LABORATORY MANUAL CH3CH2OH

+

Nao

CH3CH2ONa

OH CH3CH2ONa +

ONa

+ CH3CH2OH

ONa CH3(CH2)3Br

+ 1/2 H2

+

ORGANIC CHEMISTRY YEAR TWO

O(CH2)3CH3

+

NaBr

Year 2

Organic Chemistry

Contents

ORGANIC CHEMISTRY CONTENTS

Page Radas Dengan Penyambung Kaca Yang Boleh Ditukarganti

i

Experiment 1

SN2 Reaction - Butil Fenil Eter

1

Experiment 2

Grignard Reaction - Triphenylcarbinol

3

Experiment 3

Diels-Alder Reaction

5

3.1 Reaction of cyclopentadiene with malic anhydride

5

3.2 Reaction of Furan with Maleic Anhydride

6

Experiment 4

Separation of Piperine from Black Paper

9

Experiment 5

Stim Distillation of impure essential oil sample

11

Experiment 6

6.1 Beckmann-benzanilide rearrangement

13

6.2 Preparation of Caprolactam through Beckmann rearrangement

14

Preparation of an Azo Dye: 1-(p-nitrophenylazo)-2naphthol

16

Qualitative Organic Analyis

18

Laboratory Notebooks

21

Experiment 7

Attachment

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Year 2

Organic Chemistry

RADAS DENGAN PENYAMBUNG KACA YANG BOLEH DITUKARGANTI Penyambung kaca ‘ground’ cepatsuai” Menjangkau suku pertama abad ini, cara yang terdapat untuk menyambung radas kaca makmal ialah dengan menggunakan gabus, penyumbat getah, pembuluh getah dan pembuluh kaca. Memasang benda-benda tersebut adalah rumit dan kadangkala berbahaya dan selalunya memakan masa. Satu pembaharuan yang patut diperhatikan datang dalam awal tahun 1930 apabila penyambung kaca ‘ground’ berbentuk “kun” diperkenalkan dalam arena perniagaan. Dengan cara asahan, kun dan soket dibuat dengan tepat agar keduanya terhubung dengan cepat dan berkesan. Dengan itu nama perniagaannya ialah “cepatsuai”.

Ukuran penyambung kaca Terdapat 3 ukuran yang berlainan yang diakui oleh ukurtentu BSI, disediakan dalam satu susunan lengkap radas “cepatsuai” iaitu, B24, B19, B14 dalam susunan garispusat penyambung kaca dari besar ke kecil. Istilah “kun” digunakan sebagai bahagian yang disisipkan dan “soket” digunakan sebagai bahagian yang menerima sisipan kun itu.

Penjagaan penyambung kaca ‘ground’ Semua penyambung kaca ‘ground’ mesti disimpan supaya terhindar daripada kekotoran. Habuk yang melekat pada penyambung kaca ‘ground’ mungkin menyebabkan bocor dan retak atau seterusnya pecah. Oleh sebab itu, sebagai satu aturan biasa sebelum ia digunakan, penyambung kaca ‘ground’ mesti disapu bersih dari sebarang bendasing. Lepas digunakan penyambung kaca ‘ground’ mesti dipisahkan secepat mungkin, lebihlebih lagi ketika masih panas untuk mengelakkan pengetatan.

Pengetatan Ini berlaku apabila penyambung kaca ‘ground’ menjadi ketat dan susah untuk dipisahkan semula. Jangan biarkan soda api melekat pada permukaan penyambung kaca ‘ground’. Ia bertindakbalas dengan pantas ke atas permukaan yang “kesat” itu dan ini menyebabkan berlakunya “pengetatan”. Pengetatan juga boleh disebabkan oleh sepitan.

Pelicinan Dalam kerja pada tekanan udara, tiada pelicin harus digunakan. Tetapi apabila menjalankan penyulingan di bawah tekanan udara yang rendah atau apabila terdapat kemungkinan larutan alkali terkena bahagian permukaan penyambung kaca ‘ground’, maka gris diperlukan sebagai pelicin. Kegunaan bahan pelicin bergantung kepada keadaan radas yang dikendalikan. Biasanya petrolium jeli atau gris silikon stopcock digunakan tetapi pelicin silikon vakum tinggi layak digunakan pada suhu yang tinggi, dan kerja-kerja vakum. Cuma satu lapisan nipis pelicin sahaja perlu digunakan. Jika

i

Year 2

Organic Chemistry

berlebihan, ia akan mengotori hasil tindakbalas. Apabila menggunakan gris silikon, hendaklah cermat kerana perkakas yang bersambung tidak boleh ditinggal terbiar beberapa lama kerana jika pelicin menjadi kering, pengetatan penyambung kaca akan terjadi. Untuk menanggalkan silikon dari penyambung, sapulah sehingga kering dengan sehelai kertas tisu, dan gris yang tertinggal kemudian ditanggalkan dengan segumpal bulu kapas yang dibasahi dengan eter atau kloroform.

Penyambung kaca “terangsuai” Penyambung kaca ‘ground’ kun mempunyai kekurangan yang tak dapat dielakkan kerana apabila permukaan licin asli itu dibinasa oleh asahan, beberapa keistimewaannya akan hilang. Kemajuan terbaharu dalam teknik pengeluaran telah membolehkan dicipta satu jenis perkakas baharu makmal yang boleh ditukarganti dengan penyambung kaca kun yang terang dimana permukaan kaca yang mulanya licin tersimpan dan dinamakan “terangsuai”. Penyambung terangsuai mempunyai lebih keistimewaan daripada penyambung ‘ground’ seperti berikut: (a) Pelicin tidak perlu dalam semua kerja. (b) Buatannya yang teliti, permukaan penyambung terangsuai memberi meterai yang lebih baik dari penyambung kaca ‘ground’ dan kurangkan keupayaan wap terkondensasi dan menjalar di antara permukaan penyambung oleh tindakan rerambut. (c) Kurang berbahaya terhadap pengetatan kerana penyambung terangsuai dimeterai dengan baik. Oleh itu, larutan beralkali boleh dielakkan daripada meresap ke dalam penyambung. (d) Permukaan asli yang licin terdapat penahanan minima terhadap benda-benda yang mengotori permukaan penyambung terangsuai yang bersentuhan. (e) Penyambung “terangsuai” memberi pemeteraian vakum yang baik. Untuk vakum maksima, pelicinan ringan pada penyambung adalah perlu. (f) Kekuatan mekanikal penyambung terangsuai adalah lebih besar dari penyambung dasar kerana apabila penyambung kaca dilaraskan ada kemungkinan terjadinya retakan kecil yang boleh melemahkan penyambung. (g) Radas yang dipasang dengan penyambung terangsuai adalah lutsinar termasuk permukaan penyambung itu. Semua perubahan kimia, skala jangkasuhu kekal sepenuhnya dapat dilihat melalui penyambung itu. Harga perkakas kaca terangsuai adalah lebih mahal dari cepatsuai.

Pengapitan perkakas kaca cepatsuai dan terangsuai Oleh kerana penyambung kun adalah teguh, cuma satu pengapit dikenakan pada sebuah radas dengan cermat. Lebihan sokongan kepada pengapitan sebagai satu prinsip dalam penyusunan perkakas kaca. Pengapit cuma mesti diketatkan kepada ketatan-hujung jari sebelum pengapit itu diketatkan pada sokong, mula-mula mesti periksa yang radas bebas dari tegangan fizikal.

