synthesis of acetylenes, allenes and cumulenes || procedures and equipment

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E:/Archive files/4188-Brandsma/Printer-Files/4188-Chapter-01.3d

1Procedures and Equipment

1.1 GENERAL

For most of the procedures described in this book a round-bottomed, three-

necked flask equipped with a combination of a dropping funnel and an inlet

for inert gas, a mechanical stirrer and a combination of a thermometer and

an outlet is recommended (Figure 1.1). If during the performance of the pro-

cedure no gases are evolved from the reaction mixture, the inlet for inert gas

may be omitted and the outlet connected to a balloon or relatively big flask

filled with inert gas. Depending upon the required efficiency of stirring a simple

glass rod with a flattened end, a chromium-plated paddle (Figure 1.2) or other

types may be used. A flask having both of the outer necks in a non-vertical

position is impractical since it is difficult to place the thermometer or gas inlet

tube such that contact with the stirrer is avoided. Instead of the usual mercury,

alcohol or pentane thermometer an electronic thermometer may be used.

If relatively small volumes of reagents have to be added over a short period,

the combination of a syringe and a rubber septum may be more convenient

than the dropping funnel.

Magnetic stirring may be carried out if the volume of the reaction mixture is

limited, not much suspended material is present and continuous control of the

temperature by using a cooling bath is not very essential.

1.2 REACTIONS IN LIQUID AMMONIA

Anhydrous liquid ammonia is an excellent solvent for many reactions involving

acetylenic compounds. The conversions can be carried out under atmospheric

pressure at the boiling point (�33 �C) or if necessary, at lower temperatures.

Depending upon the conditions of the procedure, the standard set-up

(Figure 1.1) or a variant may be used. Liquid ammonia of good quality

(water content less than 0.1%, absence of rust particles) can be drawn from

cylinders with or without a dip tube (cf. A. I. Vogel’s Textbook of Practical

1

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Organic Chemistry, 4th edn., Longmans, p. 98) and transferred through a

plastic tube into the reaction flask. Plugs of cotton wool are temporarily

placed on the necks, after which the flask is equipped as desired.

However, in many laboratories no ammonia of good quality is available and

purification by distillation may be necessary. Small pieces of sodium are added

with manual swirling to �0.6 litre of ammonia in a 1-litre round-bottomed

flask. After the blue colour has persisted, an additional amount (�2 g) of

sodium is introduced and connection is made with the flask as shown in

Figure 1.9. The flask containing the solution of sodium is occasionally

placed in a bath at �35 �C, while condensation of the vapour is achieved by

(occasionally) cooling the flask (Figure 1.9) in liquid nitrogen. The distillation

can be completed in 1 to 1.5 h. Disposal of the sodium residue by addition of

ethanol should be carried out immediately after termination of the distillation.

Many reactions in liquid ammonia can be carried out at its boiling point.

Evaporation can be limited by insulating the flask in cotton wool.

If a volatile compound is to be prepared or a volatile or ammonia-sensitive

reagent (e.g. methyl iodide) is added, it is desirable to keep the reaction mixture

below the boiling point of ammonia (�33 �C). This can be done by occasional

cooling with liquid nitrogen or a mixture of dry ice and acetone in a Dewar

vessel (Figure 1.6).

Strong evaporation of ammonia during exothermic reactions can be avoided

by cooling the reaction mixture below the boiling point of ammonia.

For slow reactions, which require several hours and which can be carried out

without stirring, a flask with an evacuated space between the walls (Figure 1.4)

is recommended. If the flask is covered with aluminium foil, the rate of eva-

poration of ammonia is very low. An example is the reaction between lithium

acetylide and oxirane (Chapter 4, exp. 4.5.16).

If a reaction in ammonia is very fast and work-up has to be carried out imme-

diately, it may be more convenient to use a wide-necked round-bottomed flask

with the stirrer placed centrally (Figure 1.5). An example is described in

Chapter 3, exp. 3.9.28.

