Basic Guidelines for Microwave Reactor and Reactions

Basic Guidelines for

Microwave Organic Chemistry Applications

By Laura Favretto Microwave Organic Chemistry

Application Specialist

MicroSYNTH START

Basic Guidelines for Microwave Organic Chemistry Applications

Rev. 0/04 Milestone Srl

UNI EN ISO 9001:2000 Vision certified

Basic Guidelines for Microwave Organic Chemistry Application

Basic Guidelines for Microwave Organic Chemistry Application Rev. 0/04 Milestone Srl

Page 1

INDEX

1. Introduction Page 2 2. How to convert a conventional reaction

into a microwave reaction Solvent Page 3 Temperature-Time Page 3 Vessel Page 4 Microwave program Page 5 Stirring Page 6

3. When and how to use Weflon Page 6 4. How to regulate microwave power Page 7 5. How to optimize the microwave program Page 8

6. How to optimize the reaction condition Page 9

7. How to use the rotor Page 9

8. When it is possible to open the reactor Page 10

9. What to do when an exothermic is present Page 10

10. Is it possible to use microwave at constant

power Page 11

11. How to perform solid state reaction Page 11

12. How to work with metal powder (heterogeneous solution) Page 13

13. Maximum heating time Page 13

14. Which chemistry is not suitable for microwave Page 14

15. Solvent Library Solvent List Page 15 Solvent Graphics Page 28



Page 2

1. INTRODUCTION The main advantages of microwave assisted organic synthesis are: a) Faster reaction: the microwave can use higher temperatures than conventional heating system, and consequently the reactions are completed in few minutes instead of hours. b) Better yield and higher purity: less formation of side product are observed using microwave irradiation, and the product is recovered in higher yield. Consequently, also the purification step is faster and easier. c) Easy scale-up: MicroSYNTH, with its technology and large range of reactor vessels, allows scale-up from few milliliters to one liter without changing reaction parameters. d) Reproducibility: the patented microwave diffuser for homogeneous microwave irradiation inside the cavity and precise control of reaction parameters, such as temperature, pressure and power, always re-produces the same reaction conditions. It is very simple to save and use an optimized synthesis method. e) Easy to use: all the reactors and software are very easy to use and all reactions can be easily moved from conventional to microwave heating.



Page 3

2. HOW TO CONVERT A CONVENTIONAL REACTION INTO A

MICROWAVE REACTION When the reaction is performed the first time under microwave irradiation, run the reaction in small scale, slowly increasing the temperature. The parameters that are needed to be defined are: - solvent - temperature-time - vessel - microwave program Solvent The same solvent that is usually used with conventional heating chemistry can also be used with microwave heating. Solvents interact differently with microwaves, depending on their polarity. Polar solvents (alcohols, DMF, water, ketone, acid) couple well with microwaves and reach high temperatures in a short time. Non-polar solvents (toluene, chloroform, hexane) are transparent to microwaves. Therefore, two situations are possible:

1) non polar solvent, but polar reagents or at least one polar reagent: the reaction mixture is heated by microwave.

2) non polar reaction mixture (both solvent and reagents). (Weflon has to be added in order to heat the mixture. For more information, see chapter 3 When and how to use Weflon).

Temperature-Time a) If the reaction has already been performed with conventional heating, take in consideration the standard reaction temperature and time. Based on these two parameters, consider the Arrhenius equation, e.g. how the time decreases when the temperature increases. This law defines that every ten degrees that the temperature increases, the time of the reaction is halved.



Page 4

For example, if a reaction is run in EtOH at 80C for 8 hours and the Arrhenius law is applied, the time is reduced in accordance to the table below:

Temperature(C)

Time

80 8 h 90 4 h

100 2 h 110 60 min120 30 min130 15 min140 8 min150 4 min

By increasing the temperature of 70C, the time is reduced from 8 hours (480 minutes) to 4 minutes. This simple procedure can be applied to all the reactions. b) If the reaction has never been performed before with conventional or microwave heating, fix the temperature at 30-40C higher than the boiling point of the solvent, and run the reaction for 10 minutes. Then check the obtained reaction mixture. Vessel All reactors that work with the MicroSYNTH have different:

a) volume limit b) temperature limit c) pressure limit

When the target temperature is fixed, consult the solvent library in chapter 15 (also present in the EasyWAVE software). Check which vapor pressure is developed from the solvent at the chosen temperature. Based on this value, and on the volume that is needed, decide the appropriate reactor vessel.



