Lithium diisopropylamide (LDA)-Preparation and usage

Lithium diisopropylamide is the chemical compound with the formula [(CH₃)₂CH]₂NLi.  Generally abbreviated LDA, it is a strong base used in organic chemistry for the deprotonation of weakly acidic compounds. The reagent has been widely accepted because it is soluble in non-polar organic solvents and it is non-pyrophoric. LDA is a non-nucleophilic base. Potassium diisopropylamide (KDA) is a similar compound, but it has a potassium cation instead of a lithium cation.  LDA is cheaper than KDA and is more widely used.

Preparation:

In the preparation of lithium diisopropylamide (LDA), the only other product is the gaseous alkane butane.  Because of its solubility in THF, LDA is a widely used base for enolate anion formation. In this application one equivalent of diisopropylamine is produced along with the lithium enolate, but this normally does not interfere with the enolate reactions and is easily removed from the products by washing with aqueous acid.

                

(2R,5S)-2-tert-Butyl-5-methyl-1-aza-3-oxabicyclo[3.3.0]octan-4-one: In a 250-mL, round-bottomed flask equipped with a magnetic stirrer, 18.3 mL (0.131 mol) of diisopropylamine is mixed with 120 mL of dry tetrahydrofuran (THF) under argon. At −78 °C bath temperature, 88.6 mL of a 1.6 M solution of butyllithium (0.142 mol) in hexane is added and the mixture is allowed to warm to room temperature for 20 min. After the mixture is recooled to −78 °C, the lithium diisopropylamide (LDA) solution is added over a period of 20 min to a solution of 20.0 g (0.109 mol) of (2R,5S)-2-tert-butyl-1-aza-3-oxabicyclo[3.3.0]octan-4-one in 600 mL of dry THF in a 1-L, round-bottomed flask, precooled to −78 °C. Tetrahydrofuran (20 mL) is used to rinse the 250-mL flask. After keeping the resulting solution at −78 °C for 45 min, 8.8 mL (0.142 mol) of iodomethane   is added over a period of 10 min. The resulting mixture is allowed to warm to 0 °C over a period of 3 hr, and 300 mL of a saturated aqueous solution of ammonium chloride is added. After separation, the organic layer is washed with 300 mL each of saturated aqueous solutions of sodium carbonate and brine. Each aqueous layer is extracted twice with 200 mL of ethyl acetate. The combined organic layers are dried over magnesium sulfate and the solvent is removed in a rotary evaporator at ca. 15 mm. Traces of solvent are removed by drying the residue at 60 °C/0.05 mm for 2 hr under an oil pump vacuum to yield19.8–20.5 g (0.100–0.104 mol, 93–95%) of the desired product. It is used directly in the next step.

Reference: Organic Syntheses, Coll. Vol. 9, p.626 (1998); Vol. 72, p.62 (1995)

Stability:

Since i-Pr₂NLi is a sufficiently strong base to deprotonate and cleave solvents such as Et₂O, THF, and especially DME and HMP [(Me₂N)₃PO] at temperatures above 0 ^oC, it is not practical to prepare stock solutions of i-Pr₂NLi in these solvents. However, we have found that if commercial solutions of n-BuLi in hexane are diluted with additional hexane or pentane and then treated with 1 molar equiv of i-Pr₂NH, stable solutions of i-Pr₂NLi (0.5-0.6 M) in hexane or hexane-pentane mixtures are formed. Provided that these hexane solutions are not cooled or concentrated to induce the irreversible separation of solid i-Pr₂NLi, they may be standardized (titration with 2,2'-bipyridyl indicator) and stored at 25 ^oC without deterioration for weeks. Thus, it is especially convenient to prepare solutions of i-Pr₂NLi for reactions by adding a known volume of the stable hexane solution to the desired volume of cold (<O ^oC) ethereal solvent such as Et₂0 or THF.