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Organic Chemistry

Pembersihan perkakas kaca Membersih hingga kering radas adalah satu keperluan dalam praktikal kimia organik. Perkakas kaca mesti dicuci dengan air sabun yang panas atau bahan pembersih (Teepol). Jika pembasuhan dilakukan dengan cepat mungkin selepas selesai satu-satu percubaan, adalah lebih mudah menanggalkan sebatian organan yang terlekat pada radas gelas itu. Jika berus digunakan di dalam kelalang adalah mustahak bahagian logam dilindungi rapat untuk mengelakkan sebarang calaran. Pelarut organik jangan selalu digunakan, cuma apabila cara lain tidak berkesan. Bila bertar boleh dikeluarkan dengan menggunakan campuran pembersih dikromat. Bila radas kaca telah bersih dan bebas daripada gris, ia cepat kering kerana air tidak terkumpul dalam titik-titik. Adalah baik ditinggalkan di dalam satu rak supaya air mengalir keluar atau ia boleh dikeringkan dalam satu oben. Pengeringan dengan cepat boleh dilakukan dengan menggunakan penyembur udara panas. Perhatian istimewa diberi dalam meletakkan perkakas kaca pada hujung penyembur kerana getaran boleh menyebabkan retakan kecil ke atas permukaan kaca. Bahagian luar radas kaca mesti selalu dikeringkan dan digilap dengan kain kaca; cuma setelah diluarnya bersih, dapat diketahui keadaan di dalamnya.

Calaran Perhatian mesti diberi untuk mengelakkan calaran ke atas permukaan perkakas kaca. Jika tidak ini mengurangkan kekuatan mekanikal ke atas permukaan kaca yang menyenangkan pecahan melalui kejutan haba, istimewa bila calaran terdapat di bahagian dalam permukaan kaca. Hati-hati dalam pemegangan, pembasuhan dan penyimpanan kelalang-kelalang, akan membolehkannya digunakan lebih lama. Calaran cukup untuk menyebabkan pecahan, didapati dengan pengacau kaca yang tidak dilindungi getah, dengan geseran atau ketokan antara dua kelalang atau dengan batang logam berus pembersih. Teknik calaran dengan pembuluh kaca untuk menggalakkan penghabluran jangan sekali dijalankan di dalam satu kelalang cepatsuai atau terangsuai.

iii

Year 2

Organic Chemistry

Experiment 1

EXPERIMENT 1 SN2 REACTION - BUTYL PHENYL ETHER Alkyl halides can undergo a general reaction as indicated in the following:

+

R-X

Nu :

-

X-

+

R-Nu

Two examples are shown as follows:

+

CH3Cl

CH3CH2Br

OH -

+

-

CH3OH

Cl -

+

+ Br -

CH3CH2OCH3

OCH3

In this reaction, a species having an unshared pair of electron called nucleophile, reacts with an alkyl halide to replace the substituent; halogen. Substitution reaction has occurred and the halogen leaves as a halide ion. Thus this reaction is called the nucleophilic substitution reaction. The carbon-halogen bond may be cleaved before or during the formation of the new bond between the carbon and the nucleophile. This depends on the structure of the alkyl halide involved in the reaction. Primary alkyl halides undergo bimolecular nucleophilic substitution reaction, SN2. In this experiment, n-butyl phenyl ether is prepared through SN2 reaction, between n-butyl bromide with phenoxide ion. As phenol is more acidic than ethanol (or water), it is added to sodium ethoxide in absolute ethanol and then the phenoxide ion formed is left to react with the alkyl halide. o

CH3CH2OH

+

CH3CH2ONa

Na

OH CH3CH2ONa

+

ONa

+

+

ONa CH3(CH2)3Br

1/2 H2

+

CH3CH2OH

O(CH2)3CH3

+

NaBr

Apparratus 2 necked round bottom flask,250 ml B14/B19 and B19/B24 Drying tube CaCl2

Reduction adapters B19/B24 Water-condenser Separating funnel

Chemicals 1.9g sodium 7.8g phenol AR

Absolute ethanol n-butyl bromide (13ml, 16.6g)

1

Year 2

Organic Chemistry

Experiment 1

Method All apparatus must be dried. Prepare the apparatus as depicted in figure III(Appendix), and add 44ml of absolute ethanol. Cut 1.9g sodium ( note 1) into 3 or 4 pieces, and add all the pieces into the reaction flask. ( cool the flask in waterbath to make sure the ethanol is refluxed slowly, if needed ). After all the sodium has dissolved , add 7.8g phenol (note 2) in absolute ethanol (10ml) into the reaction flask and then mix the mixture thoroughly. Add n-butyl bromide through a dropper funnel in 1 minute and heat the flask in a waterbath and left to reflux for 15 minutes. Remove excess ethanol by distillation. Then, pour 20ml water into the cold reaction flask (note 3). Then transfer the mixture into a separating funnel. Wash the organic layer with 10% NaOH solution (2x5ml). (Do not shake too strongly as emulsion may be formed !!!!). Then wash the organic layer with 10% H2SO4 solution followed by water. After that, add anhydrous MgSO4 to dry the organic layer (note 3). Pour the filtered organic layer into a pear shaped 25ml flask. Finally, distill the compound using an air-bath. State the boiling point and weight of the n-butyl phenyl ether obtained.

Note 1.

All the safety procedures must be followed while conducting sodium. Lab assistant will do the measurements. Prepare all apparatus needed before taking the sodium! ( Sodium can be replaced by potassium hydroxide, 4.9g. Weigh hygroscopic material immediately).

2.

Chemicals are dangerous. Beware of your skin !!!!

3.

If time is limited, stop here.

Question 1.

Why must the excess alcohol be separated ?

2.

If (R)-2-bromobutane reacted with phenoxide ion through SN2 reaction, what will be the expected product. State the stereochemistry of the compound. (Draw the structure of the compound with the correct stereochemistry).

2

Year 2

Organic Chemistry

Experiment 2

EXPERIMENT 2

GRIGNARD REACTION-PREPARATION OF TRIPHENYLCARBINOL

An example of a class of reaction that involves a formation of a new carbon-carbon bond in the carbon skeleton of a molecule is the Grignard reaction. In 1912, Victor Grignard (University Of Lyons, France) was awarded the Nobel Prize in Chemistry for the discovery of the Grignard reaction. The Grignard reaction is typical class of "organometallic" reaction in which a Grignard reagent acts as a source of nucleophilic carbon reacting with a relatively electron deficient or electropositive carbon, typically an aldehyde, ketone or organic ester. In general, Grignard reagent is prepared by reacting an organic halide with magnesium metal in dry ether or THF.

