Reagents for Chemical Synthesis

Fluorinating reagents and fluoroalkylation

The introduction of fluorine atoms or fluoroalkyl groups into active agents leads to greater effectiveness in many cases. This step frequently occurs in a late stage of synthesis. This process is reflected in the term “late-stage-fluorination”.

Gaseous fluorine, hydrogen fluoride, hydrogen fluoride pyridine mixtures, halogen fluorides (e.g. iodine pentafluoride), xenon difluoride, sulfonylfluorides, sulfur tetrafluoride (SF₄) and derivates such as DAST or quaternary ammonium fluorides are available to the chemist as reagents for fluorination, amongst others. Recent developments represent bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor®), 4-tert-Butyl-2,6-dimethylphenylsulfur trifluoride (Fluolead®) as well as (diethylamino)difluorosulfonium tetrafluoroborate (XtalFluor-E®) and difluoro(morpholino)sulfonium tetrafluoroborate (XtalFluor-M®).

Metal fluorides such as aluminium, antimony, silver, molybdenum or cobalt(III)-fluoride are used, depending on the substrate. You can also find gaseous fluorides such as arsenic pentafluoride (AsF₅) or rhenium hexafluoride (ReF₆) in the abcr catalogue.

You can also choose between the following for the fluoroalkylation of diverse reagents:

Fluoroiodomethane (FIM) represents an easy to handle reagent for the introduction of fluoromethyl groups. Trifluoromethyl or difluoromethyl groups can typically be transferred via so-called Togni reagents. These hypervalent iodine compounds act as electrophilic CF₃ sources, having been continuously refined over the years.

Besides electrophilic CH₂F, CHF₂ and CF₃ sources, nucleophilic, radical or carbenoid sources are also used. Many of these reagents are based on sulfonium or sulfonyl compounds, thus for instance the Umemoto reagents.

Other examples of trifluoromethylation reagents are represented by trifluoromethyltrimethylsilane (TMSCF₃), trifluoromethane (CHF₃), trifluoromethyliodide (CF₃I) and sodium trifluoromethanesulfinate (CF₃SO₂Na). On account of its instability, trifluoromethyllithium (CF₃Li) is not available to synthesis chemists. Complexed trifluorumethyl copper reagents provide alternatives here.

You can also find a series of trifluorumethoxy- or trifluoromethylthio-substituted building blocks in the abcr catalogue.

Although trifluoromethyl-substituted building blocks are long known, the corresponding pentafluoroethyl compounds have only become accessible recently. For the introduction of pentafluoroethyl groups, abcr recommends the new reagent tetraphenylphosphonium pentakis(pentafluoroethyl)stannate. This is available as a solid with long-term stability and does not require any gaseous educts.

Brominating reagents

Elementary bromine and phosphorus tribromide have long been known as common brominating reagents. However, these substances exhibit certain disadvantages in respect to their handling, dosing and toxicity. abcr offers you a safe and also highly selective alternative in the form of tetraalkylammonium nonabromide salts. These salts that are both stable in air and good to dose enable high selectivity when brominating double bonds, triple bonds or heterocycles.

Organometallic reagents: Grignard and organozinc compounds

Organic chemists have been utilising organometallic reagents for over 100 years. The organomagnesium halide compounds developed by the French chemist Victor Grignard are among the best known organometallic compounds under the collective terms “Grignard reagents”. Victor Grignard received the Nobel Prize for Chemistry in 1912 for his research.

The Grignard reaction represents one of the most important reactions for linking carbon-carbon bonds. The linking of carbon-phosphorus, carbon-silicon or carbon-boron bonds is also possible via Grignard reagents.

Alkyl- or aryl-magnesium halides react here as nucleophiles with electrophilic groups such as cyano- or carbonyl groups:

In combination with nickel salts (Kumada coupling) or copper salts, Grignard reagents are used for aryl-alkyl coupling reactions.

Grignard reagents are accessible from many alkyl and aryl halides. In many cases, however, electronic effects, steric hindrance or particularly high reactivity impede synthesis of the desired Grignard compounds. A complementary alternative exists in the form of organozinc halides in many of these cases.

