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79-490: A protecting group or protective group is introduced into a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction. It plays an important role in multistep organic synthesis . In many preparations of delicate organic compounds , specific parts of the molecules cannot survive the required reagents or chemical environments. These parts (functional groups) must be protected . For example, lithium aluminium hydride

158-652: A carbamate . When a carbamate deprotects, it evolves carbon dioxide . The commonest-used carbamates are the tert -butoxycarbonyl, benzoxycarbonyl, fluorenylmethylenoxycarbonyl, and allyloxycarbonyl compounds. Other, more exotic amine protectors are the phthalimides , which admit reductive cleavage, and the trifluoroacetamides, which hydrolyze easily in base. Indoles , pyrroles und imidazoles  — verily any aza-heterocycle — admit protection as N ‑sulfonylamides,which are far too stable with aliphatic amines. N ‑benzylated amines can be removed through catalytic hydrogenation or Birch reduction, but have

237-498: A chromophore , which is activated through radiation with an appropriate wavelength and so can be removed. For examples the o -nitrobenzylgroup ought be listed here. The rare double-layer protecting group is a protected protecting group, which exemplify high stability. The classical protecting groups for alcohols are esters , deprotected by nucleophiles ; triorganosilyl ethers , deprotected by acids and fluoride ions; and (hemi)acetals , deprotected by weak acids. In rarer cases,

316-515: A carbon ether might be used. The most important esters with common protecting-group use are the acetate , benzoate , and pivalate esters , for these exhibit differential removal. Sterically hindered esters are less susceptible to nucleophilic attack: Triorganosilyl sources have quite variable prices, and the most economical is chlorotrimethylsilane (TMS-Cl), a Direct Process byproduct. The trimethylsilyl ethers are also extremely sensitive to acid hydrolysis (for example silica gel suffices as

395-466: A carefully chosen catalyst can be used to hydrogenate some functional groups without affecting others, such as the hydrogenation of alkenes without touching aromatic rings, or the selective hydrogenation of alkynes to alkenes using Lindlar's catalyst . For example, when the catalyst palladium is placed on barium sulfate and then treated with quinoline , the resulting catalyst reduces alkynes only as far as alkenes. The Lindlar catalyst has been applied to

474-654: A curiosity than a useful technology. Heterogeneous catalysts for hydrogenation are more common industrially. In industry, precious metal hydrogenation catalysts are deposited from solution as a fine powder on the support, which is a cheap, bulky, porous, usually granular material, such as activated carbon , alumina , calcium carbonate or barium sulfate . For example, platinum on carbon is produced by reduction of chloroplatinic acid in situ in carbon. Examples of these catalysts are 5% ruthenium on activated carbon, or 1% platinum on alumina. Base metal catalysts, such as Raney nickel , are typically much cheaper and do not need

553-412: A decided drawback relative to the carbamates or amides: they retain a basic nitrogen. Carbamates: Other amides: Benzylamines: The most common protecting groups for carbonyls are acetals and typically cyclic acetals with diols. The runners-up used are also cyclic acetals with 1,2‑hydroxythiols or dithioglycols – the so-called O , S – or S , S -acetals. Overall, trans-acetalation plays

632-443: A few protecting groups can be detached oxidatively: the methoxybenzyl ethers, which oxidize to a quinomethide . They can be removed with ceric ammonium nitrate (CAN) or dichlorodicyanobenzoquinone (DDQ). Allyl compounds will isomerize to a vinyl group in the presence of noble metals . The residual enol ether (from a protected alcohol) or enamine (resp. amine) hydrolyzes in light acid. Photolabile protecting groups bear

711-458: A finely powdered form of nickel, which is widely used to catalyze hydrogenation reactions such as conversion of nitriles to amines or the production of margarine. In the 1930s, Calvin discovered that copper(II) complexes oxidized H 2 . The 1960s witnessed the development of well defined homogeneous catalysts using transition metal complexes, e.g., Wilkinson's catalyst (RhCl(PPh 3 ) 3 ). Soon thereafter cationic Rh and Ir were found to catalyze

