Multicomponent Reaction (MCR) Is a Synthetic Methodology in in 1891, an Italian Chemist, P

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Multicomponent reaction (MCR) is a synthetic methodology in In 1891, an Italian chemist, P. Biginelli has reported the three- which three or more reactants come together in a single reaction component MCR using b-keto esters such as ethyl acetoacetate vessel to form a new product. The characteristic aspect of MCRs [A0649], aromatic aldehydes such as benzaldehyde [B2379], is that the final products contain almost all portions of substrates, and ureas (or thioureas) in the presence of acid catalyst (Brönsted generating almost no by-products. That makes MCRs an or Lewis acids), affording dihydropyrimidinone derivaties.4) extremely ideal and eco-friendly reaction system. Target Dihydropyrimidinones have been paid much attention because of compounds can be obtained in one pot with much fewer steps. their various bioactivities such as anti-inflammatory or anti- Therefore, MCRs have been paid much attention in various bacterial activities. For an example of pharmaceuticals developed research fields, such as discovery of lead compounds in by using the reaction, several anti-tubercular agents have been medicinal chemistry, or combinatorial chemistry. reported as below.5)

There have been a number of reports on MCRs so far, and Examples of Anti-tubercular Agents using Biginelli Reaction typical examples are described as below.

NO2 1. Strecker reaction N N (Three-component reaction: 3CR) O F EtO C N NH 2 NH H Strecker Reaction (Amino Acid Synthesis) N O N O H H O NH2 + NH2 NaCN, NH3 H3O R H R CN R COOH 4. Passerini reaction (3CR) This reaction was reported by A. Strecker in 1850, and is Passerini Reaction extremely famous as the synthesis of a-amino acids. This O R2 H reaction is an MCR which comprises three components, N R1 COOH + R2 CHO + R3 NC R1 O R3 aldehydes, hydrogen cyanide, and ammonia as substrates, and O is recognized as the world’s first MCR.1) In 1921, an Italian chemist, M. Passerini et al. have reported the 2. Hantzsch dihydropyridine synthesis (3CR) three-component reaction using carboxylic acids, aldehydes, and isonitriles, affording a-acyloxy amides.6) The Passerini Hantzsch Dihydropyridine Synthesis 3 O O R O reaction also has been applied into pharmaceutical research, for O 2 2 R2O R O OR example, Hulme et al. have reported the library synthesis of novel 2 + 3 + NH3 R H 7) 1 R1 N R1 norstatine derivatives bearing benzimidazole moieties. R O H

This reaction was reported by A. R. Hantzsch in 1881, and is the NHBoc BocHN R2 2 CN BocHN R O NHBoc best-known three-component MCR, which affords 1,4-dihydro- 1 H R COOH ++ N 2) CHO R1 O b CH2Cl2, rt, 18 h pyridine derivatives using -keto esters, aldehydes, and ammonia. O For an example, a calcium channel blocker, “Nifedipine”, is also Passerini Products 3) 2 synthesized by this reaction. H2N R O NH2 H Acyl Migration N R1 O 10% TFA / CH2Cl2, Et3N / MeOH (1 : 3), rt, 24 h O rt, 2 h

1 CHO NO2 R O

MeO C NH MeO C CO Me 2 2 2 + + 3 2 2 HN R O R N NH2 O NO2 H 1 N 10% TFA / DCE, R N N HO H H N MW, 100°C, 20 min OH H O Nifedipine

3.Biginelli reaction (3CR)

N O N O O CH3 N N N N N N N Biginelli reaction H H H H OH H H OH MeO OH O R3 O R3 X H+ 2 4 CH3 4 5 R O NR R2O + + R R Ph Ph H O N N O CH3 N O N O N H H R1 N X N HN R1 O 5 N N N N N N (X = O or S) R H H H H H H OH OH OH

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8) OMOM OMe 5. Gröbcke-Blackburn-Bienaymé reaction Me BnO Me CH3 CHO + NH2 ++MeO NC O I (3CR) MeOH, reflux O BocHN OTBDPS CO H Gröbcke-Blackburn-Bienaymé Reaction 2 R3 NH OMe OMe + H Me OBn HO Me N N MeO 1 2 3 1 2 OAc R + R CHO + R NC R R H I Me NH2 N OMOM NH N Me NHBoc S Me CH3 N O O N O H OH O O This reaction is a three-component MCR using aldehydes, O O O TBDPSO MeO isonitriles, and a-aminoazines such as 2-aminoimidazole or NH Ugi Products (Y. 90%) HO 2-aminopyridine in the presence of acid catalyst. The reaction is Ecteinascidin 743 applicable for the synthesis of fused nitrogen-containing aromatic compounds as below. Other examples of MCR N N ●MCR using p-toluenesulfonylmethyl isocyanide N S N N N N (TosMIC) (3CR) N NHBn NHBn NHBn p-Toluenesulfonylmethyl isocyanide (TosMIC) [T1046] is a synthetic reagent, developed by Leusen et al., and has both an 6. Kabachnik-Fields reaction (3CR) isonitrile group and a tosyl group (leaving group) in one molecule.13) Different from other isonitrile compounds with odor Kabachnik-Fields Reaction R2 character, TosMIC is an odorless and solid compound. Because O O HN OR3 2 O 3 + R NH2 + H P OR of its easy-handling property, TosMIC has been widely used for R1 H OR3 R1 P OR3 the synthesis of nitrogen-containing aromatic heterocyclic compounds, such as oxazoles.14) TosMIC also has been used In 1952, M. I. Kabachinik et al. have reported the three-component for MCRs, for example, Tsoleridis et al. have reported the MCR using aldehydes, amines, and dialkyl phosphites in the synthesis of quinoxaline derivatives via the three-component presence of acid catalyst (Brønsted or Lewis acids), affording condensation of o-phenylenediamines, aromatic aldehydes and a-aminophosphonates.9) In recent years, much attention has been TosMIC.15) paid to a-aminophoshonates since they can be considered as structural analogues of the corresponding a-amino acids and 1 R NH2 O transition state mimics of peptide hydrolysis. Thus, a-amino- + ArCHO + CH3 S CH2NC R2 NH phoshonates have been applied into several research areas, such 2 O TosMIC [T1046] as development of renin inhibitors or HIV protease inhibitors.10)

