CHEM2005 Pyrazole Heterocycle 2016(1)

7/24/2019 CHEM2005 Pyrazole Heterocycle 2016(1)

1/15

Year 2

2016

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2/15

Year 2 Semester 2 PYRAZOLE HETEROCYCLE Lab 29:5005

2 R = Cl CHEM2005 2016

Underlying theory

The carbonyl group is a component of many different functional groups: aldehydes, ketones, acids,

esters and amides being the most common. The reactivity of compounds containing these func-

tional groups is dependent on one of two different electronic effects. The most direct is the induc-

tive polarisation of the carbonyl bond resulting in a higher electron density on the electronegative

oxygen and a reduced electron density on the attached carbon (see Figure 1a). The impact on re-

activity is that the carbonyl carbon is susceptible to attack by nucleophiles.

A second influence on reactivity is observed in carbonyl containing compounds which have at least

one hydrogen atom attached to the -carbon (see Figure 1b). This hydrogen atom may be re-

moved by a suitable base more easily than might be anticipated. This is because of the resonance

stabilisation in the conjugate base where the enolate anion (with the negative charge on electro-

negative oxygen) is a significant contributor to the electronic structure. To put it another way the

carbonyl group increases the acidity of the hydrogen on an -carbon (the acidity being measured

by the pKa scale). Note that the enolate formed is a reactive nucleophile.

O-

+

electrophilicreaction centre

O

HBase

Base

O O

H

enolate anion

Acidic compound: pKaof acetone is 20

Conjugate base - areactive nucleophile

(a) (b)

Figure 1: The influence on reactivity of the carbonyl group

These two different effects on reactivity can both be exploited in carbon-carbon bond forming reac-

tions, a class of reactions that are very important in building complex structures from simple mo-

lecular building blocks. For example, you have seen the addition of organometallic reagents (for

example, Grignard reagents) to ketones to form a new carbon-carbon bond which exploits the re-

activity noted in Figure 1(a). You have also discussed formation of enolates and reaction with

electrophilic alkyl halides which exploits the reactivity noted in Figure 1(b).

The carbon-carbon bond forming reactions that you will be doing today exploit both these reactivi-

ties by taking a carbonyl compound and using a base to generate an equilibrium mixture containing

both the enolate and the starting carbonyl material. Given that the former is a nucleophile and the

latter an electrophile it is not a surprise that they react. This reaction also forms a new carbon-

carbon bond. The simplest form of this reaction is called theAldol reaction(Figure 2).

H3C

O

H

Base

O-

H

H3C

O

H

H

O

CH3

OH

H

O

CH3

-H2O

Figure 2: Aldol Reaction


3/15


2016 CHEM2005 R = Cl 3

A further important class of reactions are conjugate addition reaction involving carbonyl com-

pounds conjugate with, for example, an alkene. Resonance interaction between the two double

bonds renders the -carbon of the alkene more electrophilic that the -carbon. Therefore conju-

gated carbonyl compounds can undergo reaction with nucleophiles at either the carbonyl carbon

(also called 1,2 addition) or the -carbon of the alkene (1,4 addition). Conjugate addition is when

reaction occurs at the latter of these two sites and a common example is called the Michael addi-tionreaction (Figure 3).

O

O

1

2

3

4

1

2

3

4

O OH

Nu

O

Nu

1,2 addition ofNu

1,4 addition ofNu

Figure 3: Conjugate addition the Michael addition reaction

These classes of reactions both pose challenges with regard to chemoselectivity (ensuring that on-

ly one reaction pathway is followed when more than one is possible). For example, with the Aldolreaction what happens when you try the reaction with two different carbonyl containing starting ma-

terials? How is the reactivity of the carbonyl in an ester different from an amide? How can you

control the addition of a nucleophile to a conjugate to ketone to favour 1, 2- or 1, 4-addition? This

experiment will help you understand how to manage some of the issues relating to controlling the

chemoselectivity of the reactions of carbonyl compounds.

The experiment will also require that you refresh your knowledge of conformational analysis in six

membered rings (cyclohexane and its derivatives) as one of your products is a cyclic structure. So,

as mechanism will predict the configuration of the product your application of conformational anal-

ysis will allow you to predict the most likely conformation.

