synthesis of acetylenes, allenes and cumulenes || acetylenic and allenic derivatives by substitution...

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E:/Archive files/4188-Brandsma/Printer-Files/4188-Chapter-12.3d

12Acetylenic and Allenic Derivatives by

Substitution on sp- and sp2-Carbon

12.1 NUCLEOPHILIC 1,1-SUBSTITUTION ON sp-CARBON

1-Alkynyl ethers, RC�COEt, react with lithium dialkylamides, LiNR12, to

afford yneamines, RC�CNR12, in good yields [1]. This substitution is probably

not a direct one (as generalised by equation (1)), but the result of an addition of

the dialkylamide group across the triple bond and subsequent elimination of

ethoxide from the adduct as visualised in the general scheme (2). In this scheme

S represents the dialkylamide group and L the OEt substituent.

Strong evidence for this mechanism is obtained by heating 1-alkynyl ethers,

RC�COEt, with R1C�CLi in dioxane for 12 h at 100 �C. In addition to the

substitution product RC�CC�CR1, appreciable amounts of the adduct

(E)-RCH¼C(OEt)C�CR1 are formed. Lengthening of the reaction time

gives exclusively the diyne. Using t-butyllithium it is possible to prepare

t-butyl-substituted acetylenes [2].

The above-mentioned yneamines can also be prepared from 1-chloro-1-

alkynes and lithium dialkylamides, but in analogy with the formation of

the adducts 1-chloro-2-alkylthioalkenes, RS(R1)C¼CHCl, from 1-chloro-

1-alkynes, R1C�CCl, and thiolate RS–, the reaction may proceed through

a b-adduct, which loses chloride with simultaneous migration of the

235

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N,N-dialkylamino group [3,4]:

As an excellent alternative to the preparation from alkynyllithium and

the poisonous cyanogen chloride [5] alkynenitriles, RC�CC�N, are acces-

sible by reaction of 1-bromo-1-alkynes, RC�CBr, with copper(I) cyanide in

THF in the presence of a small amount of anhydrous lithium bromide,

which solubilises the copper cyanide. 2,3-Alkadienenitriles, RCH¼C¼CHC�N, similarly are obtainable by reaction between the corresponding

allenic nitriles and copper(I) cyanide (see Chapter 20 for these substitution

reactions).

12.2 NUCLEOPHILIC 1,3-SUBSTITUTION ON sp- AND sp2-CARBON

The impressive number of nucleophilic substitution reactions with acetylenic,

allenic and cumulenic derivatives may be considered to proceed as indicated by

the general equations (3), (4) and (5).

These equations, in general, give only the overall results of the interactions.

In a number of cases there is clear evidence for an addition-elimination

mechanism [6]. It has been shown that transition metal salts, e.g. iron salts,

considerably facilitate the formation of allenic compounds from Grignard

reagents and acetylenic halides or ethers [7–9]. The leaving group L in the

236 12. ACETYLENIC AND ALLENIC DERIVATIVES

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equations may represent halide [7,10], tosylate [11], acetate [12], sulphinate [13],

an ether [9] or epoxide function [14,15]. Some reactions are carried out with

pre-formed organocopper reagents. The formation of allenic alcohols

by reaction of lithium alanate with an acetylenic alcohol bearing a suitable

leaving group on the other side of the triple bond proceeds in the absence of

any catalyst:

Table 12.1 gives several examples of nucleophilic and electrophilic 1,3-substi-

tutions. In the experimental section a number of representative procedures are

given (indicated with * in this table).

12.3 ELECTROPHILIC 1,3-SUBSTITUTIONS

Electrophilic 1,3-substitutions (S0

E) of acetylenic and allenic derivatives may be

represented by the generalised equations (6) and (7), respectively.

In this scheme M mostly represents a metal (e.g. ZnHlg, SnR3, SiR3) and

the electrophile Eþ can be a proton [16–18] (from an alcohol HOR), an acyl

group (from ClC(¼O)R), a sulphonyl group [19] (from RSO2Cl) or halogen

(e.g. from I2) [20]. Synthetically useful examples are the reduction of acetylenic

halides with a zinc–copper couple in alcohols [18,21] (as a variant acetylenic

acetates may be used [22]) or with lithium alanate [23–25] and the formation

of alkyl propargyl ketones by reaction of the readily available allenyl tributyl-

tin with acid chlorides [38].

12.3 ELECTROPHILIC 1,3-SUBSTITUTIONS 237

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Table 12.1

1,3-Substitutions with acetylenic, allenic and cumulenic derivatives

Reactants, catalyst (additive) Conditionsa,b Product

HC�CCH2OMe,

n-BuMgCl, CuBr*

Et2O, –5 ! rt n-BuCH¼C¼CH2

HC�CCH2Cl,

t-BuMgCl, CuBr*

THF, –15 ! rt t-BuCH¼C¼CH2

HC�CCH2OMe,

c-C6H11MgCl, CuBr

Et2O, –5 ! rt c-C6H11CH¼C¼CH2

HC�CCH2OMe,

PhMgBr, CuBr

Et2O, –5 ! rt PhCH¼C¼CH2

HC�CCH(Cl)Me,

MeMgBr, CuBr

THF, –20 ! 0 MeCH¼C¼CHMec

EtC�CCH2OMe,

PhMgBr, CuBr

Et2O, reflux Et(Ph)C¼C¼CH2

t-BuC�CCH2OTs,

t-BuMgCl, CuBr

THF, 0 ! rt (t-Bu)2C¼C¼CH2

MeC�CCH2OTs,

PhCu, (MgBr2)*

THF, –10 Me(Ph)C¼C¼CH2

HC�CCH(Ph)OSOMe,

PhCu, (MgBr2)d

THF, –40þ 30 PhCH¼C¼CHPh

THF, –10

H2C¼C(Me)C�CCH2OMe,

EtMgBr, CuBr

Et2O, rt H2C¼C(Me)C(Et)¼C¼CH2

Et2NCH2C�CCH2OMe,

MeMgBr, CuBr

Et2O, reflux Et2NCH2(Me)C¼C¼CH2

HC�CCH(OEt)2,n-BuMgCl,

CuBr*

Et2O, 0þ 30 n-BuCH¼C¼CHOEt

HC�CCH(OEt)2,

t-BuMgCl, CuBr

Et2O, reflux t-BuCH¼C¼CHOEt

MeC�CCH(OEt)2,

EtMgBr, CuBr

Et2O, rtþ 30 Me(Et)C¼C¼CHOEt

2-THP–C�CH,

EtMgBr, CuBre,*

Et2O, rtþ 30 EtCH¼C¼CH(CH2)4OH

Me3SiC�CCH2OSOMe,

n-BuCu, LiBrd,*

THF, –50 ! 0 Me3Si(n-Bu)C¼C¼CH2

H2C¼C¼CHOMe,

c-C5H9MgCl, CuBr*

Et2O, 0 ! rt c-C5H9CH2C�CH

H2C¼C¼CHOMe,

PhMgBr, CuBr

Et2O, 0 ! rt PhCH2C�CH

H2C¼C¼CHOMe,

p-FC6H4MgBr, CuBr

Et2O, 0 ! rt p-FC6H4CH2C�CH

(Continued)


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Table 12.1

Continued


BuCH¼C¼CHOEt,

n-BuMgBr, CuBr

Et2O, reflux (n-Bu)2CHC�CH

EtOCH¼C¼C¼CHOEt,

MeMgBr, CuBr

Et2O, rtþ 90 EtOCH¼C(Me)C�CH

HC�CCH(Me)OTs,

CuCH2COOBut, (LiBr)

THF, –30! –10 ButOOCCH2CH¼C¼CHMe

HC�CCH(Me)OTs,

CuCH2C�N, (LiBr)*

THF, –30! rt N�CCH2CH¼C¼CHMe

THF, 25 Me(Ph)C¼C¼C(Me)CH2OH

HC�CCH2Br, KC�N, CuCN H2O, 55 N�CCH¼C¼CH2f

HC�CCH(Me)Br,

KC�N, CuCN*

H2O, EtOH, 70 N�CCH¼C¼CHMe

HC�CCH(Me)Cl,

CuCl, (LiCl)

