synthesis of acetylenes, allenes and cumulenes || preparation, purification and storage of some...

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E:/Archive files/4188-Brandsma/Printer-Files/4188-Chapter-02.3d

2Preparation, Purification and Storage of

Some Solvents and Reagents

2.1 SOLVENTS

Many syntheses described in this book are carried out in tetrahydrofuran

(THF). This solvent sometimes contains peroxides and small amounts of

water, especially after a long period of careless storage. Peroxides are easily

detected by shaking a few millilitre of the solvent with an aqueous solution

of alkali iodide. The intensity of the brown colour developed gives a rough

indication of the peroxide content. Peroxides and water are effectively

removed by shaking the THF with machine-powdered potassium hydroxide

(�100 g/2 litre). If no special machine for grinding pellets is available, mechan-

ical stirring with a relatively large amount of pellets may be considered. For

most of the procedures in this book the THF, dried over KOH, can be used

after rapid filtration. For use in sluggishly proceeding preparations of

Grignard reagents, e.g. t-butylmagnesium chloride, distillation from lithium

alanate, LiAlH4, or sodium-benzophenone is necessary. THF is best stored

in a brown flask under inert gas, preferably argon.

Diethyl ether (Et2O) may be purified by a similar procedure. For most pur-

poses (except some Grignard preparations, e.g. t-butylmagnesium chloride),

however, it suffices to dry the solvent over KOH followed by rapid filtration,

distillation being unnecessary.

The addition of HexaMethylPhosphoric Triamide (Me3N)3P¼O (HMPT,

the English abbreviation is HMPA) as a co-solvent in small amounts (in

molarity equal to the organometallic intermediate) can cause a considerable

acceleration of some reactions, especially alkylations and reactions with

oxiranes. The commercial solvent often contains water and other impurities.

Purification may be carried out by distillation from commercial t-BuOK

(a few grams for 200ml) in a high vacuum followed by redistillation at

5 to 20Torr (bp � 110 �C/15Torr). HMPT is a cancer-suspect compound,

moreover it has become very expensive. For these reasons, in cases of

11

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frequent use dimethylsulphoxide should be seriously considered as an

alternative. However, this solvent cannot be used in reactions with strongly

basic organometallic intermediates because of an easy proton/metal exchange.

The non-toxic cyclic urea derivative 1,3-dimethyl-2-oxo-hexahydropyrimidine

(N,N-dimethylpropyleneurea, DMPU), has been proposed [1], but unfortu-

nately large amounts (compared to HMPT) of it seemed to be required.

Dimethylsulphoxide (DMSO) can be made water-free by a procedure

similar to that applied for HMPT. Although DMSO can replace HMPT as a

co-solvent for some reactions involving organometallics that are not more

strongly basic than acetylides, care should be taken to keep the temperature

as low as possible during the functionalisations. Upon heating solutions of

acetylides RCH2C�CM (M¼ alkali metal) proton/metal exchange between

the alkali acetylide and DMSO occurs. The resulting free acetylene,

RCH2C�CH, undergoes a subsequent isomerisation to the 2-alkyne,

RC�CMe, catalysed by the DMSO anion formed in small equilibrium concen-

trations from the alkali acetylide and DMSO [2]. In the case of metallated

allenes (e.g. H2C¼C¼CHM) or 2-alkynes (e.g. MeC�CCH2M), much more

strongly basic than RCH2C�CM, this exchange will be very easy, making

DMSO unsuitable as a co-solvent for derivatisations of mesomeric acetyle-

nic-allenic anions.

It has been shown that in liquid ammonia 1-metallated allenic ethers,

H2C¼C¼C(Na)OR, are rapidly converted into the 3-metallated species

NaCH¼C¼CHOR and metallated propargylic ethers, NaC�CCH2OR.

Obviously, these isomerisations are the result of a proton donation (by ammo-

nia) and subsequent deprotonation (by alkali amide) at the 3-position of the

allenic system [11,12]. 1-Metallated allenic sulphides, R1CH¼C¼C(M)SR,

have a reasonable kinetic stability in liquid ammonia [13].