Organozinc halides are primarily used in the transfer of alkenyl, benzyl, pyridyl or quinolinyl groups. As nickel or palladium-catalysed cross-coupling, this reaction was named by the term “Negishi reaction”.

Organozinc halides are somewhat less reactive than Grignard reagents and therefore easier to handle.

Organometallic reagents: Organolithium compounds

Organolithium compounds serve in organic chemistry as strong bases for deprotonation with simultaneous lithiation of the substrates or as alkylating reagents. A defined lithiation of aromatic compounds is typically obtained by ortho-directing groups such as amino or methoxy groups.

Like Grignard reagents, organolithium compounds react with electrophiles such as aldehydes, ketones and carboxylic acid esters. Brominations, iodinations and carboxylations are possible through reaction of the lithium organyls with elementary bromine and iodine or solid carbon dioxide (“dry ice”).

The best known representatives among the organolithium compounds are methyllithium (MeLi) as well as n-butyllithium (n-BuLi) and tert-butyllithium (t-BuLi). You can find these and other lithium organyls as solutions in various solvents in the abcr catalogue.

Derivatising reagents

Derivatising reagents are used in GC, GC/MS and NMR analytics. For applications in coupled gas chromatography/mass spectrometry, silylated and fluorinated amides such as N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA), N,O-bis(trimethylsilyl)acetamide or N-methyl-N-trimethylsilyltrifluoroacetamide (MSTFA) are used for derivatisation. Highly volatile or less stable substances are accessible to analytics in many cases by the introduction of a trimethylsilyl protecting group. A mixture known as a trimethylsilylation solution comprising hexamethyldisilazane (HMDS) and trimethylchlorsilane (TMSCl) is also used in industry.

In NMR analytics, enantiomer mixtures – in which both enantiomers exhibit the same NMR spectra in many cases – can be characterised by the addition of a suitable enantiomerically pure derivatising reagent. The resultant diastereomers exhibit different NMR spectra, thereby enabling a quantification of the enantiomers, determination of the ee value (“enantiomeric excess”) and optical purity. The carboxylic acid chlorides of (R) or (S)-α-methoxy-α-(trifluormethyl)phenylacetic acid have proven effective for determining the enantiomeric purity of chiral amines and alcohols. These are also referred to as Mosher’s acid chlorides.

Electrochemical and UV detectors are used amongst others in HPLC. The products are derivatised for electrochemical detection, e.g. with ferrocenyl groups. Fluorescence markers are used for derivatisation for UV detection.

Protecting group chemistry

The use of protecting groups has become firmly established in the field of peptide synthesis in particular. Amino and carboxy groups can be blocked selectively by using BOC (tert-butyloxycarbonyl), FMOC (fluorenylmethyloxycarbonyl), Cbz (benzyloxycarbonyl) or Trt (trityl) protecting groups. This enables the targeted build-up of di- or oligopeptides.

The carboxy groups are activated by activating reagents such as DCC (dicyclohexylcarbodiimide) or active esters of N-hydroxybenzotriazole (HOBt), 1-hydroxy-7-azabenzotriazole (HOOBt) and N-hydroxysuccinimide (HOSu).

You can also find other coupling reagents such as HATU, HCTU or TBTU in the abcr catalogue.

Depending on the substrate, the protecting groups is eliminated in a hydrogenolytic, basic or acidic manner. These different reaction conditions correspond to the orthogonality principle, according to which each protecting group can be eliminated individually and in any order when using different protecting groups, without one or the other protecting group being attacked.

Protecting groups are also used in organic synthesis. Hydroxy groups can be blocked with reagents such as TBDMS (tert-butyldimethylchlorosilane) or TMSCl (trimethylchlorosilane). Aldehyde functions can be stabilised as acetals by reaction with diols.

Boronic acids & esters

Suzuki coupling has become established as one of the most versatile cross-coupling reactions in organic chemistry. After discovering it, Aguri Suzuki received the Nobel Prize for Chemistry in 2010 together with Richard Heck and Ei-ichi Negishi.

For Suzuki coupling, aryl, alkenyl or alkyl boronic acids are reacted with aryl halides or vinyl halides via palladium catalysis, whereby new carbon-carbon bonds are linked. In case of reactive or unstable boronic acids, the corresponding boronic acid pinacol esters are available as a substitute. Potassium aryl and potassium alkyl trifluoroborates round off the pallet of boronic acids.

