Propargyl Chloride

(X = Cl)

[624-65-7]  · C3H3Cl  · Propargyl Chloride  · (MW 74.51) (X = Br)

[106-96-7]  · C3H3Br  · Propargyl Bromide  · (MW 118.96) (X = OTf)

[41029-46-3]  · C4H3F3O3S  · Propargyl Triflate  · (MW 188.14)

(three-carbon alkylating agent;1 acetone carbenium ion equivalent and annulating agent;2 propargylic or allenic nucleophile after conversion to an organometallic3)

Alternate Name: 3-chloro-1-propyne.

Physical Data: X = Cl: bp 58 °C; d 1.030 g cm-3. X = Br: bp 88-90 °C; d 1.579 g cm-3; d (80% toluene solution) 1.335 g cm-3.

Form Supplied in: propargyl chloride is supplied as a liquid in 98% purity. Because of a reported shock-sensitivity of the neat material, propargyl bromide is supplied as an 80% (by weight) solution in toluene.

Preparative Method: propargyl triflate is not commercially available but is prepared by treating Propargyl Alcohol with Pyridine/Trifluoromethanesulfonic Anhydride.4

Handling, Storage, and Precautions: in the presence of copper(I) halides, propargyl halides can isomerize to a mixture of the parent compound and a halopropadiene.5 Because of an instability at ambient temperature, the triflate is typically prepared in solution and used directly. Purification of the triflate by distillation is possible, albeit in low yield.6

Electrophilic Alkylation.

As an electrophile, propargyl chloride has been employed in the propynylation of a variety of substrates, including Grignard reagents,1,7 carbanions,8 enolates,9 carbonyl compounds,10 alcohols,4,11 phenols,12 carboxylates,13 amines,14 amides,15 sulfonamides,16 sulfones,17 thiols,18 thioamides,19 and alkyl phosphonates.20 An unusual N-alkylation of a phenothiazine has been reported whereby the 1-propynyl derivative is isolated.21 Because of the basic nature of the above alkylation reactions, isomerization to the allene can take place.22 The extent to which isomerization occurs is dependent upon the reaction time, temperature, and the specific base employed.15a,23 Trialkyl borates24 and alkylaluminum species,25 in the presence of a copper(I) halide, couple with propargyl bromide (preferred over the chloride) to give exclusively the terminal allene. By contrast, the reaction of bromopropadiene (derived from propargyl bromide) with an alkylaluminum affords solely the terminal alkyne.26 Alkylation of a trithiocarbonate, followed by intramolecular cyclization, leads to the formation of a thione.27 In a similar manner, thioamides can be alkylated and further elaborated to thiazoles28 or thiophenes.29

Annulation Reactions.

When the alkylation with propargyl bromide is followed by hydration with Mercury(II) Oxide the net result is equivalent to an alkylation with Acetone. More often, when alkylation occurs a to a carbonyl, the product is further treated with base to give a fused cyclopentenone (eq 1) (see also Isopropenyl Acetate, Methallyl Chloride, 2-Methoxyallyl Bromide).2,30 A radical-based annulation is also possible. By generating a radical center d to the triple bond, cyclization to a five-membered ring system with an exocyclic methylene occurs.16,31

Sigmatropic Rearrangements.

Because of the triple bond, alkylation with propargyl chloride can provide intermediates further capable of intramolecular rearrangement. Crotyl propargyl ethers undergo [2,3]-Wittig rearrangement with high erythro or threo selectivity, dependent upon the starting alkene geometry.32 The corresponding chiral analog allows for an asymmetric [2,3]-Wittig rearrangement with a high degree of enantioselectivity.33 Under thermal conditions, propargylated phenols undergo a [3,3]-sigmatropic rearrangement to give an allenyl enol. A [1,5]-hydrogen shift, followed by electrocyclic ring closure results in the formation of a benzopyran (eq 2).34,35


When appropriately appended, the propargyl group can serve as a dienophile for the intramolecular Diels-Alder reaction with Furan,36 styrene,37 and triazine38 derivatives. Under the typically basic reaction conditions, cycloaddition is believed to proceed via the allenyl ether intermediates. Propargyl bromide can also function as a 1,3-dipolarophile in the [3 + 2] cycloaddition reaction with nitrile oxides to form isoxazoles.39

Nucleophilic Additions.

As a halide, propargyl bromide can be converted to a variety of organometallic species, which then add to aldehydes and ketones. The Grignard reagent40 is proposed to exist in the allenic form,41 and reacts to form predominantly homopropargylic alcohols. Whereas the organozinc reagent reacts to give both a-allenic and b-alkynic alcohols,42 the organoaluminum reagent can be used to generate products which are free of allenic isomers.43 The reaction between carbonyl compounds and the tin reagent favors a-allenic alcohol formation.44 However, the mixed metal system of tin and aluminum allows for selective formation of the homopropargylic alcohol.45 A chiral tin complex can be formed with propargyl bromide and (+)-diethyl tartrate and made to react with aldehydes to give enantiomerically enriched a-allenic alcohols.46 Other organometallic species prepared from propargyl halides include those of chromium,3 lead,47 and mercury.48

The Grignard reagent reacts with Trimethyl Borate to give, after hydrolysis, allenylboronic acid (eq 3). Further reaction with diethyl tartrate (DET) generates a chiral allenylboronic ester which enantioselectively adds to aldehydes to give chiral homopropargylic alcohols.49

Because of the acidic C-H bond, deprotonation generates the propargylic anion which may also serve as a nucleophile. In addition to simple acylation,50 lithium chloropropargylide adds to trialkylboranes to give a lithium trialkylalkynylborate. Dependent upon the subsequent reaction conditions, substituted allenes,51 alkynes,52 or homopropargylic and a-allenic alcohols53 may be formed.

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Mark A. Krook

The Upjohn Company, Kalamazoo, MI, USA

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