Traces of water in tertiary amines such as triethylamine and pyridine can

be detected by adding a few drops of chloro(trimethyl)silane to 1ml of the

amine in a dry reagent tube resulting in the formation of the suspended

HCl salt of the amine. Potassium hydroxide, preferably machine-powdered,

is a suitable drying agent. Perfectly dry N1,N1,N2,N2-tetramethyl-1,2-ethane-

diamine (TMEDA, bp � 120–122 �C) can be obtained by distillation of

the KOH-dried amine from lithium alanate, LiAlH4, in a partial vacuum

(�100 Torr).

The best way to obtain dry benzene, dichloromethane, chloroform, carbon

tetrachloride, alkyl halides, etc. is to subject the liquid to a distillation under

normal pressure until clear condense (no longer turbid) flows through the

condenser. After � 10% of distillate has been collected, the condenser should

be cleaned and the distillation continued to ensure the absence of turbid

condense. The remaining liquid in the distillation flask is perfectly dry.

Another effective method of removing small amounts of water is to shake

12 2. PURIFICATION OF SOLVENTS AND REAGENTS

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the liquid during half a minute with a small amount of phosphorus pentoxide.

After decanting the liquid from the syrup it is shaken with a second small

portion of phosphorus pentoxide. When this remains in suspension after shak-

ing, the drying procedure can be considered to be complete and (after

filtration) a distillation can be carried out.

Chloroform and carbon tetrachloride, used as solvents for NMR spectroscopy,

may contain traces of HCl (or DCl). These can cause E/Z interconversion in the

case of systems with the structural units C¼C–X in which X represents an

amino, ether or thioether group. The measured integration ratio of the signals

for the two isomers therefore may be different from the actual ratio. For surety

the solvents may be shaken with a very small amount of aqueous potassium

carbonate, dried over the anhydrous salt and finally distilled as described

above. Storage in brown bottles under inert gas may prevent the formation

of acid.

2.2 REAGENTS

Acetaldehyde polymerises very easily giving the cyclic trimer ‘paraldehyde’. It is

therefore absolutely necessary to use the freshly distilled (bp 21 �C at normal

pressure) reagent for reactions, even after opening of a sealed bottle. Since

traces of acid on the glass of the distillation apparatus can cause trimerisation,

the condenser and receiver should be first rinsed with a dilute solution of

a volatile amine in acetone and subsequently blown dry. Monomeric acetal-

dehyde can also be obtained by addition (with manual swirling) of 1ml of

concentrated sulphuric or phosphoric acid to 300ml of the (commer-

cially available) cyclic trimer followed by distillation through a column of

30 to 40 cm.

Aliphatic aldehydes also can undergo trimerisation (and oxidation) during

storage, therefore it is absolutely necessary to distil the reagents before

use: the lower homologues at atmospheric pressure, hexanal and higher

homologues under reduced pressure.

Acrolein, croton aldehyde and methyl vinyl ketone should always be distilled

before use and be stored in the refrigerator.

Extensive advice and instructions for handling and storage of alkali metals

can be found in the laboratory manual [3] and in Houben-Weyl, Vol. E/19d,

Thieme-Verlag, Stuttgart, 1994, p. 99.

Alkali amides are extensively used reagents in the chemistry of acetylenes and

allenes. Improved procedures for their preparation in liquid ammonia are

described in this chapter.

Alkynyl- and allenylzinc halides are simply prepared by addition of anhy-

drous zinc salts to solutions of the corresponding alkynyl- or allenyllithium

2.2 REAGENTS 13

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compounds. The analogous organomagnesium halogenides may be prepared

from the lithium derivatives and magnesium bromide � etherate, MgBr2 �Et2O

(for the preparation of this reagent see below).