THF, reflux ! 87 ClCH¼C¼CHMeg

HC�CCH(Ph)Cl,

CuCl, (LiCl)*

THF, 40þ 45 ClCH¼C¼CHPh

HC�CCH2Br,

CuBr, (LiBr)*

THF, reflux, 3 h BrCH¼C¼CH2

HC�CCH(C6H13)Br,

CuBr, (LiBr)*

THF, reflux, 3 h BrCH¼C¼CHC6H13

HC�CCH(Me)OH, HBr,

CuBr, (NH4Br)*

H2O, rtþ 18 h BrCH¼C¼CHMe

HC�CC(Me)2OH, HBr,

CuBr, (NH4Br)*

H2O, 40þ 15 BrCH¼C¼CMe2

HC�CCH(Ph)OH, HBr,

CuBr, (NH4Br)*

H2O, 0þ 2 h BrCH¼C¼CHPh

HC�CCH(Ph)OH, HI,

CuI, (NH4I)*

H2O, 0þ 1 h ICH¼C¼CHPh

HC�CCH(Me)OH,

(PhO)3PþMeI*

DMF, 100þ 30 ICH¼C¼CHMe

HC�CCH(Me)OH, HI,

CuI, (NH4I)*

H2O, 0þ 1 h ICH¼C¼CHMe

HC�CC(Cl)Me2,

PhSLi, CuBr, (LiBr)

THF, reflux, 15 PhSCH¼C¼CMe2

ClCH2C�CCH2OH,

LiAlH4*

Et2O, reflux, 30 H2C¼C¼CHCH2OH

Me2C(OR)C�CCH2OH, LiAlH4h,* Et2O, reflux, 1 h Me2C¼C¼CHCH2OH

(Continued)

12.3 ELECTROPHILIC 1,3-SUBSTITUTIONS 239

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Table 12.1

Continued


HC�CCH2OH,

HC�CCH2Cl, CuCl*

H2O, MeOH HOCH2C�CCH¼C¼CH2

HC�CCH(Me)Cl, Zn/Cu* EtOH, heat H2C¼C¼CHMe

HC�CC(Me)2Cl, Zn/Cu* EtOH, heat H2C¼C¼C(Me)2EtOH, heat

HC�CCH¼CHCH(Me)Br,

Zn/Cu*

hexanol, heat H2C¼C¼CHCH¼CHMe

Bu3SnCH¼C¼CH2,

MeC(¼O)Cl, ZnCl2*

heat HC�CCH2C(¼O)Me

Meaning of *: procedure is described in this chapter.aExperiments carried out and checked in the author’s laboratory.bFor more details see Experimental Section; temperatures in �C; reaction time in

minutes or hours.cRatio of MeCH¼C¼CHMe/Me2CHC�CH � 70:30, separation by fractional distil-

lation.dOSO ¼ sulphinate group; introduced by reaction of the corresponding alcohol with

MeS(¼O)Cl in the presence of Et3N.e2-THP ¼ 2-tetrahydropyranyl.fInitially, a mixture of the acetylenic and allenic nitriles might have formed; the acet-

ylenic nitrile isomerises under the influence of KCN.g15% of the starting compound was present; separation by fractional distillation.hR ¼ OCH(Me)OEt.


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12.4 EXPERIMENTAL SECTION

Note

In most of the procedures the reaction mixture is kept under inert gas.

12.4.1 N,N-dialkylaminoalkynes from 1-alkynyl ethersand lithium dialkylamides

Scale: 0.30 molar; Apparatus: Figure 1.1, 500 ml, see further below

12.4.1.1 Procedure

The dialkylamine (0.31 mol) is added to a solution of 0.30 mol of BuLi in

�270 ml of Et2O (prepared from butyl bromide and lithium, Chapter 2,

exp. 2.3.6) with cooling below 0 �C. The 1-alkynyl ether (0.30 mol, Chapter

4, exp. 4.5.7) is subsequently added in one portion at 0 �C. The mechanical

stirrer is then replaced with a magnetic stirring bar and the flask is equipped for

a distillation, using a 40-cm Vigreux column. The Et2O is slowly distilled off

over �2 h while a slow stream of N2 is passed through the apparatus. The

temperature of the heating bath is gradually raised to 100–110 �C. Then most

of the ether has distilled off. After heating for an additional half an hour at this

temperature, the reaction mixture is allowed to cool to rt. The Vigreux column

is replaced with a much shorter (�10 cm) one and two stoppers are placed on

the flask (Note 1). The receiver is placed in a bath at –78 �C (Figure 1.10) and a

tube filled with KOH pellets is placed between the receiver and the water

aspirator. The system is evacuated and the temperature of the heating bath

gradually raised to 200 �C (Note 2). When the distillation has stopped comple-

tely, nitrogen is admitted. The contents of the receiver are carefully redistilled

through an efficient column. The following compounds have been obtained in

yields between 60 and 70%:

N,N-diethyl-1-butyn-1-amine, EtC�CNEt2, bp 42 �C/10 Torr; N,N-

dipropyl-1-butyn-1-amine, EtC�CNn-Pr2, bp 65 �C/10 Torr; 1-(1-butynyl)pi-

peridine, EtC�C-piperidine, bp 73 �C/10 Torr; N,N-diethyl-1-pentyn-

1-amine, n-PrC�CNEt2, bp 56 �C/10 Torr; N,N-diethyl-1-hexyn-1-amine,

n-BuC�CNEt2, bp 71 �C/10 Torr.

12.4 EXPERIMENTAL SECTION 241

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Notes

1. Distillation at oil-pump pressure may be more effective.

2. In the final stage of the distillation, hot oil may be poured on the column

by means of a spoon. In this way as much as possible of the product is

forced to pass over.

12.4.2 1-(N,N-Dimethylamino)-2-phenylacetylene from1-chloro-2-phenylacetylene and lithium dimethylamide

Scale: 0.10 molar; Apparatus: Figure 1.1, 500 ml; at a later stage the thermo-

meter-outlet combination is replaced with a reflux condenser

12.4.2.1 Procedure

Liquefied dimethylamine (0.12 mol) is mixed with 50 ml of dry Et2O, cooled

to –40 �C. The solution is added to a solution of 0.10 mol of BuLi �LiBr in

�120 ml of Et2O (Chapter 2, exp. 2.3.6) with cooling between –20 and

–40 �C. Subsequently 0.10 mol of 1-(2-chloroethynyl)benzene (Chapter 9,

exp. 9.2.1) is added dropwise over 15 min with cooling between –15 and

–20 �C. After the addition, the cooling bath is removed and the temperature

is allowed rising. At rt a weakly exothermic reaction can be observed. The

dark brown mixture is then heated for 1 h under reflux. After cooling to rt,

the salt is filtered off on a (dry) sintered-glass funnel and rinsed well with

dry Et2O. The solution is concentrated in vacuo, 5 ml of paraffin oil is

added (to conduct the heat supplied by the oil bath during the distillation)

and the product is distilled in a high vacuum (mercury diffusion pump)

through a 5 to 10-cm Vigreux column. The product is collected in a

(single) receiver, cooled in a bath at a temperature of –20 �C or lower

(Figure 1.10). During the distillation the temperature of the heating bath

is gradually raised to �150 �C. Redistillation of the contents of the receiver

gives N,N-dimethyl-2-phenyl-1-acetylenamine, bp 107 �C/10 Torr, in at least

60% yield.

2-(1-Cyclohexenyl)-N,N-diethyl-1-acetylenamine, 1-cyclohexenylC�CNEt2,

is obtained in 40% yield from the corresponding chloroenyne and LiNEt2 by

a similar procedure.