790-425: A hydrogenation. This is achieved by either using a graduated tube containing a coloured liquid, usually aqueous copper sulfate or with gauges for each reaction vessel. Since many hydrogenation reactions such as hydrogenolysis of protecting groups and the reduction of aromatic systems proceed extremely sluggishly at atmospheric temperature and pressure, pressurised systems are popular. In these cases, catalyst

869-431: A large number of branched or ring alkanes that have specific names, e.g., tert-butyl , bornyl , cyclohexyl , etc. There are several functional groups that contain an alkene such as vinyl group , allyl group , or acrylic group . Hydrocarbons may form charged structures: positively charged carbocations or negative carbanions . Carbocations are often named -um . Examples are tropylium and triphenylmethyl cations and

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948-423: A lesser role in forming protective acetals; they are formed as a rule from glycols through dehydration. Normally a simple glycol like ethylene glycol or 1,3-propadiol is used for acetalation.Modern variants also use glycols, but with the hydroxyl hydrogens replaced with a trimethylsilyl group. Acetals can be removed in acidic aqueous conditions. For those ends, the mineral acids are appropriate acids. Acetone

1027-554: A metal catalyst. Hydrogenation can, however, proceed from some hydrogen donors without catalysts, illustrative hydrogen donors being diimide and aluminium isopropoxide , the latter illustrated by the Meerwein–Ponndorf–Verley reduction . Some metal-free catalytic systems have been investigated in academic research. One such system for reduction of ketones consists of tert -butanol and potassium tert-butoxide and very high temperatures. The reaction depicted below describes

1106-455: A molecule with distinctive chemical properties , regardless of the other atoms in the molecule. The atoms in a functional group are linked to each other and to the rest of the molecule by covalent bonds . For repeating units of polymers , functional groups attach to their nonpolar core of carbon atoms and thus add chemical character to carbon chains. Functional groups can also be charged , e.g. in carboxylate salts ( −COO ), which turns

1185-434: A proton donator) and are consequently rarely used nowadays as protecting groups. Aliphatic methyl ethers cleave with difficulty and only under drastic conditions, so that these are in general only used with quinonic phenols. However, hemiacetals and acetals are much easier to cleave. Esters: Silyl ethers: Benzyl ethers: Acetals: Other ethers: The 1,2‑diols ( glycols ) present for protecting-group chemistry

1264-579: A related sequence of steps: Alkene isomerization often accompanies hydrogenation. This important side reaction proceeds by beta-hydride elimination of the alkyl hydride intermediate: Often the released olefin is trans. The hydrogenation of nitrogen to give ammonia is conducted on a vast scale by the Haber–Bosch process, consuming an estimated 1% of the world's energy supply . Oxygen can be partially hydrogenated to give hydrogen peroxide , although this process has not been commercialized. One difficulty

1343-405: A rule, the introduction of a protecting group is straightforward. The difficulties honestly lie in their stability and in selective removal. Apparent problems in synthesis strategies with protecting groups are rarely documented in the academic literature. Orthogonal protection is a strategy allowing the specific deprotection of one protective group in a multiply-protected structure. For example,

1422-456: A special class of alcohols. One can exploit the adjacency of two hydroxy groups, e.g. in sugars , in that one protects both hydroxy groups codependently as an acetal . Common in this situation are the benzylidene , isopropylidene and cyclohexylidene or cyclopentylidene acetals. An exceptional case appears with the benzylideneprotecting group,which also admits reductive cleavage. This proceeds either through catalytic hydrogenation or with

1501-402: A suitable electrophile. For example, isophorone diamine, a precursor to the polyurethane monomer isophorone diisocyanate , is produced from isophorone nitrile by a tandem nitrile hydrogenation/reductive amination by ammonia, wherein hydrogenation converts both the nitrile into an amine and the imine formed from the aldehyde and ammonia into another amine. The earliest hydrogenation was that of

