SYNTHESIS OF PENTA-1,4-DIENE (Divinylmethane)

STEP 1:    1,5-Diacetoxypentane. 

• Equip a 5-litre three-necked flask with an efficient sealed stirrer unit of the Hirschberg type, a double-surface reflux condenser and screw-capped adapter carrying a thermometer. 
• Add 516 g (582 ml, 6.0 mol) of tetrahydropyran, 480 g (434 ml, 6.0 mol) of acetyl chloride and 4g of powdered fused zinc chloride. 
• Heat the mixture with a heating mantle with vigorous stirring under reflux, and continue to heat until the temperature of the reaction mixture reaches 150 °C (about 3-5 hours). 
• Allow the reaction mixture to cool to near room temperature and add 980 g (10 mol) of solid potassium acetate and 20 g of sodium iodide. 
• Heat the mixture again with stirring to 160 °C and maintain the temperature for 12 hours. 
• Cool to room temperature, add 1 litre of light petroleum (b.p. 40-60 °C), filter under suction and wash the residue thoroughly with more light petroleum. 
• Combine the filtrate and washings and remove the solvent on a rotary evaporator. 
• Fractionally distil the residue under reduced pressure and collect the 1,5- diacetoxypentane at 108-114 °C/3.5-4 mmHg. 
• The yield is about 790 g (70%); the product is sufficiently pure for use in the next stage, but a sample may be purified by redistillation and then has b.p. 102-104 °C/3 mmHg (or 92-94 °C/ 1.0 mmHg).

Figure 1

STEP 2:      Penta-1,4-diene.

• Assemble the pyrolysis apparatus shown in with the pyrolysis tube packed with glass beads but with the acetone-Cardice cooling trap arrangement attached to the water condenser. 
• Pass a gentle stream of nitrogen gas through the apparatus and heat the com­bustion tube to 580 °C when 900 g of 1,5-diacetoxypentane is added dropwise, during about 12 hours (1). 
• Fractionally distil the total pyrolysate carefully and slowly at atmospheric pressure and collect the fraction boiling below 50 °C which should be refractionated to give penta-1,4-diene of b.p. 24-27 °C.
• The yield is 170 g (52%). Assign the i.r. absorptions which occur at 3100, 1840, 1650, 995 and 910 cm ^-1. The 13C-n.m.r. (CDC1₃, TMS) reveals signals at 6 38.1 (C₃), 115.5 (C₁ and C₅), 136.6 (C₂ and C4).

Notes to keep in mind: 

1. Solidified acetic acid often blocks the flow of nitrogen in the cooling trap.It can be dislodged by careful warming with a warm-air blower.

SYNTHESIS OF CYCLOHEXA-1,3-DIENE

STEP 1: In a 100-ml round-bottomed flask place 16.1 g (0.10 mol) of 3-bromocyclo­hexene, 38.7 g of dried, redistilled quinoline and a magnetic stirrer follower. 

STEP 2: Attach to the flask a Claisen still-head fitted with a thermometer and a condenser set for downward distillation. 

STEP 3: Protect the apparatus from atmospheric moisture by a calcium chloride guard-tube attached to the side­arm of the receiver. 

STEP 4: Support the reaction flask in an oil bath which rests on a magnetic stirrer/hotplate, commence stirring rapidly and heat the oil bath to 160-170 °C. 

STEP 5: The cyclohexadiene steadily distils as colourless liquid, b.p. 80­82 °C, over a period of about 30 minutes, yield 5.4 g (68%). 

STEP 6: The product is 99 per cent pure by g.l.c. analysis; use either a 2.7 m column of 10 per cent poly­ethyleneglycol adipate on Chromosorb W held at 60 °C with a flow rate of carrier gas of 40 ml/minute, t_R 2.4 minutes, or, a 1.5 m column of 10 per cent Silicone oil on Chromosorb W held at 6 °C with a flow rate of carrier gas of 40 ml/minute, t_R 1.5 minutes.

SYNTHESIS OF 2-METH YLBUT-2-ENE

STEP 1: Place 25.0 g (31 ml, 0.28 mol) of 2-methylbutan-2-ol and 10 ml of 85 per cent orthophosphoric acid in a 100-m1, round-bottomed flask and swirl to mix thoroughly. 