Chromium Reagents (Chromate)

All forms of Cr(VI) are powerful oxidizing agents, and oxidize any CH bonds on a carbon with an oxygen as far as possible without breaking any carbon-carbon bonds; for example, secondary alcohols are converted to ketones, and aldehydes to carboxylic acids. The most common reagents are: H₂CrO₄; K₂Cr₂O₇ + H₂SO₄; CrO₃ + H₂SO₄; they are approximately equivalent. They oxidize the activated CH bonds next to an aromatic ring, the "benzyl" hydrogens, so completely that they usually convert any alkyl benzene to a benzoic acid. Cr(VI) reagents are so powerful that they can also oxidize alkenes and alkynes, breaking the carbon-carbon bond as ozone does, but this reaction is not synthetically useful.

In non-aqueous solutions, oxidation by Cr(VI) does not go to completion (the intermediate partially oxidized material containing Cr must be hydrolyzed for oxidation to continue); thus, under these conditions, primary alcohols may be oxidized to aldehydes without forming carboxylic acid. The most common reagents for this partial oxidation are: PCC, or pyridinium chlorochromate (formed by dissolving CrO₃ and HCl in pyridine); Collins reagent (CrO₃ in CH₂Cl₂); chromyl chloride (CrO₂Cl₂).

Some of the oxidizing reagents containing Cr(VI) are listed below:

Sarett reagent: CrO₃.2C₅H₅N     (where C₅H₅N = pyridine): The highly exothermic reaction of chromium trioxide when added to an excess of pyridine leads to the formation the CrO₃ • 2 Py complex (Sarett Reagent). Compared to the Jones Reagent, Sarett Reagent allows the oxidation of various primary alcohols to aldehydes due to the non-aqueous conditions (see  Jones Oxidation for an explanation). Unfortunately, the complex is highly hygroscopic and the preparation of the reagent is not without risk because the solvent occasionally catches fire during preparation. In addition, the use of pyridine as solvent does not permit the oxidation of base-sensitive substrates.

The reagent is named after the American chemist Lewis Hastings Sarett (1917– 1999).

Collins reagent: CrO₃.2C₅H₅N diluted in CH₂Cl₂ : A solution of CrO₃ • 2 Py (Sarett Reagent) in methylene chloride is called the "Collins Reagent". One advantage over the Sarett Reagent is that the addition of one equivalent chromium trioxide to a stirred solution of two equivalents of pyridine in methylene chloride allows the convenient and safe preparation of the oxidant. In addition, the use of methylene chloride as solvent and stoichiometric amounts of pyridine makes the Collins Reagent less basic than the Sarett Reagent. Thus, most acid and base-sensitive substrates can be oxidized with Collins Reagent, unlike both the Sarett and Jones Reagent.

As the Collins Reagent does not contain water (compared to the Jones Reagent) and is not as hygroscopic as is the Sarett Reagent, the oxidant is especially useful for the oxidation of primary alcohols to aldehydes where traces of water can lead to overoxidation.

This complex is both difficult and dangerous to prepare, as it is very hygroscopic and can inflame during preparation. It is typically used in a sixfold excess in order to complete the reaction. Nowadays, PCC or PDC oxidation have largely supplanted Collins oxidation for these very reasons.

Cornforth reagent: CrO₃/ Pyridine / H₂O: The Cornforth reagent or pyridinium dichromate (PDC) is a pyridinium salt of dichromate with the chemical formula [C₅H₅NH]2[Cr₂O₇]. This compound is named after the Australian-British chemist Sir John Warcup Cornforth (born. 1917) who introduced it in 1962. The Cornforth reagent is a strong oxidizing agent which can convert primary and secondary alcohols to aldehydes and ketones respectively. In its chemical structure and functions it is closely related to other compounds made from hexavalent chromium oxide, such as pyridinium chlorochromate and Collins reagent. Because of their toxicity, these reagents are rarely used nowadays.

The Cornforth reagent is prepared by slow addition of a concentrated aqueous solution of chromium trioxide to pyridine. The reaction may cause explosion, which is avoided by thoroughly dissolving the trioxide in water and cooling the solution by ice. The product is filtered, washed with acetone and dried, yielding an orange powder. The powder is stable in air, not particularly hygroscopic and has an almost neutral pH that facilitates its handling; it is only slightly acidic owing to the presence of pyridinium cations. The Cornforth reagent is readily soluble in water, dimethylformamide and dimethyl sulfoxide (DMSO). It is poorly soluble in acetone and chlorinated organic solvents, such as dichloromethane, and forms suspensions.