Page 5

Example: The target temperature of the reaction is 150C in EtOH. Based on the solvent library and on the graphic temperature vs. pressure (see graphic below), it is possible to predict that a pressure of 10 bar will be developed during the reaction.

If the reaction is completely unknown, and there is possible exothermic reaction or development of gas during the test, use the vessel with the highest specification of temperature and pressure (for example the 100 ml High Pressure reactor (Tmax = 250C, pmax = 55 bar)). Microwave program The microwave program usually consists of two steps: The first step is the ramp to reach the target temperature. The second step is to keep the temperature for the desired reaction time. The second step is always the same for all sample amounts. In any case, a maximum total program time of 1 hour is advised. The first step must be regulated on the base of:

- sample amount - characteristics of solvent



Page 6

- Polar mixture:

- small amount (up to 30 mL): the increasing of the temperature can be fixed in the rate 25C/min.

For example a suitable ramp for 15 mL of DMF could be

Time (min)

Power (Watt)

Temperature (C)

Step1 6 500 room temp to190

- large amount (more than 30 mL): the first step needs to be longer. In this case, its advised an increase of 10C/min

- Non polar mixture: see the below When and how to use Weflon . Stirring Always put a stir bar in every reactor/vessel when a reaction is run. This enhances temperature, and therefore, reaction uniformity. 3) WHEN AND HOW TO USE WEFLON When the reaction mixture (reagents and solvent) are not polar, the Weflon is necessary in order to heat the solution. When Weflon is used, its necessary to use low value of microwave power and long heating ramp. This is necessary as there is a time lapse due to the transfer of heat from the Weflon to the solution. In this case, its advised to build the ramp with 4 steps: ramp up to the boiling point of the solvent with a rate of 15C/min and keep the temperature for 1-2 minutes; ramp up to the fixed temperature with a rate of 5C/min and keep the temperature for the desired time. The maximum power value to use is 500 Watt. If Weflon is used in one vessel, then it should be used in every vessel when processing multiple reactions simultaneously.



Page 7

An example of Toluene heating ramp with Weflon is reported below: MonoPREP P/N MOP0000, 20 mL of toluene in P/N QRS1550, stirring bar P/N 86116 and Weflon button P/N WO1703:

Time (min)

Power (Watt)

Temperature (C)

Step1 5 500 110 Step2 2 400 110 Step3 15 500 160 Step4 5 500 160

Below is the temperature profile of 20 mL of Toluene

Toluene,20 mL, 160C

T1 Set Values Power Temp. 1 Temp. 2

Time [hh:mm:ss]00:35:0000:30:0000:25:0000:20:0000:15:0000:10:0000:05:00

Tem

pera

ture

[C

]

200

150

100

50

0

Pow

er [W

att]

1,000

900

800

700

600

500

400

300

200

100

0

20

[1] 110 [2] 110

[3] 160 [4] 160

If the temperature is not following the temperature profile, change the time using longer ramp, but do not increase the power. 4) HOW TO REGULATE THE MICROWAVE POWER The value of the maximum microwave power depends on the amount of sample and of the number of reaction vessel. Up to 30 mL of volume and/or up to three vessels, 400-500 Watt of microwave power is enough to heat the reaction mixture. If the temperature is not following the designed temperature profile, use longer heating time (step n. 1), but do not increase the power.



Page 8

For example: MonoPREP with 15 mL of water:

Time (min)

Power (Watt)

Temperature (C)

Step1 3 400 150 Step2 5 300 150

When large volume or more than three reactors are used with the rotor, its better to use an higher value of power (about 700-800 watt) and longer heating ramp. For example: PRO-6 with 15 mL of water in each vessel, use the following heating program:

Time (min)

Power (Watt)

Temperature (C)

Step1 10 800 150 Step2 5 700 150

PRO-24 with 10 ml of isopropanol in each vessel, use the following heating program:

Time (min)

Power (Watt)

Temperature (C)

Step1 16 1000 150 Step2 10 800 150

5) HOW TO OPTIMIZE A MICROWAVE PROGRAM

1) if the temperature doesnt follow the designed profile, make the ramp longer and/or increase the power.