STEP 2: Fit the flask with a 20-cm fractionating column filled with glass helices, a Claisen still-head and a condenser leading to a 50-m1 receiving flask cooled in a beaker of iced water. 

STEP 3: Add a few pieces of porous por­celain and heat the reaction mixture gently with a Bunsen burner. 

STEP 4: Collect the alkene fraction which distils in the range 35-38 °C during a period of 30 minutes. 

STEP 5: Dry the distillate with 1-2 g of magnesium sulphate. 

STEP 6: Wash and dry the distillation apparatus, decant the dried distillate into a 50-m1 flask and redistil in the reassembled apparatus. 

STEP 7: Collect the fraction boiling at 37-38 °C; the yield is 12.5 g (64%). Record the infrared spectrum of the product using a fixed path-length cell (0.025 mm). 

STEP 8: The stretching bands of the terminal (1645 cm '} and non-terminal (1670 cm ') carbon–carbon double bonds can both be observed; bands at 890 and 805 cm (=C—H deformation) also establish the presence of both terminal and non-terminal olefinic systems. 

STEP 9: Analyse the product by g.l.c. on a Silicone oil column at 30 °C; 2- methylbut-1 -ene appears first, closely followed by 2-methylbut-2-ene; the areas under the peaks are in the ratio of 1:4.

SYNTHESIS OF HEXACOSANE

STEP 1: Dissolve 5.0 g of pure myristic acid (tetradecanoic acid) in 25 ml of absolute methanol to which 0.1 g of sodium has been added. 

STEP 2: Place the solution in a cylindrical cell (25 cm long, 3 cm diameter) provided with two platinum plate electrodes (2.5 x 2.5 cm) set 1-2 mm apart. 

STEP 3: Electro­lyse at about 1 amp until the electrolyte is just alkaline (pH 7.5-8). 

STEP 4: Cool the cell in an ice bath during the electrolysis. 

STEP 5: Reverse the current from time to time; this will help to dislodge the coating of insoluble by-products on the electrodes. 

STEP 6: Neutralise the cell contents by adding a few drops of glacial acetic acid, and evaporate most of the solvent under reduced pressure using a rotary evaporator. 

STEP 7: Pour the residue into the water and extract the crude product with ether. 

STEP 8: Wash the ethereal solution with dilute sodium hydroxide solution, dry (magnesium sulphate) and evaporate the solvent. 

STEP 9: Recrystallise the resi­due from light petroleum (b.p. 40-60 °C). 

STEP 10:The yield of hexacosane, m.p. 57­58 °C is 2.4 g (65%).

SYNTHESIS OF UNDECANE

STEP 1: Place 9.53 g (0.05 mol) of copper(i) iodide in a two-necked, 500-m1 round-bottomed flask containing a glass-covered magnetic follower bar. 

STEP 2: Fit a rubber septum to one of the necks of the flask and connect the other neck to one arm of a three-way stopcock. 

STEP 3: Connect the second arm of the stopcock to a supply of dry, oxygen-free nitrogen and the remaining arm to a vacuum pump. 

STEP 4: Evacuate the flask by opening the stopcock to the vacuum pump (1) and then, with a rapid stream of nitrogen flowing, carefully open the stopcock to the nitrogen supply to fill the flask with nitrogen. Repeat this process twice; flame the flask gently on the final occasion it is evacuated. Maintain a static atmosphere of nitrogen in the flask throughout the reaction by passing a slow stream of nitrogen through the nitrogen line. Cool the flask in an acetone/Cardice bath and transfer 100 ml of dry tetrahydrofuran (2) to the flask via the septum using a hypodermic syringe (3). 

STEP 5: Stir the cooled (— 78 °C) suspension and add 52.0 ml of a 1.92 molar solution of butyllithium in hexane (4) from a hypodermic syringe. 

STEP 6: Stir the flask solution at — 78 °C for 1 hour, and then add a solution of 3.39 g (0.015 mol) of 1-iodoheptane in 10 ml of dry tetrahydrofuran dropwise from the syringe. 

STEP 7: Stir the solu­tion at —78 °C for 1 hour and then at 0 °C (ice bath) for a further 2 hours ((5) and (6)). 