Benzaldehyde can be freed from benzoic acid by shaking with a 2% aqueous

solution of KOH, followed by drying over magnesium sulphate and distillation

under reduced pressure. The purified aldehyde should be stored under inert

gas in a well-closed bottle.

n-Butyllithium in hexane is commercially available in screw-capped bottles

provided with a self-closing septum through which the needle of the syringe

can be stuck for taking the desired volume. The solution in hexane (often

1.6 molar, in this case 63ml of the solution contains 0.10mol of the reagent)

is stable at room temperature.

For many reactions the hexane solution of butyllithium has to be

mixed with a certain volume of THF. During this operation care should be

taken to keep the temperature of the mixture below 0 �C in order to

prevent attack of THF by the reagent [4]. Et2O reacts much less fast with

butyllithium. If desired, the hexane can be completely replaced by another

solvent. For this, the hexane is removed under reduced pressure, the last

traces in a high vacuum. The remaining viscous liquid is then dissolved in

the desired solvent, e.g. a high-boiling alkane, in the case of THF with cooling

below �70 �C.

n-Butyllithium in hexane or Et2O can be easily prepared from butyl chloride

or bromide and lithium containing � 1% of sodium (see experimental part).

The ethereal butyllithium solution obtained from the reaction between lithium

and butyl bromide contains complexed lithium bromide. For extensive infor-

mation about alkyllithium reagents the reader should consult the above-men-

tioned laboratory manual and the Houben-Weyl volume.

The n-BuLi � t-BuOK reagent is prepared by combining equimolar amounts

of the ingredients in THF–hexane mixtures, while keeping the temperature

below �85 �C. In many cases it is simpler to generate the reagent in situ,

i.e. by adding BuLi under strong cooling to a mixture of the substrate and

t-BuOK or the latter to a strongly cooled mixture of the substrate and BuLi.

The reagent is used for deprotonations that proceed sluggishly with BuLi

or BuLi �TMEDA.

The complex n-BuLi �TMEDA in hexane can be obtained by adding

TMEDA at room temperature to a solution of BuLi in hexane.

Chloro(trimethyl)silane may contain hydrogen chloride and hexamethyl-

disiloxane, Me3SiOSiMe3, formed by entrance of moisture due to repeated

use and careless closing of the bottle. Purification can best be carried out

by adding a small amount (�10%) of N,N-diethylaniline, followed by dis-

tillation through an efficient column (the difference between the boiling

points of Me3SiCl and Me3SiOSiMe3 is about 40 �C). The reagent should


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never be stored in the refrigerator since moisture can leak between the

screw cap and the glass.

It is, in general, not necessary to use analytically pure copper halides

for the coupling and substitution reactions described in this book. The

commercially available salts as a rule can be used as such.

The polymer of formaldehyde (‘paraformaldehyde’) sometimes contains

some moisture. This can be removed by heating the powder for �1 h

at � 60 �C in a vacuum of 10–20Torr. Under these conditions some

depolymerisation occurs.

The preparation of Grignard reagents from alkyl or aryl bromides in

THF or Et2O, dried over potassium hydroxide, usually can be carried

out without problems if the magnesium is first activated by addition of

iodine or 1,2-dibromoethane (cf. [8]). Traces of water in the bromides

can be removed by azeotropic distillation as described above for some sol-

vents. The reaction of magnesium with alkyl chlorides, especially t-butyl

chloride, is often difficult to get started. It seems essential to use carefully

dried and distilled solvents. It may be even considered to heat the magne-

sium for a limited period in a high vacuum if the presence of moisture is

suspected. t-Butyl chloride may contain small amounts of dissolved hydro-

gen chloride and t-butyl alcohol formed by hydrolysis. These can seriously

hamper the reaction with magnesium. We found that this problem does

not occur when this halide is shaken with a relatively large amount of

finely powdered calcium carbonate and distilled.

The only way to prepare allenylmagnesium bromide, H2C¼C¼CHMgBr,

with satisfactory results is to carry out the reaction of propargyl bromide in

diethyl ether at �0 �C with magnesium activated with mercury chloride.

For extensive practical information about other special Grignard reagents

the manual [6] should be consulted.