1 Base R N Ar 7. Ugi reaction (4CR) Toluene, reflux, 4 h R2 N Ugi Reaction 2 O R Entry 1 2 O R R Ar Base Quinoxaline (Y. %) 3 4 2 3 4 R N R + R NH2 + R NC + R COOH N 1 H H phenyl DABCO 91 R1 H H R1 O 2 HH2,4-dimethylphenyl DABCO 81

3 HH 4-chlorophenyl DABCO 84

This reaction is the four-component MCR reported by I. K. Ugi et 4 Me Me phenyl DBU 86 al. in 1962 for the first time.11) It enables one-pot condensation of 5 Me Me 2-methylphenyl DBU 85 four components (aldehydes, amines, isonitriles, and carboxylic acids), thus, it can be said that the Ugi reaction is the most versatile among MCRs. For an example of applications using this reaction, ●MCR using benzynes (3CR) Fukuyama et al. have reported the synthesis of a marine tunicate, Recently, there also have been several reports on MCRs using Ecteinascidin 743, which has extremely potent antitumor acitivity, benzynes. For example, Yoshida et al. have reported the three- using the Ugi reaction as a key step below.12) component MCR using in situ generated benzynes, imines, and carbon dioxide, affording benzoxadinones.16) Recently, much attention has been paid on organic synthesis using carbon dioxide as a carbon source from the ecological point of view, thus, the reaction above is an extremely useful and eco-friendly MCR.

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KF Me TCI offers a variety of aldehyde, amine, carboxylic acid, b-keto TMS NMe 18-Crown-6 N Ar R + + CO R 2 O ester, urea & thiourea, and dialkyl phosphite compounds readily OTf Ar H THF, 0 °C available in MCRs. For aldehyde, amine, and carboxylic acid Benzyne Precursor O Ar = 2,4,6-trimethyphenyl compounds, typical products selected are listed judging from reports on MCRs so far. In addition, benzyne precursors, Lewis Benzyne Precursor Reaction time (h) Product acids, and ionic liquids used in MCRs are also listed in this Me TMS N Ar brochure. 15 O OTf O (Y. 82%)

Me Me F TMS N Ar F N Ar 63 O O OTf F and O (Y. 63%, 4 : 1) O References OMe Me TMS N Ar 1) A. Strecker, Ann. 1850, 75, 27. 46 O OTf 2) A. Hantzsch, Ber. 1881, 14, 1637. OMe O (Y. 73%) 3) R. Alajarin, J. J. Vaquero, J. L. G. Navio, J. A-Builla, Synlett 1992, 297; R. Alajarin, Me TMS N Ar P. Jordan, J. J. Vaquero , J. A-Builla, Synthesis, 1995, 389; B. M. Khadilkar, A. A. 60 O OTf Chitnavis, Ind. J. Chem. 1995, 34B, 652; B. M. Khadilkar, V. G. Gaikar, A. A. O (Y. 44%) Chitnavis, Tetrahedron Lett. 1995, 36, 8083. Thus, MCR is a strong synthetic methodology to enable 4) P. Biginelli, Ber. 1891, 24, 1317; P. Biginelli, Ber. 1891, 24, 2962. condensation of various substrates in one pot, however, in 5) A. R. Trivedi, V. R. Bhuva, B. H. Dholariya, D. K. Dodiya, V. B. Kataria, V. H. some cases, reactions require long times for completion or Shah, Bioorg. Med. Chem. Lett. 2010, 20, 6100; V. Virsodia, R. R. S. Pissurlenkar, result in undesired side reactions even after optimization of D. Manvar; C. Dholakia, P. Adlakha, A. Shah, E. Coutinho, Eur. J. Med. Chem. reaction conditions such as solvents or Lewis acid catalysts. For 2008, 43, 2103 resolving these problems, there have been some successful 6) M. Passerini, Gazz. Chim. Ital. 1921, 51, 181. reports on accelerating MCRs. For example, Shaabani et al. 7) A. Y. Shaw, F. Medda, C. Hulme, Tetrahedron Lett. 2012, 53, 1313. have reported the ionic liquid promoted Gröbcke-Blackburn- 8) K. Gröbke, L. Weber, F. Mehlin, Synlett, 1998, 661; C. Blackburn, B. Guan, K. Bienaymé reaction.17) As indicated in the table below, in the Shiosaki, S. Tsai, Tetrahedron Lett. 1998, 39, 3635; H. Bienaymé, K. Bouzid, case of using ionic liquids as solvents, reactions proceed Angew. Chem. 1998, 110, 2349; H. Bienaymé, K. Bouzid, Angew. Chem. Int. Ed. smoothly to afford the desired products in excellent yields. On 1998, 39, 2234. the other hand, the yield of product is poor even in the prolonged 9) M. I. Kabachnik, T. Y. Medved, Dokiady Akademii Nauk SSSR, 1952, 83, 689; E. reaction time (Entry 2’). Moreover, as indicated in Entry 1, the K. Fields, J. Am. Chem. Soc. 1952, 74, 1528. ionic liquid can be reused for the same reactions, maintaining 10) S. Shibuya, YAKUGAKU ZASSHI 2004, 124, 725; M. C. Allen, W. Fuhrer, B. Tuck, the high yields. R. Wade, J. M. Wood, J. Med. Chem. 1989, 32, 1652; M. K. Manthey, D. T. C. Huang, W. A. Bubb, R. I. Christpherson, J. Med. Chem. 1998, 41, 4550. 11) I. Ugi, Angew. Chem. Int. Ed. 1962, 1, 8. R1 N [bmim]Br HN 2 + R CHO + NC R1 12) A. Endo, A. Yanagisawa, M. Abe, S. Tohma, T. Kan, T. Fukuyama, J. Am. Chem. N NH2 rt, 3 h 2 R Soc. 2002, 124, 6552. N CH3 N 13) A. M. V. Leusen, Org. Synth. 1977, 57, 102. Br [bmim]Br = N 14) O. Possel, A. M. V. Leusen, Heterocycles, 1977, 7, 77; A. M. V. Leusen, O. H. (CH2)3CH3 Oldenziel, Tetrahedron Lett. 1972, 23, 2373.