RX

+

Mg

Dry Ether or THF

RMgX

A Grignard reagent has a formula RMgX where X is a halogen, and R is an alkyl or aryl group. Since the Grignard reagent is very reactive, it will also attack any of a large variety of acidic or electropositive reagents. The Grignard reaction involves a nucleophilic attack of a carbanion (the Grignard reagent) on a carbonyl carbon. The C=O pi-bond is broken and a new carbon-carbon bond is formed between the Grignard reagent and the carbonyl carbon. Upon hydrolysis, an alcohol is isolated as the product. This experiment aims to prepare triphenylcarbinol through a Grignard reaction by reacting methylbenzoate with phenylmagnesium bromide as shown in the scheme below:

O

2C6H5MgBr

+ Ph

C

OMgBr OCH3

Ph

C

Ph

+

Ph

+

MgBrOCH3

Ph OMgBr Ph

C Ph

Ph

OH

+

H3O

+

Ph

C

MgBrOH

Ph

3

Year 2

Organic Chemistry

Experiment 2

Procedure

Placed about 1.4 g of magnesium turnings and sodium-dried ether (enough to “cover the magnesium turnings, about 10 mL) in a dry 250 mL two-necked flask fitted with a 50 mL dropping funnel and a reflux condenser (all apparatus must be completely dry). Place a drying tube filled with calcium chloride at the top of the condenser. This is to prevent the entrance of moisture through the condenser and the dropping funnel during the addition. Into the dropping funnel, place a mixture of bromobenzene (9.2 g, 6.2 mL) in dried ether (30 mL). Run in a small amount of the mixture of bromobenzene in ether (about 5 mL) slowly into the reaction flask and shake the flask gently. Add one or two iodine crystal as catalyst to initiate the reaction. If the reaction does not start after 2-3 minute (iodine color dissappears, cloudy solution is formed, and ether solution start to boil) warm the reaction flask gently (use water bath) until the reaction start on its own, then remove the water bath (if the reaction still does not start, use ultrasonic or add 1 mL of Grignard reagent prepared by lab assistant). When the reaction has started (not before), add the rest of the mixture of bromobenzene in dry ether into the reaction vessel at such a rate as to cause refluxing (cool in ice-bath if the reflux becomes to vigourous). When the addition is completed, continue refluxing the solution on water bath for another 15 minute to ensure that the reaction is complete. At this point, there should not be any magnesium left. Cool the reaction mixture to room temperature or below. To the Grignard solution, 3.5 g (3.2 mL) of methyl benzoate in 10 mL dry ether is added (through a dropping funnel) at such a rate that the mixture refluxes gently (within 20 minute). From time to time shake the flask gently to ensure the reaction mixture mix throughly. After the addition is completed, the mixture is refluxed for about 10-15 min on a steam bath. The reaction mixture is cooled in an ice bath and then poured slowly, with constant stirring, into a 600 mL beaker contains mixture of 75 g of cracked ice and 30 mL 10% aqueous sulfuric acid. The mixture is stirred until all the solid has dissolved. If necessary, additional ether may be added if the amount present is insufficient to dissolve all the product. When the solids have completely dissolved, the ether layer is transferred into separating funnel. Remove the bottom layer (aqueous) and wash the ether layer, successively with 15 mL 10% aqueous H2SO4, 12 mL water and finally with 1 g sodium bisulfite in 12 mL water. The solution is dried with anhydrous Na2SO4. Filter and add 15 mL petroleum ether (60-80) to the ethereal solution. Concentrate the solution gently on steam bath until triphenylcarbinol crystal start to come out. Leave the mixture to cool to room temperature o

then place the flask into an ice-bath (0 C) to ensure all the triphenylcarbinol has crystallized out. The crude triphenylcarbinol is recrystallized from methyl spirit (4 mL of solvent per gram of solid). Weight of the dried crystals, take the melting point and calculate the total yield of triphenylcarbinol obtained.

4

Year 2

Organic Chemistry

Experiment 2

QUESTIONS: 1.

Why must all the apparatus used in the reaction be completely dry?

2.

Compare the molar quantities of magnesium, bromobenzene and methyl benzoate used and explain the sense to the specified reactant ratios.

3.

How does using ether solvent help decrease the formation of the by-products resulting from reaction with oxygen and carbon dioxide of the atmosphere?

4.

NaHSO3 solution is used in the work-up to remove iodine used as catalyst early in the reaction? Write the equation for what happened between iodine and NaHSO3.

References:

1. Techniques & Experiments for Organic Chemistry, Ault, Addison, 6th Edition, University Science Books, 1997 2. W. E. Bachmann and H. P. Hetzner, Organic Syntheses, CV 3, 839

3. Org. Syn. Coll. Vol. 3, 841 4. Operational Organic Chemistry: A Problem-Solving Approach to the Laboratory rd

Course, John W. Lehman, Prentice Hall; 3 edition, 1998

5

Tahap 2

Kimia Organik

Eksperimen 3

EXPERIMENT 3 Diels-Alder Reaction Background The formation of new carbon-carbon bonds is one of the most important aspects of synthetic organic chemistry. Many reactions, such as the Grignard reaction and the use of acetylide ions in SN2 reactions, have been developed with this one goal in mind. One problem associated with most of these C—C bond-forming reactions is the necessity for exotic conditions — the Grignard reaction requires completely water-free conditions and acetylide ions must be generated in liquid ammonia solution. When a synthetic sequence calls for the formation of a ring of carbon atoms, this problem is compounded. Fortunately, the formation of six-membered carbon rings is much simpler than it would first appear. As described in Organic Chemistry by Carey (Section 10.12), the Diels-Alder reaction was discovered in 1928. This reaction forms a six-membered ring from two pieces: a conjugated "diene" (which provides four of the ring atoms) and a "dieneophile" (which provides two of the ring atoms). The main requirements for these species are that the conjugated diene must be somewhat electron rich (which is normally the case for dienes) and able to achieve the s-cis conformation, and that the "dieneophile" have a two-atom π system that is relatively electron poor. In this experiment you will react cyclopentadiene (the diene) with maleic anhydride (the dienophile) to produce the bicyclic compound, endo-bicyclo[2.2.1]hept-5-ene-2,3dicarboxylic anhydride. The endo-adduct is formed exclusively. Why? O

O

H H

O

+

O

+

O H

H

O

O

O

O

exo-

endo-

One important aspect of this experiment is that the cyclopentadiene must be freshly distilled within one day before the reaction is carried out. Why? Answer at end of experiment! Experiment 3.1 Reaction of cyclopentadiene with maleic anhydride Procedure Part A: Distillation of Cyclopentadiene. Place dicyclopentadiene (10 mL) in a 25 mL round-bottomed flask (in the fumehood). Complete the set-up with a Vigreux column (for fractional distillation), an adapter and a condenser for distillation. Heat the dicyclopentadiene on a hot-plate until it refluxes briskly. The monomeric cyclopentadiene should start to distill within a few minutes. Continue to heat the dimer reagent to promote fairly rapid distillation and collect the cyclopentadiene into a receiver flask which is cooled to 0 oC using an ice-water bath.