1580-613: A support. Also, in the laboratory, unsupported (massive) precious metal catalysts such as platinum black are still used, despite the cost. As in homogeneous catalysts, the activity is adjusted through changes in the environment around the metal, i.e. the coordination sphere . Different faces of a crystalline heterogeneous catalyst display distinct activities, for example. This can be modified by mixing metals or using different preparation techniques. Similarly, heterogeneous catalysts are affected by their supports. In many cases, highly empirical modifications involve selective "poisons". Thus,

1659-438: A temporary protection of the carbonyl group the presence of ketones as hemiaminal ions is shown below. Here it is applied, that aldehydes are very much more activated carbonyls than ketones and that many addition reactions are reversible. The most important protecting groups for carboxylic acids are the esters of various alcohols. Occasionally, esters are protected as ortho-esters or oxazolines . Many groups can suffice for

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1738-415: Is 2, 3, or 4), carbyne for methylidyne, and trityl for triphenylmethyl. Hydrogenation Hydrogenation is a chemical reaction between molecular hydrogen (H 2 ) and another compound or element, usually in the presence of a catalyst such as nickel , palladium or platinum . The process is commonly employed to reduce or saturate organic compounds . Hydrogenation typically constitutes

1817-403: Is a common cosolvent, used to promote dissolution. For a non-acidic cleavage technique, a palladium(II) chloride acetonitrile complex in acetone or iron(III) chloride on silica gel can be performed with workup in chloroform. Cyclic acetals are very much more stable against acid hydrolysis than acyclic acetals. Consequently acyclic acetals are used practically only when a very mild cleavage

1896-410: Is a highly reactive reagent that usefully reduces esters to alcohols . It always reacts with carbonyl groups, and cannot be discouraged by any means. When an ester must be reduced in the presence of a carbonyl, hydride attack on the carbonyl must be prevented. One way to do so converts the carbonyl into an acetal , which does not react with hydrides. The acetal is then called a protecting group for

1975-491: Is activity (speed of reaction) vs. cost of the catalyst and cost of the apparatus required for use of high pressures. Notice that the Raney-nickel catalysed hydrogenations require high pressures: Catalysts are usually classified into two broad classes: homogeneous and heterogeneous . Homogeneous catalysts dissolve in the solvent that contains the unsaturated substrate. Heterogeneous catalysts are solids that are suspended in

2054-488: Is added is called hydrogenolysis , a reaction that may occur to carbon-carbon and carbon-heteroatom ( oxygen , nitrogen or halogen ) bonds. Some hydrogenations of polar bonds are accompanied by hydrogenolysis. For hydrogenation, the obvious source of hydrogen is H 2 gas itself, which is typically available commercially within the storage medium of a pressurized cylinder. The hydrogenation process often uses greater than 1 atmosphere of H 2 , usually conveyed from

2133-473: Is added to a solution of reactant under an inert atmosphere in a pressure vessel . Hydrogen is added directly from a cylinder or built in laboratory hydrogen source, and the pressurized slurry is mechanically rocked to provide agitation, or a spinning basket is used. Recent advances in electrolysis technology have led to the development of high pressure hydrogen generators , which generate hydrogen up to 1,400 psi (100 bar) from water. Heat may also be used, as

2212-426: Is carried out at different temperatures and pressures depending upon the substrate and the activity of the catalyst. The same catalysts and conditions that are used for hydrogenation reactions can also lead to isomerization of the alkenes from cis to trans . This process is of great interest because hydrogenation technology generates most of the trans fat in foods. A reaction where bonds are broken while hydrogen

2291-493: Is not preferred in industrial syntheses, they are still used in industrial contexts, e.g. sucralose (sweetener) or the Roche synthesis of oseltamivir (Tamiflu, an antiviral drug) An important example of industrial applications of protecting group theory is the synthesis of ascorbic acid (Vitamin C) à la Reichstein . Functional group A functional group is a group of atoms in

2370-603: Is now known as the Sabatier process . For this work, Sabatier shared the 1912 Nobel Prize in Chemistry . Wilhelm Normann was awarded a patent in Germany in 1902 and in Britain in 1903 for the hydrogenation of liquid oils, which was the beginning of what is now a worldwide industry. The commercially important Haber–Bosch process , first described in 1905, involves hydrogenation of nitrogen. In