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12.4.3 1,2-Heptadiene from methyl propargyl etherand n-butylmagnesium chloride

Scale: 0.40 molar; Apparatus: Figure 1.1, 1 litre

12.4.3.1 Procedure [8]

To a mixture of 0.40 mol of freshly distilled 3-methoxy-1-propyne (Chapter 20,

exp. 20.6.1 ) and 80 ml of dry Et2O is added 1 g of finely powdered copper(I)

bromide. A solution of butylmagnesium chloride (Note) in 250 ml of Et2O

(prepared from 0.60 mol of BuCl, Chapter 2, exp. 2.3.7) is added with vigorous

stirring and efficient cooling, so that the temperature of the reaction mixture

can easily be kept between 0 and –10 �C. The addition takes 30 min. The

cooling bath is then removed, a small additional amount (� 0.5 g) of CuBr

is added, after which stirring is continued for a further 30 min. The greyish

suspension is cautiously poured with manual swirling on to a mixture of 200 g

of finely crushed ice, 20 g of ammonium chloride and 100 ml of 36% hydro-

chloric acid in a 2-litre conical flask. The remaining salt mass in the reaction

flask is treated with dilute (2N) hydrochloric acid. After separation of the

layers, the aqueous layer is extracted four times with small portions of Et2O

and the combined ethereal solutions are dried over magnesium sulphate.

Careful distillation through an efficient column gives 1,2-heptadiene, bp

105 �C/760 Torr. The remaining liquid is distilled in a partial vacuum

(60–100 Torr, bp 40–70 �C) and the distillate is redistilled at normal pressure

to gives an additional amount of 1,2-heptadiene, bringing the yield to >70%.

Closely similar procedures (cf. Table 12.1) can be followed for the reactions

between 3-methoxy-1-propyne, HC�CCH2OMe, and c-C6H11MgCl or

PhMgBr; between 1-methoxy-2-pentyne, EtC�CCH2OMe, or PhMgBr;

between EtMgBr and 5-methoxy-2-methyl-1-pentene-3-yne; between

H2C¼C(Me)C�CCH2OMe and t-BuMgCl or 1,1-dimethyl-2-pentynyl-

4-methylbenzenesulphonate, t-BuC�CCH2Otosyl; between N,N-diethyl-

1-methoxy-2-butyn-1-amine, Et2NCH2C�CCH2OMe and MeMgBr. If the

volatility of the products allows, the extract may be concentrated under

reduced pressure.

Note

Butylmagnesium bromide can also be used, but the yield is lower (� 65%) due

to the inactivation of the CuBr in a later stage of the reaction by the MeOMgBr

slurry. Moreover, this makes efficient mixing of the reagents difficult.


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12.4.4 t-Butylallene from propargyl chloride andt-butylmagnesium chloride


12.4.4.1 Procedure

A mixture of 50 ml of dry THF, 0.50 mol of propargyl chloride and 2 g of

copper(I) bromide is cooled to � –40 �C. A solution of �0.60 mol of t-BuMgCl

(Chapter 2, exp. 2.3.8) in � 300 ml of THF is added from the dropping funnel

over 1 h. The temperature of the reaction mixture is initially kept between –20

and –15 �C, but precipitation of large amounts of salt makes it necessary to

increase the temperature gradually to 0–10 �C. Stirring then becomes more

efficient (Note 1). After the addition of the Grignard solution stirring is

continued for an additional 30 min, then the mixture is poured into 500 ml

of ice-cold 3 N hydrochloric acid. High-boiling petroleum ether (150 ml, bp

>170 �C at normal pressure) is added and, after vigorous shaking, the layers

are separated. The organic layer is shaken at least ten times with 150-ml por-

tions of 3 N HCl in order to remove the THF. The combined aqueous layers

are extracted once with 50 ml of petroleum ether and the upper layer is freed

from THF by shaking five times with 50-ml portions of 3 N HC1. The com-

bined petroleum ether solutions are dried over a small amount of magnesium

sulphate, then the solution is decanted from the magnesium sulphate and

poured into a 1-litre round-bottomed flask. After adding some boiling

stones, the flask is connected to a 40-cm Vigreux column, condenser a receiver

cooled at –70 �C and the system is evacuated (10–20 Torr) the flask being

heated in a water bath (Figure 1.10). The volatile allene condenses in the

receiver. The ‘distillation’ is stopped when the temperature in the top of the

column has reached 55–60 �C. Redistillation of the contents of the receiver

through an efficient column gives 4,4-dimethyl-1,2-pentadiene, bp 79–82 �C/

760 Torr, in �80% yield (Note 2).

Notes

1. If the reaction mixture becomes too thick, more THF should be added.

2. In order to minimise the hold-up, a partial vacuum (� 100 Torr) may be

applied during the last stage of the distillation; the fraction obtained in this

way can be redistilled at normal pressure in a small apparatus.


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12.4.5 1-Ethoxy-1,2-heptadiene from 3,3-diethoxy-1-propyneand butylmagnesium chloride

Scale: 0.10 molar; Apparatus: Figure 1.1, 500 ml

12.4.5.1 Procedure [9]

To a mixture of 0.10 mol of 3,3-diethoxy-1-propyne (Chapter 3, exp. 3.9.21)

and 150 ml of dry Et2O is added 0.7 g of finely powdered copper (I) bromide.

The mixture is cooled to –30 �C and from the dropping funnel is added over

20 min a solution of n-BuMgCl in 100 ml of Et2O, prepared from 0.12 mol of

butyl chloride (Chapter 2, exp. 2.3.7). During the first 10 min the temperature

is kept at � –30 �C. The remainder of the Grignard solution is added at a

somewhat higher temperature (–10 �C to rt) since stirring becomes more diffi-

cult at –30 �C. A thick suspension of ethoxymagnesium chloride is formed.

After stirring for an additional 30 min at 0 �C, the mixture is hydrolysed by

cautious addition of and solution of 3 g of KCN and 10 g of NH4Cl in 50 ml

of ice water. During this operation, carried out with vigorous stirring, the flask

is cooled in a bath with ice water. After separating the layers, three extractions

with Et2O are carried out. The combined ethereal solutions are washed with a

saturated ammonium chloride solution and dried over potassium carbonate.

The Et2O is removed under reduced pressure. Careful distillation of the

remaining liquid through an efficient column gives 1-ethoxy-1,2-heptadiene,

bp 63 �C/15 Torr, in �80% yield.

A similar procedure is applicable for the reaction between 3,3-diethyoxy-

1-propyne and t-BuMgCl or the reaction between 1,1-diethoxy-2-butyne,

MeC�CCH(OEt)2, and EtMgBr (cf. Table 12.1).

12.4.6 1-(2-Propynyl)cyclopentane from cyclopentylmagnesiumchloride and methoxyallene



[13.1.2004–9:57pm] [235–266] [Page No. 246]


12.4.6.1 Procedure [26]

A solution of � 0.20 mol of cyclopentylmagnesium chloride in 130 ml of Et2O,

prepared from 0.25 mol of cyclopentyl chloride (cf. Chapter 2, exp. 2.3.7) is

added over 30 min to a mixture of 0.20 mol of freshly distilled methoxyallene

(Chapter 17, exp. 17.2.8), 150 ml of Et2O and 0.5 g of finely powdered

copper(I) bromide. During this addition the temperature of the reaction mix-

ture is kept between –5 and þ5 �C by cooling in a bath of dry ice and acetone.

A white suspension is formed. After the addition, the cooling bath is removed

and stirring is continued for a further 45 min, then the reaction mixture is

poured cautiously into 200 ml of ice water (some cooling may be necessary).

After dissolution of the solid material a small amount of 4 N HCl is added,

so that the layers become clear. The aqueous layer is extracted three times with

small portions of Et2O. The combined extracts are washed with concentrated

ammonium chloride solution and subsequently dried over magnesium sul-

phate. The greater part of the Et2O is distilled off at normal pressure through

a 40-cm Vigreux column. The remaining liquid is distilled and collected in a

single receiver, cooled at 0 �C. 1-(2-Propynyl)cyclopentane, bp 30 �C/20 Torr, is

obtained in a high yield.