Entry R1 R2 Yield (%) 15) C. Neochoritis, J. Stephanidou-Stephanatou, C. A. Tsoleridis, Synlett 2009,

1 Br Ph 98 (95, 92, 90, 85)a 302. 2 Me Ph 98 16) H. Yoshida, H. Fukushima, J. Ohshita, A. Kunai, J. Am. Chem. Soc. 2006, 128, 2'ｂ Me Ph 25 11040.

3 Me 4-CH3C6H4 99 17) A. Shaabani, E. Soleimani, A. Maleki, Tetrahedron Lett. 2006, 47, 3031.

4 Me 4-O2NC6H4 92

5 Me 4-Pyridyl 97

a The same ionic liquid is used for each of the five runs. b Ionic liquid is not used. Reaction time is 12 h.

Ionic liquids can be generally recovered and recycled, which can help to reduce the waste of traditional solvents which are rarely reused. In addition, ionic liquids have attracted much attention as excellent solvents due to their low volatility. Judging from these points, this reaction can be regarded as a more eco- friendly reaction example.

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B0751 25mL 500mL I0101 25mL 500mL P0847 5mL 25mL

O O O CH3 CH3 Aldehydes CH3 H H H CH3 CH3 CH3 Butyraldehyde Isobutyraldehyde Pivalaldehyde CAS RN: 123-72-8 CAS RN: 78-84-2 CAS RN: 630-19-3 I0192 25mL 100mL 500mL V0001 25mL 500mL H0133 25mL 100mL 500mL F0073 25g 500g B2379 500g

OH O CH3 O O CH3 O CH3 H H CH3 H OCH

Isovaleraldehyde Valeraldehyde Hexanal Furfural Benzaldehyde CAS RN: 590-86-3 CAS RN: 110-62-3 CAS RN: 66-25-1 CAS RN: 98-01-1 CAS RN: 100-52-7 P0425 25g 100g 500g N0090 25mL 100mL 500mL I0143 25mL 500mL T0725 25mL 100mL 500mL C1707 1g 5g

OH O C H O O SCH C H NCH N N O 2-Thiophenecarboxaldehyde 2-Pyridinecarboxaldehyde 3-Pyridinecarboxaldehyde 4-Pyridinecarboxaldehyde (stabilized with HQ) Cyclopropanecarboxaldehyde CAS RN: 1121-60-4 CAS RN: 500-22-1 CAS RN: 872-85-5 CAS RN: 98-03-3 CAS RN: 1489-69-6 C3019 1mL 5mL C0880 25mL 100mL T1073 25mL 500mL T0259 25mL 100mL 500mL H0197 25g 100g 500g O OH OH OH C H

O H OH Cyclopentanecarboxaldehyde CH3 CH3 (stabilized with HQ) Cyclohexanecarboxaldehyde p-Tolualdehyde p-Tolualdehyde 3-Hydroxybenzaldehyde CAS RN: 872-53-7 CAS RN: 2043-61-0 CAS RN: 104-87-0 CAS RN: 104-87-0 CAS RN: 100-83-4 H0198 25g 100g 500g C0443 5g 25g C0352 25mL 500mL I0153 25g 250g T0010 25g 100g 500g O O O OH C H C H O C H

H H C H OH CN O O 4-Hydroxybenzaldehyde 4-Cyanobenzaldehyde trans-Cinnamaldehyde Isophthalaldehyde Terephthalaldehyde CAS RN: 123-08-0 CAS RN: 105-07-7 CAS RN: 14371-10-9 CAS RN: 626-19-7 CAS RN: 623-27-8 A0479 25g 100g 500g A0478 25mL 100mL 500mL A0480 25mL 500mL D0564 25g 100g 500g C0561 25g 500g O O O O O C H C H C H C H CH

OCH3 OH Cl

OCH3 OCH3 OH o-Anisaldehyde m-Anisaldehyde p-Anisaldehyde 2,4-Dihydroxybenzaldehyde 2-Chlorobenzaldehyde CAS RN: 135-02-4 CAS RN: 591-31-1 CAS RN: 123-11-5 CAS RN: 95-01-2 CAS RN: 89-98-5 C0124 25g 100g 500g C0125 25g 100g 500g T1368 25mL N0130 25g 100g 500g N0129 25g 500g O O O O O C H CH C H C H C H

CH3 CH3 NO2

Cl NO2

Cl CH3 3-Chlorobenzaldehyde 4-Chlorobenzaldehyde 2,4,6-Trimethylbenzaldehyde 2-Nitrobenzaldehyde 3-Nitrobenzaldehyde CAS RN: 587-04-2 CAS RN: 104-88-1 CAS RN: 487-68-3 CAS RN: 552-89-6 CAS RN: 99-61-6 N0559 25g 100g 500g N0002 25mL 100mL 500mL N0003 5g 25g C1465 1g 5g B2019 1g 5g O O O C H C H O C H O C H Cl H C O