Grignard reagents react with oxygen. Their preparation therefore has to be

carried out under inert gas.

Grignard solutions should be stored at room temperature in flasks closed

with regularly greased ground-glass stoppers. In some cases (especially in

THF) part of the dissolved compound crystallises out. It is therefore necessary

to warm the solution in a bath at � 35 �C until all solid has dissolved before

using the reagent for a synthesis.

Lithium dialkylamides, LiNR2, are less strongly basic than BuLi. The

reagents are used for chemoselective deprotonations and for dehydrohalogena-

tions. The reagents are prepared by adding the aliphatic secondary amine to a

solution of BuLi in THF or Et2O.

Lithium halides are very hygroscopic and the salts in bottles that have

been frequently opened may contain some water. The best way to remove

this is to put the salt in a thin layer on the bottom of a relatively big

2.2 REAGENTS 15

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round-bottomed flask and to heat this for at least 1 h in a bath at 150–180 �C

under a low pressure, preferably less than 1Torr. The salts should be stored in

a bottle or flask closed with a rubber stopper.

Magnesium bromide–Et2O is readily obtained by adding 1,2-dibromoethane

to a mixture of magnesium (slight excess) and refluxing diethyl ether.

Sodium t-butoxide and potassium t-butoxide, both uncomplexed bases, are

commercially available. The reagents are used in isomerisation, metallation

and elimination reactions. It is not easy to remove the alcohol from the 1:1

complexes obtained by dissolving the metals in t-butyl alcohol. The uncom-

plexed reagents are soluble in THF and DMSO. Potassium t-pentyloxide

dissolves also in pentane and hexane. A good quality of the commercially

available reagent is maintained if stored in a bottle closed by a rubber stopper.

Mixtures of palladium(II) chloride-bis(triphenylphoshane), PdCl2(PPh3)2,

or tetrakis(triphenylphosphane)palladium(0), Pd(PPh3)4, and copper(I)

bromide or iodide are efficient catalysts in cross-couplings involving acetylenic

compounds. The complexes can be readily prepared. Pd(PPh3)4 should

be stored under inert gas. After long periods the colour of the powder, originally

yellow, can become dark brown. However, the catalytic activity is maintained.

The usual procedure for making commercial anhydrous zinc chloride

water-free consists of heating (with swirling) the salt (50 g) in an evacuated

(<1Torr) round-bottomed flask until practically all solid has melted [7].

This procedure may be repeated a few times. After cooling, the salt may be

dissolved in Et2O.

2.3 EXPERIMENTAL SECTION

2.3.1 Alkali amides in liquid ammonia

Scale: 0.40 molar; Apparatus: Figure 1.3, 1 litre

2.3.1.1 Procedure for LiNH2

In the flask is placed � 400ml of anhydrous liquid ammonia. Iron(III) nitrate

(� 100mg, the hydrate may be used, Note 1) is added. After formation of a

uniformly brown solution � 0.2 g of lithium is introduced in a few small pieces.

The outlets are removed so that some air can enter (Note 2). After a few min

a dark-grey suspension has formed. A stopper and a powder funnel are

placed on the necks and 0.40mol of lithium minus 0.2 g, cut in pieces of


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� 0.1 g above the powder funnel, is introduced in three equal portions (Note 3).

After addition of the last portion the powder funnel is replaced again with the

outlet. When all lithium has converted, a rather thick white suspension has

formed.

Notes

1. If much more ferric nitrate is added, problems may arise during the

aqueous work-up in further syntheses. Under the influence of oxygen

the zerovalent iron is converted into a gel of Fe(OH)3 making separation

of the layers difficult.

2. In the absence of air (especially when nitrogen is introduced) the conver-

sion into zerovalent iron, the actual catalyst, may proceed very sluggishly

during this initial stage. It may be more effective to introduce air

during a few seconds. Also for the preparation of sodamide some air

appears to be necessary, but in the case of potassium it is not necessary

to introduce air.

