Copper Click Chemistry

“Click” chemistry is a term coined by Barry Sharpless to describe chemical reactions that are modular, wide in scope, give very high yields, and generate only inoffensive byproducts. The most well-known example of a “click” reaction is the Huisgen copper(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC), which yields a 1,4-disubstituted five-membered 1,2,3-triazole ring. This reaction between azides and alkynes offers high yields and involves functionalities that can be introduced relatively easily in a variety of molecules such as: synthetic polymers, fluorophores, small molecules or into specific locations in biomolecules. A positive aspect of this reaction for biological purposes is that the azide and alkyne functional groups are largely inert towards biological molecules and aqueous environments. “Click” chemistry continues to gain popularity and is used in a variety of research fields with significant contributions to the fields of polymer chemistry, bioconjugation, and drug discovery.

Sigma-Aldrich is pleased to offer a variety of azides, alkynes, catalysts, and ligands to help accelerate your research in the exciting arena of “click” chemistry.

Learn More about "Click" Chemistry
Click Chemistry
Catalytic Azide-Alkyne Cycloaddition: Reactivity and Applications
Copper-Free Click Chemistry: Bioorthogonal Reagents for Tagging Azides
Functionalized Alkynes

Amino Acid Azides/Alkynes

Peptide synthesis using natural and non-natural amino acids is a powerful tool in the development of therapeutics and understanding biological chemistry. Sigma-Aldrich offers a variety of Fmoc and Boc protected azido amino acids for your peptide or amino acid based chemical ligation needs, such as azide-alkyne or Huisgen cycloaddition reactions and Staudinger ligations.

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690651 (S)-(−)-2-Azido-6-(Boc-amino)hexanoic acid (dicyclohexylammonium) salt ≥97% C11H20N4O4 · C12H23N
712175 (S)-2-Azido-3-(4-tert-butoxyphenyl)propionic acid cyclohexylammonium salt ≥98% (CE) C13H17N3O3 · C6H13N
712779 (S)-2-Azido-3-tert-butoxypropionic acid cyclohexylammonium salt ≥98% (CE) C7H13N3O3 ·C6H13N
714291 (S)-5-Azido-2-(Fmoc-amino)pentanoic acid ≥97.0% (HPLC) C20H20N4O4
714259 (S)-2 Azido-3-(3-indolyl)propionic acid cyclohexylammonium salt ≥98% (HPLC) C11H10N4O2 · C6H13N
714275 (S)-2-Azido-3-methylbutyric acid cyclohexylammonium salt ≥98% (CE) C5H9N3O2·C6H13N
714267 (S)-2-Azido-4-(methylthio)butanoic acid cyclohexylammonium salt ≥98% (CE) C5H9N3O2S · C6H13N
690767 (S)-2-Azido-3-phenylpropionic acid (dicyclohexylammonium) salt ≥98% C9H9N3O2 · C12H23N
714283 (S)-2-Azido-propionic acid cyclohexylammonium salt ≥98% (CE) C3H5N3O2 · C6H13N
714232 (R)-2-(Boc-amino)-5-hexynoic acid ≥96% (HPLC) C11H17NO4
714240 (S)-2-(Boc-amino)-5-hexynoic acid ≥96% (HPLC) C11H17NO4
712612 Boc-3-azido-Ala-OH (dicyclohexylammonium) salt ≥97% (CE) C20H37N5O4
712620 N-Boc-4-azido-L-homoalanine (dicyclohexylammonium) salt ≥97% (CE) C21H39N5O4
712647 N-Boc-6-azido-L-norleucine (dicyclohexylammonium) salt ≥98.0% (CE) C23H43N5O4
712639 N-Boc-5-azido-L-norvaline (dicyclohexylammonium) salt ≥98.0% (CE) C22H41N5O4
712248 Boc-4-azido-Phe-OH ≥95% (HPLC) C14H18N4O4
712221 Boc-propargyl-Gly-OH ≥98.0% (HPLC) C10H15NO4
711977 Boc-(R)-4-(2-propynyl)-L-proline ≥96% C13H19NO4
690554 (S)-5-tert-Butyl hydrogen 2-azidoglutarate (dicyclohexylammonium) salt 99% C9H15N3O4 · C12H23N
690430 (S)-(−)-4-tert-Butyl hydrogen 2-azidosuccinate (dicyclohexylammonium) salt ≥98.0% C8H13N3O4 · C12H23N
774995 N2-[(1,1-Dimethylethoxy)carbonyl]-N6-[(2-propynyloxy)carbonyl]-L-lysine 90% C15H24N2O6
714151 Fmoc-β-azido-Ala-OH ≥98.0% (HPLC) C18H16N4O4
F5312 Fmoc-(R)-propargyl-Ala-OH C21H19NO4
F5437 Fmoc-(S)-propargyl-Ala-OH C21H19NO4

