New synthesis of solanone...

Facultad de Ciencias Experimentales

1

G

rad

o e

n Q

uím

ica

Facu

Auth

r

Uni

ultad de

hor: Ale

Ja

Tr

Newrace

iversid

e Ciencia

ejandro

aén, De

rabajo d

w syemic

dad de

as Expe

o José

ecembe

de fin d

ynthec So

Jaén

eriment

é Rome

er 2016

e grado

esisolano

tales

ero Muñ

6

o

s of one

ñoz

Memoria Trabajo Fin de Grado Alejandro José Romero Muñoz

2

Mem

N

Auth

moria Tr

New

hor: Ale

rabajo F

Univ

Trab

w syn

ejandro

in de Gr

versid

bajo de f

ntheSo

o José

ado Ale

dad de

fin de g

esislano

é Rome

Jaén

ejandro J

e Jaé

grado

s of rone

ero Muñ

n, Dece

José Rom

n

race

ñoz

ember 2

mero Mu

emic

2016

uñoz

3

c


4

Acknowledgements

Technical and human support provided by CICT of Universidad de Jaén (UJA, MINECO, Junta de Andalucía, FEDER) is gratefully acknowledged.

To my tutor Dr.Justo Cobo for his unlimited patience


5

New synthesis of racemic Solanone

Index

RESUMEN ................................................................................................................................................ 7

1 ABSTRACT ........................................................................................................................................ 9

2 INTRODUCTION ............................................................................................................................. 11

2.1 2.1 History of semiochemicals and classification .................................................................. 11

2.2 Methods for identifying and studying semiochemicals ........................................................ 14

2.3 Bioassays ............................................................................................................................... 15

2.4 Using semiochemicals: applications of pheromones ............................................................ 16

2.4.1 Pheromones in pest management ................................................................................ 17

2.4.2 Mating disruption .......................................................................................................... 18

2.4.3 ”Lure and kill” (attracticide) and mass trapping ........................................................... 19

2.4.4 The mango white schale Aulacaspis tubercularis .......................................................... 20

2.4.5 Aulacaspis spp semiochemicals ..................................................................................... 20

2.5 Review ................................................................................................................................... 22

2.5.1 Method HO: Synthesis of racemic Solanone ................................................................. 22

2.5.2 Method HO: Synthesis of R‐Solanone ........................................................................... 23

2.5.3 Number of reaction steps and reaction timing ............................................................. 25

2.5.4 Number of reaction steps with temperature changes .................................................. 25

2.5.5 Solvent amount ............................................................................................................. 25

2.5.6 Reagents price ............................................................................................................... 26

2.5.7 Enantiomer .................................................................................................................... 26

3 OBJECTIVES .................................................................................................................................... 27

4 METHODS AND MATERIALS .......................................................................................................... 29

4.1 General .................................................................................................................................. 29

4.2 Instrumental .......................................................................................................................... 30

4.3 Experimental ......................................................................................................................... 31

4.3.1 General procedure for the synthesis of pyrrolidine 1‐(3‐methylbut‐1‐enyl) ................ 31

4.3.2 Alkylation of pyrrolidine 1‐(3‐methylbut‐1‐enyl) .......................................................... 32


6

4.3.3 Preparation of methallyltriphenylphosphonium chloride ............................................ 33

5 RESULTS AND DISCUSSION ........................................................................................................... 35

5.1.1 Preparation of pyrrolidine 1‐(3‐methylbut‐1‐enyl) ....................................................... 35

5.1.2 Preparation of methallyltriphenylphosphonium chloride ............................................ 38

5.1.3 Alkylation of pyrrolidine 1‐(3‐methylbut‐1‐enyl) .......................................................... 39

6. CONCLUSION ................................................................................................................................... 43

7. BIBLIOGRAPHY ............................................................................................................................... 43

8. ATTACHEMENTS ............................................................................................................................ 45


7

RESUMEN

El termino semioquímico es utilizado para una sustancia química o mezcla utilizada

por los organismos como “mensajeros” ya sea entre miembros de la misma especie

o intraespecífica. Los semioquímicos pueden ser usados como sistemas de alarma,

demarcación de territorio o con fines sexuales.

