMF | |||||||||
| 16 |
|
|
— | White LEDs 50 W, HOAc | 4 h | 83% | Visible light cyclization, radical pathway | Catalyst free, mild (9,6) | 76 |
| 17 |
|
|
DABCO | DMSO, N2, 40 °C, 18W, blue LED light | 24 h | 96% | Visible-light induced, cascade reaction | Metal-free, broad scope (3,9) | 77 |
| Limitation: DMSO, long time | |||||||||
| 18 |
|
|
LAILs | EtOH, MeCN/DCE, 12W purple LED, rt | 12 h | 73% | Light mediated, metal-free, ionic lquid catalyst | Recyclable catalyst, high atom economy, scalability (9,5,6) | 78 |
| Limitation: MeCN/DCE less green | |||||||||
| 19 |
|
|
Eosin B | Air, 24 W white LED, DMSO, 70 °C | 24 h | 75% | Light-mediated, radical cascade reaction | Metal free, additive free, cost effective, simple (3,6) | 79 |
| Limitation: DMSO | |||||||||
| 20 |
|
|
— | (NH4)2S2O8, Na2CO3, 4CzIPN, blue LEDs 45W, DMSO, ar, rt | 10 h | 81% | Visible-light photoredox, radical pathway | Mild, scalable, versatile (1,2,6) | 80 |
| Limitation: DMSO | |||||||||
| 21 |
|
|
Eosin B | (NH4)2S2O8, 10W blue LED, rt | 15 h | 84% | Visible-light photoredox, No metals/bases | Mild, broad substrate scope (6) | 81 |
| 22 |
|
|
Photocatalyst: DCA, HAT catalyst: 3-Acetoxyquinuclidine | MeCN, 10W blue LEDs, N2, rt | 30 h | 70% | Visible-light assisted, HAT, EDA complex | Hydrogen gas by-product, atom economy, metal-free (2,3,6) | 84 |
| Limitation: MeCN, long time | |||||||||
| 23 |
|
|
[Ir(dtbbpy)(ppy)2]PF6 | DMA, blue LED, N2, rt | 12 h | 80% | Visible-light assisted, alkyl radical source | Mild, no oxidants/bases, metal free (6,3) | 85 |
| Limitation: DMA | |||||||||
| 24 |
|
|
Cu2O@MHAM | Neat, 100 °C | 2 h | 95% | Nano-catalyst | Low E-factor, recyclable, high mass efficiency, neat (1,6,9) | 90 |
| 25 |
|
|
Fe3O4-MNPs | H2O, 80 °C | 2 h | 87% | Nano-catalyst | Green synthesis, magnetic recovery (5,9,1) | 91 |
| 26 |
|
|
KF/CP NPs | H2O, rt | 3 h | 95% | Nano-catalyst | Natural material, reusable (5,9,1,7) | 92 |
| 27 |
|
|
KF/CP NPs | rt | 3 h | 95% | Nano-catalyst | Fast, recyclable, solvent-free (6,9,5) | 93 |
| 28 |
|
|
KF/CP@MWCNTs NPs | H2O, rt | 4 h | 95% | Nano-catalyst | Easy recovery, high yield (5,9,1) | 94 |
| 29 |
|
|
CuO@NiO | 90 °C, ethylene glycol (EG) | 1 h | 92% | Nano-catalyst | Short time, recyclable, low leaching, base/additive-free (6,9) | 95 |
| Limitation: EG is only semi green | |||||||||
| 30 |
|
|
Fe3O4-MNPs | NaOH, 80 °C | 6 h | 87% | Nano-catalyst | Atom economy, low loading, reusable (2,9) | 96 |
| 31 |
|
|
— | Langlois reagent, C | Pt, N2, LiClO4, AcOH, MeCN/H2O | 10 h | 56% | Electrochemical, anodic oxidation | Mild, fluorinated, sustainable, metal-free (6,10,1) | 100 |
| Limitation: Pt, MeCN | |||||||||
| 32 |
|
|
— | Langlois reagent, (+) GF | Pt (−), 3 mA, CF3SO3H, 80 °C, MeCN/H2O | 6 h | 87% | Electrochemical, undivided cell | Broad scope, no metals, no oxidants (3,6) | 101 |
| Limitation: Pt, MeCN | |||||||||
| 33 |
|
|
— | Piperidinium acetate, MeOH | 3 h | 85% | Metal-free, one-pot | Cascade, broad scope (8,5,1) | 102 |
| 34 |
|
|
— | MeCN, air, 90 °C | 5 h | 92% | Metal-free, ring-opening/closing | Dual-state fluorescence, mild (6,3) | 103 |
| Limitation: MeCN | |||||||||
| 35 |
|
|
— | CH3NO2, K2CO3, DMSO, 110 °C | 8 h | 75% | Metal-free, domino Michael SNAr (nucleophilic aromatic substitution) | One-pot, nitromethane as a carbanion (1,8) | 106 |
| Limitation: DMSO | |||||||||
| 36 |
|
|
— | KHCO3, THF, 100 °C, Ar | 8 h | 80% | Metal-free, gem-difluoroalkene intermediates | Simple, eco-friendly (6) | 107 |
| THF is okay but not optimal | |||||||||
| 37 |
|
|
— | H2O, 100 °C | 4 h | 99% | Metal-free | Regioselective, scalable, no additives (1,3,5) | 108 |
| 38 |
|
|
— | DTBP, MeCN. Air, 70 °C | 12 h | 82% | Metal-free | Safe, simple, radical cascade (3,6,10) | 109 |
| Limitation: MeCN | |||||||||
| 39 |
|
|
— | MeCN, rt | 12 h | 95% | Metal-free, three-component, sulfoxide insertion | Mild reaction conidtion (6) | 110 |
| Limitation: MeCN | |||||||||
| 40 |
|
|
[Cp*Co(CO)I2] | NaOAc, TFE, 110 °C | 12 h | 93% | Metal-catalyzed | Atom economy, scalable (2,1,9) | 111 |
| Limitation: TFE | |||||||||
| 41 |
|
|
[Ru(p-cymene)Cl2]2 – Cu(Oac)2 | AgSbF6, PEG 400, 110 °C, air | 12 h | 90% | Metal-catalyzed | High atom economy, green solvent, recyclable (2,5,9) | 112 |
| 42 |
|
|
Pd(acac)2,bpy | TsOH-H2O, H2O, 80 °C | 24 h | 94% | Metal catalyzed, tandem reaction | Mild, broad tolerance (5) | 113 |
| Limitation: Metal, long time |
a
Numbers in parentheses indicates the reference of Green Chemistry Principles: 1 (Prevention – waste minimization), 2 (Atom economy), 3 and 4 (Less hazardous synthesis/products), 5 (Safer solvents/auxiliaries), 6 (Energy efficiency), 7 (Renewable feedstocks), 8 (Reduce unnecessary derivatization), 9 (Catalysis/recyclability), 10 (Design for degradation).