1H NMR analysis will be more sophisticated than in the past as you will use it to differentiate struc-

tural and configurational isomers (those interconverted only by bond breaking and making pro-

cesses) and also conformational isomers (those interconverted by rotation or ring inversions).

Risk assessment and COSHH form

Hazardis the potential to cause harm; riskis the likelihood that the harmfrom the hazardwill be

realised; dangeris the riskof injury. When executing a risk assessment the targets are to become

aware of the risks and to put into place a protocol that minimises the risk of a given experiment in

order to avoid injury.

When assessing a specific experiment all of the following must be taken into account:

Nature of the substances used (reagents, products, solvents) this information can be gathered

from Material Safety Data Sheets (MSDS).

Amounts used in the reaction information taken from the procedure.

Procedures in place at the work place Good Laboratory Practice (GLP) inter aliastates that chemi-

cal work be performed in a well-ventilated fume cupboard, and that a dress code is adhered to.

How a reaction is to be executed.

How waste products are disposed of e.g.chemical and physical waste.

How to handle unplanned events and emergencies, e.g.spillages, decontaminations or fire. How canthe unforeseen be contained?


4/15


4 R = Cl CHEM2005 2016

COSHH stands for Control of Substances Hazardous to Health. A COSHH form takes all the points

listed above into account. Information from MSDS is geared to provide (a) exhaustive details, and

(b) to cater for large amounts. In a research or teaching setting the actual amounts are much

smaller and general protocols are in place targeting typical activities:

E.g. a teaching activity in the level 5 teaching laboratory can take place in a well-ventilated fume

cupboard or on the bench. Fire-fighting equipment available would be water, sand, powder, CO2,

and fire-blankets. There is a dress code and waste disposal provision.

For this practical you are required to produce a COSHH assessment for each reaction by filling the

empty COSHH form BEFORE coming to the lab (a prelab requirement). You will find all relevant

MSDS, a sample assessment and an empty form on BB under this experiments folder. Additional

guidance can be taken from this manual.

Make sure your assessment is relevant to the setting, the amounts used and the services actually

available in the laboratory and used for the assessed reaction. Two forms areto be filled with all de-

tails combined (one per reaction). The COSHH also forms part of this experiments assessment.

Please submit as PDF via Turn-it-in and bring printed copies to the lab. You must sign theseand reference them in your laboratory notebook.The safety tabulation is then obsolete but your

notes must make clear the actual amounts used in the experiment.

Hydrazine hydrate - special safety instructions:

Commonly used as a blowing agent in the formation of expanded polymers, as well as in the pes-

ticide industry, this reagent has been subject to close scrutiny with regard to the hazards associat-

ed with its use. Its specified hazard of possible cause of cancer is associated with the fact that

cancerous cells have been produced in extreme conditions in non-human cells. Whilst in industrial

scale preparations this is a real concern the risks of using hydrazine hydrate are minimal providing

the following guidelines are observed:

o Only use the quantities outlined in the experimental detail.

o Use the reagent in the fume cupboard and wear gloves.

o Rinse all contaminated glassware (in the fume cupboard) with acetone and allow this solu-

tion to stand for 30-60 min before you dispose of it into the chlorinated waste container.

o Immediately inform a member of staff in event of a spillage.

Understanding hazard, minimizing risk

In the table below hazard statements are explicitly given whereas for precautionary statements you

need to consult any of the resources mentioned above. Either in the COSHH assessments or in

your laboratory notebook both, H and P statements must be mentioned together with the planned

amounts of substance (the places in the COSHH form will differ from the typical lab tabulation,

though). This assessment/tabulation must be prepared BEFORE coming to the laboratory class!

All reactions have to be performed in a fume cupboard. Assume that your intermediates and prod-

ucts are toxic.

Acetone

0.7925 g/mL

58.05 g/mol

Highly flammable liquid and vapour. Causes serious eye irrita-

tion. May cause drowsiness or dizziness.

P210, P261,

P305+351+338,

EUH066

AcetonitrileHighly flammable liquid and vapour. Harmful if swallowed, in

contact with skin or if inhaled. Causes serious eye irritation.