Este trabajo se centra en la síntesis de una feromona sexual, la Solanona, utilizada

por las hembras vírgenes de la cochinilla del mango Alacaspics murrayae Takahasi.

La Solanona sintetizada por una nueva ruta pretende ser utilizada con otro individuo

de distinta familia dentro de la misma especie (Aulacaspis tubercularis) para su uso

en el control de plagas que afectan a la zona sureste de Andalucía. Para la síntesis

de este semioquímico partimos de los estudios realizados por John y Nicholson

(1965) y posteriormente Hsiao-Yung HO (et al.2014) que ya describen la Solanona

como semioquímico sexual y proponen una estrategias sintéticas que utilizaremos

de base para la que se desarrollara en este trabajo.

Una vez sintetizado con éxito, se estudiara mediante bio-analisis la eficacia de este

en su forma racémica y, una vez estudiado el resultado, se analizara la utilización de

la misma de forma enantioselectiva.


8


9

1 ABSTRACT

The mango scale Aulacaspis tubercularis (Newstead) (Diaspididae: Hemiptera) is

the biggest pest in mangoes located in Andalucía. The chemical compound (5R,

6E)-5-isopropyl-8-methyl-6,8-nonadien-2-one (R-Solanone) has been identified as

a A. murrayae Takahasi sex pheromone (Ho,H. et al., 2014) .However, Solanone

is not recently discovered sex pheromone, its synthesis has not been used in

industrial applications among other reasons because it is possible to get it from

tobacco volatile products of distillation, even if the reaction yield is really low. The

design of a new and clear strategy for Solanone synthesis and confirm its sex

pheromone attractaction ability, with enough yield and low costs, are the objective

of this work.


10


11

2 INTRODUCTION

2.1 2.1 History of semiochemicals and classification

All animals produce a chemical profile, present on the body surface, released as

volatile molecules, and also, animals of all kinds gain chemosensory information from

other organisms. Chemical senses are used for example, to locate potential food

sources and detect predators or moreover mediate the social interactions, as

illustrated by the dogs or ants above. We can probably say that almost organisms

use chemosensory communication than any other mode. A chemical involved in the

chemical interaction between alive organisms is called semiochemical. Some of the

semiochemicals emitted by animals are pheromones, acting as signals for

communication. Other semiochemicals, such as the carbon dioxide in exhaled

breath, did not act as a signal, but can be exploited as a cue by blood-sucking

mosquitoes as a way of finding a host. Pheromones and signature mixtures are

semiochemicals used within a species. Semiochemicals acting between individuals

from different species are called allelochemicals and are further divided depending

on the costs and benefits to signaller and receiver (Nordlund & Lewis 1976; Wyatt

2011).


12

Fig 1. Semiochemicals classification. (+) If it is positive to the signaller or receiver; (-) if it is negative to the signaller or receiver

Pheromone signals can be eavesdropped (“overheard”) by unintended recipients: for

example, specialist predatory beetles use the pheromones of their bark beetle prey to

locate them. The predators are using the bark beetle pheromones as kairomones.

Animals of one species can emit fake, counterfeit signals that benefit themselves at

the cost of the receiving species. Chemical signals used in such deceit or

propaganda are termed allomones: for example, bolas spiders synthesize particular

moth pheromones to lure male moths of those species into range for capture.