5

Tahap 2

Kimia Organik

Eksperimen 3

(Note 1). Do not allow the distillation temperature to exceed about 45oC, which is slightly above the boiling point of cyclopentadiene (40-43oC). After all the cyclopentadiene has been collected, stop the distillation and discard the unused residue from the reaction flask, into the liquid waste container. If the cyclopentadiene is cloudy, add a few pieces of anhydrous sodium sulfate (or anhydrous magnesium sulfate). Decant the dry cyclopentadiene from the drying agent for use in the experiment below. Part B: Diels-Alder Reaction Grind 5 g maleic anhydride using a small mortar and pestle to break up any chunks, and dissolve it in 20 mL of ethyl acetate (you may need to heat it) in a 125-ml Erlenmeyer flask. Once the maleic anhydride is dissolved, add 20 mL of petroleum ether and place the solution in an ice bath to cool to well below room temperature. Add (in the hood) about 5 mL of the freshly distilled cyclopentadiene directly to the cold maleic anhydride solution (if the solution contains any crystals, dissolve them before adding the cyclopentadiene). Swirl the reaction mixture in an ice bath until the product has finished precipitating. After crystals have formed, recrystallize your product by simply heating the product mixture on a hot plate until the solid dissolves (but do not boil). Allow the solution to cool at room temperature until recrystallization has finished. Collect the crystals using a Büchner funnel. (If you have crystals still present in the flask, do not use water to wash the crystals, as the acid anhydride will react; use the filtrate (mother liquor) to wash the flask. Collect as much crystals as possible. NOTE 1: Safety Cyclopentadiene (and its dimer, dicyclopentadiene) is an irritant, is flammable, has an unpleasant odor and is harmful if inhaled — avoid breathing its vapors. No flames will be allowed in the lab. Wear gloves while handling these chemicals. Dispense and use these chemicals in the hood to minimize inhalation hazards. Maleic anhydride is corrosive and toxic--wear gloves while handling it. Be sure to wash your gloves and your hands after handling it. Questions: 1. How many new bonds, and of what type (σ or π), are created in a Diels-Alder reaction? 2. What is the theoretical yield of product, based on the amount of cyclopentadiene used in the experiment. 3. What is the structure of the dicyclopentadiene? Experiment 3.2 Reaction of Furan with Maleic Anhydride The objective of this experiment is to perform a Diels-Alder reaction between the furan and maleic anhydride.

6

Tahap 2

Kimia Organik

Eksperimen 3 O

O

+

O

Endo or Exo Adduct?

O

Procedure: Prepare 10 mL of a 4M solution of maleic anhydride in CH2Cl2. (Use the calculations in your lab notebook). Filter off the insoluble maleic acid using a Hirsch funnel and suction filtration. Measure 1 mL furan into a test-tube and add the appropriate equimolar amount of maleic anhydride to the reaction tubes (use calculations in prelab). Cork the test tubes, seal the corks with Parafilm, and set them in your locker until the next laboratory period because the reaction takes 24 - 48 hours to reach completion. (Progress of reaction could be monitored through TLC. The TLC plate should have three spots (or lanes) on the origin: one for the main organic starting material that is being transformed, one for a co-spot (starting material and the reaction mixture), and one for the reaction mixture). Isolation and Purification: If crystals haven't formed, insert a clean stirring rod or boiling stick into the reaction tube, remove the wet rod or stick, and allow it to dry, forming seed crystals. When reinserted, crystallization should be instantaneous. Pipet off the remaining liquid, wash the crystals with ice-cold CH2Cl2 or 1:1 (V/V) CH2Cl2:hexane, let the crystals dry, and determine the yield and melting point. Take the melting point of the furan adduct before recrystallization. Use a 5:2 mixture of hexane:ethyl acetate to dissolve only part of the crude product and place the flask in hot water bath. The temperature of the water bath should be adjusted to just below the melting point obtained to dissolve the adduct. Alternatively, acetone could be used as the solvent for recrystallisation and crystallization could be induced by dripping hexane into the acetone solution. Obtain melting points of all recrystallized products. The furan adduct requires much more "finesse" to recrystallize since it undergoes a reverse or retro Diels-Alder reaction at the melting point. Caution: Maleic anhydride and the Diels-Alder adducts are intense skin irritants Furan is very low boiling. Questions: 1. Determine which of the possible products were produced, exo or endo, by comparing your melting points with the literature values. 2. How would you prepare 5 mL of a 4M solution of maleic anhydride in CH2Cl2? Show calculations. 3. How many moles are in 0.5 mL furan? How many mL of the 4M maleic anhydride in CH2Cl2 would be an equimolar amount?

7

Tahap 2

Kimia Organik

Eksperimen 3

4. Explain why the 4M solution of maleic anhydride is made in CH2Cl2 and not in water. Show the reaction between maleic anhydride and water. 5. Give structures for the major Diels-Alder product of the following reactions: 1,3-cyclohexadiene and tetrachloroethene 1,3-cylcohexadiene and fumaric acid, the trans isomer of maleic acid. References: References: 1. Techniques & Experiments for Organic Chemistry, Ault, Addison, 6th Edition, University Science Books, 1997. 2. Operational Organic Chemistry: A Problem-Solving Approach to the Laboratory Course, John W. Lehman, Prentice Hall; 3rd edition, 1998.

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Year 2

Organic Chemistry

Experiment 4

EXPERIMENT 4 SEPARATION OF PIPERINE FROM BLACK PEPPER Some of the organic compounds found in nature have specific smell or odour and they are usually known, in general, as aromatic compound. In the early days, aromatic compounds meant then that the compound had a low hydrogen/carbon ratio and that it was fragrant. The parent compound of the aromatics is benzene. Today, not all aromatic compounds are fragrant but they are called aromatic compounds because of their structure. Some examples of aromatic compounds that have specific smell are vanillin (1) and safrol (2).

CH2CH=CH

CHO

OCH3

O

OH

O

(1)

(2)

Vanillin is obtained from vanilla and is widely used as deodorant, food flavour and one of the ingredients in pharmaceutical products. A related compound is bourbonal (3) or 3-ethoxy-4hydroxibenzaldehyde while safrol can be obtained from sasafras and camphor oil. Piperonal (4) is derived from safrol through isomerization to isosafrol followed by oxidation. Piperonal is used as flavour in soap and deodorant because of its sweet smell.

CHO

CHO

OCH2CH3

O

OH

O

(3)

(4)

One of the spice which is widely known is black pepper or Piper nigrum . It has a rather hot and sharp taste. This is due to the presence of piperine (5). Piperine has a unit of methylenedioxy as in safrol and piperonal.

O CH

CH

CH

CH

C

N

O O

(5)

9

Year 2

Organic Chemistry

Experiment 4

Separation method Extract the grounded black pepper (20g) with 95% ethanol (150ml) in a Soxhlet extractor for 2 hours. Filter the mixture and concentrate it in vacuum using rotary evaporator. Add an alcoholic potassium hydroxide solution (10%, 10ml) to the concentrated filtrate. Then separate the solution from the undissolved solid filtrate by slanting the flask. Leave the alcoholic solution for a night. Piperine will be obtained as yellow needles. Collect the crystals by suction filtration. Take the melting point and calculate the percentage yield. Record the UV spectrum (in ethanol) and IR spectrum (disk KBr) piperine.

Thin Layer Chromatography Dissolve a small amount of piperine in acetone and blotch it on the thin layer chromatography plate ( silica gel Merck 60,F254). Place the TLC plate in a chromatography tank and develop it using toluene-ethyl acetate solution (volume/volume 2:1). Place the plate under UV light (UV365) and take note of your observation and the Rf value of the sample. Reference 1.

Operational Organic Chemistry, A Laboratory Course, Second Edition, John W. Lehman, Allyn and Bacon, 1988.

2.

Organic Chemistry, Volume 2: Stereochemistry and the Chemistry of Natural Products, Fifth Edition, I.L.Finar, Longman, 1989.

3.

Natural Products, A Laboratory Course, Second Edition, Raphael Ikan, Academic Press, 1991.

Question 1.

Why was 10% potassium hydroxide solution added to the filtrate ?

2.