2) if during the heating ramp the temperature overshoots, reduce

the value of microwave power of about 100-150 Watt.



Page 9

In any case, remember that at high temperatures the solvents change their behavior. In general, their polarity decreases and they require more power to reach the desired temperature. For this reason, temperature spikes may be present at the beginning, but decrease or disappear at higher temperatures.

6) HOW TO OPTIMIZE THE REACTION CONDITIONS After the first run of the reactions, there could be four different cases:

1) the reaction is complete (the starting material is not present any more): transfer the mixture in a proper glassware and proceed with the usual work-up of the reaction

2) the reaction starts to work but is not complete (some starting material is still present):

- extend the reaction time - increase the temperature (not over the temperature and

pressure limit of the vessel) 3) the reaction doesnt work at all: - extend the time - increase the temperature

- use more equivalent of one of the starting material or of the catalyst

4) decomposition of the reagents: - use lower temperature - use short reaction time

Note: always remember to check the temperature and pressure limit of the vessel before increasing the temperature.

7) HOW TO USE THE ROTOR When a rotor is utilized (with multiple vessels), it is necessary to use

- the same solvent in all the vessels - similar chemistry, i.e. same reaction, changing only one

substituent of one reagent at time Temperature and pressure are measured in one vessel, called reference vessel. This ensures the same conditions of temperature and pressure in all the vessels of the rotor.



Page 10

For example, if the Heck reaction is considered:

Br

R

+ MeOOCPd(OAc)2, PPh3

DMF

RCOOMe

Heck reaction

R = - OMe - NO2 - Cl - H - CHO The nature of the group R- in the aryl bromide compound could be changed in each vessel in order to verify how the R- substituent influences the coupling reaction. If the catalyst varies from vessel to vessel, use the high concentration of catalyst in the reference vessel. In fact, the higher concentration of catalyst is usually the most reactive one, and needs to be controlled. The rotor can be used also to perform the same reaction in all the vessels. 8) WHEN IT IS POSSIBLE TO OPEN THE REACTOR Before opening the vessel, its always better to wait at least until the temperature is 10C below the boiling point of the solvent to be sure there isnt any pressure inside the vessel. It is recommended to open the reactor slowly under a fume hood. 9) WHAT TO DO WHEN AN EXOTHERMY IS PRESENT If a very fast increase of temperature is noticed during the ramp-step of the reaction (80-100C/min), immediately stop the microwave program. Probably one reagent is highly reactive and the efficient microwave heating creates a large exothermic effect in the reaction. For example, a big exothermic effect (100C in less than minute) has been observed in the alkylation of a primary ammine. No problem is observed with secondary or tertiary ammine.



Page 11

Also, the presence of a salt in a solution (for example salt plus water) has shown a large reactivity with microwave. In this case, it is better to use: - a small amount of salt (to have a small ionic conduction effect) - a small quantity of power - long heating ramp. 10) IS IT POSSIBLE TO USE MICROWAVE AT CONSTANT POWER A microwave program at constant power can be used, but only with an open system. In this case the maximum temperature that can be reached is the boiling point of the solvent. The two parameters that need to be fixed are: time and power. Constant power is not recommended in closed vessels because the temperature can rise without limit, and the vessels can be damaged. 11) HOW TO PERFORM SOLID STATE REACTION In the case of solid state reaction, two situations can be considered:

a) reagent absorption on solid support (as silice or alumina) b) reaction between neat reagent (liquid-liquid, liquid-solid) a) reagents absorption on solid support: in this case a very efficient

stirring is needed. Magnetic stirring is not enough, and mechanical stirring is required in order to have an homogeneous heating of the solid and to be sure that no hot spots are present in the mixture. In this case, a specific modification of the labstation is required to have a more efficient stirring

b) reaction between neat reagents: here, three cases can be distinguished:

- the two reagents are liquid: proceed as standard reaction with

solvent

For example, the synthesis of the ionic liquid 1-Butyl-3-methylimidazolium chloride is run between neat reagents under microwave irradiation. Both reagents, the butyl chloride (bp = 77C) and the 1- methylimidazole (bp = 198C), are liquid at room temperature.