Azide Sources

Incorporating azido functional groups into organic molecules is becoming an increasingly important task as these moieties continue to impact organic chemistry as well as biology in uses ranging from amino group protection to chemical ligation. Sigma-Aldrich offers a wide selection of azide sources, from sodium azide to diphenyl phosphoryl azide, to facilitate azide synthesis and the preparation of tailor-made organic azides.

Learn More about Azide Sources
Organic Azides and Azide Sources
Azide Building Blocks for Chemical Ligation
MRT - Staudinger Hydration
Staudinger Ligation
Staudinger Ligation: A High-Yield, Chemoselective, and Mild Synthetic Method

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762415 2-Azido-1,3-dimethylimidazolinium hexafluorophosphate 97% C5H10F6N5P
155071 Azidotrimethylsilane 95% C3H9N3Si
349488 Azidotrimethyltin(IV) 97% C3H11N3Sn
178756 Diphenyl phosphoryl azide 97% C12H10N3O3P
480525 Lithium azide solution 20 wt. % in H2O LiN3
438456 Sodium azide ≥99.99% trace metals basis N3Na
651664 Tetrabutylammonium azide C16H36N4

Carbohydrate Azides

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670995 2-Acetamido-2-deoxy-β-D-glucopyranosyl azide ≥98% (HPLC) C8H14N4O5
671118 2-Acetamido-2-deoxy-β-D-glucopyranosyl azide 3,4,6-triacetate ≥98.0% (HPLC)  
671215 2-Acetamido-3,4,6-tri-O-benzyl-2-deoxy-β-D-glucopyranosyl azide ≥98.0% (HPLC) C29H32N4O5
A7355 N-Azidoacetylglucosamine, Acetylated C16H22N4O10
A7605 N-Azidoacetylmannosamine, Acetylated C16H22N4O10
712736 6-Azido-6-deoxy-1,2:3,4-di-O-isopropylidene-α-D-galactopyranose ≥96% (HPLC) C12H19N3O5
513989 1-Azido-1-deoxy-β-D-galactopyranoside 97% C6H11N3O5
513970 1-Azido-1-deoxy-β-D-galactopyranoside tetraacetate 97% C14H19N3O9
712752 6-Azido-6-deoxy-D-galactose ≥98.0% (HPLC) C6H11N3O5
514004 1-Azido-1-deoxy-β-D-glucopyranoside C6H11N3O5
513997 1-Azido-1-deoxy-β-D-glucopyranoside tetraacetate C14H19N3O9
712795 2-Azido-2-deoxy-D-glucose ≥98.0% (HPLC) C6H11N3O5
712760 6-Azido-6-deoxy-D-glucose ≥98% (HPLC) C6H11N3O5
514012 1-Azido-1-deoxy-β-D-lactopyranoside 97% C12H21N3O10
497029 3-Azido-2,3-dideoxy-1-O-(tert-butyldimethylsilyl)-β-D-arabino-hexopyranose 98% C12H25N3O4Si
712809 2-Azido-D-galactose tetraacetate ≥97% (HPLC) C14H19N3O9
712787 2-Azido-β-D-glucose tetraacetate ≥98% (HPLC) C14H19N3O9
712825 1,2-Di-O-acetyl-3-azido-3-deoxy-5-O-(p-toluoyl)-D-ribofuranose ≥95% (HPLC) C17H19N3O7
G4168 α-D-Mannopyranosyl azide tetraacetate ≥90% (TLC) C14H19N3O9
712817 2,3,4,6-Tetra-O-acetyl-1-azido-1-deoxy-α-D-galactopyranosyl cyanide ≥98.0% (HPLC) C15H18N4O9
670790 2,3,4-Tri-O-acetyl-β-D-xylopyranosyl azide ≥98.0% (HPLC) C11H15N3O7