P210, P280,

P305+351+338


5/15


2016 CHEM2005 R = Cl 5

Diethyl etherExtremely flammable liquid and vapour. Harmful if swal-

lowed. May cause drowsiness or dizziness.

P210, P261,

EUH019, EUH066

Ethanol Highly flammable liquid and vapour. P210

Ethylene glycol

(1,2-ethanediol)Harmful if swallowed.

Hydrazine mono-

hydrate

1.03 g/mL

50.1 g/mol

Flammable liquid and vapour. Toxic if swallowed. Toxic in

contact with skin. Causes severe skin burns and eye dam-

age. May cause an allergic skin reaction. Toxic if inhaled.

May cause cancer. Very toxic to aquatic life with long last-

ing effects.

P201, P261, P273,

P280, P301+310,

P305+351+338

Ammonia (1M)Causes skin irritation. Causes serious eye damage. Very

toxic to aquatic life.

P273, P280,

P305+351+338

p-Chlorobenzalde-

hyde, 140.6 g/mol

Harmful if swallowed. Causes skin irritation. Causes serious

eye irritation. May cause respiratory irritation.

P261,

P305+351+338

Petroleum ether

Highly flammable liquid and vapour. May be fatal if swal-

lowed and enters airways. Causes skin irritation. May cause

drowsiness or dizziness. Suspected of damaging fertility or

the unborn child. May cause damage to organs through

prolonged or repeated exposure. Toxic to aquatic life with

long lasting effects.

P210, P261, P273,

P281 P301+310,

P331

Potassium hydroxideMay be corrosive to metals. Harmful if swallowed. Causes

severe skin burns and eye damage.

P280, P310,

P305+351+338

Quinuclidin-3-one

(HCl salt)

161.6 g/mol

Causes skin irritation. Causes serious eye irritation. May

cause respiratory irritation.P271, P280

Sodium hydroxide Causes severe skin burns and eye damage.P280, P310,

P305+351+338

Methanol

Toxic if swallowed. Toxic in contact with skin. Toxic if in-

haled. Causes damage to organs.

P210, P260, P280,

P301+310, P311

Dichloromethane

Causes skin irritation. Causes serious eye irritation. May

cause respiratory irritation. May cause drowsiness or dizzi-

ness. Suspected of causing cancer. May cause damage to

organs through prolonged or repeated exposure.

P261, P281,

P305+351+338

Physical hazards involve the handling of sharp items like TLC spotters and needles, UV light and

the heating of the reaction mixture using an oil bath. Take care to dispose of the TLC spotters into

the glass bins and the needles with the tip down into the collection beaker. Needles must be rinsed

and if put back to the oven, then point the tip towards the back. Oil baths and stirrer hotplates must

be returned clean, spillages should be cleaned up once the temperature is down with light pe-

troleum ether. UV light can cause harm, do not look directly at the lamp and protect your eyes.


6/15

Year 2

6

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7/15


2016 CHEM2005 R = Cl 7

i.e. a slow distribution of one reagent in a reaction mixture could allow competing reactions to de-

termine the outcome of a reaction. Pearl grade exhibits a high surface to volume ratio due to

smaller particle size. As a consequence it dissolves faster, e.g. in water (NaOH is hygroscopic!).

To a stirred solution of 3-quinuclidinone.HCl (20 mmol) in ANALAR*ethanol (30 mL) was added

the specified aromatic aldehyde ** (34 mmol) followed by PEARL*** sodium hydroxide (1.12 g).The reaction mixture was placed in a stirred oil bath (such that the level of the reaction mixture was

slightly above the level of the oil) and then the oil bath was carefullywarmed to 60-65 C and the

reaction stirred at this temperature (it is essential that the oil bath does not go above the tempera-

ture range specified and that you monitor it with a temperature sensor).

The reaction was monitored by TLC (see note 1) (40 % diethyl ether in light petroleum ether) from

30 minutes onwards, until complete consumption of starting material had occurred. When all the

quinuclidinone starting material had been consumed (around 60 minutes) the reaction was allowed

to cool before pouring into water (100 mL) and stirring vigorously until a solid formed. The crude

product was collected by filtration. Purification was accomplished by crystallisation from the mini-

mum quantity of hot ethanol (with the addition of water if necessary). The crystals were collectedby filtration, dried in a vacuum desiccator, and weighed. The yield was calculated, the melting

point determined and the mass spec acquired.