NO2 F 4-Nitrobenzaldehyde 1-Naphthaldehyde 2-Naphthaldehyde 2-Chloro-4-fluorobenzaldehyde 3,4-Ethylenedioxybenzaldehyde CAS RN: 555-16-8 CAS RN: 66-77-3 CAS RN: 66-99-9 CAS RN: 84194-36-5 CAS RN: 29668-44-8

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T1281 25g T1091 5g 25g 250g D1666 25g 500g B0242 5g 25g 250g B0836 25g 100g 500g O O O O CH C H C H CH

CF3 Cl O Br C H Cl CF3 2-(Trifluoromethyl)benzaldehyde 4-(Trifluoromethyl)benzaldehyde 2,3-Dichlorobenzaldehyde 4-Phenylbenzaldehyde 2-Bromobenzaldehyde CAS RN: 447-61-0 CAS RN: 455-19-6 CAS RN: 6334-18-5 CAS RN: 3218-36-8 CAS RN: 6630-33-7 B0548 25g 100g 500g B0549 25g 250g P0746 5g 25g T2651 5g 25g O O O O C H C H C H C H

F F CH3O OCH3

Br F F

Br F OCH3 3-Bromobenzaldehyde 4-Bromobenzaldehyde Pentafluorobenzaldehyde 2,4,6-Trimethoxybenzaldehyde CAS RN: 3132-99-8 CAS RN: 1122-91-4 CAS RN: 653-37-2 CAS RN: 830-79-5 P0911 5mL 25mL A0219 25mL 500mL I0165 25mL 500mL

CH3 CH2 CH NH Amines HC CCH2NH2 NH2 3 2

Propargylamine Allylamine Isopropylamine CAS RN: 2450-71-7 CAS RN: 107-11-9 CAS RN: 75-31-0 B0709 25mL 100mL 500mL B0707 25mL 500mL I0095 25mL 500mL A1859 5g 25g A0432 25g 100g 500g

NH2 NH2 CH3 N CH3 CH NH CH NH NH2 N N 3 2 3 2 N N CH H H CH3 3 tert-Butylamine Butylamine Isobutylamine 3-Aminopyrazole 3-Amino-1,2,4-triazole CAS RN: 75-64-9 CAS RN: 109-73-9 CAS RN: 78-81-9 CAS RN: 1820-80-0 CAS RN: 61-82-5 C0887 25mL 500mL A0445 25mL 100mL 500mL A0463 500g A0411 25g 100g 500g A0989 5g 25g

NH2 N CH3 NH2 NNH2 NNH2 NH2 Cyclopentylamine Amylamine Aniline 2-Aminopyridine 2-Aminopyrazine CAS RN: 1003-03-8 CAS RN: 110-58-7 CAS RN: 62-53-3 CAS RN: 504-29-0 CAS RN: 5049-61-6 A0412 25g 500g F0091 25mL 100mL 500mL C0494 25mL 500mL A0633 25g 100g 500g A1060 5g 25g

NH2 N NN N

OCH2NH2 S NH2 S NH2 NNH2

2-Aminopyrimidine Furfurylamine Cyclohexylamine 2-Aminothiazole 2-Amino-1,3,4-thiadiazole CAS RN: 109-12-6 CAS RN: 617-89-0 CAS RN: 108-91-8 CAS RN: 96-50-4 CAS RN: 4005-51-0 B0406 25mL 500mL A1161 25g 250g P0085 25mL 100mL 500mL A0850 5g 25g B0541 25g 250g

CH2NH2 NH2 N Br

N NH2 NH2 NCH2NH2 H

Benzylamine 2-Picolylamine 2-Phenylethylamine 2-Aminobenzimidazole 2-Bromoaniline CAS RN: 100-46-9 CAS RN: 3731-51-9 CAS RN: 64-04-0 CAS RN: 934-32-7 CAS RN: 615-36-1 F0513 300mL A2035 300mL A0141 25g 500g

O O O CH2 HOH OH Carboxylic Acids CH3 OH Acrylic Acid Formic Acid Acetic Acid (stabilized with MEHQ) CAS RN: 64-18-6 CAS RN: 64-19-7 CAS RN: 79-10-7

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P0500 25mL 500mL B0754 25mL 500mL C0439 25g 500g M0052 25g 500g C2123 25g 500g

O O O O O NC HS CH3 OH OH CH3 OH OH ClCH2 C OH

Propionic Acid Butyric Acid Cyanoacetic Acid Thioglycolic Acid Chloroacetic Acid CAS RN: 79-09-4 CAS RN: 107-92-6 CAS RN: 372-09-8 CAS RN: 68-11-1 CAS RN: 79-11-8 P1862 1g 5g B2635 25g 500g C0387 25mL 100mL 500mL C0888 10g 25g C0512 5g 25g O O C OH O C OH COH