Note

The complicated equipment prescribed for performing reactions in liquid

ammonia,* even in some Organic Synthesis procedures (use of a reflux

*Some examples: A. L. Henne and K. W. Greenlee, J. Am. Chem. Soc. 67, 484 (1945);

Inorg. Synth. 2, 128 (1946); K. E. Schulte and K. P. Reiss, Chem. Ber. 86, 777 (1953); 87,

964 (1954); R. F. Parcell and C. B. Pollard, J. Am. Chem. Soc. 72, 2385 (1950); R. W.

Bradshaw, A .C. Day, E. R. H. Jones, C. B. Page, V. Thaller and R. A. V. Hodge,

J. Chem. Soc. [C], 1156 (1971).

2 1. PROCEDURES AND EQUIPMENT

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condenser, cooled with dry ice, placed on the reaction flask) may be an impor-

tant reason to prefer organic solvents. It should be emphasised, however, that

it is possible to carry out most reactions in ammonia without using a

reflux condenser. If strong evaporation is expected, for example during

dehydrohalogenations, the reaction flask may be insulated in cotton wool or

be placed in a bath with a dry ice–acetone mixture or liquid nitrogen as

described above.

1.3 SOME PRACTICAL HINTS

During some conversions in liquid ammonia, frothing may occur, especially

in the case of very thick suspensions. This can result in the loss of part of

the reaction mixture. The reaction flask therefore should never be more

than half-filled. Frothing may effectively be suppressed by adding small

amounts of diethyl ether (if the product to be isolated is not volatile), by

lifting the stirring motor so that the paddle rotates just below the surface

of the reaction mixture or by shortly cooling the flask in a bath with

liquid nitrogen.

If the product of a reaction in liquid ammonia is not very volatile (bp>110 �C

at atmospheric pressure), the ammonia may be allowed to evaporate

overnight or during the weekend. After removal of the usual equipment, the

flask is connected with a tube filled with cotton wool placed on the level of

the bottom of the flask so that a protecting atmosphere of ammonia remains

in the flask (Figure 1.7). Alternatively, the ammonia may be quickly removed

by placing the flask in a bath at 34–40 �C.

In the case of volatile products (bp<110 �C), removal of the ammonia

by evaporation gives rise to considerable losses. These can be considerably

minimised by adding a high-boiling solvent (e.g. a petroleum ether

fraction with bp>170 �C) to the reaction mixture after the reaction

has finished. Subsequently the mixture is poured on to a relatively

large amount of finely crushed ice in a large wide-necked round-bottomed

flask (Figure 1.8) or in a large beaker. The reaction is carried out at tempera-

tures below the boiling point of ammonia (cooling in dry ice–acetone or

liquid nitrogen).

In some elimination reactions in liquid ammonia an alkali acetylide

is formed. In some cases, for example in the preparation of methoxy-

and ethoxyacetylene, it is for reasons of safety essential to hydrolyse the

alkynylide before all ammonia has evaporated. This can be done by

successively adding the extraction solvent and a large amount of crushed

1.3 SOME PRACTICAL HINTS 3

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ice over a very short period (cf. Chapter 3, exp. 3.9.28). For this reason

the reaction is carried out in a large one-necked round-bottomed flask

(Figure 1.5).

For the isolation of volatile or unstable products from the solution in a high-

boiling solvent the set-up of Figure 1.10 is used. After evacuation (between <1

and 25 Torr) the solution is warmed until a small amount of the extraction

solvent has passed over. The volatile product is collected in a strongly

cooled (bath with dry ice–acetone, �78 �C) receiver. If a water aspirator

is used, and entrance of moisture is undesired (for example in Chapter 3,

exp. 3.9.48), a tube filled with a drying agent should be placed between the

receiver and the aspirator.