STEP 8: Hydrolyse the reaction mixture by pouring it carefully into 100 ml of 1 M hydrochloric acid. 

STEP 9: Separate the upper organic layer and extract the aqueous layer with two 50 ml portions of pentane. 

STEP 10: Wash the combined organic layers with water (50 ml), dry over magnesium sulphate and evapor­ate the solvents on the rotary evaporator. 

STEP 11: Distil the residue at atmospheric pressure using a semimicro scale distillation unit fitted with a short fractio­nating side-arm packed with glass helices. 

STEP 12: Undecane has b.p. 194-197 °C; the yield is 1.24 g (53%).

Notes to keep in mind:

1. This operation should be carried out behind a safety screen.

2. Tetrahydrofuran should be freshly distilled from lithium aluminium hydride. It is convenient to store a supply of peroxide-free tetrahydrofuran under nitrogen over lithium aluminium hydride and distil appropriate quantities as required.

3. The syringes and long flexible needles can be obtained from Aldrich Chemical Co.

4. Solutions of butyllithium, and other lithium reagents, may be purchased from Aldrich.

5. The progress of the reaction may be conveniently followed by g.l.c. Remove samples (c. 2-3 ml) from the reaction mixture by means of a hypodermic syringe and submit them to a small-scale hydrolysis and extraction procedure similar to that described for the main reaction mixture. Analyse the organic layer on a 10 per cent squalane on Chromosorb W column held at 140 °C. Under these conditions 1-iodo­heptane has a slightly longer retention time than undecane.

6. Complete reaction of the alkyllithium can be tested by means of the Gilman test.

SYNTHESIS OF 7-ACETOXYHEPTANAL

STEP 1:           1-Acetoxy-4-iodobutane

• A 500-ml flask is fitted with an addition funnel, condenser and magnetic stirrer. Tetrahydrofuran (50 ml, 0.61 mol), acetic anhydride (100 ml, 1.0 mol), zinc dust (0.1 g, 1.5 mmol) are placed in it. Aqueous hydriodic acid (55%, 40 ml, 0.29 mol) is added dropwise at a rate that keeps the exothermic reaction at reflux.
• After the addition is complete, the mixture is allowed to cool for 1 hour and then poured into 200 ml of saturated aqueous sodium carbonate.
• The mixture is extracted with dichloromethane, dried with magnesium sulphate and the solvent evaporated.
• The residual oil is distilled to give the product, yield 56.7 g (80%), b.p. 76-78 °C/0.5 mmHg; p.m.r. (CDC1₃, TMS) 6 1.88 (m, 4H), 2.02 (s, 3H), 3.20 (t, 2H, J = 6 Hz, —CH₂I) 4.05 (t, 2H, J = 6 Hz, —CH₂.0Ac).

STEP 2:           2-(6-Acetoxyhexyl)-1,3-dioxane

• Copper(i) iodide (0.60 g, 3.1 mmol) and 1- acetoxy-4-iodobutane (12.1 g, 50.0 mmol) are cooled in a dry ice/propan-2-ol bath under a nitrogen atmosphere (1). 
• The Grignard reagent (2), prepared from 2-(2-bromoethyl)-1,3-dioxane' (12.19 g, 62.5 mmol) in 50 ml of tetra­hydrofuran, is added dropwise to the cooled solution. 
• This is stirred at —80 °C for 30 minutes, slowly raised to reflux temperature over a 2-hour period, and then heated at reflux for 6 hours. 
• The tetrahydrofuran is removed by rotary evaporation and the residue poured into aqueous ammonia/ ammonium chloride solution (800 ml). 
• The product is extracted with ether (3 x 50 ml), dried with magnesium sulphate and distilled.
•  A small amount of 1-acetoxy-4-iodobutane is recovered, and then the product is obtained in a yield of 8.86 g (77%), b.p. 90-100 °C/0.3 mmHg.