Closely similar procedures can be followed for the preparation of: 1-(3-

butynyl)benzene, PhCH2C�CH, from PhMgBr and methoxyallene; of 1-

ethoxy-4,4-dimethyl-1,2-pentadiene, t-BuCH¼C¼CHOEt, from t-BuMgCl

and HC�CCH(OEt)2; of 3-butyl-1-heptyne, (n-Bu)2CHC�CH, from 1-

ethoxy-1,2-heptadiene, n-BuCH¼C¼CHOEt, and n-BuMgBr; of 1-ethoxy-2-

methyl-1-buten-3-yne, HC�CC(Me)¼CHOEt, from 1,4-diethoxybutatriene,

EtOCH¼C¼C¼CHOEt, and MeMgBr (Table 12.1).

12.4.7 Reaction of an acetylenic sulphinate with alkylcopper


12.4.7.1 Procedure [27]

To a solution of � 0.10 mol of butylmagnesium bromide in 200 ml of THF,

prepared from 0.12 mol of butyl bromide, a solution of 0.12 mol of dry

copper(I) bromide and 0.12 mol of anhydrous lithium bromide in 50 ml of

dry THF is added with cooling between –50 and –60 �C. After an additional


[13.1.2004–9:57pm] [235–266] [Page No. 247]


30 min at –50 �C a solution of 0.10 mol of O-[3-(trimethylsilyl)-2-propynyl]

methanesulphinothioate, prepared from 0.10 mol of 3-trimethylsilyl-

2-propyn-1-ol, Me3SiC�CCH2OH, (Chapter 7, exp. 7.2.12) and MeS(¼O)Cl,

as described in Chapter 20, exp. 20.5.3 (Note 1), in 40 ml of dry THF is added

in 15 min with cooling at � –50 �C. The cooling bath is removed after this

addition and the temperature is allowed to rise to 0 �C. The greyish solution is

poured into 250 ml of an aqueous solution of 40 g of ammonium chloride and

25 g of KCN or NaCN. After vigorous shaking, the layers are separated. The

aqueous layer is extracted three times with redistilled pentane and the com-

bined solutions are dried over magnesium sulphate (Note 2). The greater part

of the solvents is distilled off at normal pressure through a 40-cm Vigreux

column (bath temperature not higher than 110 �C). The remaining liquid

is carefully distilled through the same column to afford 3-trimethylsilyl-

1,2-heptadiene, bp 55 �C/15 Torr, in �70% yield.

Notes

1. Several experimental examples are given in Ref. 26 (see also Table 12.1). In

some cases methanesulphonates can be successfully applied when the use of

the sulphinic esters leads to mixtures of 1,1-and 1,3-substitution products.

2. The remaining aqueous layer should not be poured into a waste container

containing acids!

12.4.8 Reaction of an acetylenic tosylate with phenylcopper


12.4.8.1 Procedure [11]

A solution of PhMgBr in 200 ml THF is prepared from 21 g of bromobenzene

and 5 g of magnesium. This solution is transferred into the reaction flask and a

solution of 17 g of copper(I) bromide and 11 g of anhydrous lithium bromide in

50 ml of THF is added over 10 min at –30 �C. Fifteen minutes later a solution

of 0.10 mol 2-butynyl tosylate (Chapter 20, exp. 20.5.4) in 30 ml of THF is

added over 20 min at –35 �C. The cooling bath is then removed and the tem-

perature is allowed to rise to –10 �C. The dark reaction mixture is poured into a


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solution of 25 g of NaC�N and 25 g of ammonium chloride in 250 ml of water.

After vigorous shaking, the layers are separated and the aqueous layer is

extracted three times with Et2O (cf. Note 2 of preceding exp.). The combined

solutions are dried over magnesium sulphate and subsequently concentrated

under reduced pressure. The remaining liquid is distilled through and 25-cm

Vigreux column to give 1-(1-methyl-1,2-propadienyl)benzene, bp 75 �C/15

Torr, in �80% yield.

12.4.9 Copper bromide-catalysed reaction of2-ethynyltetrahydropyran with alkylmagnesium bromide


12.4.9.1 Procedure

A solution of 0.25 mol of ethylmagnesium bromide in 200 ml of Et2O, prepared

from 0.30 mol of ethyl bromide, is added dropwise to a mixture of 0.20 mol of

2-ethynyltetrahydropyran (Chapter 4, exp. 4.5.20), 100 ml of dry Et2O and 1 g

of finely powdered copper(I) bromide. During this addition, which is carried

out over 30 min, the temperature is kept between –5 and þ5 �C. The cooling

bath is then removed and stirring is continued for a further 30 min. The dark

reaction mixture is poured into 200 ml of an aqueous solution of 20 g of NH4Cl

and 5 g of KCN or NaCN. The black copper suspension disappears after

vigorous shaking. The aqueous layer is extracted with Et2O. The ethereal

solutions are dried over magnesium sulphate and then concentrated under

reduced pressure. Distillation of the residue through a 40-cm Vigreux

column gives 5,6-nonadien-1-ol, bp 110 �C/24 Torr, in �80% yield.

Ring opening reactions with acetylenic oxiranes can be carried out by a simi-

lar procedure. An example is given in Table 12.1.

12.4.10 3,4-Hexadienenitrile from 1-methyl-2-propynyl-4-methylbenzenesulphonate and the copperderivative of acetonitrile


[13.1.2004–9:57pm] [235–266] [Page No. 249]



12.4.10.1 Procedure [28]

To a solution of 0.12 mol of dry diisopropylamine in 200 ml of dry THF is

added at rt a solution of 0.10 mol of butyllithium in 63 ml of hexane. After

cooling the solution to –40 �C, 0.13 mol of dry acetonitrile (dried over phos-

phorus pentoxide and subsequently distilled) is added over 10 min. A white

suspension is formed. Ten minutes after this addition a solution of 18.0 g of

CuBr and 12.0 g of anhydrous LiBr in 50 ml of dry THF is added at rt over

10 min. After an additional 15 min (at rt) the mixture is cooled to –35 �C and a

solution of 0.12 mol of the acetylenic tosylate (Chapter 20, exp. 20.5.4) in 30 ml

of THF is added over 15 min. During this addition the temperature is kept

between –25 and –35 �C. A two-layer system is formed. The temperature is

allowed to rise to –10 �C, then the mixture is poured into 300 ml of a solution

of 50 g of ammonium chloride to which 40 ml of 36% HCl (Note) has been

added. Seven extractions with Et2O are carried out. The combined extracts are

washed with 100 ml of a saturated solution of ammonium chloride to which

10 ml of 20% ammonia solution has been added (for removing traces of copper

salts) and are subsequently dried over magnesium sulphate. After the greater

part of the solvents has been distilled off at 760 Torr through a 30-cm Vigreux

column, the remaining liquid is distilled to give 3,4-hexadienenitrile, bp 56 �C/

15 Torr, in �75% yield.

t-Butyl 3,4-hexadienoate, MeCH¼C¼CHCH2COO-t-Bu, is prepared in a

fair yield by a similar procedure starting from MeCOO-t-Bu and 1-methyl-2-

propynyl-4-methylbenzenesulphonate, HC�CCH(Me)OTs.

Note

No cyanide should be used for removing the copper salts, since the nitrile is

probably very base-sensitive (isomerisation to a conjugated diene).

12.4.11 2,3-Alkadienenitriles from the reaction betweenacetylenic bromides and alkali cyanide in thepresence of catalytic amounts of copper(I) cyanide



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12.4.11.1 Procedure

(Note 1) In the flask are placed 20 ml of ethanol, 5 ml of water, 6 g of finely

powdered CuCN and 0.20 mol of 3-bromo-1-butyne (Chapter 20, exp. 20.1.5).