The oxidation is usually carried out at ambient conditions, in nearly neutral pH conditions, in dimethylformamide or dichloromethane or their mixture. The choice of solvent or their ratio affects the reaction rate; in particular, higher content of dimethylformamide results in stronger oxidation. The slow oxidation rate for some alcohols can be accelerated by the addition of molecular sieves, organic acids or acetic anhydride or of their combinations. The acceleration by molecular sieves works best when their pore diameter is about 0.3 nm, and it is apparently unrelated to their water absorption capability. Among organic acids, acetic acid, pyridinium trifluoroacetate or pyridinium tosylate can be added, the first one being most efficient and easiest to remove. The achieved acceleration is remarkable, but the reaction inevitably turns from neutral (pH) to acidic. Comparable acceleration is achieved with acetic anhydride, which is used in sugar and nucleoside chemistry. Reaction acceleration depends not only on the additives but also on their form, so all reagents are preferred dry and freshly prepared, and PDC and molecular sieves should be finely ground. The disadvantange of the accelerators is that they may simultaneously promote several oxidation routes thereby reducing the selectivity of the reaction.

Fieser reagent: CrO₃ in acetic acid: Fieser's reagent is a mixture of chromium trioxide in acetic acid.

Jones reagent: CrO₃ + H₂SO₄ : The Jones Reagent is a solution of chromium trioxide in diluted sulfuric acid that can be used safely for oxidations of organic substrates in acetone. The reagent can also be prepared from sodium dichromate and potassium dichromate. Jones Reagent is especially suitable for the oxidation of secondary alcohols to ketones and of primary alcohols to carboxylic acids and in a few cases to aldehydes (Jones Oxidation). Some alternative chromium reagents allow the selective preparation of aldehydes, such as PCC and PDC.

Although the reagent is very acidic, the substrate in acetone is essentially titrated with the oxidant solution and only very acid-sensitive groups are incompatible. For example esters, even tert-butyl esters, remain unchanged. The concentration of sulfuric acid can be decreased to minimize side reactions, although the oxidation power increases too.

Depending on the reaction conditions, the aldehydes may then be converted to carboxylic acids. For oxidations to the aldehydes and ketones, two equivalents of chromic acid oxidize three equivalents of the alcohol:

2 HCrO₄^– + 3 RR'C(OH)H + 8 H⁺ + 4 H₂O → 2 [Cr(H₂O)₆]³⁺ + 3 RR'CO

For oxidation of primary alcohols to carboxylic acids, one equivalent of Jones reagent is required for each substrate. The aldehyde is an intermediate.

4 HCrO₄^– + 3 RCH₂OH + 16 H⁺ + 11 H₂O → 4 [Cr(H₂O)₆]³⁺ + 3 RCOOH

The inorganic products are green, characteristic of chromium(III) aquo complexes.  Although the reagent is very acidic, the substrate in acetone is essentially titrated with the oxidant solution and only very acid-sensitive groups are incompatible. For example esters, even tert-butyl esters, remain unchanged. The concentration of sulfuric acid can be decreased to minimize side reactions, although the oxidation power increases too.

Thiele reagent: CrO₃ + acetic anhydride + H₂SO₄

Corey-Suggs reagent (Pyridinium Chlorochromate (PCC) in CH₂Cl₂): [C₅H₅NH]+[CrO₃Cl]^-

Corey-Schmidt reagent (Pyridinium Dichromate (PDC) in CH₂Cl₂ or DMF):(C₅H₅NH)₂Cr₂O₇

Brown-Garg H2CrO4/(ether or benzene)/water

Kiliani Reagent H2CrO4 /H2SO4/ water/ acetic acid

Chromic anhydride CrO3/ water/ acetic acid

Snatze Reagent CrO3/ DMF

CrO3/ acetic anhydride/ acetic acid

CrO3 /HMPT

All the above reagents can be used with co-catalysts like mercuric acetate, ceric ammonium nitrate, manganous nitrate, oxalic acid and special effects come with controlled amounts of water in the reagent.