The abcr catalogue contains a broad spectrum of more than 8000 different boronic acids, pinacol esters and trifluoroborate salts. N-heterocyclic boronic acid MIDA esters are also part of our portfolio.

Use our structural search to find the boronic acid or building blocks of your choice!

Boranes

The main application of boranes of the formula B_xH_y lies in hydroboration. Born-hydrogen bonds add double and triple bonds by forming organoboranes. Although these organoboranes can be isolated, these are mostly reacted further in a further reaction step (e.g. an oxidation). Alcohols are derived from alkenes in this way.

Free borane (BH₃) is highly reactive, but can be stabilised well in the form of adducts. Borane tetrahydrofuran or borane dimethylsulfide adducts are available to chemists in the laboratory as easy to handle sources for BH₃.

The pinacol boranes Bpin-H and (Bpin)2 serve for the production of boronic acid pinacol esters and free boronic acids.

Oxidising agents

Familiar examples of oxidising agents are hydrogen peroxide H2O2 and potassium permanganate. Chromium (VI) compounds are also used in industry, but are problematic on account of their high toxicity. Cerium (IV) oxide (CeO2), silver (II) salts as well as halogen oxoacids and their salts (e.g. hypochlorite, periodate, bromate) are also used to a large extent in oxidation reactions.

In gunpowder, potassium nitrite forms the oxidizing component. Besides nitrate salts, nitric acids and peroxo-sulfuric acids are also used for oxidation purposes.

Reducing agents

Hydride reagents such as lithium aluminium hydride (LiAlH₄) or sodium borhydride (NaBH₄) are used actively as reducing agents in organic syntheses. Sodium bis(2-methoxyethoxy)aluminium hydride known by the trade name Vitride® represents an easy to handle alternative to pure hydrides. Pure alkaline and alkaline earth metals also have a strongly reductive effect, for instance sodium in the Birch reduction of aromatic compounds.

In combination with heterogeneous precious metal catalysts such as Pd/C or Pt/C, elementary hydrogen is used for reductions in industrial applications.

In the Fischer-Tropsch process, synthesis gas (mixture comprising CO/H₂) is converted into a series of gaseous or liquid hydrocarbons by heterogeneous iron or cobalt catalysis. Amongst other applications, these serve as low-sulfur synthetic fuels and engine oils.

In analytical chemistry, sodium sulfite, sodium dithionite and sodium thiosulfate are used for redox titrations.

Finally, hydrazine is used as rocket fuel in aerospace.

Solvents

You can find all common organic solvents from A for acetone to X for xylene in the abcr catalogue, in practical small containers for your application in the laboratory. For applications in analytics or biochemistry, we provide solvents in special purities.

Ionic liquids

Ionic liquids is the name given to molten salts with a melting temperature below 100 °C. They primarily comprise iminium cations and complex halide anions or other very weakly coordinated anions. The cations in ionic liquids are mostly substituted imidazolium, pyridinium, pyrrolidinium, guanidinium, piperidinium, morpholinium, ammonium or phosphonium ions. Triflates, tosylates, tetrafluoroborates, halides, trifluoroacetates, hexafluorophosphates or also amides are used as anions.

Ionic liquids are used as solvents for organic, inorganic and polymer synthesis. They also serve as electrolyte in fuel cells and batteries as well as in metallurgy.

Typical applications of ionic liquids in process technology include use as parting agents, lubricants and hydraulic fluids. On account of their ability to store and transfer heat, they are also used as coolants.

Other reagents at abcr

The Burgess reagent Burgess reagent was first described as a mild dehydration reagent in 1970. This reagent allows the production of alkenes from alcohols and cyano compounds from amides.

Schwartz's reagent CpZr(H)Cl reacts with alkene via hydrozirconation. The resultant alkyl zirconium complexes can typically be oxidised during hydroboration.

Photoinitiators decay after absorption of (UV) light (= photolysis) in reactive species, which can start (initiate) a (chain) reaction. Photoinitiators such as triaryl sulfonium, ferrocenium, diaryliodonium, or diazonium salts are therefore used as starters for radical or cationic polymerisations.