1,3-Dibromoacetone

(1; R1 = H, R2 = H, R3 = H, R4 = H)

[816-39-7]  · C3H4Br2O  · 1,3-Dibromoacetone  · (MW 215.87) (2; R1 = H, R2 = Br, R3 = H, R4 = Br)

[22612-89-1]  · C3H2Br4O  · 1,1,3,3-Tetrabromoacetone  · (MW 373.66) (3; R1 = Me, R2 = Br, R3 = H, R4 = Br)

[27992-54-7]  · C4H4Br4O  · 1,1,3,3-Tetrabromo-2-butanone  · (MW 387.69) (4; R1 = Me, R2 = H, R3 = Me, R4 = H)

[815-60-1]  · C5H8Br2O  · 2,4-Dibromo-3-pentanone  · (MW 243.93) (5; R1 = Me, R2 = Me, R3 = Me, R4 = H)

[37010-00-7]  · C6H10Br2O  · 2,4-Dibromo-4-methyl-3-pentanone  · (MW 257.95) (6; R1 = Me, R2 = Me, R3 = Me, R4 = Me)

[17346-16-6]  · C7H12Br2O  · 2,4-Dibromo-2,4-dimethyl-3-pentanone  · (MW 271.98) (7; R1 = Et, R2 = H, R3 = Me, R4 = Me)

[69204-79-1]  · C7H12Br2O  · 3,5-Dibromo-2-methyl-3-hexanone  · (MW 271.98) (8; R1 = Et, R2 = H, R3 = Et, R4 = H)

[36461-40-2]  · C7H12Br2O  · 3,5-Dibromo-4-heptanone  · (MW 271.98) (9; R1 = Me, R2,R3 = -(CH2)3-, R4 = Me)

[56829-67-5]  · C8H12Br2O  · 2,6-Dibromo-2,6-dimethylcyclohexanone  · (MW 283.99) (10; R1 = i-Pr, R2 = H, R3 = Me, R4 = Me)

[56829-66-4]  · C8H14Br2O  · 2,4-Dibromo-2,5-dimethyl-3-hexanone  · (MW 286.01) (11; R1 = i-Pr, R2 = H, R3 = i-Pr, R4 = H)

[30957-25-6]  · C9H16Br2O  · 3,5-Dibromo-2,6-dimethyl-4-heptanone  · (MW 300.03) (12; R1 = n-Pr, R2 = Me, R3 = Me, R4 = Me)

[56829-63-1]  · C9H16Br2O  · 2,4-Dibromo-2,4-dimethyl-3-heptanone  · (MW 300.03) (13; R1 = Et, R2 = Me, R3 = Et, R4 = Me)

[56829-64-2]  · C9H16Br2O  · 3,5-Dibromo-3,5-dimethyl-4-heptanone  · (MW 300.03) (14; R1 = Ph, R2 = H, R3 = Me, R4 = H)

[38651-07-9]  · C10H10Br2O  · 1,3-Dibromo-1-phenyl-2-butanone  · (MW 306.00) (15; R1 = n-Pr, R2 = Me, R3 = Et, R4 = Me)

[56829-65-3]  · C10H18Br2O  · 3,5-Dibromo-3,5-dimethyl-4-octanone  · (MW 314.06) (16; R1 = Ph, R2 = H, R3 = Me, R4 = Me)

[64097-38-7]  · C11H12Br2O  · 1,3-Dibromo-4-methyl-1-phenyl-2-butanone  · (MW 320.02) (17; R1 = t-Bu, R2 = H, R3 = t-Bu, R4 = H)

[23438-05-3]  · C11H20Br2O  · 3,5-Dibromo-2,2,6,6-tetramethyl-4-heptanone  · (MW 328.09) (18; R1 = Ph, R2 = H, R3 = Ph, R4 = H)

[958-79-2]  · C15H12Br2O  · 1,3-Dibromo-1,3-diphenyl-2-propanone  · (MW 368.07)

(three-carbon units for reductive [3 + 2]14,15 and [3 + 4]14,16 cyclocoupling with certain alkenes and 1,3-dienes)

Alternate Name: 1,3-dibromo-2-propanone.

Physical Data: (1) mp 26-27 °C; bp 80-81 °C/9 mmHg.1 (2) mp 37-38 °C; bp 129-130 °C/7 mmHg.1 (3) mp 53-54 °C.1 (4) bp 51-57 °C/3 mmHg,2 67-68 °C/8 mmHg,1 67-82 °C/10 mmHg,3 115-118 °C/45 mmHg.4 (5) bp 40 °C/0.15 mmHg.5 (6) bp 80 °C/5 mmHg,6 85-87 °C/10 mmHg,7 87-89 °C/10 mmHg.8 (7) bp 42 °C/0.15 mmHg.5 (8) bp 100-101 °C/17 mmHg,9 118-121 °C/25 mmHg.4 (9) mp 27-28 °C; bp 64 °C/0.3 mmHg.6,10 (10) bp 41 °C/1 mmHg,11 45 °C/0.3 mmHg,6 51 °C/0.1 mmHg.5 (11) bp 145-147 °C/28 mmHg.4 (12) bp 63 °C/0.6 mmHg.6 (13) bp 68 °C/0.6 mmHg.6 (14) mp 34-45 °C.12 (15) bp 68 °C/0.6 mmHg.6 (16) mp 59-60 °C.12 (17) mp 69-70 °C.4 70-71 °C,13 (18) mp 81-84 °C,14 112-114 °C.14

Solubility: freely or fairly sol most organic solvents.

Form Supplied in: colorless or slightly yellow liquid or crystals; usually prepared in the laboratory.