STEP 3:           7-Acetoxyheptanal 

• 2-(6-Acetoxyhexyl)-1,3-dioxane (4.60 g, 20.0 mmol), methanol (150 ml), glacial acetic acid (35 ml) and concentrated hydrochloric acid (1 ml) are stirred and left to stand for 3 days. 
• This mixture is poured cautiously into saturated sodium hydrogen carbonate solution (500 ml) and the product extracted with ether (3 x 200 ml). 
• The extract is dried with mag­nesium sulphate and evaporated to give the crude dimethyl acetal, which is then dissolved in glacial acetic acid (100 ml), water (10 ml) and hydrochloric acid (1 ml) and left to stand for 3 days. 
• The solution is poured cautiously into saturated aqueous sodium hydrogen carbonate (1 litre), made basic with additional sodium hydrogen carbonate, and the product extracted with ether (3 x 50 ml). 
• The extract is dried with magnesium sulphate, evaporated and the residue distilled to give the product, yield 3.10 g (90%), b.p. 93-98 °C/ 0.7 mmHg.

Notes to keep in mind:

1. The editors suggest that the apparatus consists of a 100-m1 two-necked flask fitted with a silicone rubber septum into which is inserted a syringe needle connected to a nitrogen feed and through which the reagents may be syringe-injected; the second arm of the flask is fitted with a reflux condenser the outlet of which is connected to a mercury bubbler.

2. The Grignard reagent is prepared by the following procedure ^{1 6}' with suitable adjustment of the quantities of reagents employed. A 50-m1 flask is equipped with a reflux condenser, a nitrogen atmosphere and magnetic stirring. In it are placed magne­sium turnings (0.97 g, 40 mmol), dry tetrahydrofuran (25 ml) and 2-(2-bromoethyl)- 1,3-dioxane^{l 6b} (5.85, 30 mmol) (or from Aldrich). This is heated to reflux and the heat immediately removed.The exothermic reaction is moderated at reflux by the occa­sional application of an ice bath. After 10 minutes, heat is applied to maintain reflux­ing for an additional 10 minutes. After cooling to room temperature the solution is drawn up into a 50-m1 syringe leaving excess magnesium behind. 

SYNTHESIS OF HEPT-1-ENE

STEP 1: In a 1-litre three-necked flask prepare the Grignard reagent, butylmagnesium bromide, from 12.2 g (0.5 mol) of dry magnesium turnings, a small crystal of iodine, 68.5 g (53 ml, 0.5 mol) of butyl bromide and 260 ml of anhydrous ether. 

STEP 2: Equip a 500-m1 three-necked flask with a sealed stirrer unit, a 100-m1 separatory funnel and a double surface condenser. Force the solution of the Grignard reagent with the aid of pure, dry nitrogen and a tube containing a plug of purified glass wool (1) into the 500-m1 flask through the top of the double surface con­denser. 

STEP 3: Charge the separatory funnel with a solution of 50 g (35 ml, 0.42 mol) of allyl bromide in 25 ml of anhydrous ether; place calcium chlor­ide drying tubes into the top of the double surface condenser and of the drop­ping funnel. Immerse the flask containing the Grignard reagent in cold water,stir vigorously, and add dip allyl bromide at such a rate that the ether boils gently; cool momentarily in ice if the reaction becomes too vigorous. 

STEP 4: It is im­portant that the allyl bromide reacts when added, as indicated by gentle boil­ing of the solution (2). 

STEP 5: When all the allyl bromide has been introduced, continue stirring for 45 minutes while refluxing gently by immersing the flask in a bath of warm water. 

STEP 6: Allow to cool (3). 

STEP 7: Pour the reaction mixture cautiously on to excess of crushed ice contained in a large beaker. 

STEP 8: Break up the solid magnesium complex and decompose it with ice and dilute sulphuric acid or concentrated ammonium sulphate solution. 

STEP 9: Separate the ether layer, wash it with ammoniacal ammonium sulphate solution to remove any dis­solved magnesium salts and dry over magnesium sulphate. 

STEP 10: Distil the dry ethereal solution through a fractionating column: after the ether has passed over, collect the hept-l-ene at 93-95 °C. The yield is 29 g (71%).

   Notes to keep in mind:

    1. Solid magnesium must be absent to avoid the formation of biallyl via allyl 

magnesium bromide; the insertion of a short plug of glass wool effectively removes
any finely divided magnesium or alternatively use a tube terminating in a glass frit.