2449-556: Is preferred over functional class nomenclature (marked as suffix in table) for sulfides, disulfides, sulfoxides and sulfones. Compounds that contain phosphorus exhibit unique chemistry due to the ability of phosphorus to form more bonds than nitrogen, its lighter analogue on the periodic table. Compounds containing boron exhibit unique chemistry due to their having partially filled octets and therefore acting as Lewis acids . methyllithium methylmagnesium chloride trimethylaluminium trimethylsilyl triflate Fluorine

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2528-621: Is preventing the catalysts from triggering decomposition of the hydrogen peroxide to form water. Catalytic hydrogenation has diverse industrial uses. Most frequently, industrial hydrogenation relies on heterogeneous catalysts. The food industry hydrogenates vegetable oils to convert them into solid or semi-solid fats that can be used in spreads, candies, baked goods, and other products like margarine . Vegetable oils are made from polyunsaturated fatty acids (having more than one carbon-carbon double bond). Hydrogenation eliminates some of these double bonds. In petrochemical processes, hydrogenation

2607-405: Is required or when two different protected carbonyl groups must be differentiated in their liberation. Besides the O , O -acetals, the S , O - and S , S -acetals also have an application, albeit scant, as carbonyl protecting groups too. Thiols , which one begins with to form these acetals, have a very unpleasant stench and are poisonous, which severely limit their applications. Thioacetals and

2686-477: Is sometimes important to mask the acidic hydrogen atom. This normally proceeds from deprotonation (via a strong base like methylmagnesium bromide or butyllithium in tetrahydrofuran/ dimethylsulfoxide ) and subsequently reaction with chlorotrimethylsilane to a terminally TMS-protected alkyne. Cleavage follows hydrolytically – with potassium carbonate in methanol – or with fluoride ions like for example with tetrabutylammonium fluoride . In order to protect

2765-413: Is sufficient to raise the temperature of the oil by 1.6–1.7 °C per iodine number drop. However, the reaction rate for most hydrogenation reactions is negligible in the absence of catalysts. The mechanism of metal-catalyzed hydrogenation of alkenes and alkynes has been extensively studied. First of all isotope labeling using deuterium confirms the regiochemistry of the addition: On solids,

2844-407: Is that no other protecting group is attacked by the cleavage conditions. Lipases and other enzymes cleave ethers at biological pH (5-9) and temperatures (30–40 °C). Because enzymes have very high substrate specificity, the method is quite rare, but extremely attractive. Catalytic hydrogenation removes a wide variety of benzyl groups : ethers, esters, urethanes, carbonates, etc. Only

2923-420: Is too electronegative to be bonded to magnesium; it becomes an ionic salt instead. These names are used to refer to the moieties themselves or to radical species, and also to form the names of halides and substituents in larger molecules. When the parent hydrocarbon is unsaturated, the suffix ("-yl", "-ylidene", or "-ylidyne") replaces "-ane" (e.g. "ethane" becomes "ethyl"); otherwise, the suffix replaces only

3002-440: Is used to convert alkenes and aromatics into saturated alkanes (paraffins) and cycloalkanes (naphthenes), which are less toxic and less reactive. Relevant to liquid fuels that are stored sometimes for long periods in air, saturated hydrocarbons exhibit superior storage properties. On the other hand, alkenes tend to form hydroperoxides , which can form gums that interfere with fuel handling equipment. For example, mineral turpentine

3081-412: Is usually effected by adding solid catalyst to a round bottom flask of dissolved reactant which has been evacuated using nitrogen or argon gas and sealing the mixture with a penetrable rubber seal. Hydrogen gas is then supplied from a H 2 -filled balloon . The resulting three phase mixture is agitated to promote mixing. Hydrogen uptake can be monitored, which can be useful for monitoring progress of