ATTENTION: Cr(VI) reagents have been shown to be carcinogenic, upon ingestion either through the stomach or the lungs. Not many years ago chromic acid solutions were the way to clean glassware (they remove organic compounds very well and leave the glass sparkling). They have been shown to leave traces of Cr(VI) on the glass, which can be death to a Grignard reagent, for example. The cancer-causing properties have resulted in strict regulations for disposal (you can't!), and thus these reagents are no longer used routinely. Interestingly, the chromate (CrO4-) looks like sulfate to cells, and is readily incorporated. Once in the cell, it oxidizes something and is converted to Cr(III); the Cr(III) looks a lot like Zn(II) and other biologically important ions. It is the Cr(III) that actually causes the damage that leads to cancer but the Cr(III) itself cannot get into the cells - it has to enter as Cr(VI).

Pyridinium Chlorochromate (PCC) Corey-Suggs Reagent

Pyridinium chlorochromate is a reddish orange solid reagent used to oxidize primary alcohols to aldehydes and secondary alcohols to ketones. Pyridinium chlorochromate, or PCC, will not fully oxidize a primary alcohol to the carboxylic acid as does the Jones reagent. A disadvantage to using PCC is its toxicity. PCC was developed by Elias James Corey and William Suggs in 1975.  Pyridinium dichromate has the advantage of being less acidic than its class of oxidizing agents.

Preparation:

First chlorochromic acid is prepared by the dissolution of chromium trioxide in 6M aq. hydrochloric acid. Addition of pyridine gives pyridinium chlorochromate as orange crystals.

The properties of PCC can be compared with those of PDC: it is not particularly hygroscopic, is stable, commercial available and can be stored. PCC is soluble in many organic solvents, and especially dichloromethane at room temperature has been used in most cases, whereas DMF promotes the over-oxidation of primary alcohols into carboxylic acids.

PCC is more acidic than PDC, but acid-labile compounds can be oxidized in the presence of sodium acetate or other buffers such as carbonates. Another drawback is the formation of viscous materials that complicate product isolation. Addition of Celite, powdered molecular sieves or magnesium sulfate to PCC oxidation reaction mixtures can simplify the work-up, because the reduced chromium salts and other reagent-derived byproducts are deposited onto these solids, which can then be readily removed by filtration.

How does it work?

Oxidation reactions of this sort are actually a kind of elimination reaction. We’re going from a carbon-oxygen single bond to a carbon-oxygen double bond. The elimination reaction can occur because we’re putting a good leaving group on the oxygen, namely the chromium, which will be displaced when the neighboring C-H bond is broken with a base.

Attention: Chromium (VI) compounds are toxic and must be handled with care as it is a known carcinogen. Other methods for oxidizing alcohols using less toxic reagents have been introduced and are more preferred by green chemists:

• DMSO-based oxidations (Swern oxidation, Moffatt oxidation)
• hypervalent iodine based oxidation (such as the Dess-Martin periodinane)

Procedures:

A 500-mL, round-bottomed flask equipped with a 4.5-cm, egg-shaped Teflon-coated magnetic stir bar is charged with 130 mL of CH₂Cl₂, the alcohol (10.4 g, 40.0 mmol), and 15 g of freshly powdered 3 Å molecular sieves. Pyridinium chlorochromate (21.5 g, 100 mmol) is added portionwise over 10 min and the resulting mixture is stirred at room temperature for 15 hr. Ether (200 mL) is added slowly with vigorous stirring and the solution is filtered under vacuum through a pad of 35 g of Celite. The solids remaining in the reaction flask are transferred to the Celite pad by scraping with a spatula and washing with three 50-mL portions of ether. The resulting cloudy brown filtrate is concentrated by rotary evaporation at room temperature to give a brown solid. To this solid is added 25 mL of 1:1 ether:hexane and the solids are scraped with a spatula. The mixture is then poured onto 60 g of Whatman 60 Å (230-400 mesh) silica gel packed in a 4-cm diameter chromatography column and the liquid is adsorbed onto the silica gel by gravity. The material remaining in the flask is further washed with 1:1 ether:hexane and transferred onto the silica gel; this process is repeated until all the material has been loaded onto the silica gel. The ketone is eluted using 500 mL of 1:1 ether:hexane and the eluent is concentrated by rotary evaporation to afford the crude ketone as a white solid. This material is dissolved in 40-45 mL of boiling hexane. Upon cooling the solution to room temperature, the ketone begins to crystallize. The flask is then cooled to −25°C for 2 hr. The resulting solids are collected by filtration, washed with three 25-mL portions of cold (−25°C) hexane, and dried to afford 8.84-9.08 g, (86-88%) of the ketone as a white solid.