N N OOH H O OH Pyrazole-3-carboxylic Acid Benzoic Acid Cyclopropanecarboxylic Acid Cyclobutanecarboxylic Acid Cyclopentanecarboxylic Acid CAS RN: 1621-91-6 CAS RN: 65-85-0 CAS RN: 1759-53-1 CAS RN: 3721-95-7 CAS RN: 3400-45-1 C0470 25g 500g H0206 25g 500g B0531 25g 500g F0112 25g 250g P0610 5g 25g O O OOH C OH C OH O OH Br O OH CC OH F Cyclohexanecarboxylic Acid 2-Hydroxybenzoic Acid Bromoacetic Acid 4-Fluorobenzoic Acid Phenylpropiolic Acid CAS RN: 98-89-5 CAS RN: 69-72-7 CAS RN: 79-08-3 CAS RN: 456-22-4 CAS RN: 637-44-5 C0353 25g 100g 500g P0281 25g 100g 500g A1075 5g 25g N0155 25g 500g B3764 5g 25g O O O O C OH COH O C OH C CH NO HO C O OH 3 2 O C H O O trans-Cinnamic Acid Phthalaldehydic Acid 2-Acetylbenzoic Acid 2-Nitrobenzoic Acid 1,4-Benzodioxane-6-carboxylic Acid CAS RN: 140-10-3 CAS RN: 119-67-5 CAS RN: 577-56-0 CAS RN: 552-16-9 CAS RN: 4442-54-0 T1145 5g 25g B0552 25g 100g 500g D0869 25g 100g 500g I0053 25g 100g 500g O O O C OH COH C OH Br O I CH C OH

CF3 4-(Trifluoromethyl)benzoic Acid 2-Bromobenzoic Acid Diphenylacetic Acid 2-Iodobenzoic Acid CAS RN: 455-24-3 CAS RN: 88-65-3 CAS RN: 117-34-0 CAS RN: 88-67-5 A0650 25g 500g A0649 25g 500g M2315 5g 25g

O O O O O O

b -Keto Esters CH3 OCH3 CH3 OCH3 CH3O Cl

Methyl Acetoacetate Ethyl Acetoacetate Methyl Malonyl Chloride CAS RN: 105-45-3 CAS RN: 141-97-9 CAS RN: 37517-81-0 A1981 25g 500g M2277 5g 25g M0799 25g 100g 500g K0035 25g 100g 500g K0031 5g 25g

O OO O O O O OO O CH2 CH3 CH3 CH3 CH3 O OCH3 OCH3 OCH3 O O CH3 Methyl 3-Cyclopropyl- Meldrum's Acid (=2,2-Dimethyl- Allyl Acetoacetate 3-oxopropionate 1,3-dioxane-4,6-dione) Methyl 3-Oxovalerate Ethyl 3-Oxovalerate CAS RN: 1118-84-9 CAS RN: 32249-35-7 CAS RN: 2033-24-1 CAS RN: 30414-53-0 CAS RN: 4949-44-4 I0826 25g 500g A0817 25mL 500mL E0484 5g 25g A0815 25mL A0816 25mL 100mL 500mL

O O CH3 O O O O OOCH3 OOCH3 CH3 CH3 CH3 O CH3 CH3 O CH3 O Cl CH3 O CH3 CCH2 COCCH3

CH3 Isopropyl Acetoacetate Propyl Acetoacetate Ethyl Malonyl Chloride sec-Butyl Acetoacetate tert-Butyl Acetoacetate CAS RN: 542-08-5 CAS RN: 1779-60-8 CAS RN: 36239-09-5 CAS RN: 13562-76-0 CAS RN: 1694-31-1

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A0795 25mL E0882 5g 25g K0037 25mL 500mL K0030 25mL 500mL A0814 25mL 500mL

OO O O O O O O OO CH3 CH3 CH3 OCH3 O CH3 CH OCH 3 3 CH3 OCH3 CH3 O CH3 CH3 Butyl Acetoacetate Ethyl Isobutyrylacetate Methyl 3-Oxohexanoate Ethyl 3-Oxohexanoate Isobutyl Acetoacetate CAS RN: 591-60-6 CAS RN: 7152-15-0 CAS RN: 30414-54-1 CAS RN: 3249-68-1 CAS RN: 7779-75-1 A1583 25g 500g C0911 25g 500g A0811 25mL 500mL D1891 5mL 25mL O0216 10g 25g

OO O O OO OO O O CH3 CH OCH Cl CH3 3 3 CH O OCH3 CH3 O OCH3 3 OCH3 CH3 CH3

2-Methoxyethyl Acetoacetate Ethyl 4-Chloroacetoacetate Amyl Acetoacetate Ethyl 4,4-Dimethyl-3-oxovalerate Ethyl 3-Oxoheptanoate CAS RN: 22502-03-0 CAS RN: 638-07-3 CAS RN: 6624-84-6 CAS RN: 17094-34-7 CAS RN: 7737-62-4 A0812 25mL 500mL A0813 25mL T0810 25g 100g 500g A0913 25mL O0073 5g 25g

CH3 OO O O OO CH3 OO O O

CH3 CH3 O CH OCH O CH3 CH3 O CH3 CH3 O CF3 OCH3 3 3 O

Isoamyl Acetoacetate 3-Pentyl Acetoacetate Ethyl 4,4,4-Trifluoroacetoacetate Hexyl Acetoacetate Diethyl Oxalacetate CAS RN: 2308-18-1 CAS RN: 13562-81-7 CAS RN: 372-31-6 CAS RN: 13562-84-0 CAS RN: 108-56-5 A1080 25mL 100mL 500mL B0097 25g 100g 500g T1530 25g A0916 25mL F0435 1g 5g 25g O O C CH C OCH CH 2 2 3 O O CH 3 OO O O OO CH3 CH3 O CH3 C CH2 C OCH2 CF3 O CH3 F CCH2C OCH2CH3