Page 12

NNMe + NNMeBu

+BuCl

Cl- Synthesis of 1-butyl-3-methylimidazolium chloride

- one reagent is liquid (in large quantity as a solvent), one is solid: presence of heterogeneous mixture, use a good magnetic stirring and proceed as a standard reaction in an open or closed system

For example, in the hydrolysis of benzamide, one reagent (benzamide) is solid, the other one, the 20% sulfuric acid, is a liquid present in large quantity (ratio benzamide/sulfuric acid: 100 mg benzamide/ml sulfuric acid)

NH2

O20% H2SO4 OH

O

Hydrolysis of benzamide

- the two reagents are solid: two cases can be considered:

the two solid reagents are melted during the heating: if the quantity is small (up to 5-10 grams), the reaction can be run with standard magnetic stirring. if quantity is large, a specific stirring system is required (see chapter 11, point a). For example, in the synthesis of 4,5-diphenyl-4-imidazolin-2-one,

OH

+NH2

NH2O N

N O

O

Condensation of benzoine and urea



Page 13

the two reagents (benzoin and urea) have a melting

point of 130C. The reaction is usually performed at 150C. At this temperature both the reagents are liquid and the reaction can be run under standard conditions.

- the two solid reagents remain solid during the reaction:

specific stirring system is required (see chapter 11, point a) 12) HOW TO WORK WITH METAL POWDER (HETEROGENEOUS

SOLUTION) Metal powders in the reaction mixture can create a spark and source of ignition that it is possible to prevent in a solvent environment. In order to reduce the risk of exothermic reaction, it is recommended:

- That the metal powders always be completely submerged in the solvent and that the vessel be purged with inert gas (Nitrogen, Argon) before closing.

- Good stirring of the mixture is needed to ensure a homogeneous distribution of the powders.

- Use the minimum amount of catalyst. - Make sure when using the 100 mL/ 270 mL/ or PRO 16/24 TFM

reactors, that all the reaction solids (catalyst, etc.) are rinsed down into the solvent pool and do not adhere to the sides of the vessel. Catalyst sticking to the side of the vessel wall can absorb microwave energy excessively, resulting in vessel melt down.

- Never use metal without solvent. 13) MAXIMUM HEATING TIME To avoid overheating the reactor, the maximum heating time for a reaction is one hour. If a longer reaction time is needed, repeat the same program more times for one hour.



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14) WHICH CHEMISTRY IS NOT SUITABLE FOR MICROWAVE

Reactions that are extremely exothermic should not be performed in the instrument. Hydrogen peroxide is, for example, not suitable to use at high temperature, regardless of the technique, because it is explosive. When working with reaction mixtures that contain large amounts of ions or that can release gases, extra precaution is advisable since the heating rate might be very high and the pressure increase may be correspondingly quick due to the closed vessel system. In this case, the experiment can be performed at low concentration (very diluted solution). Ionic liquids are often used as an alternative for organic solvent or as a co-solvent for microwave transparent (non polar) reaction mixtures. Ionic liquids are environmentally friendly, recyclable alternatives to dipolar solvents. Their dielectric properties make then highly suitable for use as solvents or additives as they absorb microwaves efficiently. Consequently, their heating rate is very high and the temperature rises very quickly. Therefore, to avoid an exothermic reaction, it is recommended to use a small amount of the ionic liquid. The recommended ratio is 0.2 mmol of ionic liquid/ 2 ml of solvent. Example: 1-butyl-3-methylimidazolium hexafluorophosphate:

NNMeBu

+PF6

-

PM = 284.2 and density 1.37 g/ml 0.2 mmol correspond to 56 mg of reagent and in term of volume is 41 l, or 0.04 ml. The ratio solvent: ionic liquid is: 2:0.04 = 50. The amount of ionic liquid needed to heat up the solvent is very small but sufficient and ensures safety when working with them.