Clickable Sterol Probes

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807737 Photo-reactive Clickable cis-Sterol Probe C30H46N2O3

Click Chemistry: Catalysts, Ligands and Reagents

Click Catalyst and Ligands

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326755 Copper(II) acetate 98% Green Alternative C4H6CuO4
212865 Copper(I) bromide 98% BrCu
205540 Copper(I) iodide 98% CuI
C1297 Copper(II) sulfate ReagentPlus®, ≥99% CuO4S
209198 Copper(II) sulfate pentahydrate ACS reagent, ≥98.0% CuO4S · 5H2O
673293 Pentamethylcyclopentadienylbis(triphenylphosphine)ruthenium(II) chloride C46H45ClP2Ru
A7631 (+)-Sodium L-ascorbate crystalline, ≥98% C6H7NaO6
696773 TentaGel TBTA extent of labeling: 0.17 mmol/g loading  
696854 Tripotassium 5,5′,5′′-[2,2′,2′′-nitrilotris(methylene)tris(1H-benzimidazole-2,1-diyl)]tripentanoate hydrate 95% C39H42K3N7O6 · xH2O
696862 Tris(2-benzimidazolylmethyl)amine 97% C24H21N7
678937 Tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine 97% C30H30N10
762342 Tris(3-hydroxypropyltriazolylmethyl)amine 95% C18H30N10O3

Fluorophore Alkynes/Azides

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30154 Alkyne cyanine dye 718 for copper catalyzed click labeling C40H49N3O6S2
79249 Alkyne MegaStokes dye 608 for copper-free click labeling C34H40F6N3OP
52225 Alkyne MegaStokes dye 673 for copper catalyzed click labeling C25H26N2O5S
79252 Alkyne MegaStokes dye 735 for copper catalyzed labeling C24H26N2O4S
89524 Azide cyanine dye 728 for copper catalyzed click labeling C40H52N6O6S2
760765 Azide-fluor 488 ≥90% (HPLC) C29H30N6O7
760757 Azide-fluor 545 C33H39N6O7
90561 Azide MegaStokes dye 673 for copper catalyzed click labeling C23H25N5O5S
87564 Azide MegaStokes dye 735 for copper catalyzed click labeling C22H25N5O4S
762024 Azide-PEG3-biotin conjugate C18H32N6O5S
764213 Biotin-PEG4-alkyne for copper catalyzed click labeling C21H35N3O6S
777331 Cy3-alkyne for copper catalyzed click labeling C47H73N5O10S3
777315 Cy3-azide 90% (HPLC) C35H44N6O10S3 · xC6H16N
777323 Cy5-azide 95% (HPLC) C49H78N8O10S3
777366 DBCO-Cy3 for Copper-free Click Chemistry C62H84N6O11S3
777374 DBCO-Cy5 for Copper-free Click Chemistry C64H86N6O11S3
760781 Dibenzocyclooctyne-fluor 488 for Copper-free Click Chemistry C39H26N2O7
761621 Fluor 488-Alkyne 95% (HPLC) C32H33N3O8
761613 Fluor 545-Alkyne for copper catalyzed click labeling C36H41N3O8
768693 NVOC2-Q-rhodamine-5-PEG3-azide 95% C55H56N8O19