What are the compounds that will be formed when piperine is hydrolysed with potassium hydroxide in alcohol solution?

3.

Besides using UV light, what other method can be used to detect piperine.

4.

Predict the H NMR spectrum for piperine.

1

10

Year 2

Organic Chemistry

Experiment 5

EXPERIMENT 5 STEAM DISTILLATION OF IMPURE ESSENTIAL OIL SAMPLE Introduction Volatile compounds that are present in a mixture with the non-volatiles may be separated using steam distillation. This can be achieved by exposing the mixture to steam. The volatile components will then be extracted out from the mixture and follow the flow of the steam. For example, o-nitrophenol can be separated from p-nitrophenol by using this method. Essential oils from plants can also be separated from the plant aqueous mixture by steam distillation. You will be given a mixture (X, Y, Z, etc.) which contain an essential oil sample such as limonene (lemon), citronelal (lemongrass), isoeugenol (nutmeg), cineol (eucalyptus oil) and many others. The mixture will consist of about 15% essential oil and 85% mixing agent; filtered of palm oil, which has been discoloured and deodorized ( or r.b.d. – “refined, bleached, deodorized”). The essential oil can be separated from the mixing agent by using steam distillation.

Formula and IR Spectrum IR spectrum (intensity)

CH3 CH3

O-H stretch 3500 cm-1 (moderate,wide) C=C and stretch benzene 1597 cm-1 (moderate,wide)

CH=CHCH3 iso-eugenol (buah pala)

CH3

C

CH2

stretch 1650 cm-1 (medium)

H C

bending 890 cm

C

-1

(strong)

H H3C

CH2

limonen [(S) lemon, (R) oren]

11

Year 2

Organic Chemistry

Experiment 5

CHCHO C=CH-CHO CH3

Stretch 1650 cm-1 (strong)

for conjugated C=O stretch of C-H aldehyde 2750 cm-1 and 2850 cm-1 (weak)

H3C

CH3

sitral (serai)

C=C non conjugated 1645 cm-1 (weak) C=C conjugated 1625 cm-1

OH OCH3

O-H 3500 cm-1 (moderate, wide) C=C 1640 cm-1 (moderate)

CH2CH=CH2 eugenol

Chemicals Sample W, X, Y or Z containing palm oil (r.b.d) and essential oil Diethyl ether 10 ml Sodium sulphate

Method Prepare the apparatus as in figure VI. Take one sample (10g) oil mixture (W, X, Y, Z etc) and add it into the flask. The steam distilled product will have two layers: aqueous and organic; essential oil. Pour the product into the separatory funnel. Add NaCl to the product, then extract the essential oil with 30 ml diethyl ether. Separate the ether layer, and dry it with anhydrous sodium sulphate. Filter the mixture using cotton and distill the ether out (using water-bath). Weigh the essential oil obtained and give to the lab assistant for further analysis. Identification of the oil can be made from its odour. Use IR spectrum to confirm its structure. Note -1 the absorption reading (cm ) for your sample.

Question 1.

o-hydroxybenzaldehyde can be separated from p-hydrobenzaldehyde by steam distillation. Compare the structures of o-nitrophenol and p-nitrophenol. Suggest the factor/s that makes o-nitrophenol more volatile the p-nitrophenol based on their structures ?

2.

Draw the structures of R&S-limonenes.

3.

How do you differentiate the R&S limonenes?

12

Year 2

Organic Chemistry

Experiment 6 EXPERIMENT 6

6.1

BECKMAN-BENZANILIDE REARRANGEMENT

Condensation of a ketone with hydroxylamine hydrochloride in the presence of excess sodium hydroxide solution forms a ketoxime. R2C=O + NH2OH.HCl + NaOH

R2C=NOH + NaCl + 2H2O

Reaction of an ethereal solution of an oxime with either phosphorus pentachloride or thionyl chloride gives an amide, a product which is formed through a rearrangement reaction. R'

SOCl2 or

C N R

OH

PCl5

O

HO

C

C N R

R'

R

NHR'

Conversion of any oximes to substituted amides in the same reaction condition as mentioned above is known as Beckmann rearrangement. The reaction involves the formation of an electron-deficient nitrogen atom, followed by a migration/shift, normally involves a migration of an alkyl group to the electron deficient centre. This is an example of a reaction that involves a 1, 2- shift/migration. Apparatus Round-borttomed flask B19, 50 mL Condenser B19 Vacuum desiccator Round-borttomed flask B19, 100 mL Still-head B19/19/14 Beaker 250 mL Chemicals 2.5 g benzophenone 20 mL diethyl ether (anhydrous) 1.5 g hydroxylamine hydrochloride

7.5 mL conc. hydrochloric acid 2.8 g sodium hydroxide pellets 5 mL rectified spirit

Method (a) Preparation of benzophenone oxime Place a mixture of 2.5 g benzophenone, 1.5 g hydroxylamine hydrochloride, 5 mL rectified spirit and 1 mL of water in a 50 mL round-bottomed flask. Add 2.8 g of sodium hydroxide pellets in portions with shaking; if the reaction becomes too vigorous, cool the flask with running tap water. When all the sodium hydroxide pellets has been added, attach a reflux condenser to the flask, heat to boiling and reflux for 5 minutes. Cool and pour the contents of the flask into a solution of 7.5 mL of concentrated hydrochloric acid in 50 mL of water contained in a 250 mL beaker. Filter the precipitate at the pump, wash thoroughly with cold water and dried. Recrystallise the precipitate from methanol and record the weight of the product, and its melting point. (Note: The oxime is gradually decomposed by oxygen and traces of moisture into benzophenone and nitric acid; it should be kept in a vacuum desiccator filled with pure dry carbon dioxide or nitrogen).

13

Year 2

Organic Chemistry

Experiment 6

(b) Beckmann Rearrangement of benzophenone oxime (Note 1) Dissolve 2 g of benzophenone (prepared in (i)) in 20 mL of anhydrous ether in a 100 mL, B 19 round-bottomed flask (all the apparatus must be dried!!) and add 3 mL of pure thionyl chloride (this step should be carried out in a fume cupboard). Distill of the solvent or other volatile products (as shown in Diagram V) on a water bath. Add 25 mL of water, boil for several minutes and break up any lumps which may be formed. Decant the supernatant liquid (filter at the pump if necessary), and recrystallise the product from methanol (toxic!). Record the weight of the product and its melting point. Exercise 1. Condensation of a ketone with hydroxylamine hydroxide in the presence of sodium hydroxide gives a ketoxime. Can the reaction occur in the absence of sodium hydroxide? Suggest explanations. 2. Suggest the product formed from the rearrangement of sulphuric acid induced cycloheptanone oxime? 3. Suggest the mechanism of the following reaction:Ph

O

OH C N

MePh

+

SOCl2

H2O

C6H5

C

NH PhMe

Note 1: All apparatus must be dried. Use thionyl chloride (SOCl2) in a fume cupboard, cool the flask containing diethyl ether before adding thionyl chloride. References 1. Elementary Practical Organic Chemistry Pt 1: Small scale Prepparation by A.I Vogel. 2. Laboratory text in organioc chemisrry by Cason & Rapport 3. Laboratory Experiments in organic chemistry by Adams, Johnson, Wilcox.