Purification: the pure liquid compounds can be obtained by distillation or passage through basic alumina, while the pure crystalline derivatives are obtainable by recrystallization.

Handling, Storage, and Precautions: dibromo ketones, especially cyclic analogs, are allergenic and lachrymatory and hence should be handled in a well-ventilated hood. Use of rubber gloves is recommended for handling. Since the dibromo ketones are sensitive to moisture and light, they should be stored in a tightly stoppered brown bottle or a brown ampule in a refrigerator. Occasionally, the compounds bear deep yellow or orange color on long storage. All procedures of the iron carbonyl-promoted reactions, including workup, should be carried out in a well-ventilated hood.

Generation of 2-Oxyallyl Species.

Two-electron reduction of an a,a-dibromo ketone, generating a reactive zwitterionic 2-oxyallyl or related species, is effected with many low-valent metallic reagents such as Sodium Iodide-Copper in acetonitrile,17,18 Zinc/Copper Couple in DME or acetone,19 Zinc/Silver Couple in THF,20 and Nonacarbonyldiiron in benzene (eq 1).21 A similar species is generated by the reduction with Sodium Iodide in acetone or acetonitrile.13,22 The reactive C3 intermediates undergo cycloaddition to certain alkenes or 1,3-dienes to give five- or seven-membered cyclic ketones, respectively.

The [3 + 2 -> 5] Cyclocoupling Reactions.

Reduction of an a,a-dibromo ketone with Fe2(CO)9 in the presence of an aryl-substituted alkene gives a 3-arylcyclopentanone (eq 2).23 The reaction of an unsymmetrically substituted dibromo ketone proceeds with high regioselectivity.24,25

Enamines serve as excellent C2 substrates in the Fe2(CO)9-promoted cyclocoupling. Secondary dibromides initially form labile 3-aminocyclopentanones which readily eliminate amines to give 2-cyclopentenones (eq 3).2,26 Fe2(CO)9 is the only efficient reducing agent for this cyclopentenone-forming reaction. The reaction with a tertiary dibromide gives a stable 3-aminocyclopentanone26b,27 or 2-amino-5-alkylidenetetrahydrofuran.26b The latter type of product is obtained by the reaction with 1,1-dimethoxyethylene promoted by Cu-NaI.18

The secondary dibromides similarly cyclocouple with N,N-dimethylcarboxamides with the aid of Fe2(CO)9 to give 3(2H)-furanones (eq 4).28 Use of Zn/Cu couple usually affords 2-amino-4-alkylidene-1,3-dioxolanes, which readily rearrange to the 3(2H)-furanones.29 A similar 1,3-dioxolane product is formed in the reaction with a ketone promoted by ultrasonically dispersed Hg.30 The NaI-assisted cyclocoupling with tetracyanoethylene or diethyl azodicarboxylate affords the corresponding five-membered products but in low yield.13 Reduction of tertiary dibromo ketones with Zn/Cu couple31 or Fe2(CO)914b in the presence of acetonitrile produces 5-alkylidene-2-oxazolines in low yields.

The Fe2(CO)9-aided [3 + 2] cyclocoupling with 2-methylpropene does not proceed smoothly,32 while the intramolecular version gives a bicyclic product (eq 5).33

The [3 + 4 -> 7] Cyclocoupling Reactions.

Reduction of an a,a-dibromo ketone with Fe2(CO)9 in the presence of open-chain 1,3-dienes affords the [3 + 4] products, 4-cycloheptenones.34 High yields are obtained with the dienes having a high population of the s-cis conformation. The butadiene-Fe(CO)3 complex acts as a good reducing agent and receptor (eq 6). Fe(CO)534 or Zn/Cu couple31,35 promotes the reductive coupling but less effectively.

Substituted and unsubstituted cyclopentadienes,13,17,19,22,31,34,36,37 1,3-cyclohexadiene,38 fulvenes,17b N-protected pyrroles,34b,39-41 and furans,13,17,19,22,34b,36,39,42-45 in which the diene is frozen to the s-cis conformation, serve as excellent C4 components (eq 7). Intramolecular [3 + 4] reaction has also been achieved.33,46 Pyrrole and its N-alkyl derivatives can be employed for the Cu-NaI assisted reaction of acyclic dibromo ketones,39,41 whereas cyclic dibromides give the substitution products. The reaction using Zn/Cu couple or iron carbonyls results only in the substitution products.34b,39,40a The aromatic substitution of furan is often observed in the Fe2(CO)9-promoted reaction of cyclic dibromides.34b

a,a-Dibromoacetone itself cannot be used as the C3 unit. However, 1,1,3,3-Tetrabromoacetone acts as its synthetic equivalent. Iron carbonyls,34b,37b,47,48 Zn-(EtO)3B,45b Zn/Cu couple,40c or Zn/Ag couple20,48c promote the [3 + 4] cyclocoupling with reactive 1,3-dienes. Debromination of the resulting dibromo ketones with Zn/Cu couple and ammonium chloride in methanol gives the desired ketonic products (eq 8). This modification is generally applicable to the reaction of other methyl ketone polybromides.20,36,34b,39,44,49

Miscellaneous Reactions.

Reaction of a,a-dibromo ketones and h1-allyl(cyclopentadienyl)iron dicarbonyl affords substituted cyclohexanones (eq 9).27 Reaction of the dibromide and an isocyanide assisted by Cu in benzene or Zn in pyridine-benzene provides a facile way to a 2-(N-alkylimino)cyclobutanone (eq 10).50 Reaction of an a,a-dibromo ketone and an organocuprate is used to prepare a-monoalkylated and a,a-dialkylated ketones (eq 11).42


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Yoshihiro Hayakawa & Ryoji Noyori

Nagoya University, Japan



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