The mixture is warmed to 55 �C and a solution of 13 g of KCN in 30 ml of

water is added dropwise or in small portions. Care is taken to avoid complete

dissolution of the copper cyanide (Note 2). The temperature of the mixture is

maintained close to 60 �C throughout the period of addition. The conversion

is terminated by heating the mixture for a further 30 min at 65–70 �C with

vigorous stirring. After cooling to rt, 150 ml of ice water is added and the

product is extracted seven times with small portions of Et2O. The extracts are

combined and washed twice with saturated ammonium chloride solution. After

drying over magnesium sulphate, most of the Et2O is distilled off at normal

pressure through a 30 or 40-cm Vigreux column. Distillation of the remaining

liquid gives 2,3-pentadienenitrile , bp 39 �C/15 Torr, in �90% yield.

2,3-Butadienenitrile, H2C¼C¼CHC�N, is obtained by a similar procedure

from propargyl bromide and potassium cyanide [29].

Notes

1. The product has lachrymatory properties and may cause blisters on the

skin.

2. If the addition is performed at too fast a rate, all of the copper cyanide may

dissolve temporarily. The free KCN, present in the solution, may cause

partial resinification of the allenic cyanide.

12.4.12 CuCl-catalysed isomerisation of 3-phenyl-3-chloro-1-propyne to 1-(3-chloro-1,2-propadienyl)benzene

Scale: 0.10 molar; Apparatus: 100-ml round-bottomed flask and thermometer,

manual swirling or magnetic stirring

12.4.12.1 Procedure (cf. [30])

To a solution (Note 1) of 2 g of copper(I) chloride (commercial product) and 4 g

of dry lithium chloride in 15 g of dry THF is added with swirling 0.10 mol of

3-phenyl-3-chloro-1-propyne (prepared from the corresponding alcohol and


[13.1.2004–9:57pm] [235–266] [Page No. 251]


SOCl2, cf. Chapter 20, exp. 20.1.5). The refractive index nD (Note 2) of the

solution rises during 40 min of warming at 40 �C from the initial value of 1.487

to a maximum of 1.505. The solution is then poured into 100 ml of 4 N

hydrochloric acid. After vigorous shaking, the product is extracted with a

1:1 mixture of Et2O and pentane. The extracts are washed with water and

dried over magnesium sulphate. Concentration under reduced pressure gives

1-(3-chloro-1,2-propadienyl)benzene in more than 90% yield. The NMR spec-

trum shows that no starting compound is present and that the purity is satis-

factory. Attempts to distil the allene lead to extensive polymerisation.

Notes

1. Obtained by briefly heating the mixture under reflux.

2. After placing the solution on the prism, the apparatus should be closed

immediately because evaporation of the THF will give rise to too high

values.

12.4.13 Copper bromide-catalysed isomerisationof propargyl bromide to bromoallene

Scale: 1.0 molar; Apparatus: 250-ml flask with gas inlet-thermometer combina-

tion and reflux condenser

12.4.13.1 Procedure [cf. 31]

A mixture of 10 g of copper(I) bromide, 35 ml of dry THF and 20 g of

anhydrous lithium bromide is heated gently until a clear solution has

formed, then 1.0 mol of freshly distilled propargyl bromide (Chapter 20,

exp. 20.1.1) is added. The mixture is heated under reflux for 3 h. The tempera-

ture in the boiling solution, initially � 87 �C, is then dropped to the minimum

value of 82.5 �C. NMR spectroscopy indicates that the ratio of bromoallene

and propargyl bromide is � 70:30 (Note 1). After cooling to rt, the mixture is

shaken vigorously with a cold (0 �C) solution of 20 g of NaCN in 500 ml of

water. The heavy lower layer is separated as sharply as possible. The aqueous

layer (warning) is extracted twice with 30-ml portions of high-boiling petroleum

ether (bp >170 �C). The extracts and the undiluted liquid are combined and


[13.1.2004–9:57pm] [235–266] [Page No. 252]


transferred (without drying) into a 250-ml three-necked flask provided with a

dropping funnel, a mechanical stirrer and a thermometer combined with an

outlet. The solution is cooled to 10 �C and a mixture of 0.6 mol of diethylamine

and 40 ml of water is added over 10 min with vigorous stirring, while keeping

the temperature between 10 and 5 �C (Note 2). Stirring is continued for an

additional 15 min at þ5 �C. The mixture is then poured into 500 ml of cold

(0 �C) 2 N hydrochloric acid. After vigorous shaking, the organic layer is

separated off. The aqueous layer is extracted twice with 70-ml portions of

petroleum ether. The combined solutions are washed (Note 3) seven times

with l00-ml portions of 2 N HCl, saturated with ammonium chloride and

then dried over magnesium sulphate and transferred into a 1-litre distillation

flask, equipped for distillation at water-aspirator pressure (Figure 1.10). By

gradually heating the solution under 10–15 Torr, bromoallene condenses in the

receiver cooled at –75 �C. The evacuation is terminated as soon as petroleum

ether begins to distil (bp>50 �C/15 Torr). The contents of the receiver are

freed from traces of petroleum ether by repeating the procedure in the same

apparatus, but keeping the temperature of the heating bath below 40 �C so that

the small amount of petroleum ether remains in the distillation flask. The

receiver now contains pure bromoallene, the yield being 50–60%.

Notes

1. This ratio corresponds to the equilibrium value.

2. This operation is necessary to remove the propargyl bromide. At higher

temperatures bromoallene also reacts with the amine.

3. The washing procedure is necessary to remove the dissolved THF.

Warning: The aqueous layer should never be poured into a waste container

for acids.

12.4.14 Copper bromide-catalysed isomerisationof 3-bromo-1-nonyne to 1-bromo-1,2-nonadiene

Scale: 0.10 molar; Apparatus: 100 ml two-necked round-bottomed flask with

inlet and reflux condenser


[13.1.2004–9:57pm] [235–266] [Page No. 253]


12.4.14.1 Procedure

A mixture of 40 ml of dry THF, 6.0 g of anhydrous LiBr, 2.5 g of CuBr and

0.10 mol of 3-bromo-1-nonyne (Chapter 20, exp. 20.1.4) is heated under reflux.

The solid material disappears after a short time. The refractive index ( nD) of a

sample, taken from the liquid after cooling to � 50 �C, which is � 1.460 after

dissolution of the solids, rises to the maximum value of � 1.466 after refluxing

for 2.5 h (Note). After 3 h the mixture is cooled to rt and poured into a solution

of 10 g of ammonium chloride and 5 g of NaCN (or KCN) in 100 ml of water.

The mixture is shaken vigorously, then five extractions with Et2O are carried

out. The combined extracts are dried over magnesium sulphate and subse-

quently concentrated under reduced pressure. Careful distillation of the residue

affords 1-bromo-1,2-nonadiene, bp 90 �C/15 Torr, in �75% yield. The small

first fraction contains some starting compound.

Note

In order to obtain reliable values, the determination should be carried out very

quickly: A few drops are placed on the prism and the apparatus is closed

immediately, otherwise the THF will evaporate and a too high value is mea-

sured.

12.4.15 1-(3-Bromo-1,2-propadienyl)benzene byCuBr-catalysed reaction of 1-phenyl-2-propyn-1-olwith concentrated aqueous hydrogen bromide


12.4.15.1 Procedure [32]

To a mixture of 50 ml of 47% hydrobromic acid, 0.03 mol of copper(I)

bromide, 0.1 mol of ammonium bromide and 0.1 g of copper bronze (reduces

traces of Cu(II) to Cu(I)) is added 0.10 mol of 1-phenyl-2-propyn-1-ol (Chapter

5, exp. 5.2.2) dissolved in 30 ml of pentane at 0 �C in 3 min. After stirring for

2 h at this temperature, 150 ml of pentane and 200 ml of ice water are succes-

sively added. The pentane layer is shaken with 25-ml portions of 47% aqueous

HBr until the aqueous layer remains colourless. The pentane solution is dried

over magnesium sulphate and then concentrated under reduced pressure.