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Basic Guidelines for Microwave Organic Chemistry Application Rev. 0/04 April 2004 Milestone Srl

LIST OF THE COMMON SOLVENTS USED Solvent Name Boiling Point [C] dH evap [KJ/mol]

(+)-Camphor 207,4 59,5

(Trifluoromethyl)benzene 102,1 32,6

1,1,2,2-Tetrabromoethane 243,5 48,7

1,1,2,2-Tetrachloro-1,2-d 92,8 35

1,1,2-Trichloroethane 113,8 34,8

1,1,2-Trichlorofluoroetha 47,7 27

1,1-Dichloroethane 57,4 28,9

1,1-Dichloroethylene 31,6 26,1

1,1-Difluoroethane -24,9 21,6

1,2,3,4-Tetrahydronaphtha 207,6 43,9

1,2,3-Trichloropropane 157 37,1

1,2-Dibromoethane 131,6 34,8

1,2-Dibromopropane 141,9 35,6

1,2-Dibromotetrafluoroeth 47,3 27

1,2-Dichloroethane 83,5 32

1,2-Dichlorotetrafluoroet 3,8 23,3

1,2-Epoxybutane 63,3 30,3

1,2-Propanediol 187,6 52,4

1,3-Butanediol 207,5 58,5

1,3-Propanediol 214,4 57,9

1,4-Dioxane 101,5 34,2

1,5-Pentanediol 239 60,7

1-Bromobutane 101,6 32,5

1-Bromonaphthalene 281 39,3

1-Bromopentane 129,8 35

1-Bromopropane 71,1 29,8


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Solvent Name Boiling Point [C] dH evap [KJ/mol]