Isopropyl Benzyl Acetoacetate Ethyl Benzoylacetate 4,4,4-Trifluoroacetoacetate Heptyl Acetoacetate Ethyl (4-Fluorobenzoyl)acetate CAS RN: 5396-89-4 CAS RN: 94-02-0 CAS RN: 175230-50-9 CAS RN: 42598-96-9 CAS RN: 1999-00-4 E0489 25g 500g A0915 25mL M1380 5g 25g O0229 1g 5g T1285 10g 25g O O C CH C OCH CH CH2 O O 2 2 3 O O O O O O OO CH3 OCH3 CH3 OCH3 CH3 OOCH3 O Cl3COCH3 Ethylene Glycol Monoaceto- acetate Monomethacrylate OCH3 (stabilized with BHT) n-Octyl Acetoacetate Ethyl 4-Methoxybenzoylacetate Diethyl 3-Oxopimelate Ethyl 4,4,4-Trichloroacetoacetate CAS RN: 21282-97-3 CAS RN: 16436-00-3 CAS RN: 2881-83-6 CAS RN: 40420-22-2 CAS RN: 3702-98-5 P1062 5g N0513 5g 25g N0875 5g 25g E0759 25g E0811 5g 25g O O O O C CH2 C OCH2CH3 C CH2 C OCH2CH3 O O O O F F C CH C OCH CH O O 2 2 3 CF CF O CH CH C CH C OCH NO 3 2 3 3 2 2 2 F F Cl NCl F Ethyl 4,4,5,5,5-Pentafluoro- NO2 Ethyl (2,3,4,5-Tetrafluoro- Ethyl 3-(2,6-Dichloro-5-fluoro- 3-oxovalerate Ethyl 4-Nitrobenzoylacetate 4-Nitrobenzyl Acetoacetate benzoyl)acetate 3-pyridyl)-3-oxopropionate CAS RN: 663-35-4 CAS RN: 838-57-3 CAS RN: 61312-84-3 CAS RN: 94695-50-8 CAS RN: 96568-04-6 B1274 5mL 25mL C1438 1g 5g I0562 5g 25g

NC O CH 3 CN Isonitriles CH3 C NC OCH3 CH3 tert-Butyl Isocyanide Cyclohexyl Isocyanide Ethyl Isocyanoacetate CAS RN: 7188-38-7 CAS RN: 931-53-3 CAS RN: 2999-46-4 B2185 1g 5g T1054 1mL 5mL I0455 1g 5g I0824 1g 5g T1046 5g 25g

CH NC 2 N NC CH3 CH3 N O N CH S CH NC CH3 C CH2 C NC 3 2 CH2NC O CH3 CH3 1-(Isocyanomethyl)- p-Toluenesulfonylmethyl Benzyl Isocyanide 1,1,3,3-Tetramethylbutyl Isocyanide 1H-benzotriazole 1-Isocyanoadamantane Isocyanide (= TosMIC) CAS RN: 10340-91-7 CAS RN: 14542-93-9 CAS RN: 87022-42-2 CAS RN: 22110-53-8 CAS RN: 36635-61-7

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U0073 300g M0455 25g 500g D0289 25g 500g

O O O

H3C CH3 H2NNH2 H2N NHCH3 N N Ureas H H

Urea 1-Methylurea 1,3-Dimethylurea CAS RN: 57-13-6 CAS RN: 598-50-5 CAS RN: 96-31-1 E0192 25g 500g A0237 25g 250g A0124 25g H0700 25g A0101 25g

O O OO O O O CH2 CH3 CH3 N NH2 N NH2 CH3 N NH2 H NCNHCH CH OH CH3 N N H H H 2 2 2 H H

Ethylurea Allylurea Acetylurea 2-Hydroxyethylurea 1-Acetyl-3-methylurea CAS RN: 625-52-5 CAS RN: 557-11-9 CAS RN: 591-07-1 CAS RN: 2078-71-9 CAS RN: 623-59-6 B1831 25g D0534 25g 500g D5170 1g 5g H0655 25g D0767 25g 500g

O O O O O H CH2 CH2 H2N N CH3 N NH2 H3CNN CH3 N N OH HO N N OH H H H H H O H H

Butylurea 1,3-Diethylurea 1,3-Diallylurea Hydantoic Acid 1,3-Bis(hydroxymethyl)urea CAS RN: 592-31-4 CAS RN: 623-76-7 CAS RN: 1801-72-5 CAS RN: 462-60-2 CAS RN: 140-95-4 C0173 25g C1101 25g 250g C2034 25g B0449 25g T0802 25g O O O CH NH C NH O O O NH C NH2 2 2 NH C NH2 CH Cl NC 3 N NH2 N NH2 H H

2-Chloroethylurea Cyanoacetylurea Cyclohexylurea Benzylurea o-Tolylurea CAS RN: 6296-42-0 CAS RN: 1448-98-2 CAS RN: 698-90-8 CAS RN: 538-32-9 CAS RN: 614-77-7 T0328 25g H0438 25g C2657 5g 25g B1103 25g C0031 25g 100g 500g O

NH C NH2 O O CH3 O CH3 O O NOCH3 CH3 N N CH Si NH CNH Si CH H H 3 3 NH CNH HO N NH2 CN CH CH H 3 3 CH3 p-Tolylurea 3-Hydroxyphenylurea Cymoxanil N,N'-Bis(trimethylsilyl)urea 1,3-Diphenylurea CAS RN: 622-51-5 CAS RN: 701-82-6 CAS RN: 57966-95-7 CAS RN: 18297-63-7 CAS RN: 102-07-8 T2890 5g B2833 5g B2834 5g 25g T1915 25g 250g B2842 25g O O O SO NH C NH 2 2 NH C NH2 NH C NH2 CH3 O O Br O OCH3 H N C NH(CH ) Si OCH 2 2 3 3 CH3 N NH2 OCH H 3 Br CH3 Br 1-[3-(Trimethoxysilyl)- p-Toluenesulfonylurea (2-Bromophenyl)urea (4-Bromophenyl)urea propyl]urea 1-(2-Bromoisovaleryl)urea CAS RN: 1694-06-0 CAS RN: 13114-90-4 CAS RN: 1967-25-5 CAS RN: 23843-64-3 CAS RN: 496-67-3 D0441 25g 100g 500g C2266 5g C0926 5g 25g U0048 25mL 500mL C1220 25g O O SO NH C NH SO2NH C NHCH2CH2CH3 2 2 Cl O O O OCH2CH3