3. If all lithium is cut in at once, serious frothing may occur. In the prepara-

tion of the other alkali amides, which form a less thick suspension

(NaNH2) or solution (KNH2), the metals can be introduced very quickly

after the initial generation of zerovalent iron.

2.3.1.2 Procedure for NaNH2 and KNH2

After the generation of the catalyst from � 100 mg of iron nitrate and � 1 g of

alkali metal as described above (introduction of air is not necessary in the

case of potassium) the cleaned metal (0.40mol minus � 1 g, Note 1) is intro-

duced in 1-g pieces. The conversion into the alkali amides is usually ready

within half an hour (Note 2). Sodium amide appears as a white, rather

coarse suspension in a greyish-black solution (colloidal iron), potassium

amide is completely soluble (greyish-black solution).

Notes

1. The crust of oxide is first removed, in the case of potassium preferably

under paraffin oil or high-boiling petroleum ether. The cleaned lumps are

dipped into a volatile petroleum ether fraction in order to remove the

non-volatile protecting liquid. Subsequently, the required amount of

metal is weighed, cut into � 1-g-pieces, which in the case of potassium

are immediately introduced into a beaker containing a sufficient amount

of a dry volatile liquid.

2. In spite of thoroughly removing the oxide crusts minute particles of potas-

sium surrounded by oxide and protecting oil remain present. These are not

2.3 EXPERIMENTAL SECTION 17

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converted into the alkali amide and may cause a fire during the aqueous

work-up and extraction with Et2O of the product from a further synthesis.

It is therefore necessary to remove these particles. This has to be done by

cooling the solution of potassium amide to below�50 �C followed by quick

filtration through a small plug of glass wool kept in a funnel by means of a

glass rod. This simple operation, taking only about 3 min, may result in

some loss of potassium amide. This should be compensated for by using

� 0.5 g excess of potassium.

Warning: One should never try to dissolve remnants or small particles of

potassium by adding ethanol to the solvents used for cleaning and protection

of potassium as this may cause fire. Paraffin oil or high-boiling petroleum

should be returned into the storing bottle, volatile cleaning and protecting sol-

vents are best poured outside (never in the waste container!). If tissues are used

for removal of paraffin oil, these should never be directly thrown into the waste

container since small particles of metal may adhere to the tissue. The safest way

of disposal consists of burning it down outside.

2.3.2 Lithium diisopropylamide

A solution of 0.05mol of lithium diisopropyl amide, LiN(i-Pr)2, in 40ml of

THF or Et2O and 32ml of hexane may be obtained by adding a solution of

0.05mol of n-BuLi in 32ml of hexane to a mixture of 0.05mol of diisopropyl

amine and 40ml of THF or Et2O, cooled at ��40 �C. External cooling is not

necessary and the BuLi can be added within a few seconds. Inverse-order

addition is also possible. Other secondary amines react under similar condi-

tions. The lithiations are extremely fast.

2.3.3 n-BuLi �TMEDA in hexane

A solution of n-BuLi �TMEDA in hexane is obtained by adding 0.05mol of

TMEDA to a solution of 0.05mol of BuLi in 32ml of hexane. External cooling

is not necessary.

2.3.4 n-BuLi–t-BuOK in tetrahydrofuran

A solution of the n-BuLi–t-BuOK reagent (0.05mol) in 32ml of hexane

and 40ml of THF may be obtained by adding 0.05mol of BuLi–hexane

solution over a few min to a solution of 0.05mol of t-BuOK in the

THF. During this mixing the temperature has to be kept between �100 and


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�85 �C in order to avoid attack of the THF by the strongly basic complex. As

the solution of t-BuOK in THF is rather viscous at very low temperatures, the

mixing is less efficient. It is therefore more convenient to add the solution of

t-BuOK to the BuLi solution, likewise with strong cooling. The obtained

solution of the complex should be used without delay.