1-Butanethiol 98,5 32,2

1-Butanol 117,7 43,3

1-Chloro-2-methylpropane 68,5 29,2

1-Chloro-3-methylbutane 98,9 32

1-Chlorobutane 78,6 30,4

1-Chloronaphthalene 259 52,1

1-Chloropentane 107,8 33,2

1-Chloropropane 46,5 27,2

1-Decene 170,5 38,7

1-Dodecene 213,8 44

1-Hexanol 157,6 44,5

1-Hexene 63,4 28,3

1-Iodo-2-methylpropane 121,1 33,5

1-Iodobutane 130,6 34,7

1-Iodopropane 102,6 32,1

1-Methylcyclohexanol 155 79

1-Methylnaphthalene 244,7 45,5

1-Nitropropane 131,1 38,5

1-Octanol 195,1 46,9

1-Octene 121,2 34,1

1-Pentanol 137,9 44,4

1-Pentene 29,2 25,2

1-Propanol 97,2 41,4

2,2,3-Trimethylbutane 80,8 28,9

2,2,3-Trimethylpentane 110 31,9

2,2,4,4-Tetramethylpentan 122,2 32,5

2,2,4-Trimethylpentane 99,2 30,8

2,2,5-Trimethylhexane 124 33,7


Page 17



2,2-Dimethylbutane 49,7 26,3

2,2-Dimethylhexane 106,8 32,1

2,2-Dimethylpentane 79,2 29,2

2,3,3-Trimethylpentane 114,8 32,1

2,3,5-Trimethylhexane 131,4 34,4

2,3-Dimethylbutane 57,9 27,4


2,4,6-Trimethylpyridine 170,6 39,9


2,4-Lutidine 158,5 38,5

2,4-Xylenol 210,9 47,1

2,5-Xylenol 211,1 46,9

2,6-Lutidine 144,1 37,5

2,6-Xylenol 201 44,5

2-Bromo-2-methylpropane 73,3 29,2

2-Bromobutane 91,2 30,8

2-Bromopropane 59,5 28,3

2-Butanol 99,5 40,8

2-Chloro-2-methylpropane 50,9 27,6

2-Chlorobutane 68,2 29,2

2-Chloropropane 35,7 26,3

2-Ethyl-1-butanol 147 43,2

2-Ethyl-1-hexanol 184,6 54,2

2-Ethylhexyl acetate 199 43,5

2-Ethylhexylamine 169,2 40

2-Hexanol 140 41

2-Iodobutane 120 33,3

2-Iodopropane 89,5 30,7


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2-Methyl-1-butanol 128 45,2

2-Methyl-1-pentanol 149 50,2

2-Methyl-1-propanol 107,8 41,8

2-Methyl-2-butanol 102,4 39

2-Methyl-2-pentanol 121,1 39,6

2-Methyl-2-propanol 82,4 39,1

2-Methylheptane 117,6 33,3

2-Methylhexane 90 30,6

2-Methylpentane 60,2 27,8

2-Methylpropanenitrile 103,9 32,4

2-Methylthiophene 12,6 33,9

2-Nitropropane 120,2 36,8

2-Octanol 180 44,4

2-Pentanol 119,3 41,4

2-Picoline 129,3 36,2

2-Propanol 82,3 39,9

3,3-Diethylpentane 146,3 34,6


3,3-Dimethylpentane 86 29,6


3,4-Xylenol 227 49,7

3,5-Xylenol 221,7 49,3

3-Ethyl-2-methylpentane 115,6 32,9

3-Ethyl-3-methylpentane 118,2 32,8

3-Ethylhexane 118,6 33,6

3-Ethylpentane 93,5 31,1

3-Heptanol 157 42,5

3-Methyl-1-butanol 131,1 44,1


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3-Methyl-2-butanol 112,9 41,8


3-Methylhexane 92 30,9

3-Methylpentane 63,2 28,1

3-Methylthiophene 115,5 34,2

3-Pentanol 116,2 43,5

3-Picoline 144,1 37,4

4-Methyl-2-pentanol 131,6 44,2


4-Picoline 145,3 37,5

Acetal 102,2 36,3

Acetaldehyde 20,1 25,8

Acetic acid 117,9 23,7

Acetic anhydride 139,5 38,2

Acetone 56 29,1

Acetonitrile 81,6 29,8

Acetonphenone 202 38,8

Acetylacetone 138 34,3

Acrolein 52,6 28,3

Acrylonitrile 77,3 32,6

Allyl acetate 103,5 36,3

Allyl alcohol 97 40

Aniline 184,1 42,4

Anisole 153,7 39

Benzaldehyde 179 42,5

Benzene 80 30,7

Benzenethiol 169,1 39,9

Benzonitrile 191,1 45,9


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Benzyl acetate 213 49,4

Benzyl alcohol 205,3 50,5

Benzyl benzoate 323,5 53,6

Bis(2-chloroethyl) ether 178,5 45,2

Bromochloromethane 68 30

Bromoethane 38,5 27

Bromoethylene 15,8 23,4

Bromomethane 3,5 23,9

Butanal 74,8 31,5

Butane -0,5 22,4

Butanenitrile 117,6 33,7

Butanoic anhydride 200 50

Butyl acetate 126,1 36,3

Butyl ethyl ether 92,3 31,6

Butyl formate 106,1 36,6

Butyl methyl ketone 127,6 36,4

Butyl vinyl ether 94 31,6

Butylamine 77 31,8

Butylbenzene 183,3 38,9

Butyrolactone 204 52,2

Carbon disulfide 46 26,7

Chlorobenzene 131,7 35,2

Chlorodifluoromethane -40,7 20,2

Chloroethane 12,3 24,7

Chloroethylene -13,3 20,8

Chloromethane -24 21,4

Chloropentafluoroethane -37,9 19,4

Chlorotrifluoromethane -81,4 15,8


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cis-1,2-Dichloroethylene 60,1 30,2

cis-1,2-Dimethylcyclohexa 129,8 33,5

cis-2-Pentene 36,9 26,1

cis-Decahydronaphthalene 195,8 41

Cumene 152,4 37,5

Cyclohexane 80,7 30

Cyclohexanone 155,4 40,3

Cyclohexene 82,9 30,5

Cyclohexylamine 134 36,1

Cyclopentane 49,3 27,3

Cyclopentanone 130,5 36,4

Decane 174,1 38,8

Dibromomethane 97 32,9

Dibutyl ether 140,2 36,5

Dibutyl phthalate 340 79,2

Dibutyl sulfide 185 41,3

Dibutylamine 159,6 38,4

Dichlorodifluoromethyane -29,8 20,1

Dichlorofluoromethane 8,9 25,2

Dichloromethane 40 28,1

Diethanolamine 268,8 65,2

Diethyl carbonate 126 36,2

Diethyl ether 34,5 26,5

Diethyl ketone 101,9 33,5

Diethyl malonate 200 54,8

Diethyl oxalate 185,7 42

Diethyl sulfide 92,1 31,8

Diethylamine 55,5 29,1


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Diethylene glycol 245,8 52,3