3160-483: Is usually hydrogenated. Hydrocracking of heavy residues into diesel is another application. In isomerization and catalytic reforming processes, some hydrogen pressure is maintained to hydrogenolyze coke formed on the catalyst and prevent its accumulation. Hydrogenation is a useful means for converting unsaturated compounds into saturated derivatives. Substrates include not only alkenes and alkynes, but also aldehydes, imines, and nitriles, which are converted into

3239-476: Is virtually impossible (see also § Industrial applications ). A further important example of orthogonal protecting groups occurs in carbohydrate chemistry. As carbohydrates or hydroxyl groups exhibit very similar reactivities, a transformation that protects or deprotects a single hydroxy group must be possible for a successful synthesis. Many reaction conditions have been established that will cleave protecting groups. One can roughly distinguish between

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3318-540: The Fischer–Tropsch process , reported in 1922 carbon monoxide, which is easily derived from coal, is hydrogenated to liquid fuels. In 1922, Voorhees and Adams described an apparatus for performing hydrogenation under pressures above one atmosphere. The Parr shaker, the first product to allow hydrogenation using elevated pressures and temperatures, was commercialized in 1926 based on Voorhees and Adams' research and remains in widespread use. In 1924 Murray Raney developed

3397-402: The cyclopentadienyl anion. Haloalkanes are a class of molecule that is defined by a carbon– halogen bond. This bond can be relatively weak (in the case of an iodoalkane) or quite stable (as in the case of a fluoroalkane). In general, with the exception of fluorinated compounds, haloalkanes readily undergo nucleophilic substitution reactions or elimination reactions . The substitution on

3476-400: The hydroxyl functional group ( −OH ) and hydroxyls interact strongly with each other. Plus, when functional groups are more electronegative than atoms they attach to, the functional groups will become polar, and the otherwise nonpolar molecules containing these functional groups become polar and so become soluble in some aqueous environment. Combining the names of functional groups with

3555-405: The phosphonium borate 2 which can reduce simple hindered imines . The reduction of nitrobenzene to aniline has been reported to be catalysed by fullerene , its mono-anion, atmospheric hydrogen and UV light. Today's bench chemist has three main choices of hydrogenation equipment: The original and still a commonly practised form of hydrogenation in teaching laboratories, this process

3634-466: The Fmoc peptide synthesis, in which peptides are grown in solution and on solid phase, is very important. The protecting groups in solid-phase synthesis regarding the reaction conditions such as reaction time, temperature and reagents can be standardized so that they are carried out by a machine, while yields of well over 99% can be achieved. Otherwise, the separation of the resulting mixture of reaction products

3713-516: The accepted mechanism is the Horiuti- Polanyi mechanism: In the third step, the alkyl group can revert to alkene, which can detach from the catalyst. Consequently, contact with a hydrogenation catalyst allows cis-trans -isomerization. The trans -alkene can reassociate to the surface and undergo hydrogenation. These details are revealed in part using D 2 (deuterium), because recovered alkenes often contain deuterium. For aromatic substrates,

3792-430: The addition of pairs of hydrogen atoms to a molecule, often an alkene . Catalysts are required for the reaction to be usable; non-catalytic hydrogenation takes place only at very high temperatures. Hydrogenation reduces double and triple bonds in hydrocarbons . Hydrogenation has three components, the unsaturated substrate, the hydrogen (or hydrogen source) and, invariably, a catalyst . The reduction reaction

3871-595: The alcoholic component, and the specific cleaving conditions are contrariwise generally quite similar: each ester can be hydrolyzed in a basic water-alcohol solution. Instead, most ester protecting groups vary in how mildly they can be formed from the original acid. Alkenes rarely need protection or are protected. They are as a rule only involved in undesired side reactions with electrophilic attack, isomerization or catalytic hydration. For alkenes two protecting groups are basically known: For alkynes there are in any case two types of protecting groups. For terminal alkynes it

3950-434: The amino acid tyrosine could be protected as a benzyl ester on the carboxyl group, a fluorenylmethylenoxy carbamate on the amine group, and a tert -butyl ether on the phenol group. The benzyl ester can be removed by hydrogenolysis, the fluorenylmethylenoxy group (Fmoc) by bases (such as piperidine), and the phenolic tert -butyl ether cleaved with acids (e.g. with trifluoroacetic acid). A common example for this application,