Distillation can be accompanied by foaming especially in the case of com-

pounds with a long carbon chain. Foaming can be suppressed by completely

immersing the distillation flask in the liquid of the heating bath or by

adding a few drops of some anti-foaming liquid prior to carrying out the

distillation. Although special columns can be used for preventing the

foam passing over, it is, in general, advisable to use a relatively big distilla-

tion flask in such cases. Recovery by distillation of acetylenes or allenes that

have been stored for a long period may involve the risk of an explosive

decomposition of the residue. This danger can be minimised by adding a

certain amount (�20ml for the distillation of 50ml of product) of paraffin

oil prior to the distillation. The residue will not remain as a compact mass

but as an emulsion or dispersion in the oil after termination of the

distillation.

Concentrations of reactants in the procedures described in this book

generally are between 0.5 and 1mol/litre of solvent. A good estimate of the

time necessary for �100% conversion requires much experience and knowledge.

For the lithiation of a 1-alkyne with butyllithium, for example, one has to

know that the deprotonation of acetylenes with such very strongly basic

reagents is an extremely fast reaction. This means that the heat of this depro-

tonation is liberated over a very short period. Metallation of allenes, com-

pounds which are much less strongly acidic than 1-alkynes, proceeds less

fast. Nevertheless, one can make a rather good estimate of the time necessary

for (almost) complete lithiation of, for example methoxyallene,

H2C¼C¼CHOMe, by performing the following experiment. A solution of

0.05mol of n-BuLi in 33ml of hexane (the usual 1.6mol/litre concentration

of the commercially available reragent) and 40ml of tetrahydrofuran is

cooled down to �70 �C, then the cooling bath is removed and the flask is insu-

lated in cotton wool. The increase of the temperature of the slowly stirred solu-

tion is observed during a few minutes (an electronic thermometer is more

convenient than the usual one). Usually, rising of the temperature will

amount by a few degrees only. The temperature of the solution is adjusted


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again at �70 �C by dipping the reaction flask for a few seconds in the cooling

bath. Methoxyallene (0.05mol) is then added in one portion. This will result in

a rising of the temperature by several (at least 20) degrees over less than 1 min.

Even if smaller amounts of the allenic ether are added in one portion, the effect

is clearly visible. One may carry out a blank experiment by adding at �70 �C

the same volume of THF. In this case the temperature rises by a few (<5)

degrees only. Of course, for completion of the lithiation the reaction

mixture has to be stirred for a (limited) additional period at a temperature

higher than �70 �C. Reactions between strongly basic anionic species and

aldehydes or ketones usually proceed almost instantly, even at temperatures

far below 0 �C in solvents of low polarity. Silylations (with R3SiCl) and sulphe-

nylations (with disulphides, RSSR or thiocyanates, RSC�N) of organoalkali

compounds are other examples of very fast reactions, which are easy to

follow by temperature observation. Reactions in boiling liquid ammonia

(bp �33 �C) may be followed by keeping the end of a small slip of paper 1 cm

from the outlet. When there is no or a very slow reaction (e.g. when the reac-

tion has subsided) the flow of escaping ammonia is relatively weak and the

position of the slip remains vertical. In the case of very fast reactions much

ammonia may evaporate in a short time and the vigorous flow from the

outlet causes the slip to move off from the outlet. Dehydrohalogenations as

mentioned in Chapter 3, Section 3.3 are extremely fast and exothermic so

that addition of small portions of the halogen compound causes a vigorous

outward flow of ammonia. For reactions carried out at temperatures below

the boiling point of ammonia the method described above for methoxyallene

may be used.

It should be pointed out that heating effects can also be made visible by

performing the reaction on a very small (1mmolar) scale in a reagent tube

(wrapped in cotton wool) using an electronic thermometer.