Diethylene glycol diethyl 188 49

Diiodomethane 182 42,5

Diisobutyl ketone 169,4 39,9

Diisopentyl ether 172,5 35,1

Diisopropyl ether 68,5 29,1

Diisopropyl ketone 125,4 34,6

Diisopropylamine 83,9 30,4

Dimethyl disulfide 109,8 33,8

Dimethyl ether -24,8 21,5

Dimethyl sulfide 37,3 27

Dimethyl sulfoxide 189 43,1

Dimethylamine 6,8 26,4

Diphenyl ether 258 48,2

Dipropyl ether 90 31,3

Dipropylamine 109,3 33,5

Dodecane 216,3 44,5

Ethanol 78,2 38,6

Ethanolamine 171 49,8

Ethyl acetate 77,1 31,9

Ethyl acrylate 99,4 34,7

Ethyl butanoate 121,5 35,5

Ethyl formate 54,4 29,9

Ethyl isovalerate 135 37

Ethyl propanoate 99,1 33,9

Ethyl vinyl ether 35,5 26,2

Ethylbenzene 136,1 35,6

Ethylcyclohexane 131,9 34


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Ethylene glycol 197,3 50,5

Ethylene glycol diacetate 190 45,5

Ethylene glycol diethyl e 119,4 36,3

Ethylene glycol dimethyl 85 32,4

Ethylene glycol monoethyl 143 43,9

Fluorobenzene 84,7 31,2

Formic acid 101 22,7

Furan 31,5 27,1

Furfural 161,7 43,2

Furfuryl alcohol 171 53,6

Glycerol 290 61

Heptane 98,5 31,8

Hexafluorobenzene 80,2 31,7

Hexane 68,7 28,9

Hexylene glycol 197,1 57,3

Iodobenzene 188,4 39,5

Iodoethane 72,5 29,4

Iodomethane 42,5 27,3

Isobutane -11,7 21,3

Isobutyl acetate 116,5 35,9

Isobutyl formate 98,2 33,6

Isobutyl isobutanoate 148,6 38,2

Isobutylamine 67,7 30,6

Isobutylbenzene 172,7 37,8

Isopentane 27,8 24,7

Isopentyl acetate 142,5 37,5

Isopentyl isopentanoate 190,4 45,9

Isopropyl acetate 88,6 32,9


Page 24



Isopropylamine 31,7 27,8

Isoquinoline 243,2 49

m-Cresol 202,2 47,4

m-Dichlorobenzene 173 38,6

m-Toluidine 203,3 44,9

m-Xylene 139,1 35,7

Mesityl oxide 130 36,1

Mesitylene 164,7 39

Methanol 64,6 35,2

Methyl acetate 56,8 30,3

Methyl acrylate 80,7 33,1

Methyl ethyl ketone 79,5 31,3

Methyl formate 31,7 27,9

Methyl isobutyl ketone 116,5 34,5

Methyl pentyl ketone 151 38,3

Methyl propyl ketone 102,2 33,4

Methyl salicylate 222,9 46,7

Methylacrylonitrile 90,3 31,8

Methylamine -6,3 25,6

Methylcyanoacetate 200,5 48,2

Methylcyclohexane 100,9 31,3

Methylcyclopentane 71,8 29,1

Methylmethycrylate 100,5 36

Morpholine 128 37,1

N,N-Dimethylacetamide 165 43,4

N,N-Dimethylformamide 153 38,4

Naphtalene 217,9 43,2

Neopentane 9,4 22,7


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Nitroethane 114 38

Nitromethane 101,1 34

Nonane 150,8 36,9

o-Chloraniline 208,8 44,4

o-Chlorotoluene 159 37,5

o-Cresol 191 45,2

o-Dichlorobenzene 180 39,7

o-Fluorotoluene 115 35,4

o-Toluidine 200,3 44,6

o-Xylene 144,5 36,2

Octane 125,6 34,4

Octanoic acid 239 58,5

Oleic acid 360 67,4

p-Chlorotoluene 162,4 38,7