4029-437: The application of pressures from atmospheric to 1,450 psi (100 bar). Elevated temperatures may also be used. At the bench scale, systems use a range of pre-packed catalysts which eliminates the need for weighing and filtering pyrophoric catalysts. Catalytic hydrogenation is done in a tubular plug-flow reactor packed with a supported catalyst. The pressures and temperatures are typically high, although this depends on

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4108-555: The carbon, the acidity of an adjacent proton, the solvent conditions, etc. all can influence the outcome of the reactivity. Compounds that contain C-O bonds each possess differing reactivity based upon the location and hybridization of the C-O bond, owing to the electron-withdrawing effect of sp-hybridized oxygen (carbonyl groups) and the donating effects of sp -hybridized oxygen (alcohol groups). [REDACTED] Compounds that contain nitrogen in this category may contain C-O bonds, such as in

4187-647: The carbonyl. After the hydride step is complete, aqueous acid removes the acetal, restoring the carbonyl. This step is called deprotection . Protecting groups are more common in small-scale laboratory work and initial development than in industrial production because they add additional steps and material costs. However, compounds with repetitive functional groups – generally, biomolecules like peptides , oligosaccharides or nucleotides – may require protecting groups to order their assembly. Also, cheap chiral protecting groups may often shorten an enantioselective synthesis (e.g. shikimic acid for oseltamivir ). As

4266-428: The case of amides . (acetimidamide) alkyl nitrate alkyl nitrite [REDACTED] [REDACTED] [REDACTED] 4-pyridyl (pyridin-4-yl) 3-pyridyl (pyridin-3-yl) 2-pyridyl (pyridin-2-yl) Compounds that contain sulfur exhibit unique chemistry due to sulfur's ability to form more bonds than oxygen, its lighter analogue on the periodic table. Substitutive nomenclature (marked as prefix in table)

4345-583: The catalyst, with most sites covered by the substrate. In heterogeneous catalysts, hydrogen forms surface hydrides (M-H) from which hydrogens can be transferred to the chemisorbed substrate. Platinum , palladium , rhodium , and ruthenium form highly active catalysts, which operate at lower temperatures and lower pressures of H 2 . Non-precious metal catalysts, especially those based on nickel (such as Raney nickel and Urushibara nickel ) have also been developed as economical alternatives, but they are often slower or require higher temperatures. The trade-off

4424-639: The conversion of phenylacetylene to styrene . Transfer hydrogenation uses hydrogen-donor molecules other than molecular H 2 . These "sacrificial" hydrogen donors, which can also serve as solvents for the reaction, include hydrazine , formic acid , and alcohols such as isopropanol. In organic synthesis , transfer hydrogenation is useful for the asymmetric hydrogenation of polar unsaturated substrates, such as ketones , aldehydes and imines , by employing chiral catalysts . Polar substrates such as nitriles can be hydrogenated electrochemically , using protic solvents and reducing equivalents as

4503-508: The corresponding saturated compounds, i.e. alcohols and amines. Thus, alkyl aldehydes, which can be synthesized with the oxo process from carbon monoxide and an alkene, can be converted to alcohols. E.g. 1-propanol is produced from propionaldehyde, produced from ethene and carbon monoxide. Xylitol , a polyol , is produced by hydrogenation of the sugar xylose , an aldehyde. Primary amines can be synthesized by hydrogenation of nitriles , while nitriles are readily synthesized from cyanide and

4582-535: The cylinders and sometimes augmented by "booster pumps". Gaseous hydrogen is produced industrially from hydrocarbons by the process known as steam reforming . For many applications, hydrogen is transferred from donor molecules such as formic acid , isopropanol , and dihydroanthracene . These hydrogen donors undergo dehydrogenation to, respectively, carbon dioxide , acetone , and anthracene . These processes are called transfer hydrogenations . An important characteristic of alkene and alkyne hydrogenations, both