Some reactions, if carried out on a preparative scale and with ‘preparative’

concentrations of the reactants, can be followed by observing the temperature

in the solution boiling under constant intensity of the reflux stirred at a

constant rate. A good example is the Pd/Cu-catalysed cross-coupling

between ethynyl(trimethyl)silane (bp �53 �C) and 1-bromo-1-cyclooctene in

piperidine (bp 106 �C) described in Chapter 16, exp. 16.7.15. The temperature

of the reaction mixture, in the beginning �90 �C, reaches a maximum

(�110 �C, somewhat higher than the boiling point of piperidine, due to the

presence of dissolved HBr salt) when most of the volatile acetylene

has reacted with bromocyclooctene. The isomerisation of methyl

propargyl ether (bp 61 �C) to methoxyallene (bp 51 �C) in the presence of

potassium t-butoxide in a small amount of DMSO (Chapter 17, exp. 17.2.8)

can be followed by looking at the thermometer in the refluxing solution.


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The temperature drops as a result of the formation of a more volatile

compound.

In other procedures, carried out with high concentrations of starting com-

pounds, the refractive index of the solution can be measured, for example

in the isomerisation of HC�CCH(Br)C6H13 to BrCH¼C¼CHC6H13 under

the catalytic influence of lithium dibromocuprate, CuBr �LiBr (Chapter 12,

exp. 12.4.14), and in the bromination of 1,3-diynes, RC�CC�CH, with potas-

sium hypobromite (Chapter 9, exp. 9.2.3).

In a single case the only necessary instruments are the eyes. The conversion

of propargyl bromide into the corresponding iodide, using a hot (�70 �C) solu-

tion of sodium iodide in absolute ethanol (Chapter 20, exp. 20.1.11) is accom-

panied by precipitation of sodium bromide. The reaction is finished when salt

crystals are no longer being formed in the supernatant layer (stirring is not

necessary).

Particularly in the cases of hydroxyacetylenes, the question ‘How many

extractions with diethyl ether still have to be carried out?’ may arise. The follow-

ing practical tip may be useful. Take a small (0.5ml) sample from the extract

with a Pasteur pipette and allow the solution to flow along a ground-glass

stopper. Further extraction is no longer necessary when after evaporation of

the ether no residue is visible on the ground glass.

A quick and extremely simple method to investigate whether volatile

polymerisable liquids such as oxirane, ethyl vinyl ether and vinyl bromide

contain polymers is to put � 1 ml on a watch glass and to blow air over

the liquid. If not any oil-like residue is visible on the glass, purification is

not necessary.

The following generally valid advice with respect to the work-up of reac-

tion mixtures resulting from syntheses with Grignard reagents should be

given. If water or aqueous ammonium chloride is added at too fast a

rate to the reaction mixture, much heat will be evolved and as a result

part of the reaction mixture will be lost, especially if diethyl ether is

used as a solvent. Therefore, the reaction mixture always should be (cau-

tiously) poured into water or into aqueous ammonium chloride. If the pro-

duct is not acid-sensitive, dilute mineral acid can be used. Alternatively,

water or the aqueous solution of ammonium chloride or acid may be

added slowly to the efficiently stirred reaction mixture, preferably under

cooling.


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Figure 1.1 Figure 1.2 Figure 1.3

Figure 1.4 Figure 1.5


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Figure 1.10

Figure 1.11


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ABBREVIATIONS

Et2O diethyl ether

THF tetrahydrofuran

DMSO dimethylsulphoxide

HMPT hexamethylphosphoric triamide

(Me3N)3P¼O

LDA lithium diisopropylamide

DMF N,N-dimethylformamide

TMEDA N1,N1,N2,N2-tetramethylethanediamine

rt (in experimental procedures) room temperature

BuLi n-butyllithium

t-BuOK potassium tert-butoxide

(the commercially available

non-complexed base)

TMS trimethylsilyl group

c-C6H11 cyclohexyl group

Me CH3 group

Et C2H5 group

n-Pr n-C3H7 group

n-Bu n-C4H9 group

t-Bu (CH3)3C group

(CH2)5C cyclohexane ring, in tables


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