6.2

PREPARATION OF CAPROLACTAM REARRANGEMENT REACTION

THROUGH

BECKMANN

Preparation of Cyclohexanone oxime Dissolve 7.5 g of hydroxylamine hydrochloride and 12 g of sodium acetate crystals in 30 mL of water in a 100 ML conical flask. Heat the reaction mixture to 40oC and add 7.5 g of cyclohexanone. Stopper the flask and shake vigorously for 10 minutes. Oxime will separate as crystalline solids, cool the flask in an ice bath. Filter the solid at the pump and wash with cold water, Recrystallise oxime from petroleum-ether (60-80oC) and dry the crystal in the air using a filter paper. Record the melting point and percentage of the product obtained. Interpret the infra red spectrum of your product. ( Lit.; mpt.of

14

Year 2

Organic Chemistry

Experiment 6

cyclohexanone oxime 89-90oC).

Preparation of Caprolactam Place10 mL of concentrated sulphuric acid in a 500 mL beaker. While stirring, slowly add 5 g of cyclohexanone oxime to the mixture. (Carry out this process in a fume cupboard because the reaction is exothermic and liberates heat. If heat is not liberated, heat the mixture on a steam bath for 5 minutes). Let the reaction subsides, and then cool the beaker in an ice-bath. Pour the reaction mixture into a beaker containing 150 g of ice. Cool the beaker in an ice-bath, and slowly add potassium hydroxide solution (25%) until the mixture becomes alkaline. Make sure that the temperature of the reaction is not exceeding 10oC. (If precipitate of potassium sulphate formed, add water or filter the precipitate, wash with dichloromethane and combine the dichloromethane wash with dichloromethane extracts). Extract the alkaline solution with dichloromethane (3 x 75 mL), wash the dichloromethane layer with water and dried over anhydrous magnesium sulphate. Remove the solvent using rotary evaporator, and extract crude oily product with boiling petroleum ether (60-80 oC). Cool the petroleum-ether extracts and caprolactam will crystallize out as colourless crystals. Record the melting point and percentage of product obtained. Interpret the infrared spectrum of your product. (Note: Hydroxylamine is very toxic and be careful when handling it) Exercise 1. What is the role of sodium acetate in the formation of oxime? 2. Write a mechanism for the formation of cyclohexanone oxime. 3. What is the function of adding potassium hydroxide (25%) to the acidified reaction products of cyclohexanone oxime?

15

Year 2

Organic Chemistry

Experiment 7

EXPERIMENT 7 Preparation of an Azo Dye: 1-(p-nitophenylazo)-2-naphthol Background The azo class of compound accounts for 60-70% of all dyes. Azo dyes are dyes with N=N- azo structure which links two sp2 hybridised carbon atoms. Usually, these carbons are part of an aromatic system, although this is not always the case. Most azo dyes contain only one azo group, but others may contain two (disazo), three (trisazo) or more. In theory, azo dyes can supply a complete rainbow of colours. However, commercially they tend to supply more yellows, oranges and reds than any other colours though there are now some viable blue azo dyes on the market. The general formula for making an azo dye requires two organic compounds- a coupling component and a diazo component. Since these can be altered considerably, an enormous range of possible dyes are available, especially as the starting molecules are readily available and cheap. Furthermore, the simplicity of the reactions mean that the process can be scaled up or down very easily, which is always a key factor in the cost of chemicals. Energy requirements for the reaction are low, since most of the chemistry occurs at or below room temperature. The environmental impact is reduced by the fact that all reactions are carried out in water, which is easy and cheap to obtain, clean and dispose of. As other dye classes become less viable from either an environmental or economic reasons, azo dyes become ever more attractive options. 1-(p-nitophenylazo)-2-naphthol or Para Red is an example of an azo dye. This intense orange-red dye was discovered in 1880 by von Gallois and Ullrich, and was the first azo dye made. It dyes cellulose fabrics a brilliant red, but is not very fast. NO2

+ N N: ClOH

N + N OH NO2

Procedure: Part A: Preparation of p-nitrobenzendiazonium sulfate. Dilute 2.0 mL (0.036 mol) concentrated sulfuric acid to 10 mL distilled water. Add 1.4 g (~0.01 mol) p-nitroanile and heat the solution slowly till all the amine has dissolved. Cool the solution to 10 oC in a ice-bath. While stirring, add 0.7 g (0.01 mol) sodium nitrite (dissolved) in 2 mL distilled water slowly into the solution of p-nitroaniline sulfate that was prepared earlier. Ensure that the temperation of the reaction does not rise to higher than 10 oC during the addition. Keep the product in water bath while Part B is being prepared.

16

Year 2

Organic Chemistry

Part B: Couping reaction of the diazonium salt: nitophenylazo)-2-naphthol (PARA Red)

Experiment 7 preparation of 1-(p-

Dissolve 1.44 g (0.01 mol) 2-naphthol in 25 mL 10% sodium hydroxide solution. Cool the mixture to 10 oC and add slowly to the diazonium salts prepared earlier (in part A). Acidify the mixture and collect the mixture (use suction filteration). Recrystallise the product with either toluene or acetic acid and take the melting poing of the product. Question: 1. Why do you have to keep the temperature at 10 oC when preparing the diazonium salt? 2. Write the mechanism for the formation of the p-nitrobenzenediazonium sulfate. 3. What causes the colour observed in PARA Red?

17

Year 2

Organic Chemistry

Qualitative Analysis

QUALITATIVE ORGANIC ANALYSIS The identification and characterization of an unknown organic compound normally refers to those processes or tests that need to be performed in order to answer the following important questions: 1. What kind of functional groups are in the compound? 2. Where in the molecule are these functional groups located? 3. What is the position of one functional group in relation to another? 4. Where a compound might exist as regio-, geometic or stereoisomers (diastereomers or enantiomers), can the type of isomerism be specified? It is usually good practice before these questions can be answered, to ask some preliminary questions? 1a What kind of elements (carbon, hydrogen, nitrogen e.t.c) are in the compound? 2a What is the melting point or boiling point (if liquid) of the compound? This question is of particular importance since if a library of compounds or a data base of previously prepared compounds is available, agreement between the melting point or spectroscopic data for your compound and the reference compound from the published literature, can play a significant role in identifying an unknown compound, provided it is pure. This leads naturally to the next point. 3a Purification of your compound by recrystallisation, chromatography or (if liquid) by distillation is often essential. Although it is possible, with modern spectroscopic equipment to completely identify a compound, thereby providing complete structural information, it is strongly recommended that you make use of other information for example, the physical state, elemental analysis (point 1a above), solubility and confirmatory tests for functional groups. Before we survey briefly the kind of tests you will need to perform, two important points need to be emphasized, firstly, laboratories can be dangerous places for the careless worker, therefore, make sure you protect your eyes by wearing safety spectacles. This will be particularly important when you have to heat reaction mixtures either to perform certain tests or during distillation. Wear a lab coat and shoes that cover the feet. Secondly, be observant! Notice what is going on around you in the laboratory for reasons of safety. Careful observation is also essential if you are to obtain the maximum possible information from the chemical and physical changes your compounds will undergo during the chemical tests.