Functionalized Alkynes

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764167 Alkyne-PEG5-acid C14H24O7
711926 (R)-3-Amino-5-hexynoic acid hydrochloride 95% C6H9NO2 · HCl
711918 (S)-3-Amino-5-hexynoic acid hydrochloride 94% C6H9NO2 · HCl
711942 (R)-3-(Boc-amino)-5-hexynoic acid 98% C11H17NO4
711934 (S)-3-(Boc-amino)-5-hexynoic acid 98% C11H17NO4
778923 N-Boc-4-pentyne-1-amine ≥95% (GC) C10H17NO2
712221 Boc-propargyl-Gly-OH ≥98.0% (HPLC) C10H15NO4
498289 3-Ethynylaniline ≥98% C8H7N
481122 4-Ethynylaniline 97% C8H7N
779407 4-Pentyn-1-amine ≥92.0% C5H9N
P50919 Propargylamine hydrochloride 95% C3H5N · HCl
460923 Propargyl chloroformate 96% C4H3ClO2
764221 Propargyl-N-hydroxysuccinimidyl ester C10H11NO5
775606 2,2,3,3-Tetramethyl-4,7,10,13,16-pentaoxa-3-silanonadec-18-yne 97% C17H34O5Si
778826 N-Z-4-pentyne-1-amine ≥95.0% (GC) C13H15NO2

Nucleoside/Nucleotide Azides/Alkynes

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A2169 3′-Azido-3′-deoxythymidine ≥98% (HPLC) C10H13N5O4
808539 γ-(2-Azidoethyl)-ATP sodium salt solution C12H19N8O13P3 · xNa+
808520 γ-[(6-Azidohexyl)-imido]-ATP sodium salt C16H28N9O12P3 · xNa+
T511293 (2′S)-2′-Deoxy-2′-fluoro-5-ethynyluridine, (F-ara-EdU) AldrichCPR C11H11FN2O5
T511307 5-Ethynyl-2′-deoxycytidine, (EdC) AldrichCPR C11H13N3O4
808490 N6-Propargyl-ATP sodium salt C13H18N5O13P3 · xNa+
808512 γ-[(Propargyl)-imido]-ATP sodium salt C13H19N6O12P3 · xNa+

Organic Azides

Since the preparation of the first organic azide, phenyl azide, by Peter Griess in 1864, this energy-rich and versatile class of compounds has enjoyed considerable interest. In more recent years, completely new perspectives have emerged, notably the use of organic azides for peptide synthesis, combinatorial synthesis, heterocycle synthesis, and the ligation or modification of biopolymers. The most prominent fields of application today are Huisgen 1,3-dipolar azide-alkyne cycloadditions and different variants of the Staudinger ligation. The azido group can also be used as a protecting group for primary amines, especially in sensitive substrates such as complex carbohydrates or peptide nucleic acids (PNA) and coordination compounds, as azides are stable to alkene metathesis conditions.

Sigma-Aldrich is proud to offer you a broad range of organic azides for your research.