NH C NH NH C NH N H2N C NH(CH2)3 Si OCH2CH3

OCH2CH3 Cl Cl 1-(2-Chloro-4-pyridyl)- 1-[3-(Triethoxysilyl)propyl]- 1-(4-Chlorophenylsulfonyl)- 1,3-Dicyclohexylurea (4-Chlorophenylsulfonyl)urea 3-phenylurea urea (40-52% in Methanol) 3-propylurea CAS RN: 2387-23-7 CAS RN: 22663-37-2 CAS RN: 68157-60-8 CAS RN: 23779-32-0 CAS RN: 94-20-2 O0209 10g T1015 25g 500g I0665 25g 250g E1171 200mg 1g

CH3CH2O Cl H H H H O O HOCH2 N N N N CH2OH O N N O O CH (CH ) NH CNH Cl NH C NH Cl O N O O N O 3 2 17 2 H H N NH2 H

N-Octadecylurea 3,4,4'-Trichlorocarbanilide Imidazolidinyl Urea (4-Ethoxyphenyl)urea CAS RN: 2158-08-9 CAS RN: 101-20-2 CAS RN: 39236-46-9 CAS RN: 150-69-6

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T2475 300g M0619 25g 100g 500g D0804 25g 100g 500g

S S S

CH3 CH3 CH3 H2NNH2 N NH2 N N Thioureas H H H

Thiourea N-Methylthiourea 1,3-Dimethylthiourea CAS RN: 62-56-6 CAS RN: 598-52-7 CAS RN: 534-13-4 A0220 25g 100g 500g B4612 1g 5g A0117 25g 500g G0234 25g 100g 500g D0530 25g 500g

S OS NH S S S CH2 N NH2 CH2NH C NH2 CH3 N NH2 H2N N NH2 H3CNN CH3 H H H H H

1-Allyl-2-thiourea Benzylthiourea 1-Acetyl-2-thiourea Guanylthiourea 1,3-Diethyl-2-thiourea CAS RN: 109-57-9 CAS RN: 621-83-0 CAS RN: 591-08-2 CAS RN: 2114-02-5 CAS RN: 105-55-5 P0237 25g 500g A0230 25g 500g D0253 25g T0657 25g B4484 1g 5g S

NH C NH2 Br S S CH3 S CH3 S CH3 CH2 OH NH NH 2 N N H3CNN CH3 N NH2 H H H H H

1-Phenyl-2-thiourea 1-Allyl-3-(2-hydroxyethyl)-2-thiourea 1,3-Diisopropylthiourea o-Tolylthiourea (4-Bromophenyl)thiourea CAS RN: 103-85-5 CAS RN: 105-81-7 CAS RN: 2986-17-6 CAS RN: 614-78-8 CAS RN: 2646-30-2 C3168 1g 5g T0656 5g F0836 5g 25g D0802 25g E0419 5g S S

NH C NH2 NH C NH2 S CH3 CH3 S NH S . HCl CH N N NH Cl N NH2 NH CNH 3 2 H H H

CH3 F 1-Ethyl-3-guanidinothiourea (3-Chlorophenyl)thiourea p-Tolylthiourea (4-Fluorophenyl)thiourea 1,3-Di(o-tolyl)thiourea Hydrochloride CAS RN: 4947-89-1 CAS RN: 622-52-6 CAS RN: 459-05-2 CAS RN: 137-97-3 CAS RN: 381670-29-7 D0301 25g 500g P1167 5g N0071 5g 25g A1403 5g D0652 10g S S HN NH S 2 NH CNH2 CH NH S NH 3 N . 2HCl H3CNN CH3 NH C NH C NH CH3 S NH2 H H 2

S-[2-(Dimethylamino)ethyl]- 1,3-Dibutylthiourea 1-Phenyl-3-guanylthiourea 1-(1-Naphthyl)-2-thiourea 1-Adamantylthiourea isothiourea Dihydrochloride CAS RN: 109-46-6 CAS RN: 15989-47-6 CAS RN: 86-88-4 CAS RN: 25444-82-0 CAS RN: 16111-27- 6 T0197 25g 500g D0440 5g 25g B0802 25g D0803 5g 25g B3452 200mg 1g

CF3 CF3 S S S O S S NH C NH CH3 NH C NH CH3 NH CNH NH C NH C NH C NH2

CF3 CF3 1,3-Bis[3,5-bis(trifluoromethyl)- 1,3-Diphenyl-2-thiourea 1,3-Dicyclohexylthiourea N-Benzoylthiourea 1,3-Di(p-tolyl)thiourea phenyl]thiourea CAS RN: 102-08-9 CAS RN: 1212-29-9 CAS RN: 614-23-3 CAS RN: 621-01-2 CAS RN: 1060-92-0 P0629 25g 500g D0300 25g D3417 25g 100g 500g

O O CH O 3 CH3 CH3 CH3 Dialkyl Phosphites CHO P OCH CH3(CH2)3O P O(CH2)3CH3 CHCH2OPOCH2CH CH CH3 CH3 CH3 3 H H H Diisopropyl Phosphite Dibutyl Phosphite Diisobutyl Phosphite CAS RN: 1809-20-7 CAS RN: 1809-19-4 CAS RN: 1189-24-8 D0907 25g 100g 500g P1016 25g 250g