    2. If reaction does not occur when a little allyl bromide is first introduced, further addition must be discontinued until the reaction has commenced. Remove 2-3 ml of the Grignard solution with a dropper pipette, add about 0.5 ml of allyl bromide and warm gently to start the reaction; after this has reacted well, add the solution to the main portion of the Grignard reagent.

   3. A slight excess of Grignard reagent should be present at this stage. Test for the presence of the reagent as follows. Remove 0.5 ml of the clear liquid with a dropper pipette and add 0.5 ml of a 1 per cent solution of Michler's ketone [4,4'-bis(dimethyl­amino)benzophenone] in benzene, followed by 1 ml of water and 3-4 drops of 0.01 M iodine in glacial acetic acid; shake. A greenish-blue colour results if a Grignard reagent is present. In the absence of iodine, the colour fades. A dye of the diphenylmethane type is produced.

SYNTHESIS OF OCTANE

STEP 1: Weigh out 23 g (1 mol) of clean sodium under sodium-dried ether, cut it up rapidly into small pieces and introduce the sodium quickly into a dry 750- or 1000-m1 round-bottomed flask. 

STEP 2: Fit a dry 30-cm double surface condenser (e.g. of the Davies type) into the flask and clamp the apparatus so that the flask can be heated on a wire gauze. 

STEP 3: Weigh out 68.5 g (53 ml, 0.5 mol) of butyl bromide previously dried over anhydrous sodium sulphate. 

STEP 4: Introduce about 5 ml of the bromide through the condenser into the flask. 

STEP 5: If no reaction sets in, warm the flask gently with a small lumin­ous flame; remove the flame immediately reaction commences (the sodium will acquire a blue colour). 

STEP 6: When the reaction subsides, shake the contents of the flask well; this will generally produce further reaction and some of the sodium may melt. 

STEP 7: Add a further 5 ml of butyl bromide, and shake the flask. 

STEP 8: When the reaction has slowed down, repeat the above process until all the alkyl bromide has been transferred to the flask (about 1.5 hours). 

STEP 9: Allow the mixture to stand for 1-2 hours. 

STEP 10: Then add down the condenser by means of a dropping funnel 50 ml of rectified spirit dropwise over 1.5 hours, followed by 50 ml of 50 per cent aqueous ethanol during 30 minutes, and 50 ml of distilled water over 15 minutes; shake the flask from time to time. 

STEP 11: Add 2-3 small pieces of porous porcelain and reflux the mixture for 3 hours; any unchanged butyl bromide will be hydrolysed. 

STEP 12: Add a large excess (500-750 ml) of water, and separate the upper layer of crude octane (17-18 g). 

STEP 13: Wash it once with an equal volume of water, and dry it with magnesium sulphate. Distil through a short fractioning side-arm and collect the fraction, b.p. 123­126 °C (15 g, 52%) (1).

Notes to keep in mind:

1. All hydrocarbons prepared by the Wurtz reaction contain small quantities of unsaturated hydrocarbons. These may be removed by shaking repeatedly with 10 per cent of the volume of concentrated sulphuric acid until the acid is no longer coloured (or is at most extremely pale yellow); each shaking should be of about 5 minutes' duration. The hydrocarbon is washed with water, 10 per cent sodium car­bonate solution, water (twice), and dried with magnesium sulphate or anhydrous cal­cium sulphate. It is then distilled from sodium; two distillations are usually necessary.

SYNTHESIS OF UNDECANE

STEP 1: To a slurry of undecan-6-one toluene-p-sulphonylhydrazone (5.08 g, 15 mmol) (1) in 50m1 of glacial acetic acid is added sodium borohydride pellets (c. 5.67 g, 150 mmol, 24 pellets) (2) at such a rate that foaming is not a problem (c. 1 hour).

STEP 2: The solution is stirred at room temperature for 1 hour and then at 70 °C for 1.5 hours. 

STEP 3: The solution is then poured into crushed ice, made basic with aqueous sodium hydroxide and extracted with three por­tions of pentane. 

STEP 4: The pentane solution is dried and concentrated in a rotary evaporator, and the residue distilled at reduced pressure (Kugelrohr appar­atus) to obtain 1.96 g (84%) of undecane. 

STEP 5: Undecane has b.p. 87 °C/20 mmHg.