Learn More about Organic Azides
Organic Azides and Azide Sources

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404764 4-Acetamidobenzenesulfonyl azide 97% C8H8N4O3S
771139 (E)-N-(2-Aminoethyl)-4-{2-[4-(3-azidopropoxy)phenyl]diazenyl}benzamide hydrochloride C18H21N7O2 · HCl
900919 Azidoacetic acid NHS ester New C6H6N4O4
276219 1-Azidoadamantane 97% C10H15N3
A1262 8-Azidoadenosine 3′:5′-cyclic monophosphate ~95% C10H11N8O6P
359556 4-Azidoaniline hydrochloride 97% C6H6N4 · HCl
573213 (4S)-4-[(1R)-2-Azido-1-(benzyloxy)ethyl]-2,2-dimethyl-1,3-dioxolane C14H19N3O3
493406 [3aS-(3aα,4α,5β,7aα)]-5-Azido-7-bromo-3a,4,5,7a-tetrahydro-2,2-dimethyl-1,3-benzodioxol-4-ol 99% C9H12BrN3O3
A2169 3′-Azido-3′-deoxythymidine ≥98% (HPLC) C10H13N5O4
CDS018989 2-azido-1-ethylquinolinium tetrafluoroborate AldrichCPR C11H11BF4N4
L511455 7-Azido-4-Methylcoumarin C10H7N3O2
244546 Azidomethyl phenyl sulfide 95% C7H7N3S
CDS018988 2-azido-1-methylquinolinium tetrafluoroborate AldrichCPR C10H9BF4N4
712256 5-Azidopentanoic acid ≥97.0% C5H9N3O2
A6057 4-Azidophenacyl bromide powder C8H6BrN3O
359564 4-Azidophenyl isothiocyanate 97% C7H4N4S
690104 3-(4-Azidophenyl)propionic acid ≥97.0% (T) C9H9N3O2
762016 3-Azido-1-propanamine 90% C3H8N4
776130 3-Azido-1-propanol ≥96% C3H7N3O
771066 tert-Butyl 2-(4-{[4-(3-azidopropoxy)phenyl]azo}benzamido)ethylcarbamate 95% C23H29N7O4
340138 4-Carboxybenzenesulfonazide 97% C7H5N3O4S
363227 4,4′-Diazido-2,2′-stilbenedisulfonic acid disodium salt hydrate 97% C14H8N6Na2O6S2 · xH2O
31755 7-(Diethylamino)coumarin-3-carbonyl azide BioReagent, suitable for fluorescence, ≥95% (HPLC) C14H14N4O3
E2028 Ethidium bromide monoazide ≥95% (HPLC), solid C21H18BrN5
77213 Ethyl azidoacetate solution ~25% in toluene (NMR) C4H7N3O2
93528 Ethyl azidoacetate solution ~25% in ethanol (NMR) C4H7N3O2
152854 4-Methoxybenzyloxycarbonyl azide 95% C9H9N3O3
R109 Ro 15-4513 solid C15H14N6O3

PEG Azides

PEG polymers contain numerous inherent favorable biological characteristics including high water solubility and a lack of toxicity and immunogenicity. Thus, the chemical modification of biologically active compounds, such as peptides, antibody fragments, enzymes, or small molecules with polyethylene glycol chains, referred to as “PEGylation”, often leads to improved pharmacokinetics and biological function in many applications. PEG azides are ideal starting materials for the synthesis of PEG derivatives via azide-alkyne cycloaddition or Staudinger ligation.

Learn More about PEG Azides
Polyethylene Glycol Building Blocks for PEGylation
Click Chemistry

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76318 O-(2-Aminoethyl)-O′-(2-azidoethyl)heptaethylene glycol ≥90% (oligomer purity) C18H38N4O8
77787 O-(2-Aminoethyl)-O′-(2-azidoethyl)nonaethylene glycol ≥90% (oligomer purity) C22H46N4O10
76172 O-(2-Aminoethyl)-O′-(2-azidoethyl)pentaethylene glycol ≥90% (oligomer purity) C14H30N4O6
727423 2-[2-(2-Azidoethoxy)ethoxy]ethanol solution ~0.5 M in tert-butyl methyl ether C6H13N3O3
71613 O-(2-Azidoethyl)-O-[2-(diglycolyl-amino)ethyl]heptaethylene glycol ≥90% (oligomer purity) C22H42N4O12
689440 O-(2-Azidoethyl)heptaethylene glycol ≥95% (oligomer purity) C16H33N3O8
712590 O-(2-Azidoethyl)-O′-methyl-triethylene glycol ≥90% (NMR) C9H19N3O4
712604 O-(2-Azidoethyl)-O′-methyl-undecaethylene glycol ≥90% (NMR) C25H51N3O12
804665 Azido-PEG4-phenyloxadiazole methylsulfone ≥95% C17H23N5O7S
744751 14-Azido-3,6,9,12-tetraoxatetradecanoic acid solution ~0.5 M in tert-butyl methyl ether, ≥90% (HPLC) C10H19N3O6
17758 11-Azido-3,6,9-trioxaundecan-1-amine technical, ≥90% (GC) C8H18N4O3
765953 1,11-Diazido-3,6,9-trioxaundecane C8H16N6O3
689807 Methoxypolyethylene glycol azide PEG average Mn 2,000  
689475 Methoxypolyethylene glycol azide  
689696 Polyoxyethylene bis(azide) 2000  
689580 Polyoxyethylene bis(azide) 5000  