2.3.5 n-Butyllithium in hexane

Scale: 0.20 molar; Apparatus: 250-ml round-bottomed two-necked flask,

equipped with a thermometer and an outlet connected to a balloon filled

with argon (Note 1). Instead of the balloon a relatively big flask filled with

argon may be used. Stirring is carried out magnetically.

2.3.5.1 Procedure

In the flask is placed 100ml of carefully dried and distilled hexane. A rod of

lithium (4 g, containing 0.5–1% of sodium) is flattened with a clean hammer on

a clean surface to a thickness of �1mm, after which the metal is immediately

cut into small pieces (� 4� 3� 1mm). These are at the same time introduced

into the flask through a powder funnel. Carefully dried and distilled BuCl

(0.25mol, Note 2) is added, after which the air in the flask is replaced by

argon (temporary vigorous flow). Stirring is started and after a few minute

the solution becomes turbid while the temperature rises slowly. The reaction

mixture is kept closely around 30 �C by occasional cooling. After about 2 h the

heating effect has become very weak and cooling is no longer necessary. After

an additional 2 h the greyish-black suspension is transferred into a 250-ml

bottle (filled with argon) with a graduated scale (a syringe may be used).

The excess of lithium (Note 3) and some salt are rinsed twice with small por-

tions of hexane. Using these solutions, the volume of the BuLi solution is

brought to 125ml. Usually this solution appears to contain � 0.20mol of BuLi.

Notes

1. Under nitrogen the conversion into BuLi proceeds sluggishly, possibly due

to covering of the metal by nitride.

2. The ‘yield’ of BuLi is at least 80%. Using an excess of 0.05 mol of BuCl

� 0.20mol of BuLi is obtained.

3. This lithium is very active and has to be disposed immediately by adding

100ml of methanol.


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2.3.6 n-Butyllithium � lithium bromide in diethyl ether

Scale: 0.20 molar; Apparatus: Figure 1.1, 500ml; instead of continuously intro-

ducing inert gas, the outlet may be connected with a balloon or relatively big

flask filled with inert gas.

2.3.6.1 Procedure

Dry Et2O (200ml) is placed in the flask. Lithium (4 g, excess), treated as

described in the preceding experiment, is added, after which the flask is

equipped as shown in Figure 1.1. After replacing the air in the flask by inert

gas (temporary vigorous flow, with stirring) the inlet is closed and the outlet

connected with the supply of inert gas. The slowly stirred mixture is cooled to

� 20 �C and a few grams of the 0.20mol of butyl bromide are added. After

about 10min the Et2O becomes turbid and heat is evolved. The remaining

butyl bromide is added over 30min while keeping the temperature of the reac-

tion mixture between �10 and �20 �C. After an additional 30min the cooling

bath is removed and stirring is continued for half an hour. The gloss on the

pieces of lithium, originally present, gradually disappears. It is not necessary to

remove the excess of lithium as the required amount of the reagent can be

withdrawn by syringe. After placing well-greased stoppers on the flask it is

stored at �20 to �30 �C. The strength of the solution (determined by titration

[5]) then remains unchanged during at least one week. The ‘yield’ is at least 85%.

For disposal of the excess of lithium see preceding experiment.

If part of the solution is needed, the flask is kept in a water bath at rt prior

to opening.

Ethyl- and methyllithium can be prepared in a similar way from the corre-

sponding bromides. Methyl bromide (bp 6 �C) is added portionwise as a cold

(�5 �C) solution in Et2O (0.20mol in 30ml).

Methyllithium � lithium iodide can be prepared in a high yield from methyl

iodide and lithium at �5 to �10 �C.

2.3.7 n-Butylmagnesium chloride in diethyl ether

Scale: 0.40 molar; Apparatus: Figure 1.1, 500ml; after the reaction has started,

the thermometer is replaced with a reflux condenser.

2.3.7.1 Procedure

The flask is charged with 100ml of dry Et2O and 15 g (excess) of dry magne-

sium turnings (see Section 2.2, Grignard reagents). After replacing the air in the


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flask by inert gas, 2ml of 1,2-dibromoethane is added. After a few minutes a

vigorous reaction starts and some cooling is applied to prevent the ether from

refluxing. When the evolution of heat has stopped, 5 g of carefully purified

n-butyl chloride (see Section 2.2) is added. As a rule the reaction starts slowly

(continuous observation of the temperature and some patience are necessary).