p-Cresol 201,9 47,5

p-Cymene 177,1 38,2

p-Dichlorobenzene 174 38,8

p-Fluorotoluene 116,6 34,1

p-Toluidine 200,4 44,3

p-Xylene 138,3 35,7

Pentachloroethane 159,8 36,9

Pentane 36 25,8

Pentanenitrile 141,3 36,1

Pentanoic acid 186,1 44,1

Pentyl acetate 149,2 41

Pentylamine 104,3 34

Perfuorobutane -1,9 22,9

Perfuorocyclobutane -5,9 23,2


Page 26



Phenetole 169,8 40,7

Phenol 181,8 45,7

Propanal 48 28,3

Propane -42,1 19

Propanenitrile 97,1 31,8

Propanoic acid 141,1 32,3

Propanoic anhydride 170 41,7

Propyl acetate 101,5 33,9

Propyl formate 80,9 33,6

Propylamine 47,2 29,6

Pyridine 115,2 35,1

Pyrrole 129,7 38,8

Pyrrolidine 86,5 33

Quinoline 237,1 49,7

Salicylaldehyde 197 38,2

sec-Butylamine 63,5 29,9

Styrene 145 38,7

Succinonitrile 266 48,5

tert-Butylamine 44 28,3

Tetrachloroethylene 121,3 34,7

Tetrachloromethane 76,8 29,8

Tetrahydrofuran 65 29,8

Tetrahydrofurfuryl alcoho 178 45,2

Tetrahydropyran 88 31,2

Tetrahydrothiophene 121 34,7

Thiophene 84 31,5

Toluene 110,6 33,2

trans-1,2-Dichloroethylen 48,7 28,9


Page 27



trans-1,2-Dimethylcyclohe 123,5 33

trans-2-Methylcyclohexano 167,5 53

trans-2-Pentene 36,3 26,1

trans-Decahydronaphthalen 187,3 40,2

Triacetin 259 57,8

Tribromomethane 149,1 39,7

Tributyl borate 234 56,1

Tributylamine 216,5 46,9

Trichloroethylene 87,2 31,4

Trichlorofluoromethane 23,7 25,1

Trichloromethane 61,1 29,2

Tridecane 235,4 45,7

Triethylamine 89 31

Triethylene glycol 285 71,4

Trifluoroacetic acid 73 33,3

Trimethylamine 2,8 22,9

Trinonafluorobutylamine 178 46,4

Vinyl acetate 72,5 34,6

Water 100 40,23


Page 28 Basic Guidelines for Microwave Organic Chemistry Application


GRAPHICS OF THE COMMON SOLVENTS USED Page Solvent

30 1-Butanol 30 1-Hexanol 31 1-Propanol 31 2-Butanol 32 2-Hexanol 32 2-Propanol 33 Acetone 33 Acetylacetone 34 Benzaldehyde 34 Butyl acetate 35 Chlorobenzene 35 Cyclohexane 36 Cyclohexene 36 Dibuthyl ether 37 Dibuthylamine 37 Dichloromethane 38 Diethyl ether 38 Ethanol 39 Ethyl acetate 39 Heptane 40 Hexane 40 Isobuthyl acetate 41 Methanol 41 Methyl ethyl ketone 42 Tetrahydrofuran 42 Toluene 43 Trichloromethane 43 Water




1-Butanol

1-Hexanol




1-Propanol

1-Butanol




2-Hexanol

2-Propanol




Acetone

Acetylacetone




Benzaldehyde

Butyl acetate




Chlorobenzene

Cyclohexane




Cyclohexene

Dibuthyl ether




Dibuthylamine

Dichloromethane




Diethyl ether

Ethanol




Ethyl acetate

Heptane




Hexane

Isobuthyl acetate




Methanol

Methyl ethyl ketone




Tetrahydrofuran

Toluene




Trichloromethane

Water

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Basic Guidelines for Microwave Reactor and Reactions