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A flame-dried, 250-mL, three-necked, round-bottomed flask is equipped with a magnetic stir bar, rubber septum, glass stopper, and an argon inlet. The flask is charged with pyridinium chlorochromate (16.4 g, 76 mmol) and 75 mL of dichloromethane. A solution of crude (6R)-(+)-1,6-dimethylcyclohex-2-en-1-ol (4.79 g, 38 mmol) prepared as described above in 25 mL of dichloromethane  is transferred into the reaction mixture via cannula over 5 min, and the resulting mixture is stirred at ambient temperature for 3 hr. The reaction mixture is then diluted with 120 mL of diethyl ether, the solution is decanted, and the remaining black resinous polymer is thoroughly washed with three 50-mL portions of diethyl ether. The combined dark brown/black ether solution is washed successively with two 100-mL portions of 5% aqueous sodium hydroxide solution, 100 mL of 5% aqueous hydrochloric acid, and two 50-mL portions of saturated aqueous NaHCO3 solution, dried over anhydrous magnesium sulfate, filtered, and concentrated by rotary evaporation at room temperature (50 mmHg) to give 4.42 g of the crude product as a yellow oil. Purification by column chromatography  yields 3.71-3.85 g (79-82% overall from 1) of (R)-(+)-3,4-dimethylcyclohex-2-en-1-one (3) as a colorless oil.

Tips:

In practice the chromium byproduct deposits with pyridine as a sticky black tar, which can complicate matters. Addition of an inert adsorbent such as crushed molecular sieves or silica gel allows the sticky byproduct to adsorb to the surface, and makes workup much easier.

Aldehydes from Acyl chlorides, Esters, Nitriles

Aldehydes from Acyl chlorides, Esters, Nitriles

Aldehydes  can be prepared by mild reduction of acyl chlorides, esters, nitriles. The reducing agents of choice are usually lithium tri-tert-butoxy aluminum hydride (LATB—H) and diisobutylaluminum hydride (DIBAL—H).  low temperature is very crucial for aldehyde conversion otherwise you may end getting an alcohol (over reduced).

Acyl chloride reduction

Acyl chlorides can be reduced by reacting them with lithium tri-tert-butoxyaluminum hydride at −78°C.

Ester and nitrile reduction

You can use diisobutylaluminum hydride to reduce both esters and nitriles to aldehydes.

The mechanism for both of these reactions is very similar to the mechanism for the reduction of acyl chlorides by LATB—H. The first step is an acid-base reaction between an unshared electron pair on oxygen or nitrogen with the aluminum atom of the DIBAL—H. The second step is the transfer of a hydride ion from the DIBAL—H to the carbon atom of the carbonyl or nitrile group. The last step is the hydrolysis of the aluminum complex to form the aldehyde.

Ester reduction mechnaism

Nitrile reduction mechanism

Procedures

Aldehyde synthesis (via cyanide):

A 200 mL round bottom flask was charged with a magnetic stir bar, 3-ethoxy-2- fluorobenzonitrile (1.000 g, 6.05 mmol), and anhydrous toluene (12.92 ml). The solution was placed under argon and cooled to 0°C with an ice bath. DIBAL-H (7.27 ml, 7.27 mmol) (1M in PhMe) was then added drop wise via syringe and the reaction was allowed to stir to rt overnight. To this mixture was added 10 % HCl until the solution reached a pH of ~ 2. The resulting mixture was then left to stir for 0.5 h. and was then poured into a separatory funnel and extracted with ethyl acetate (2 x 200 mL). The combined organic extract was dried with MgSO4, filtered, and concentrated in vacuo to yield the crude product which was purified via silica gel chromatography (80 g) using ethyl acetate/hexanes (1:4) as eluent to provide pure 3-ethoxy-2-fluorobenzaldehyde (0.810 g, 80 %).