Note 1: You will need to check the reaction mixture against both starting materials although you

should be expecting one of them to be present even at the end of the reaction. A sample of the

quinuclidinone starting material will be prepared for you as its concentration is critical if you are to

have any chance of detecting it (if you look at the structure of the compound you should under-

stand that the starting quinuclidinone will be difficult to visualise with either UV or KMnO4).

Spectroscopic dataprovided:13

C NMR, IR

Data to be collected: mp, ES-MS see below; check with a teaching assistant for help and before

submission of sample vial together with a technician

Electrospray sample preparation and submission

The preparation of samples for mass spectrometry is explained on a laminate in the laboratory and

you should seek the support from a teaching assistant or technician.

Prepapration: Accurately weigh the prescribed amount into a TLC vial and dissolve in ace-

tonitrile from the dispenser take care not to contaminate the spout! This sample must be

diluted further following the laminated instructions. It is important to have the correct di-

lution for the success of the analysis run.

Submission to mass spec system: Finally, submit in a mass spec sample vial ( full, blue

screw-cap lid) labelled with a vertical barcode sticker and carrying your name and sample

ID for ESI positiveanalysis.Take care to write legibly and submit to the correct instru-

ment: under the published login to B ESIPOS LC-MS C18 acid.

Cleaning: Dispose of the dilution solutions, vials and pipettes into the chlorinated waste and

glass bin, respectively, and keep the sample preparation area clean and tidy.

Submission to instrument: Ask a technician to accompany you as a single group of all

pyrazole students to the mass spectrometry room.

The ES+samples will run automatically once they have been submitted (ca. 5 min per sample) but

it will take some time before all samples have finished depending on the number of samples in thequeue. You can then analyse the data using the PC in the laboratory following the procedure in the


8/15

Year 2

8

yellow fol

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as filtered

e material

dissolu-

antity of

ing point

d.

isible

ith acetone

ous filtrate

f acetone

n dispose

he reac-

, and then

s for reac-

LC mix of

made for

upboard.

on each

crystallisa-

s of isolat-

.


9/15


2016 CHEM2005 R = Cl 9

N

Ha

HcHb

O

Clean-up and tidying

Collect all used TLC spotters and TLC plates from the fume cupboard, benchesand the floor, and

dispose of these into the yellow glass waste bin (spotters) or red capped TLC waste bin(plates).

Empty the traps of the rotary evaporator and the vacuum pump. Switch both off at the end of day.

Ensure that solvent used for the decontamination of hydrazine is emptied into the chlorinated solventwaste bottle and all glassware is rinsed carefully. Glassware contaminated with hydrazine and hy-

drazine-decontamination mixtures left behind are totally unacceptable. The pyrazole practical group

is responsible as a whole for ensuring that safety procedures are strictly adhered to. This will feed in-

to the practical assessment at the end of the lab-day.

Dry and solvent-free MgSO4can be dissolved in water and rinsed through the sink in a fume cup-

board. Dry filter paper can be disposed of into the bin under the sink.

Ensure that the balance area is clean, that all containers and solvent waste bottles are closed and

chemicals returned to the distribution tray.

Check the MS sample preparation area and ensure that all glass vials, lids and pipette tips are cor-rectly disposed of.

Check that your bench, fume cupboard and your own tray contents are clean and complete before

asking a teaching assistant to inspect it against the laminated checklist.

The communal nature of the glassware and equipment provision in this practical means that ALL students of

this practical group are equally responsible for a complete and clean set of lockers. This is reflected in the

assessment of this aspect: the grades of ALL students in this practical will be affected equally if one locker is

not complete or contains dirty items. Please ensure you work as an effective team!

Analysis and questions

Your quiz and work in the laboratory:Key elements are the safety assessment; quality of sample;

maintaining the working environment and finishing on time.

In the lab notebook:

Reference the COSHH assessments include a copy of each.