When it has become clear that the reaction has started (the temperature has

risen to 35 �C), the thermometer is replaced with a reflux condenser. After the

(gentle) reflux has stopped, a mixture of 200ml of Et2O and the remaining

amount (0.40mol minus � 5 g) of n-butyl chloride is added at a rate (over

� 1 h) such that a gentle reflux is maintained. The conversion is brought to

completion by refluxing for an additional 1 h. The resulting greyish solution is

transferred (under a blanket of inert gas) into a storing flask with a graduated

scale and the excess of magnesium is rinsed with two small portions of

Et2O. The ‘yield’ as derived from reactions carried out with the reagent is at

least 90%.

t-BuMgCl, c-HexylMgCl and c-PentylMgCl in Et2O are prepared as

described for n-BuMgCl. ‘Yields’ are somewhat lower.

2.3.8 t-Butylmagnesium chloride in tetrahydrofuran

Scale: 0.40 molar; Apparatus: Figure 1.1, 500ml

2.3.8.1 Procedure

Amounts of t-butyl chloride, magnesium, dibromoethane and the solvent

(THF) are the same as described for n-butylmagnesium chloride. After the

activation of the magnesium with 1,2-dibromoethane (the temperature may

rise to 50 �C or higher, while ethene is evolved), the reaction mixture is

warmed to � 55 �C and � 5 g of t-butyl chloride is added. If this addition

results in a temperature increase to above 60 �C, the remainder of the

0.40mol of the chloride, dissolved in 200ml of THF, is added at a rate such

that the temperature of the reaction mixture is maintained between 55 and

60 �C. After an additional period of � 1 h (heating at � 55 �C) the conversion

is considered to be complete and the greyish solution is transferred into a

storing flask as described for n-butylmagnesium chloride. The maximal

‘yield’ is � 70% or somewhat higher.

2.3.9 Allenylmagnesium bromide in diethyl ether


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Scale: 0.50 molar; Apparatus: Figure 1.1, 500ml

2.3.9.1 Procedure

Magnesium turnings (0.6mol, excess) and dry Et2O (250ml) are placed in the

flask. After replacing the air in the flask by inert gas, 0.7 g of mercury(II)

chloride (Note 1) is added and the mixture is stirred for 30min at rt. After

cooling to 0–2 �C in a bath with ice and ice water, � 4ml of freshly distilled

propargyl bromide (Chapter 20, exp. 20.1.1) is added. The reaction usually

starts after about 15min as evidenced by a distinct rise of the temperature

by several degrees in spite of cooling in the bath. If necessary, the mixture is

cooled for a few seconds to bring the temperature below 10 �C. The remainder

of the propargyl bromide (0.50mol minus 4ml) is added over 1 h. After an

additional 45min (at � 5 �C) the grey solution is decanted from the excess of

magnesium (Note 2) under a blanket of inert gas or withdrawn by syringe.

The solution contains � 0.40mol of the Grignard reagent and can be stored

for several days at �20 �C.

Notes

1. Attempts to prepare the reagent under the usual conditions give rise to

undesired side reactions such as the formation of 1,2,4,5-hexatetraene,

H2C¼C¼CHCH¼C¼CH2, and 1,2-hexadien-5-yne, HC�CCH2CH¼C¼

CH2 (cf. [9]).

2. This magnesium is strongly activated and should be disposed by addition

of an aqueous solution of ammonium chloride.

2.3.10 Magnesium bromide-etherate

A mixture of 120ml of dry Et2O and 0.25mol of magnesium turnings

is placed in a pre-weighed 500-ml, one-necked round-bottomed flask,

which is provided with a magnetic stirring bar and a reflux condenser.