Patent reference: WO2010001169 (Astrazeneca)

Aldehyde synthesis (via ester):

Dissolve the ester (1 equiv) in CH₂Cl₂. The temperature of the solution should be -78^oC. Add DIBAL in THF (1.2 equiv.) to the solution dropwise with a N2 inlet. Stir the resulting mixture at -78^oC for 1 hour. Quench the mixture with methanol slowly, and then add brine into the mixture. Separate the organic layer, dry and concentrate. In many cases the residue needs to be purified by column chromatography.

Sulfuryl chloride

Sulfuryl chloride

Sulfuryl chloride is an inorganic compound with the formula SO₂Cl₂. At room temperature, it is a colorless liquid with a pungent odor. Sulfuryl chloride is not found in nature, as can be inferred from its rapid hydrolysis.

Sulfuryl chloride is commonly confused with thionyl chloride, SOCl₂. The properties of these two sulfur oxychlorides are quite different: sulfuryl chloride is a source of chlorine whereas thionyl chloride is a source of chloride ions. An alternative IUPAC name is sulfuroyl dichloride.

Sulfur is tetrahedral in SO₂Cl₂, being bound to two oxygen atoms via double bonds and to two chlorine atoms via single bonds. The oxidation state of the sulfur atom is +6, as in H₂SO₄.

Synthesis

SO₂ + Cl₂ à SO₂Cl₂

SO₂Cl₂ is prepared by the reaction of sulfur dioxide and chlorine in the presence of a catalyst, such as activated carbon.  The crude product can be purified by fractional distillation. It is uncommon to prepare SO₂Cl₂ in the laboratory because it is commercially available. Sulfuryl chloride can also be considered a derivative of sulfuric acid.

Reactions

Sulfuryl chloride reacts with water, releasing hydrogen chloride gas and sulfuric acid:

2 H₂O + SO₂Cl₂ à 2 HCl + H₂SO₄

SO₂Cl₂ will also decompose when heated to or above 100 °C, about 30 °C above its boiling point.  Upon standing, SO₂Cl₂ decomposes to sulfur dioxide and chlorine, which gives the older samples a slightly yellowish color.

Uses

Sulfuryl Chloride is the Sulfuric oxychloride where as sulfinyl chloride is the sulfurous oxychloride. Sulfuryl Chloride is a colorless to yellowish liquid with a pungent odor. It boils at 69°C, decomposed by hot water and alkalies; soluble in most organic solvents (benzene, chloroform, carbon tetrachloride and acetic acid). It is not found in nature due to strong hydrolysis. It is explosive also with donor solvents such as alcohols, ethers, DMSO and DMF. It decompose at its boiling point. It has two S-Cl single bonds and two S=O solid bonds. It is prepared by the reaction of sulfur dioxide and chlorine in the presence of activated carbon. It is used as a solvent and as a source of chlorine in chemical reactions. Sulfuryl chloride is useful mainly in preparing pesticides. It is used as a chlorinating (and sulfochlorinating) agent of alcohols, alkyls, aromatics, and epoxides for the target molecules of pharmaceuticals, disinfectants, dyestuffs, rayon, and poison gases. Chlorination in organic synthesis with sulfuryl chloride is more selective than elementary chlorine. It is useful to avoid secondary reactions. Chlorination of alcohols to yield alkyl chloride.

Sulfuryl chloride is often used as a source of Cl₂. Because it is a pourable liquid, it is considered more convenient than Cl₂ to measure, store, and dispense. SO₂Cl₂ is widely used as a reagent in the conversion of C-H → C-Cl adjacent to activating substituents such as carbonyls and sulfoxides. It also chlorinates alkanes, alkenes, alkynes, aromatics, and epoxides. Such reactions occur under free radical conditions using an initiator such as AIBN.

Overall reaction

C₄H₉Cl + SO₂Cl₂+AIBNàC₄H₈Cl₂ + SO₂ + HCl

Below side reaction possible if there is more amount of sulfuryl chloride.

It can also be used to convert disulfides into their corresponding sulfenyl chlorides. SO₂Cl₂ can also convert alcohols to alkyl chlorides. In industry, sulfuryl chloride is most used in producing pesticides.