Specific equations must be included for each step.

Tabulate the quantities you used (weight and/or volumes) and the molar quantity for each substance.

Describe what youdid experimentally and include any observations you make.

Reference spectra that you acquire and submit for acquisition.

Your practical results and laboratory report: Your laboratory three key elements (i) a very short

summary of your results; (ii) your analytical results which will all spectroscopic data (you must

submit your own spectra); (iii) your answers to the mechanistic and analytical questionsbelow. Di-

agnostic peaks in the spectra (acquired or provided) should be recorded and analysed in your re-

port (tabulate all spectroscopic data!).

Your laboratory report: Compound A

1. For compoundA: Depict its structure, %-yield, mp

2. Estimate the pKavalues of the threeprotons (a, b, & c) highlighted in the start-

ing quinuclidinone hydrochloride. Briefly explain the basis of your estimates and

describe in detail (with appropriate structures) whyproton ais very much less

acidic thanproton b.


10/15


10 R = Cl CHEM2005 2016

3. Given that the reaction to make compound A is an example of an aldol reaction provide a detailed

mechanism for its formation.

The mechanism should propose which of the steps involved are reversible; show all by-products that

are formed at each step; be considerate that all the proposed intermediates are consistent with the

reaction conditions employed.

4. Tabulate the data and interpret the IR spectrum of compound A.

Briefly describe how the data supports your proposed structure.

5. Include the electrospray mass spectrum (ESI+) of your compound Aand record the data in the ap-

propriate format. Interpret your mass spectrometry data and briefly describe how the data supports

your proposed structure.

6. Analyse the provided13

C-NMR data for compound A, tabulate the data (BB decoupled and DEPT)

and interpret the spectrum referring to an appropriately labelled structure and allocating each peak to

the carbon atom(s) giving rise to it.

Your laboratory report: Compound B

7. For compoundB: Depict its structure, %-yield, mp

8. Using the following information depict a reasonable mechanism for the formation of compound B.

You need to demonstrate in your mechanism how each of the items of information provided below

was used to assemble your mechanistic proposal.

R

NNH

NH

A disubstitutedbenzene ring

A substitutedpyrazole heterocycle

A substitutedpiperidine ring

a. Compound B contains the functional groups shown above;

b. The first step of the mechanism is the Michael addition of hydrazine to compound A;

c. The second step is an intramolecular hydrazone formation (a tricyclic intermediate);

d. The tricyclic intermediate undergoes a ring opening and aromatisation process to give com-

pound B;

e. The polar protic solvent and the high temperature of the reaction are consistent with the im-

portance of charged intermediates and the need to overcome a significant activation energy

respectively;

f. pKa values for water (15.7); a secondary amine (ca 35); a secondary ammonium salt (ca 10);

a benzylic C-H (ca 45) will help you when considering the mechanism.

9. Include the IR spectrum of your compound B, tabulate the data and interpret the spectrum.

Briefly describe how the data supports your proposed structure and describe the significance of the

key differences with the IR spectrum for compound A.

10. Analyse the provided13

C-NMR data for compound B, tabulate the data and interpret the spectra.

Tabulate the data.13

C NMR (including DEPT) should assign each signal to a specific carbon atom

(or set of chemically equivalent C atoms) in compound B. Could you point out the difference with

the 13C NMR of compound A, and correlate with the actual reaction?


11/15


2016 CHEM2005 R = Cl 11

11. Analyse the provided1H NMR spectrum for compound B, tabulate the data and interpret the spec-

trum. Your answer must show which of the two conformations (see figure) is inferred by your analy-

sis (PYR indicates the substituted pyrazole).

Be aware that for this compound the2J (geminal) coupling constants have the same magnitude as

the3J ax-ax values (both around 12-13 Hz) and that some of the

3J ax-eq and

3J eq-eq coupling

constants are not fully resolved. Assign each signal to a proton in compound A which should be

identified unambiguously in a structure with each inequivalent proton(s) labelled. You must be clear

how you explain the regiochemical and conformational characteristics of compound B.

Assessment

You must complete and submit COSHH assessments before coming to the lab class and a prelab

quiz by midnight before the lab class (both summatively assessed). Your time management will be

assessed indirectly.