Procedures Preliminary observations 1. Check the purity of the sample. This can be done by either by TLC (thin layer chromatography) or by GC (gas chromatography). If purification is necessary, distillation or column chromatography will be required. 2. Note the colour. Colours may suggest to the experimenter the likely classification of the compound. But this is not final proof, which, can only be obtained by performing chemical tests and spectroscopic investigations. Common coloured diketones (yellow), quinones (yellow to red), azo compounds could include compounds (yellow to red), and polyconjugated olefins and ketones (yellow to

18

Year 2

Organic Chemistry

Qualitative Analysis

red). It is not unusual to find that phenols and amines with colours ranging from brown to dark purple because of traces of air oxidation products. 3. Note the odour. A fishy odour could suggest solid or liquid amines.The fragrance of esters can be extremely pleasant. Alcohols, ketones, aromatic hydrocarbons, and aliphatic olefins have characteristic odours. Thiols, isonitriles, and low molecular weight carboxylic acids often have a rather unpleasant odour. Caution: extreme care must be taken when the sense of smell is being used in the laboratory, inhalation of unpleasant and perhaps toxic chemicals can be dangerous. 4. For some investigations, you may be given a mixture of two compounds. In this case you will need to perform tests for the presence of acidic or basic groups followed by the appropriate extraction, where the compound is partitioned between two solvents of different polarities in a separating funnel. The laboratory assistant will teach you how to do this. Once this has been achieved, purification (distillation or chromatography) can proceed.

Ignition test Heating a small sample in a spatula in a Burnsen flame can be suggestive. If the compound burns with a smoky flame it is probably an aromatic compound. If a large ashy residue is left after is left after ignition, the unknown is probably a metal salt. Elemental Analysis, The Sodium Fusion Experiment In this test, the sample is added to hot sodium in a pyrex test tube. It is important that you follow instructions, including the advice of your instructor, faithfully and as always make sure you are wearing your safety glasses. If nitrogen, sulphur or halogen are present in the unknown compound, these will be converted to NaCN, Na2S and sodium halide (Cl, Br or I) respectively. These products can in turn be readily identified. Of course caution is advisable when drawing inferences from these observations. The presence of sulphur can interfere with the nitrogen test. In addition, the sodium fusion test does not work well with nitro compounds. Functional Group Tests It is important to attempt to detect acidic or basic groups before you begin your functional group tests. Adding a few drops of your unknown to a small volume of dilute hydrochloric acid (2M) or dilute sodium hydroxide (2M), and careful observation to see if the sample dissolves in the cold, will prove helpful. Your reference book will provide you with information on a whole series of functional group tests. For example, for aldehydes and ketones (addition of 2,4-dinitrophenyl hydrazine resulting in the formation of a bright orange precipitate), for esters (addition of KOH, HCl, FeCl3 resulting in the formation of the hydroxamic acid salt), for halogens ( the silver nitrate test), for the nitro group (the purple colour produced by the titanous chloride test). Tests for phenols, alcohols, primary and secondary amines, alkyl halides can be obtained from the laboratory manuals. Further experiments for the formation and purification of suitable derivatives for melting point determinations are also available.

19

Year 2

Organic Chemistry

Qualitative Analysis

References: The Systematic Identification of Organic Compounds, Sixth edition,; Shriner, Fuson Curtin and Morrill; Wiley,NY, 1980. Kaedah Kimia dalam Pengenalpastian Sebatian Organik (Chemical Techniques for Identification of Organic Compounds) (ISBN 983-100-069-2), Kamaliah Mahmood dan Noorsaadah Abd. Rahman, Penerbit Universiti Malaya, 1998. Kaedah Spektroskopi dalam Pengenalpastian Sebatian Organik (Spectroscopic Techniques for Identification of Organic Compounds) (ISBN 983-100-018-8), Kamaliah Mahmood dan Noorsaadah Abd. Rahman, Penerbit Universiti Malaya, 1997. Introduction to Spectroscopy, Pavia, Lampman and Kriz; Saunders, NY, 1979. Handbook of Tables for Organic Compound Identification" CRC Press.

20

Year 2

Organic Chemistry

Laboratory Notebooks

LABORATORY NOTEBOOKS An entry in a laboratory notebook constitutes the primary reference to any experiment one has personally carried out. It claims priority in any case of doubt. All relevant aspects of a conversion should be recorded, together with the order in which steps were carried out. All observations should be noted, in principle even those that at first sight appear unimportant. Only in this way can one ensure that the results of critical experiments can be reproducted. At the beginning of each experiment record:








the date structural formulae (abbreviated, if necessary) and all reagents in order of addition molecular formulae and molecular weights, preferably under the relevant structural formulae literature references on the procedure (or on analogous preparations) weights (and number of moles) of each compound used list of apparatus (with sketches in unusual cases) the purity of all compounds and solvents (which should have been determined!) e.g. "Analar grade", "Freshly distilled from LiAlH4", "filtered through basic alumina, Wolem, activity I", "single spot on t.l.c. (SiO2, hexane)", "pure by n.m.r.", etc.

During the course of the experiment keeping running notes
all observations (described exactly)
the order of individual operations and the time taken over each of them
all experiments used to keep a check on the course of the reaction At the end of the reaction record without delay:
the method of working up
purification procedures
yields and percentage yields Some hints:
Use a book with numbered pages
A book giving a carbon copy is a valuable safeguard!
Write your report on one side of the page only, using the facing page for recording weights, distillation records, titrations, preliminary tests for separating mixtures, hydrogenation curves, suggested improvements for future use, interpretation of spectra, etc.
Note reference numbers of spectra in the margin (but keep the spectra themselves in separate files).
An index makes it easier to retrieve the information.
For key experiments, write an edited report for later use and file it separately.
Some research workers also keep a diary to provide a very brief record of what work they have done each day.

21

Year 2

Organic Chemistry

Laboratory Notebooks

WRITING A REPORT A good clear report is easy to produce if one has a comprehensive description of the work including all relevant data on the starting materials and products as well as all the experimental details in one's laboratory notebook. The experimental procedure should be described concisely with neat formulae and relevant references. A report on a preparative experiment should have the following features:

Title This should include the name of the product, the names of the experiments, and, where relevant, the date. e.g. "Isolation of cyclopenten-3-one from ......." "Synthesis of cyclopenten-3-one from ......."

Report This can be arranged in the following sections: (a)

Method : Here the overall transformation carried out in each step of a multi-stage synthesis is described. e.g. "Pinacol is prepared by the reductive dimerisation of acetone" "Endo-bicyclo[2,2,1]hept-2-ene-5-carboxylic acid is formed by the cycloaddition (Diels-Alder Reaction) of cyclopentadiene and acrylic acid".

(b)

Reaction scheme : This shows the transformation of starting materials to products by means of formulae (configurational or conformational if necessary). Reaction conditions (reagents, solvents, catalysts, temperature, etc.) are indicated in abbreviated form above and below the arrows in the usual way. The molecular formulae and molecular weights can be appended to the relevant structures. All structures should be numbered. In general, diagrams showing mechanisms are presented separately.