O O CH2O O P H PH O CH2O

Diphenyl Phosphite Dibenzyl Phosphite CAS RN: 4712-55-4 CAS RN: 17176-77-1

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A1464 1g 5g T2089 1g 5g 25g M1883 1g 5g

OSO2CF3 OSO2CF3

N Si(CH3)3 (CH3)3Si CH3 N Benzyne Precursors N NH2 2-(Trimethylsilyl)phenyl 2-Methyl-6-(trimethylsilyl)phenyl 1-Aminobenzotriazole Trifluoromethanesulfonate Trifluoromethanesulfonate CAS RN: 1614-12-6 CAS RN: 88284-48-4 CAS RN: 556812-44-3 M1882 1g 5g D2503 5g 25g M1884 1g 5g M1885 1g 5g T2465 1g 5g

OSO2CF3 O OSO2CF3 . Si(CH3)3 C O H2O OSO2CF3 Si(CH3)3 Si(CH3)3 Si(CH3)3 OSO2CF3 I

CH3 OCH3 OCH3 4-Methyl-2-(trimethylsilyl)phenyl Diphenyliodonium- 3-Methoxy-2-(trimethylsilyl)phenyl 4-Methoxy-2-(trimethylsilyl)phenyl 1-(Trimethylsilyl)-2-naphthyl Trifluoromethanesulfonate 2-carboxylate Monohydrate Trifluoromethanesulfonate Trifluoromethanesulfonate Trifluoromethanesulfonate CAS RN: 262373-15-9 CAS RN: 96195-89-0 CAS RN: 217813-03-1 CAS RN: 556812-41-0 CAS RN: 252054-88-9 T2466 1g 5g P1620 1g 5g B3047 1g T2467 1g

OSO2CF3 Si(CH3)3 I OSO2CF3 (CH3)3Si Si(CH3)3 OSO CF 2 3 Si(CH3)3 CF3O2SO OSO2CF3 (CH3)3Si Si(CH3)3 CF3O2SO OSO2CF3 3-(Trimethylsilyl)-2-naphthyl Phenyl[2-(trimethylsilyl)phenyl]- 3,3'-Bis(trimethylsilyl)biphenyl-4,4'- Si(CH3)3 Trifluoromethanesulfonate iodonium Trifluoromethanesulfonate diyl Bis(trifluoromethanesulfonate) 1,3,5-Tris[4-(trifluoromethanesulfonyloxy)-3-(trimethylsilyl)phenyl]benzene CAS RN: 780820-43-1 CAS RN: 164594-13-2 CAS RN: 828282-80-0 CAS RN: 847925-63-7 L0210 25g 100g 500g N0850 25g 500g Z0014 25g 300g

Lewis Acids LiBr NiCl2 ZnCl2

Lithium Bromide Nickel(II) Chloride Anhydrous Zinc Chloride CAS RN: 7550-35-8 CAS RN: 7718-54-9 CAS RN: 7646-85-7 B0527 25mL 100mL 500mL T0267 25g 500g T2052 100mL 500mL R0074 1g 5g I0778 5g 25g

SO3H . H2O TiCl4 RuCl3 InCl3 BF3 . CH3 OCH3 CH3 Boron Trifluoride - Ethyl p-Toluenesulfonic Acid Titanium(IV) Chloride (14% in Ether Complex Monohydrate Dichloromethane, ca. 1.0mol/L) Ruthenium(III) Chloride Indium(III) Chloride Anhydrous CAS RN: 109-63-7 CAS RN: 6192-52-5 CAS RN: 7550-45-0 CAS RN: 10049-08-8 CAS RN: 10025-82-8 B3546 25g 250g T1663 1g 5g T1293 5g 25g T1610 5g 25g

O O O 3 3 3 CF3 S O Sc CF3 S O La CF3 S O Yb BiCl3 O O O 3 3 3 . xH2O Scandium(III) Lanthanum(III) Ytterbium(III) Bismuth(III) Chloride Anhydrous Trifluoromethanesulfonate Trifluoromethanesulfonate Trifluoromethanesulfonate Hydrate CAS RN: 7787-60-2 CAS RN: 144026-79-9 CAS RN: 52093-26-2 CAS RN: 54761-04-5 B2194 5g 25g 100g B2193 5g B2195 5g 25g 100g

CH3 CH3 CH3 N N N Cl Br Ionic Liquids N N N BF4 (CH2)3CH3 (CH2)3CH3 (CH2)3CH3 1-Butyl-3-methylimidazolium 1-Butyl-3-methylimidazolium 1-Butyl-3-methylimidazolium Chloride Bromide Tetrafluoroborate CAS RN: 79917-90-1 CAS RN: 85100-77-2 CAS RN: 174501-65-6 T0055 5g 25g 100g B2320 5g 25g B2337 5g 25g T0054 25g 100g 500g T1124 25g 100g 500g

CH3 CH3 N N (CH2)3CH3 (CH ) CH (CH2)3CH3 PF6 CF3SO3 2 3 3 N N CH3(CH2)3 N (CH2)3CH3 Cl CH3(CH2)3 N (CH2)3CH3 Br CH3(CH2)3 P (CH2)3CH3 Br (CH2)3CH3 (CH2)3CH3 (CH2)3CH3 (CH2)3CH3 (CH2)3CH3 1-Butyl-3-methylimidazolium 1-Butyl-3-methylimidazolium Tetrabutylammonium Chloride Hexafluorophosphate Trifluoromethanesulfonate Tetrabutylammonium Bromide Tetrabutylphosphonium Bromide CAS RN: 1112- 67- 0 CAS RN: 174501-64-5 CAS RN: 174899-66-2 CAS RN: 1643-19-2 CAS RN: 3115-68-2

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