Practical

COSHH assessments ........................................................................... 60%

Equipment & workplace cleanliness ...................................................... 20%

Experimental results (sample) ............................................................... 20%

Report

Experimental results (quality, quantity) ................................................. 20%

Experimental results (quality, analysis, presentation) ........................... 20%

Mechanisms & pKa................................................................................ 30%

NMR ...................................................................................................... 30%

Submission, deadlines and feedback

Any individual or group discussion, verbal advice and support, as well as answers to your ques-tions given to you during the lab class is a form of feedback. Although often not recognised as such

this formative feedbackis most valuable to your learning! During the laboratory class this feed-

back on performance is provided on an ongoing basis.

Lab notebooks will be assessed until 18:00 and additional feedback provided at that point. The la-

boratory will shut at 18:00 and you must ensure to finish experimental work and cleaning in good

time to allow for your trays assessment well before 18:00.

Using a glass vial with a screw-top and white sticky labels, submit clearly labelled samples into the

container provided. The label must mention the experiment title, describe the contents of the vial

(state name or structure of the isolated compound) and include your name. Please write legibly.The report must be composed electronically (text, schemes and structures bar mechanisms) and

where applicable chemistry artwork, graphs, acquired spectra or similar must be included in im-


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12 R = Cl CHEM2005 2016

maculate and clearly labelled form. Submit the report as a single PDF filevia Turnitin before 23:59

two days before your next undergraduate practical (Tuesday 23:59 for Thursday groups, Wednes-

day 23:59 for Friday groups). An early submission is strongly encouraged!

IMPORTANT: The due date listed on Turnitin is NOT the report submission deadline date. Late

submission of reports will result in a reduction of marks commensurate with lateness and reports

submitted more than five working days late will not be accepted (i.e.will receive a mark of zero).

Feedback on your report will be available online via Turnitin and will appear within ten working

days directly on your submitted report (provided it was submitted on time), together with an indica-

tion in which grade-bracket the report falls.

Appendix

IR (ATR) of product A


13/15


2016 CHEM2005 R = Cl 13

13C NMR (100 MHz, CDCl3) of product A

DEPT-135 (100 MHz, CDCl3) of product A

Pyrazole experiment starting from 4-chlorobenzaldehyde: Product A, 13C-NMR, 100 MHz, CDCl3

Cl-A_002000fid

200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24Chemical Shift (ppm)

25.

78

40.

18

47.

39

123.

64

128.

63

132.

41

133.

28

135.

38

145.

02

206.

01

No. (ppm) (Hz) Height

1 25.78 2594.2 0.9582

2 40.18 4043.3 0.4778

3 47.39 4768.3 1.0000

4 1 23 .6 4 1 24 41 .5 0 .4 708

5 1 28 .6 3 1 29 42 .9 0 .8 921

6 1 32 .4 1 1 33 23 .9 0 .1 649

7 1 33 .2 8 1 34 11 .4 0 .9 648

8 1 35 .3 8 1 36 22 .3 0 .1 334

9 1 45 .0 2 1 45 92 .3 0 .1 416

1 0 2 06 .0 1 2 07 29 .8 0 .1 508

Cl-A_003000fid.esp

208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24

Chemical Shift (ppm)

25.

78

40.

18

47.

39

123.

64

128.

62

133.

28

Pyrazole experiment starting from 4-chlorobenzaldehyde: Product A, DEPT-135, 100 MHz, CDCl3


14/15


14 R = Cl CHEM2005 2016

13C NMR (100 MHz, CDCl3) of product B

DEPT-135 (100 MHz, CDCl3) of product B

Cl-B_002000fid.esp

155 150 145 140 135 130 125 120 115 110 105 100 95 90 85 80 75 70 65 60 55 50 45 40 35 30Chemical Shift (ppm)

32.9

4

34.4

6

46.4

1

99.5

6

126.

85

128.

83

131.

31

133.

52

149.

17

151.