(c)

Experimental section : The description of the experiments (past tense, third person, passive voice) should be sufficiently detailed to permit the repetition of the reaction without further consultation of the literature. The report should be sufficiently complete for it to be used in preparing a paper for publication. The weights of all compounds (and the number of moles), the purity of starting materials and solvents (these data on substances used repeatedly in a series of experiments can be collected and placed at the beginning of the experimental section, if desired), and all relevant reaction conditions (temperature, time, pressure, etc.) should be quoted, as well as the work-up and purification procedures. One should also provide information about the apparatus used, any peculiarities observed, and simple procedures for the following the course of the reaction. In the text, names of all chemicals should be written out in full: formulae are used only in reaction schemes. On the other hand, abbreviated or trivial names (with the

22

Year 2

Organic Chemistry

Laboratory Notebooks

structure numbers used in the reaction schemes) make it easier to follow descriptions when long and complex names are involved. The yield is quoted (not the average yield over several preparations) with an indication of purity ("crude", "after recrystallisation", etc.), as well as the literature yield with reference (where relevant). Finally, the physical data used to characterise the compound should be reported (again with literature references): m.p., b.p., nD (with temperature superscript), Rf (with details of t.l.c. system, i.r., u.v., n.m.r., m.s., etc.

Some typical expressions and abbreviations


bright yellow crystals (10.5 mg, 78% based on 8)




tetramethylsuccinic anhydride (33.8 g, 0.217 mol)




nitrile (1.15 g, 8.5 mmol)




a solid residue (68.9 g) remained, and was recrystallised from ... (ca. 250 cm3) with charcoal decolorisation




a absolute ethanol (2 cm3)




poured onto ice (1.5 kg)




in sodium hydroxide solution (1 N)




with methyllithium in ether (1.49 M, 16 cm3)

23

Year 2

Organic Chemistry

Laboratory Notebooks

Notebook Entry 16.5.1998 p. 45 O

+

H2N

Pb(OAc)4

N

O

H5 C6

C6H5

N

N

CH2Cl2

C6H5 O C14H12

C8 H6N2O2

180

160

H5 C6

O C22H16N2O2 340

Reference : L.A. Carpino and R.K. Kirkley, J. Am. Chem. Soc., 92, 1784 (1970). Apparatus : 300 cm 3-neck flask; mechanical stirrer with Teflon blade Reagents :

40 mmol 6.50 g (40 mmol) N-aminophthalamide (m.p. 199.202°). It solidifies after melting, perhaps because of rearrangement to

O NH NH O

36.0 g (0.2 mol 5-fold excess) trans-stilbene (Fluka, "pursiss") 20.0 g (ca. 40 mmol) lead tetra-acetate (Fluka, "purum", 85-90% moistened with acetic acid).

N-aminophthalamide (4.50 g, 40 mmol) and trans-stilbene (36.0 g, 0.2 mol) were suspended in dichloromethane (100 cm3, distilled over P2O5) and treated at room temperature and with vigorous stirring over 10 min with lead tetra-acetate 20.0 g, ca 40 mmol), added in portions. (The reaction mixture turned orange. Virtually no heat was observed. The mixture was stirred for a further 30 min, filtered through Celite and evaporated (rotary evaporator, water bath at about 40 °C). The residue (a dark brown oil) was immediately chromatographed on Kieselgel (190 g). Dichloromethane eluted excess stilbene, a small amount of an unidentified byproduct

p.46

24

Year 2

Organic Chemistry

Laboratory Notebooks

O

O

N

N

N

N

O

O

and a yellow crystalline compound (10.0 g, 73.5% calculated as 1phthalimido-trans-2,3-diphenylaziridine. The product was recrystallised from chloroform-pentane.

Fraction 1

(Crystallisation overnight at 0°, dried for 2 h at 0.05 torr/room temp.) 5.48 g (m.p. 177-179 °C, lit. (Carpino) m.p. 165 °C) tlc (Kieselgel) Canary-yellow long needles IR 43/1 (agrees with lit.! Characterisation IR 43/1 (5% CHCl3) NMR 43/1 MS 43/1 (200 °C) C-H-N microanalysis

Fraction 2 (ditto) 4.44 g (m.p. 176-177 °C, tlc identical with Fraction 1) IR 43/2 (identical with IR 43/1) Yield :

IR 43/1 NMR 43/1 MS 43/1 microanalysis

IR 43/2

9.92 (73%)

Thermal stability: A sample was heated at 100 °C for 15 h in an open fusion tube. It showed no change (tlc, IR 43/3)

IR 43/3

25

Year 2

Organic Chemistry

Laboratory Notebooks

EXAMPLE OF A LABORATORY REPORT

1-Phthalimido-trans-2,4-diphenylaxiridine

19 July 2006

(a)

Azhar Ariffin

Method trans-Stilbene reacts with N-aminophthalimide in the presence of lead tetra-acetate in antioxidatively induced (2 + 1) cycloaddition to yield 1-phthalimido-trans-2,3diphenylaziridine.1,2

(b)

Scheme O

+

H2N

Pb(OAc)4

N

O

H5 C6

C6H5

N

N

CH2Cl2 C6H5 C14H12 mw : 180

(c)

O C8H6N2O2 160

RT

H5 C6

O C22H16N2O2 340

Experimental N-Aminophthalimide3 (6.50 g, 40 mmol) and trans-stilbene4 (36.0 g, 200 mmol) were vigorously stirred in dry dichloromethane4 (100 cm3) in a three-necked 500 cm3 flask fitted with a Teflon-bladed stirrer, a thermometer, and a powder funnel. Lead tetraacetate6 (20.0 g, 40 mmol) was added at room temperature to the suspension over 10 min. After a further 30 min stirring, the mixture was filtered through Celite and concentrated on a rotary evaporator at 40 °C. The crude

26

Year 2

Organic Chemistry

Laboratory Notebooks

product was at once transferred to a silica gel (190 g) column and the excess stilbene eluted with dichloromethane. A second fraction containing a small amount of an unidentified by-product was then eluted, followed by 1-phthalimido-trans-2,3diphenylazirdine (10 g). The product was recrystallised overnight at 0 °C from chloroform/pentane and the yellow needles dried for 2 h at 25 °C/0.05 torr. The yield of recrystallised material m.p. 177-179 °C was 5.48 g. A second crop of crystals (4.44 g), m.p. 176-177 °C, was obtained from the mother liquor. Yield after chromatography : 10.0 g (73.5%) Yield after crystallisation : 9.92 g (73.0%) (d)

Physical data Rf (t.l.c., silica gel, dichloromethane) : 0.44 m.p. 177-190 °C (lit. 1m.p. 165 °C) vmax (chloroform): 1774 (m), 1718 (s) cm-1 δ(CDCl3, 60 MHZ): 3.96 and 4.97 (2H, ABq, J 6 Hz), 7.08-7.83 (14 H, m) ppm m/z 340 (M+, 9%), 194 (100 Found: C, 77.55; H, 4.79; N, 8.29. Calculated for C22H16O2N2, C, 77.63; H, 4.74; N, 8.23%

(e)

Notes If the filtrate obtained by filtration of the reaction mixture through Celite is treated with at equal volume of pentane at 0 °C, instead of being concentrated, a crystalline precipitate is produced. Recrystallisation from pentane/dichloromethane gives a yield of 55-65%. Heating of the reaction mixture at 100 °C for 15 h did not affect the result (i.r., t.l.c.).

(f)

References 1. 2. 3. 4. 5. 6.

L.A. Carpino and R.K. Kirkley, J. Am. Chem. Soc., 1970, 92, 1784. D.J. Anderson, T.L. Gilchrist, D.C. Horwell and C.W. Rees, J. Chem. Soc. (C), 1970, 576. Fluka, pursiss. Fluka, purum, m.p. 199-202 Distilled over phosphorus pentoxide Fluka, purum, 85-90%, moistened with acetic acid.

27