4661-501: The equilibirum lies on the side of the acetal. In contradistinction to the O , O ‑acetal case, it is not needed to remove water from the reaction mixture in order to shift the equilibrium. S , O -Acetals are hydrolyzed a factor of 10,000 times faster than the corresponding S , S -acetals. Their formation follows analogously from the thioalcohol. Also their cleavage proceeds under similar conditions and predominantly through mercury(II) compounds in wet acetonitrile. For aldehydes,

4740-541: The final "-e" (e.g. " ethyne " becomes " ethynyl "). When used to refer to moieties, multiple single bonds differ from a single multiple bond. For example, a methylene bridge (methanediyl) has two single bonds, whereas a methylidene group (methylidene) has one double bond. Suffixes can be combined, as in methylidyne (triple bond) vs. methylylidene (single bond and double bond) vs. methanetriyl (three double bonds). There are some retained names, such as methylene for methanediyl, 1,x- phenylene for phenyl-1,x-diyl (where x

4819-401: The first hydrogenation is slowest. The product of this step is a cyclohexadiene, which hydrogenate rapidly and are rarely detected. Similarly, the cyclohexene is ordinarily reduced to cyclohexane. In many homogeneous hydrogenation processes, the metal binds to both components to give an intermediate alkene-metal(H) 2 complex. The general sequence of reactions is assumed to be as follows or

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4898-446: The following environments: Various groups are cleaved in acid or base conditions, but the others are more unusual. Fluoride ions form very strong bonds to silicon ; thus silicon protecting groups are almost invariably removed by fluoride ions. Each type of counterion, i.e. cleavage reagent, can also selectively cleave different silicon protecting groups depending on steric hindrance . The advantage of fluoride-labile protecting groups

4977-418: The gamma-amine in gamma-aminobutyric acid is on the third carbon of the carbon chain attached to the carboxylic acid group. IUPAC conventions call for numeric labeling of the position, e.g. 4-aminobutanoic acid. In traditional names various qualifiers are used to label isomers , for example, isopropanol (IUPAC name: propan-2-ol) is an isomer of n-propanol (propan-1-ol). The term moiety has some overlap with

5056-402: The homogeneously and heterogeneously catalyzed versions, is that hydrogen addition occurs with " syn addition ", with hydrogen entering from the least hindered side. This reaction can be performed on a variety of different functional groups . With rare exceptions, H 2 is unreactive toward organic compounds in the absence of metal catalysts. The unsaturated substrate is chemisorbed onto

5135-510: The hydride donor diisobutyl aluminum hydride (DIBAL). The cleavage with DIBAL deprotects one alcohol group, for the benzyl moiety stays as a benzyl ether on the second, sterically hindered hydroxy group. Amines have a special importance in peptide synthesis , but are a quite potent nucleophile and also relatively strong bases . These characteristics imply that new protecting groups for amines are always under development. Amine groups are primarily protected through acylation , typically as

5214-399: The hydrogenation of benzophenone : A chemical kinetics study found this reaction is first-order in all three reactants suggesting a cyclic 6-membered transition state . Another system for metal-free hydrogenation is based on the phosphine - borane , compound 1 , which has been called a frustrated Lewis pair . It reversibly accepts dihydrogen at relatively low temperatures to form

5293-411: The hydrogenation of alkenes and carbonyls. In the 1970s, asymmetric hydrogenation was demonstrated in the synthesis of L-DOPA , and the 1990s saw the invention of Noyori asymmetric hydrogenation . The development of homogeneous hydrogenation was influenced by work started in the 1930s and 1940s on the oxo process and Ziegler–Natta polymerization . For most practical purposes, hydrogenation requires

5372-410: The mixed S , O -acetals are, unlike the pure O , O -acetals, very much stabler against acid hydrolysis. This enables the selective cleavage of the latter in the presence of sulfur -protected carbonyl groups. The formation of S , S -acetals normally follows analogously to the O , O -acetals with acid catalysis from a dithiol and the carbonyl compound. Because of the greater stability of thioacetals,