Notes to keep in mind:

1. The hydrazones are prepared by the following general procedure.' The carbonyl compound and a 10 per cent molar excess of toluene-p-sulphonylhydrazine in absolute ethanol (c. 2 ml per gram of carbonyl compound) are heated on a steam bath until a clear solution results (15 minutes). Cooling affords crystalline products in good to excellent yields. Recrystallisation is accomplished from ethanol or aqueous acetone. For hindered ketones periods of up to 14 hours of reflux are suggested.

2. Obtainable from Alfa Inorganics.

SYNTHESIS OF HEPTANE

STEP 1: Place 100 g (1.53 mol) of zinc wool in a 1-litre three-necked flask and amal­gamate it. 

STEP 2: Fit the flask with a sealed stirrer unit, an efficient double surface condenser and a lead-in tube dipping almost to the bottom of the flask for the introduction of hydro­gen chloride gas; insert an empty wash bottle between the hydrogen chloride generator and the flask. 

STEP 3: Introduce through the condenser 250 ml of concentrated hydrochloric acid and 50 ml of water, set the stirrer in motion and then add 40 g (0.35 mol) of heptan-4-one. 

STEP 4: Pass a slow current of hydrogen chloride through the mixture; if the reaction becomes too vigorous, the passage of hydrogen chloride is tempor­arily stopped. 

STEP 5: After 2-3 hours most of the amalgamated zinc will have reacted. 

STEP 6: Leave the reaction mixture overnight, but disconnect the hydrogen chloride gas supply first. 

STEP 7: Remove the stirrer and the condenser from the flask. Arrange for direct steam distillation from the flask by fitting a stopper into one neck, a knee tube connected to a downward condenser in the central aperture and connect the lead-in tube to a source of steam. 

STEP 8: Stop the steam distillation when the distillate passes over as a clear liquid. Separate the upper layer, wash it twice with distilled water, dry with magnesium sulphate or anhydrous calcium sulphate and distil through a short fractionating column. 

STEP 9: Collect the fraction, b.p. 97-99 °C (1). The yield of heptane is 26 g (74%).

Notes to keep in mind:

1. The products of most Clemmensen reductions contain small amounts of unsaturated hydrocarbons. These can be removed by repeated shaking with 10 per cent of the volume of concentrated sulphuric acid until the acid is colourless or nearly so; each shaking should be of about 5 minutes duration. The hydrocarbon is washed with water, 10 per cent sodium carbonate solution, water (twice), dried with magne­sium sulphate or anhydrous calcium sulphate and finally fractionally distilled over sodium.

SYNTHESIS OF CYCLOOCTANE

STEP 1: An oven-dried 300-m1 flask, equipped with a side-arm fitted with a silicone rubber septum, a magnetic stirrer bar, and a reflux condenser connected to a mercury bubbler, is cooled to room temperature under a stream of dry nitro­gen. 

STEP 2: Tetrahydrofuran (20 ml) is introduced, followed by 7.1 g (25 mmol) of cyclooctyl tosylate (1).

STEP 3: The mixture is cooled to 0 °C (ice bath).

STEP 4: To this stirred solution, lithium triethylborohydride [33.3 ml (50 mmol) of a 1.5 M solution in tetrahydrofuran] is added, and the ice bath removed. 

STEP 5: The mixture is stirred for 2 hours (c. 25 °C). Excess hydride is decomposed with water. 

STEP 6: The organoborane is oxidised with 20 ml of 3 m sodium hydroxide solution and 20 ml of 30 per cent hydrogen peroxide [(2) and (3)]. Then the tetrahydrofuran layer is separated. 

STEP 7: The aqueous layer is extracted with 2 x 20 ml portions of pentane. 

STEP 8: The combined organic extracts are washed with 4 x 15 ml portions of water to remove ethanol produced in the oxidation. The organic extract is dried (MgSO₄) and volatile solvents removed by distillation (2). 

STEP 9: Distillation of the residue yields 2.27 g (81%) of cyclooctane as a colourless liquid, b.p. 142-146 °C, nU1.4630.

Notes to keep in mind:

1. The editors emphasise the CAUTIONARY notes relating to the handling of hydrogen peroxide, and to the distillation of extracts following the use of tetrahydrofuran/hydrogen peroxide in oxidation procedures.