High-vacuum distillation affords 1-(3-bromo-1,2-propadienyl)benzene,


[13.1.2004–9:57pm] [235–266] [Page No. 254]


bp � 50 �C/0.01 Torr, in �80% yield. In view of the low thermal stability of

the compound too high bath temperatures should be avoided.

12.4.16 1-Bromo-3-methyl-1,2-butadiene by CuBr-catalysedreaction of 2-methyl-3-butyn-2-ol with concentratedaqueous hydrogen bromide


12.4.16.1 Procedure [32]

A mixture of 50 ml of 48% HBr, 10 g of commercial CuBr, 8 g of ammonium

bromide, 0.5 g of copper bronze (reduces traces of Cu(II) to Cu(I)) and 0.20 mol

of 2-methyl-3-butyn-2-ol is stirred for 15 min at 40 �C. After cooling to rt, the

upper layer is separated as sharply as possible and is transferred into a 250-ml

flask containing 10 g of sodium hydrogen carbonate. After shaking, the flask

is fitted with a short column connected to a condenser and a receiver cooled

at –75 �C (Figure 1.10). By evacuating with the water aspirator (10–15 Torr)

and heating the flask at up to 50 �C the bromoallene condenses in the receiver.

The yield of pure product is �75%.

12.4.17 1-Bromo-1,2-butadiene by CuBr-catalysed reaction of3-butyn-2-ol with concentrated aqueous hydrogen bromide


12.4.17.1 Procedure [cf. 32]

To 200 ml of 48% hydrobromic acid is added 0.40 mol of phosphorus tribro-

mide (Note 1). The mixture is agitated vigorously, while the temperature is kept

between 20 and 30 �C by cooling in a water bath at 10–15 �C. After �1 h the

lower layer has disappeared completely. The solution is cooled to 0 �C, then

0.40 mol of ammonium bromide, 0.10 mol (Note 2) of copper(I) bromide

(commercial product), 2 g of copper bronze, 140 ml of redistilled pentane

and 0.40 mol of 3-butyn-2-ol (Note 3) are successively added. The mixture is


[13.1.2004–9:57pm] [235–266] [Page No. 255]


stirred for 5 h at � 0 �C and subsequently for 18 h at rt. After separation of

layers, two extractions with 50-ml portions of pentane are carried out. The

combined solutions are washed with water and dried over magnesium sulphate.

Most of the pentane is distilled off at normal pressure through a 40-cm Vigreux

column, keeping the bath temperature below 100 �C. The remaining liquid is

carefully distilled through an efficient column, giving 1-bromo-1,2-butadiene,

bp � 60 �C/160–170 Torr, in 60–75% yield. The product contains a small

amount (<5%) of 3-bromo-1-butyne, HC�CCH(Br)Me.

Notes

1. The concentration of the aqueous HBr solution is increased by the reaction

of phosphorus tribromide with water. If available in a cylinder, a corre-

sponding amount of gaseous HBr may be introduced into the 48% solu-

tion at 0 �C.

2. In Ref. 32 an equivalent amount of CuBr is used.

3. This compound is commercially available as a 55% aqueous solution. The

water can be removed by saturation of the solution with anhydrous potas-

sium carbonate. The upper layer is dried over a small amount of potassium

carbonate and distilled, bp � 40 �C/35 Torr.

12.4.18 1-Iodo-1,2-butadiene by reaction of3-butyn-2-ol with triphenylphosphite-methiodidein N,N-dimethylformamide

Scale: 0.10 molar; Apparatus: 250-ml two-necked round-bottomed flask,

magnetic stirring

12.4.18.1 Procedure [33]

A solution of 55 g of triphenyl phosphite methiodide in 100 ml of dry DMF is

heated at 100 �C (bath temperature) and 0.10 mol of 3-butyn-2-ol (commer-

cially available) is added in 2 min by syringe. After stirring for 30 min at

100 �C, the mixture is cooled. On the flask are placed a 20-cm Vigreux

column and the column is connected with a condenser and a receiver. The

DMF and the iodoallene distil between 40 and 50 �C/15 Torr. After addition


[13.1.2004–9:57pm] [235–266] [Page No. 256]


of 200 ml of water to the distillate, four extractions with small amounts of

Et2O or pentane are carried out. The extracts are washed with water and dried

over magnesium sulphate. The residue, remaining after evaporation of the

solvent under reduced pressure is distilled through a short column, affording

1-iodo-1,2-butadiene, bp 40 �C/15 Torr, in �75% yield.

12.4.19 1-Iodo-3-phenylpropadiene by CuI-catalysed reaction of1-phenyl-2-propyn-1-ol with concentrated aqueoushydrogen iodide

Scale: 0.10 molar; Apparatus: 250-ml round-bottomed flask, magnetic stirring

12.4.19.1 Procedure [33]

A mixture of 40 ml of 50% hydroiodic acid, 0.03 mol of copper(I) iodide,

0.1 mol of ammonium iodide, 0.2 g of copper bronze, 0.10 mol of 1-phenyl-

2-propyn-1-ol (Chapter 5, exp. 5.2.2) and 20 ml of pentane is vigorously stirred

for 1 h at 0–5 �C (bath with ice water). Ice water (200 ml) is then added and

the product is extracted three times with 50-ml portions of a 1:1-mixture of

pentane and Et2O. The combined organic solutions are washed with water,

dried over magnesium sulphate and subsequently concentrated under reduced

pressure. The weight of the residue corresponds to 90% yield of the 1-iodo-3-

phenylpropadiene. High-vacuum distillation gives the pure product, bp 70 �C/

0.01 Torr, in �60% yield. Due to its low thermal stability much of the product

polymerises during the distillation.

12.4.20 Allenic alcohols from the reaction betweenlithium alanate and chlorine-containingacetylenic alcohols

Scale: 0.20 molar; Apparatus: Figure 1.1, 500 ml, reflux condenser instead of

the thermometer


[13.1.2004–9:57pm] [235–266] [Page No. 257]


12.4.20.1 Procedure [34]

To a solution of 0.20 mol of 4-chloro-2-butyn-l-o1 (see Chapter 5, exp. 5.2.8) in

150 ml of dry Et2O is added a solution of 0.22 mol of lithium alanate in 250 ml

of Et2O. The addition is performed at a rate such that the Et2O gently refluxes.

A thick white suspension is formed. The mixture is warmed for an additional

30 min under reflux and is subsequently cooled by complete immersion of the

flask in a bath with ice water. Ice water (� 20 ml) is added dropwise with

vigorous stirring until the refluxing of the Et2O has ceased. The ethereal

layer is decanted and the white slurry is extracted ten times with small portions

of Et2O. The combined extracts are dried well over magnesium sulphate, after

which the greater part of the Et2O is distilled off at normal pressure through a

40-cm Vigreux column. Distillation of the residue (using a single receiver,

cooled at 0 �C, Figure 1.10) gives 2,3-butadien-1-ol, bp 38 �C/12 Torr, in

�75% yield.

In a similar way are prepared: 3,4-pentadien-2-ol, H2C¼C¼CHCH(Me)OH,

bp 65 �C/50 Torr, in �70% yield from 5-chloro-3-pentyn-2-ol, ClCH2C�

CCH(Me)OH, (for the preparation of this compound from LiC�CCH2Cl

and acetaldehyde see the general procedure in Chapter 5, exp. 5.2.2) and

1-phenyl-2,3-butadien-1-ol, H2C¼C¼CH–CH(Ph)OH, bp� 100 �C/2 Torr, in

�85% yield from 4-chloro-1-phenyl-2-butyn-1-ol, ClCH2C�CCH(Ph)OH.