54


1 32.94 3314.4 0.3664

2 34.46 3467.9 0.1681

3 46.41 4670.2 0.3777

4 99. 56 10018. 5 0. 1733

5 1 26 .8 5 1 276 4. 1 0. 38 57

6 1 28 .8 3 1 296 3. 4 0. 40 88

7 1 31 .3 1 1 321 3. 1 0. 06 05

8 1 33 .5 2 1 343 5. 7 0. 06 76

9 1 49 .1 7 1 501 0. 2 0. 03 53

1 0 1 51 .5 4 1 524 9. 3 0. 03 89

Pyrazole experiment starting from 4-chlorobenzaldehyde: Product B, 13C-NMR, 100 MHz, CDCl3

Cl-B_003000fid.esp

160 155 150 145 140 135 130 125 120 115 110 105 100 95 90 85 80 75 70 65 60 55 50 45 40 35 30 25Chemical Shift (ppm)

32.

94

34.

48

46.

42

99.

57

126.

86

128.

84

Pyrazole experiment starting from 4-chlorobenzaldehyde: Product B, DEPT-135, 100 MHz, CDCl3


15/15


2016 CHEM2005 R = Cl 15

1H NMR (400 MHz, CDCl3) of product B(NH peaks are not assigned)

1H NMR (400 MHz, CDCl3) of product B- expansions

Cl-B_001000fid.esp

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0


22212122

680.

13

689.

16

692.

93

701.

21

780.

51

782.

52

793.

06

794.

82

1079.

92

1082.

43

1092.

21

1094.

47

1104.

26

1106.

77

1126.

09

1265.

38

1268.

14

1271.

15

1277.

43

1280.

44

1283.

45

2540.

29

2938.

83

2947.

11

3064.

31

3072.

59


1 1.66 664.1 0.0660

2 1.67 668.1 0.0710

3 1.69 676.6 0.1837

4 1.70 680.1 0.1981

5 1.72 689.2 0.2269

6 1.73 692.9 0.2150

7 1.75 701.2 0.09618 1.76 705.0 0.0946

9 1.95 780.5 0.2324

10 1.96 782.5 0.2401

11 1.98 793.1 0.1824

12 1.99 794.8 0.1801

13 2.70 1079.9 0.1658

14 2.71 1082.4 0.1852

15 2.73 1092.2 0.3585

16 2.74 1094.5 0.3543

17 2.76 1104.3 0.1961

18 2.77 1106.8 0.1784

19 2.77 1110.3 0.0505

20 2.78 1114.3 0.0927

21 2.79 1118.3 0.0511

22 2.80 1122.3 0.0918

23 2.81 1126.1 0.1733

24 2.82 1130.1 0.0883

25 2.83 1134.1 0.0447

26 2.84 1138.1 0.0793

27 2.85 1141.9 0.0371

28 3.16 1265.4 0.1670

29 3.17 1268.1 0.287130 3.18 1271.2 0.1829

31 3.19 1277.4 0.1582

32 3.20 1280.4 0.2494

33 3.21 1283.5 0.1436

34 6.35 2540.3 1.0000

35 7.34 2938.8 0.7167

36 7.37 2947.1 0.8177

37 7.66 3064.3 0.8062

38 7.68 3072.6 0.6961

Pyrazole experiment starting from 4-chlorobenzaldehyde: Product B, 1H-NMR, 400 MHz, CDCl3

Cl-B_001000fid.esp

3.2 3.1 3.0 2.9 2.8 2.7 2.6 2.5 2.4 2.3 2.2 2.1 2.0 1.9 1.8 1.7


22212

664.0

6

668.0

8

676.6

1

680.1

3

689.1

6

692.9

3

701.2

1

704.9

7

780.5

1

782.5

2

793.0

6

794.8

2

1079.

92

1082.

43

1092.

21

1094.

47

1104.

26

1106.

77

1110.

28

1114.

30

1118.

31

1122.

33

1126.

09

1130.

11

1134.

13

1138.

14

1141.

91

1265.

38

1268.

14

1271.

15

1277.

43

1280.

44

1283.

45

Pyrazole experiment starting from 4-chlorobenzaldehyde: Product B, Expansion of 1H-NMR, 400 MHz, CDCl3

Documents

CHEM2005 Pyrazole Heterocycle 2016(1)