1,2-Dibromoethane (0.20mol) is added portionwise over � 30min through

the reflux condenser. When the intensity of the reflux has subsided, the flask

is placed in a heating bath and refluxing is continued for half an hour. A

two-layer system consisting of a small, almost colourless upper layer and

a dark-grey, oil-like under layer has formed. Et2O is removed by evacuation

until the upper layer has decreased to a few mm only. If 0.10mol is needed, the

two-layer system is homogenised by shaking and about half of the contents

(weight decrease) is used. The complex should be stored at rt. The stopper on

the flask should be regularly greased.


[13.1.2004–10:00pm] [11–24] [Page No. 23]


2.3.11 Palladium(II) chloride �bis(triphenylphosphane),PdCl2(PPh3)2

2.3.11.1 Procedure

A stirred mixture of 20mmol of finely powdered PdCl2, 4 g of anhydrous

LiCl and 150ml of methanol is heated at 60 �C until the brown solid

has dissolved (� 15min). Subsequently, a solution of 50mmol (excess) of

triphenylphosphane in 25ml of THF (50 �C) is added in one portion. After

stirring for 1–2 h at � 50 �C, the brown colour has disappeared completely. The

yellow suspension is cooled to rt, then the solid is filtered off on a sintered-

glass funnel, rinsed twice with 30-ml portions of methanol and once with Et2O.

The powder is dried in a vacuum. The yield is at least 90%.

2.3.12 Tetrakis(triphenylphosphane)palladium(0),Pd(PPh3)4

2.3.12.1 Procedure (cf. [10])

Finely powdered PdCl2 (20mmol) and triphenylphosphane (100mmol) are

dissolved in 240ml of DMSO with heating and stirring. When at � 140 �C

all PdCl2 has dissolved, heating is stopped and 4.1 g of hydrazine hydrate is

added over 1min by syringe.

The colour of the solution becomes darker and nitrogen is evolved. One

minute after this addition the flask is cooled in a water bath until the solution

becomes turbid. Stirring is continued for 20min without cooling, after which

the suspension is brought to rt. The yellow solid is filtered off on a sintered-

glass funnel and successively rinsed three times with 35-ml portions of ethanol

and twice with 40-ml portions of Et2O. The powder is dried in a vacuum

(the last traces of solvent are removed in a high vacuum with warming in a

bath at 45 �C). The yield is �95%.

REFERENCES

1. D. Seebach and T. Mukhopadhyay, Helv. Chim. Acta 65, 385 (1982).

2. J. A. P. Thyman, Synth. Commun. 5, 21 (1975).

3. L. Brandsma and H. D. Verkruijsse, Preparative Polar Organometallic Chemistry. Springer-

Verlag, Heidelberg, 1987, Vol. 1, p. 11–17.

4. H. E. Jung and R. B. Blum, Tetrahedron Lett., 3791 (1977).

5. A. I. Vogel, Textbook of Practical Organic Chemistry. Longmans, London, 1991, 5th edn.,

p. 531.

6. B. J. Wakefield, Organomagnesium Methods in Organic Synthesis. Ac. Press, London, 1995.

REFERENCES 23

[13.1.2004–10:00pm] [11–24] [Page No. 24]


7. S. Danishefsky, T. Kitahara and P. F. Schuda, Org. Synth., Coll. Vol. 7, 313 (1990).

8. A. I. Vogel, Textbook of Practical Organic Chemistry. 4th edn., p. 326, 1978.

9. H. Hopf, Angew. Chem. 82, 703, Int. edn., 732 (1970).

10. D. R. Coulson, Inorg. Synthesis 13, 121 (1972).

11. S. Hoff, L. Brandsma and J. F. Arens, Recl. Trav. Chim. Pays-Bas 87, 916 (1968).

12. J. J. van Daalen, A. Kraak and J. F. Arens, Recl. Trav. Chim. Pays-Bas 80, 810 (1961).

13. L. Brandsma, H. E. Wijers and J. F. Arens, Recl. Trav. Chim. Pays-Bas 82, 1040 (1963).


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