12.4.21 Allenic alcohols from the reaction betweenacetylenic alcohols containing an ether groupand lithium alanate

Scale: 0.20 molar; Apparatus: Figure 1.1, 1 litre, reflux condenser instead of

thermometer

12.4.21.1 Procedure [35]

To a solution of 0.24 mol of lithium alanate in 500 ml of Et2O is added

0.20 mol of the acetylenic alcohol (Note) at a rate such that the gentle reflux

of the Et2O is maintained. After the addition, the mixture is warmed under

reflux for an additional 1 h, then it is then cooled to rt. Water (�25 ml) is then

added dropwise with vigorous stirring until refluxing ceases. The ethereal layer

is decanted and the slurry is extracted several times with Et2O. The combined

ethereal solutions are dried over magnesium sulphate and subsequently


[13.1.2004–9:57pm] [235–266] [Page No. 258]


concentrated under reduced pressure. Distillation of the residue through a

30-cm Vigreux column gives 4-methyl-2,3-pentadien-1-ol, bp 76 �C/32 Torr,

in �75% yield.

In a similar way are prepared: 5-methyl-3,4-hexadien-2-ol, (Me)2C¼C¼

CHCH(Me)OH, bp 70 �C/25 Torr, in �70% yield and 3-cyclohexylidene-2-

propen-1-ol, (CH2)5C¼C¼CHCH2OH, bp 110 �C/18 Torr, in �70% yield.

Note

Prepared by converting 3-(1-ethoxyethoxy)-3-methyl-1-butyne, HC�

CCMe2OCH(Me)OEt into its lithium derivative, subsequently adding the

required amount of dry paraformaldehyde and heating the mixture for 2 h

under reflux (cf. Chapter 5, exp. 5.2.1). The acetal is prepared from

2-methyl-3-butyn-2-ol, HC�CCMe2OH, and excess of H2C¼CHOEt in the

presence of a small amount of p-toluenesulphonic acid (cf. Chapter 20,

exp. 20.6.7).

12.4.22 Allenes by reaction of propargylic chlorideswith zinc–copper in ethanol

Scale: 0.70 molar; Apparatus: 1-litre round-bottomed three-necked flask,

equipped with a dropping funnel-thermometer combination, a mechanical

stirrer and an efficient column, connected with a condenser and receiver

cooled at –10 �C.

12.4.22.1 Procedure

A Zn/Cu couple, freshly prepared from 70 g of zinc and 130 ml of 100%

ethanol (see exp. 12.4.23), are placed in the flask. Stirring is started and

� 0.20 mol of the 3-chloro-1-butyne (Chapter 20, exp. 20.1.5) is added.

When the Zn/Cu couple is of good quality, the temperature begins to rise

after a few minutes and 1,2-butadiene begins to distil. The remaining

� 0.50 mol of the chloride is added dropwise over a period of � 30 min. The

temperature of the reaction mixture is kept between 65 and 70 �C, and the

temperature in the head of the distillation column below 45 �C by occasional

cooling or heating. After the addition, the temperature of the reaction mixture

is increased gradually. Heating and stirring are stopped when ethanol begins to

pass over at � 78 �C. The distillate is carefully redistilled through the same


[13.1.2004–9:57pm] [235–266] [Page No. 259]


column, using a cold receiver. 1,2-Butadiene distils between 20 and 35 �C

(bp� 20 �C/760 Torr) and is obtained in 80–85% yield (Note).

In a similar way 3-methyl-1,2-butadiene, (Me)2C¼C¼CH2, bp 41 �C, is

prepared in �70% yield from 3-chloro-3-methyl-1-butyne, HC�CCMe2Cl

(Chapter 20, exp. 20.1.9).

Note

Some batches of zinc powder gave yields of only � 60%. The reaction then

proceeded much more slowly, and heating (at 65–70 �C) had to be continued

for 2–3 h in order to achieve complete conversion.

12.4.23 Vinylidenecyclohexane by reaction of 1-chloro-1-ethynylcyclohexane with zinc–copper in ethanol


12.4.23.1 Procedure

To a suspension of a zinc–copper couple in 150 ml of 100% ethanol, prepared

from 80 g of zinc powder (see below), is added at rt � 0.10 mol of 1-chloro-1-

ethynylcyclohexane (Chapter 20, exp. 20.1.10). After a few minutes an exother-

mic reaction starts and the temperature rises to 45–50 �C (Note). When this

reaction has subsided, the mixture is cooled to 35–40 �C and the remaining

� 0.40 mol of the chloride is added over a period of 15 min, while maintaining

the temperature around 40 �C (occasional cooling). After the addition stirring

is continued for 30 min at 65 �C, then the mixture is cooled to rt and the upper

layer is decanted. The black slurry of zinc is rinsed five times with 50-ml

portions of Et2O. The alcoholic solution and the extracts are combined and

washed three times with 100-ml portions of 2 N HC1, saturated with ammo-

nium chloride. After drying over magnesium sulphate, the greater part of the

Et2O is distilled off at normal pressure through a 40-cm Vigreux column. The

remaining liquid is distilled at 15 Torr through the same column. The (single)

receiver is cooled in an ice-bath (Figure 1.10). Vinylidenecyclohexane, bp 32 �C/

15 Torr, is obtained in �85% yield.


[13.1.2004–9:57pm] [235–266] [Page No. 260]


Note

A prompt start occurs when the Zn/Cu couple is of good quality. If the reac-

tion does not start at rt, the mixture should be warmed stepwise (first to rt, then

to � 30 �C, etc.) until a further rising of the temperature is observed.

12.4.23.2 Preparation of the zinc–copper reagent

Finely powdered zinc (70 g, Merck, Darmstadt, Germany) is transferred into a

500-ml conical flask. Dilute hydrochloric acid is prepared by mixing 50 ml of

concentrated (ca 36%) acid with 500 ml of water. The zinc powder is swirled

vigorously by hand for 30 s with one-third of the dilute hydrochloric acid

(Note), then water (200 ml) is added in order to stop the evolution of hydrogen.

The liquid is decanted from the zinc, which is treated subsequently with a

second portion of � 200 ml of dilute acid in the same way for 30 s. This

treatment is carried out (after addition of water and decanting) for a third

time with the remaining dilute acid. After decanting the acid solution, the

zinc is shaken twice with 100-ml portions of distilled water, which are decanted

from the zinc. The flask is then provided with a mechanical stirrer and a third

portion of 100 ml of distilled water is added. Stirring is started at a rate such

that all zinc powder is homogeneously suspended. A solution of CuSO4 (5 g) in

100 ml of distilled water is added to the stirred suspension in 10 s (experienced

persons can do these operations by hand). Stirring is then stopped and the

powder is allowed to precipitate. The supernatant liquid is cautiously poured

off. Distilled water (100 ml) is added and the same procedure is repeated. After

a third treatment with CuSO4 the powder is washed successively three times

with 75-ml portions of distilled water, three times with 75-ml portions of 96%

ethanol and three times with 75-ml portions of 100% ethanol. The activated

zinc powder obtained in this way is used directly. It is transferred, together with

the third portion of 100% ethanol into the reaction flask.

Note

From our first experiments with Zn–Cu couples prepared from different

batches of zinc powder we found that the results (yield, and sometimes

purity) of the allene preparations varied considerably from one batch to

another. After many experiments we concluded that there is some connection

between the results and the behaviour of the zinc during the treatment

with hydrochloric acid and CuSO4. A smooth reaction and good results were

predicted and obtained whenever the evolution of hydrogen started immedi-

ately after addition of dilute acid, causing the powder to move slowly up and

down when swirling was stopped for a while. After washing with water the


[13.1.2004–9:57pm] [235–266] [Page No. 261]


powder was still finely divided. The results were less satisfactory when during

the treatment with acid; the formation of porous spongy clusters of powder

took place. During the evolution of hydrogen the powder remained on the

bottom of the flask. Further we had the impression that the treatment with

CuSO4 solution did not result in a satisfactory fixing of the copper on the zinc

particles. Although we cannot give an explanation for the varying results, we

believe that the structure of the powder (possibly the size of the particles) has a

considerable influence on the results of the allene syntheses. It also seems

important to remove the water completely during the washing with ethanol.