5451-449: The molecule into a polyatomic ion or a complex ion . Functional groups binding to a central atom in a coordination complex are called ligands . Complexation and solvation are also caused by specific interactions of functional groups. In the common rule of thumb "like dissolves like", it is the shared or mutually well-interacting functional groups which give rise to solubility . For example, sugar dissolves in water because both share

5530-452: The names of the parent alkanes generates what is termed a systematic nomenclature for naming organic compounds . In traditional nomenclature, the first carbon atom after the carbon that attaches to the functional group is called the alpha carbon ; the second, beta carbon, the third, gamma carbon, etc. If there is another functional group at a carbon, it may be named with the Greek letter, e.g.,

5609-502: The platinum-catalyzed addition of hydrogen to oxygen in the Döbereiner's lamp , a device commercialized as early as 1823. The French chemist Paul Sabatier is considered the father of the hydrogenation process. In 1897, building on the earlier work of James Boyce , an American chemist working in the manufacture of soap products, he discovered that traces of nickel catalyzed the addition of hydrogen to molecules of gaseous hydrocarbons in what

5688-404: The pressure compensates for the associated reduction in gas solubility. Flow hydrogenation has become a popular technique at the bench and increasingly the process scale. This technique involves continuously flowing a dilute stream of dissolved reactant over a fixed bed catalyst in the presence of hydrogen. Using established high-performance liquid chromatography technology, this technique allows

5767-471: The same solvent with the substrate or are treated with gaseous substrate. Some well known homogeneous catalysts are indicated below. These are coordination complexes that activate both the unsaturated substrate and the H 2 . Most typically, these complexes contain platinum group metals, especially Rh and Ir. Homogeneous catalysts are also used in asymmetric synthesis by the hydrogenation of prochiral substrates. An early demonstration of this approach

5846-425: The source of hydrogen. The addition of hydrogen to double or triple bonds in hydrocarbons is a type of redox reaction that can be thermodynamically favorable. For example, the addition of hydrogen to ethene has a Gibbs free energy change of -101 kJ·mol , which is highly exothermic . In the hydrogenation of vegetable oils and fatty acids, for example, the heat released, about 25 kcal per mole (105 kJ/mol),

5925-407: The symbols R and R' usually denote an attached hydrogen, or a hydrocarbon side chain of any length, but may sometimes refer to any group of atoms. Hydrocarbons are a class of molecule that is defined by functional groups called hydrocarbyls that contain only carbon and hydrogen, but vary in the number and order of double bonds. Each one differs in type (and scope) of reactivity. There are also

6004-406: The term "functional group". However, a moiety is an entire "half" of a molecule, which can be not only a single functional group, but also a larger unit consisting of multiple functional groups. For example, an "aryl moiety" may be any group containing an aromatic ring , regardless of how many functional groups the said aryl has. The following is a list of common functional groups. In the formulas,

6083-427: The triple bond itself, sometimes a transition metal-alkyne complex with dicobalt octacarbonyl is used. The release of the cobalt then follows from oxidation. The use of protective groups is pervasive but not without criticism. In practical terms their use adds two steps (protection-deprotection sequence) to a synthesis, either or both of which can dramatically lower chemical yield . Crucially, added complexity impedes

6162-409: The use of synthetic total synthesis in drug discovery . In contrast biomimetic synthesis does not employ protective groups. As an alternative, Baran presented a novel protective-group free synthesis of the compound hapalindole U. The previously published synthesis according to Baran, contained 20 steps with multiple protective group manipulations (two confirmed): Although the use of protecting groups

6241-520: Was the Rh-catalyzed hydrogenation of enamides as precursors to the drug L-DOPA . To achieve asymmetric reduction, these catalyst are made chiral by use of chiral diphosphine ligands. Rhodium catalyzed hydrogenation has also been used in the herbicide production of S-metolachlor, which uses a Josiphos type ligand (called Xyliphos). In principle asymmetric hydrogenation can be catalyzed by chiral heterogeneous catalysts, but this approach remains more of

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