SO₂Cl₂ can also be used to treat wool to prevent shrinking.

Precautions

SO₂Cl₂ is toxic, corrosive, and acts as a lachrymator. As described above, it can form explosive mixtures with water, as well as donor solvents such as DMSO and DMF.

Selenium dioxide

Selenium dioxide (SeO₂)

Selenium dioxide (SeO₂) is an important reagent in organic syntheses, as it is both an oxidant and weakly acidic.  Selenium dioxide is the chemical compound with the formula SeO₂. This colorless solid is one of the most frequently encountered compounds of selenium.  The solid sublimes readily. The vapor has an odor resembling horseradish sauce and can burn the nose and throat on inhalation.  SeO₂ is considered an acidic oxide: it dissolves in water to form selenous (selenious) acid. Often the terms selenous acid and selenium dioxide are used interchangeably. It reacts with base to form selenite salts containing the SeO2−3 anion. For example, reaction with sodium hydroxide produces sodium selenite:

SeO₂ + 2 NaOH → Na₂SeO₃ + H2O

Uses in Organic synthesis:

SeO₂ is an important reagent in organic synthesis. Oxidation of paraldehyde (acetaldehyde trimer) with SeO₂ gives glyoxal and the oxidation of cyclohexanone gives cyclohexane-1,2-dione. The selenium starting material is reduced to selenium, and precipitates as a red amorphous solid which can easily be filtered off. This type of reaction is called a Riley oxidation. It is also renowned as a reagent for "allylic" oxidation, a reaction that entails the conversion

R₂C=CR'-CHR"₂ + [O] → R₂C=CR'-C(OH)R"₂

(where R, R', R" are alkyl or aryl).

Mechanism of oxidation

Procedures:

A 500-ml three-necked, round-bottomed flask is fitted with a mechanical stirrer, a thermometer, a dropping funnel, and a reflux condenser. A solution of 0.74 g. (0.0067 mole) of selenium dioxide in 150 ml. of tert-butyl alcohol is introduced into the flask, followed by 68 g. (0.50 mole) of β-pinene. The resulting mixture is warmed to 40 °C with a hot water bath before 35 ml. (0.62 mole) of 50% aqueous hydrogen peroxide is added drop wise over 90 minutes, during which time the mixture is maintained at 40–50 °C by occasional immersion in a cold water bath. After stirring for an additional 2 hours, the reaction mixture is diluted with 50 ml. of benzene, washed with three 50-ml. portions of saturated aqueous ammonium sulfate, and dried over sodium sulfate. A small amount of hydroquinone is added, and the solvents are removed on a rotary evaporator. trans-Pinocarveol is isolated by simple distillation under reduced pressure, yielding 37–42 g. (49–55%), b.p. 60–70° (1 mm.).

Procedure was taken from Organic Syntheses, Coll. Vol. 6, p.946 (1988); Vol. 56, p.25 (1977).

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1,2-Cyclohexanedione. A 3-l. round-bottomed flask, fitted with stirrer and dropping funnel, is placed in a water bath containing a coppercoil through which cooling water may be circulated. In the 3-l. flask is placed 1708 g. (17.4 moles, 1.8 l) of cyclohexanone. Tap water is circulated through the cooling coil, and a solution containing 387 g. (3 moles) of selenious acid (H₂SeO₃), 500 ml. of 1,4-dioxane, and 100 ml. of water is added drop wise and with stirring to the cyclohexanone over a period of 3 hours. The reaction mixture immediately turns yellow, and red amorphous selenium gradually appears. Stirring is continued for 5 additional hours at water-bath temperatures and then for 6 more hours at room temperature. Removal of the bulky, amorphous selenium is accomplished with the aid of a 6-in. Buchner funnel. The selenium is returned to the reaction flask and extracted with 300 ml. of boiling 95% ethanol for 1 hour. The solution, obtained by decantation from the compact gray selenium, is combined with the above filtrate in a 4-l. distilling flask. Distillation under reduced pressure gives two fractions. The lower-boiling fraction (25–60°/16 mm.) consists mainly of ethanol, water, dioxane, and cyclohexanone; the higher-boiling one (60–90°/16 mm.) contains cyclohexanone and 1,2-cyclohexanedione with traces of water and dioxane. The yield of crude product is approximately 322 g.