Trifunctional Probe Building Blocks

Small-molecule probes are widely used in chemical biology research for target ID/validation and the interrogation of biological systems. In partnership with Pfizer chemists, we have compiled a collection of trifunctional building blocks to facilitate the design and synthetic development of chemical probes. Each contains three components: a connectivity group, a reactive group, and a bioorthogonal handle for downstream applications. Not only does the collection enable simultaneous incorporation of reactive groups, but the connectivity group (e.g. amine) can be leveraged to prepare libraries of probe analogs, allowing the biologist to screen for the optimal probe for a given assay.

To learn more about the building blocks and literature examples of their use, please check out our Technology Spotlight, Trifunctional Probe Building Blocks.

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900750 (4-(2-(2-(2-Aminoethoxy)ethoxy)ethoxy)phenyl)(4-(prop-2-yn-1-yloxy)phenyl)methanone HCl salt ≥95% New C22H25NO5 · HCl
900603 (4-(2-(2-Aminoethoxy)ethoxy)phenyl)(4-(prop-2-yn-1-yloxy)phenyl)methanone ≥95% New C20H21NO4
900599 (4-(Aminomethyl)phenyl)(4-(prop-2-yn-1-yloxy)phenyl)methanone 95% C17H15NO2
900598 (4-(Bromomethyl)phenyl)(4-(prop-2-yn-1-yloxy)phenyl)methanone ≥95% C17H13BrO2
900605 3-(Bromomethyl)-5-((trimethylsilyl)ethynyl)benzenesulfonyl fluoride ≥95% C12H14BrFO2SSi
900683 2-(3-(But-3-yn-1-yl)-3H-diazirin-3-yl)ethan-1-amine 95% C7H11N3
900616 3-(But-3-yn-1-yl)-3-(2-iodoethyl)-3H-diazirine ≥95% New C7H9IN2
900600 3-(Fluorosulfonyl)-5-((trimethylsilyl)ethynyl)benzoic acid ≥95% C12H13FO4SSi
900601 3-Formyl-5-((trimethylsilyl)ethynyl)benzenesulfonyl fluoride ≥95% C12H13FO3SSi
900865 4-Formyl-2-((trimethylsilyl)ethynyl)benzenesulfonyl fluoride ≥95% New C12H13FO3SSi
900617 (4-(Hydroxymethyl)phenyl)(4-(prop-2-yn-1-yloxy)phenyl)methanone ≥95% New C17H14O3
900611 (3-Hydroxyphenyl)(4-(prop-2-yn-1-yloxy)phenyl)methanone ≥95% C16H12O3
900615 (4-Hydroxyphenyl)(4-(prop-2-yn-1-yloxy)phenyl)methanone ≥95% C16H12O3
900619 4-(4-(Prop-2-yn-1-yloxy)benzoyl)benzaldehyde ≥95% C17H12O3
900614 3-(4-(Prop-2-yn-1-yloxy)benzoyl)benzoic acid ≥95% C17H12O4
900602 4-(4-(Prop-2-yn-1-yloxy)benzoyl)benzoic acid ≥95% C17H12O4
900613 5-(4-(4-(Prop-2-yn-1-yloxy)benzoyl)phenoxy)pentanoic acid ≥95% C21H20O5