Traces of water can remain when aggregates of zinc are formed during the

treatment with acid or by inefficient washing with ethanol.

12.4.24 1,2,4-Hexatriene by reaction of 5-bromo-3-hexen-1-ynewith zinc–copper in hexanol

Scale: 0.20 molar; Apparatus: 1-litre three-necked round-bottomed flask,

equipped with a dropping funnel, a gas-tight mechanical stirrer and a 40-cm

Vigreux column connected to a condenser and receiver cooled at –75 �C

(cf. Figure 1.10). Between the receiver and the water aspirator is placed a

tube filled with KOH pellets

12.4.24.1 Procedure

A Zn/Cu couple is prepared from 70 g of zinc powder (see preceding exp.). The

black slurry is transferred into the reaction flask. After the greater part of the

absolute ethanol has been poured off from the zinc, the zinc is rinsed at least

ten times with small portions of dry Et2O. The Et2O is then decanted, 100 ml of

hexanol is added and the flask is connected to the other parts of the distillation

apparatus. The Et2O and traces of ethanol are subsequently removed by evac-

uating the apparatus (the receiver being cooled at –75 �C) and heating the

reaction flask. This operation is stopped when � 10 ml of hexanol has

passed over. The receiver and condenser are cleaned and the apparatus is

again evacuated (10–15 Torr). Stirring is started and the flask heated until

the hexanol starts to reflux in the lower part of the column. From the dropping

funnel is added over 20 min 0.20 mol of the bromide (Chapter 20, exp. 20.1.8).

The reaction is very vigorous and external heating is not necessary. A mixture

of 1,2,4-hexatriene and hexanol condenses in the receiver (Note 1). The


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conversion is completed by heating, so that 5–10 ml of hexanol distils at 55–

60 �C/15 Torr. The contents of the receiver are ‘redistilled’, using the apparatus

shown in Figure 1.10, collecting the vapour of the hexatriene in a receiver

cooled at –75 �C. The yield of this hydrocarbon is 75–85% (with comparable

amounts of the (Z)-and (E)-isomer). The compound can be distilled at normal

pressure (bp 78 �C/760 Torr), but some polymerisation occurs (Note 2).

Notes

1. If the temperature in the top of the column rises above 50 �C, the addition

should be interrupted.

2. We have carried out this synthesis also in ethanol as a solvent but the

results were not reproducible. Although a series of experiments with zinc

powder from one flask gave reasonable results (60–78% yields), a new

bottle with the same batch number gave low yields of impure products.

The main impurity is probably 1,4-hexadiene, H2C¼CHCH2CH¼CHMe,

possibly resulting from reduction of the 1,2,4-triene by the zinc. The

advantage of using hexanol is that the triene can be removed directly

from the reaction mixture, so that no further reduction can occur.

12.4.25 Copper(I) chloride-catalysed reaction of propargyl alcoholwith propargyl chloride in aqueous medium.Preparation of 4,5-hexadien-2-yn-1-ol


12.4.25.1 Procedure [36]

Methanol (70 ml), 25% aqueous NH3 solution (50 ml), freshly distilled pro-

pargyl alcohol (0.50 mol) powdered CuCl (1.5 g, technical grade) and

hydroxylamine �HCl (2 g) are placed in the flask. The air in the flask is com-

pletely replaced by nitrogen. A mixture of 0.25 mol of propargyl chloride and

40 ml of methanol is added dropwise over 1 h, while keeping the temperature

between 25 and 30 �C. After an additional 45 min a solution of 5 g of KCN or

NaCN in 150 ml of water is added with vigorous stirring. Subsequently 10

extractions with Et2O are carried out. The combined ethereal solutions are


[13.1.2004–9:57pm] [235–266] [Page No. 263]


washed once with saturated aqueous NH4Cl and are subsequently dried over

MgSO4. After complete removal of the solvent and other volatile compounds

(some HC�CCH2OH) under reduced pressure, almost pure 4,5-hexadien-2-yn-

1-ol, H2C¼C¼CHC�CCH2OH, is obtained in � 80% yield. If desired, the

compound can be distilled in a high vacuum, using a short column and a single

receiver, cooled to below –20 �C. Prior to carrying out the distillation, 40 ml of

paraffin oil (Note) should be added.

2-Methyl-5,6-heptadien-3-yn-2-ol, H2C¼C¼CHC�CC(Me)2OH, (undistilled),

is obtained in � 70% yield by a similar procedure from 2-methyl-3-butyn-2-ol,

HC�CC(Me)2OH, and HC�CCH2Cl.

Note

The addition of some paraffin oil minimises the risk of a vigorous decomposi-

tion in the last stage of the distillation. Polymeric substances remain as disper-

sion in the oil.

12.4.26 Methyl propargyl ketone by zinc chloride-catalysedreaction of allenyl tributyltin with acetyl chloride

Scale: 0.20 molar; Apparatus: Figure 1.1, 250-ml two-necked, round-bottomed

flask with thermometer and outlet, magnetic stirring

12.4.26.1 Procedure [38]

In the flask are placed 0.20 mol of tributyl(1,2-propadienyl)stannane (Chapter

7, exp. 7.2.7) and 0.20 mol of freshly distilled acetyl chloride. The mixture is

cooled to –15 �C and 300 mg of powdered anhydrous zinc chloride is added.

After stirring for 30 min at –10 to –15 �C, the cooling bath is removed and the

temperature is allowed to rise gradually in 1.5 h to rt (occasional cooling may

be necessary). The flask is then equipped for a vacuum distillation. A stopper

and a 30-cm Vigreux column are placed on the flask. This column is connected

with a condenser and a receiver, cooled at –15 �C. Between the receiver and the

water aspirator is placed a tube filled with anhydrous calcium chloride. The

apparatus is evacuated at 10–15 Torr and the flask gradually heated until the

temperature in the top of the column has risen to � 60 �C. A dark residue,

chloro(tributyl)tin, remains in the distillation flask. The contents of the


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receiver are redistilled in a partial vacuum of �40 Torr. 4-Pentyn-2-one,

bp �50 �C, is obtained in �70% yield.

12.4.27 Allenic sulphides from the copper halide-catalysedreaction between propargylic halides and lithium thiolates


12.4.27.1 Procedure [37]

Freshly distilled thiophenol (0.12 mol) is added at � –20 �C to a solution of

0.12 mol of BuLi in 75 ml of hexane and 120 ml of THF. Subsequently, a

solution of 1.5 g of CuBr and 3 g of anhydrous LiBr in 20 ml of THF is added

with cooling below 0 �C. 3-Chloro-3-methyl-1-butyne (0.10 mol) is added over

a few minutes at –15 �C, after which the cooling bath is removed. After 30 min

the light-brown solution is heated under reflux for 15 min (Note), then cooled

to rt and poured into a solution of 5 g KCN, 5 g NaOH and 20 g of NH4Cl

in 150 ml of water. After vigorous shaking and separation of the layers three

extractions with Et2O are carried out. The combined organic solutions are

dried over potassium carbonate and subsequently concentrated under reduced

pressure. 1-Phenylthio-3-methyl-1,2-butadiene, bp 75–80 �C/�0.5 Torr, is

obtained in �70% yield. The product contains 2–6% of the acetylenic

isomer 1,1-dimethyl-2-propynyl phenyl sulphide, HC�CC(Me)2SPh.

Propargyl chloride, HC�CCH2Cl, gives a mixture of 85% allenic and 15%

acetylenic sulphide, when using catalytic amounts of CuBr.

Note

Heating for a longer period will probably result in a decrease of the amount of

acetylenic isomer, due to its isomerisation under the influence of PhS �CuBr-

LiBr (cf. [37]).

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synthesis of acetylenes, allenes and cumulenes || acetylenic and allenic derivatives by substitution...

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