Procedure was taken from Organic Syntheses, Coll. Vol. 4, p.229 (1963); Vol. 32, p.35 (1952).

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Microwave-assisted selenium dioxide mediated selective oxidation of 1-tetralones to 1,2-naphthoquinones

This is a microwave reaction reported in Tetrahedron Letters Volume 50, Issue 1, 7 January 2009, Pages 39-40

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Tips: 

1. Since only catalytic quantities of selenium dioxide are required, the danger of handling large quantities of this material is avoided.
2. Formation of selenium and organoselenides commonly arise in oxidations using molar quantities of selenium dioxide, are not encountered.
3. If too much selenous acid is added at once, or the cooling discontinued, the solution will heat up and the reaction will become extremely vigorous with subsequent decrease in yield.
4. Selenium compounds are exceedingly toxic 

Palladium in synthetic organic chemistry

Palladium is a chemical element with the chemical symbol Pd (atomic number of 46) and is a soft silver-white metal that resembles platinum.  

Palladium, platinum, rhodium, ruthenium, iridium and osmium form a group of elements referred to as the Platinum Group Metals.  These have similar chemical properties, but palladium has the lowest melting point and is the least dense of them.  The metal has the uncommon ability to absorb up to 900 times its own volume of hydrogen at room temperatures.

These unique properties of palladium and other platinum group metals account for their widespread use.  Many of the drugs manufactured today either contain these metals or have a significant part in their manufacturing process played by them.

Palladium commonly exists in 0, +2, +4 (rare) oxidation states.  Elemental palladium reacts with chlorine to give palladium(II) chloride.  Palladium(II) chloride, also known as palladium dichloride is the chemical compound with the formula PdCl₂. This is a common starting material in palladium chemistry.  Palladium based catalysts are of particular value in organic synthesis. It is prepared bychlorination of palladium.

Preparation of PdCl₂:

The anhydrous salt is prepared by heating loose palladium sponge to a dull red heat in a stream of Cl₂.  For a more in-depth literature refer the below link 

http://www.erowid.org/archive/rhodium/chemistry/palladium.chloride.txt

Palladium(II) chloride is a common starting point in the synthesis of other palladium compounds. It is not particularly soluble in water or non-coordinating solvents, so the first step in its utilization is often the preparation of labile but soluble Lewis base adducts, such as those resulting from acetonitrile or benzonitrile.  The acetonitrile complex is prepared by treating PdCl₂in refluxing acetonitrile:

PdCl₂ + 2 MeCN → PdCl₂(MeCN)₂

Although rarely suggested, inert-gas techniques are not necessary if the complex is to be used in situ. As an example,bis(triphenylphosphine)palladium(II) dichloride may be prepared from palladium(II) chloride by reacting it with triphenylphosphine in benzonitrile.

PdCl₂ + 2 PPh₃ → PdCl₂(PPh₃)₂

Upon further reduction in the presence of more triphenylphosphine gives tetrakis(triphenylphosphine)palladium(0).

PdCl₂(PPh₃)₂ + 2 PPh₃ + 2.5 N₂H₄ → Pd(PPh₃)₄ + 0.5 N₂ + 2 N₂H₅⁺Cl⁻

Palladium chloride may also be used to give heterogeneous palladium catalysts: palladium on barium sulfate, palladium on carbon, and palladium chloride on carbon.

Usage in synthetic organic chemistry:

Due to its ability to adsorb huge amounts of hydrogen (900 parts of Hydrogen per 1 part of Palladium) it has got a great prospective in fast developing Hydrogen Energy industry.  Palladium is used in fuel cells to convert hydrogen and oxygen to electrical energy.  But the most impressive part of Palladium is of course the chemical catalysis. It accomplishes a precise job as a powerful role in Palladium catalyzed coupling reactions.

Palladium compounds are used as a catalyst in many coupling reactions (given below), usually as homogeneous catalysts.

Heck reaction

Suzuki reaction 

Stille reaction

Hiyama coupling

Sonogashira coupling

Negishi coupling

Buchwald-Hartwig amination

Heck-Matsuda Reaction