Semiochemicals benefiting both signaler and receiver in mutualisms, such as those

between sea anemones and anemone clownfish, are termed synomones. The

multiplicity of terms is only useful as shorthand and the terms are clearly overlapping,

not mutually exclusive (for example, a molecule used as a pheromone within a

species can be used as a kairomone by its predator). The research date of Intra-

specific semiochemicals: pheromones and signature mixtures Modern pheromone

could be said 1959, when the chemist Adolf Butenandt and his team identified the


13

first pheromone, the silk moth’s sex pheromone bombykol, which prompted the

coining of the word “pheromone,” from the Greek “pherein”, to transfer; hormone, to

excite (Butenandt et al. 1959; Karlson & Lüscher 1959). Butenandt’s discovery

established that chemical signals between animals exist and can be identified .From

the start, Karlson and Lüscher (1959) anticipated pheromones would be used by

every kind of animal, from insects and crustaceans to fish and mammals. Since then,

pheromones have been found across the animal kingdom, in every habitat on land

and underwater, carrying messages between courting lobsters, alarmed aphids,

suckling rabbit pups, mound-building termites, and trail-following ants (Wyatt 2009).

They are also used by algae, yeast, ciliates, and bacteria. It is likely that the majority

of species across the animal kingdom use them for communication of various kinds.

Fig 2 Example of semiochemicals in natural environment using bees as example.


14

The idea of chemical communication was not new in 1959. The ancient Greeks knew

that the secretions of a female dog in heat attracted males. Charles Butler (1623) had

warned in The Feminine Monarchie that if a beekeeper accidentally crushes a

honeybee, the bees “presently finding it by the ranke smell of the poisonous humor,

will be so angry, that he shall have work enough to defend himself.” However,

because the quantities emitted by an individual animal were so small, the chemistry

of the day could not identify them, until the inspired idea of using domesticated silk

moths, which could be reared in the hundreds of thousands necessary to collect

enough material for analysis using the techniques available at that time .The

enormous variety of organic molecules identified as pheromones since the first,

bombykol, in 1959 is as diverse as the animal kingdom, and offers an ongoing

challenge for chemists interested in the identification, synthesis, and exploration of

naturalfunctions of novel compounds (Cummins & Bowie 2012; El-Sayed 2013;

Francke & Schulz 2010). Between all the pheromones, Solanone is sexual

pheromones that are the main aim of thıs research; however there are more kind of

pheromones as alarm pheromones, aggregation pheromones…

2.2 Methods for identifying and studying semiochemicals

Since Butenandt’s landmark identification in 1959 of the silk moth sex pheromone

bombykol, there have been spectacular developments in our ability to identify

semiochemicals. In their work over some two decades, Butenandt’s team needed

more than 10 metric tonnes of female moths, providing 500,000 pheromone glands

from which they extracted ~12 mg of the pheromone to identify. The identification of

the first ant trail pheromone in 1971 still required 3.7 kg of Atta texana ants.Today, it

is possible to work with far, far less than a single moth’s pheromone gland. The

revolution has come from chromatographic techniques in particular and the direct

coupling of these with mass spectrometers and other detection devices including

animals’ own sensors. The ever-increasing power of nuclear magnetic resonance

(NMR) spectroscopy has made complete structure determination possible on a

microgram scale. Insect pheromone identifications can be made from picogram to

femtogram quantities, using gas chromatography–electroantennogram detector (GC-

EAD, with the insect’s antenna) to get retention indices, and microchemical reactions


15

to determine presence/absence of functional groups (e.g., with a gall midge sex

pheromone). In the approach taken to identify bombykol, Butenandt demonstrated

the “gold standard” for pheromone identification used to this day. It is the equivalent

of “Koch’s postulates” for establishing causal relationships forpheromones: initial

demonstration of an effect mediated by a semiochemical, then identification and

synthesis of the bioactive molecule(s), followed by bioassay confirmation of activity

.Chemosensory receptors interact with the three-dimensional structure of molecules,

including their stereochemistry, so it is critically important to both identify and

synthesize the correct stereoisomer(s) in high purity for. Sensitive, reliable, and

reproducible bioassays are important for pheromone identification, and for dissecting

the details of the behaviors or physiological changes mediated by pheromones.

Bioassays are also important for studying the signature mixtures used for recognition,

which differ between individuals or social insect colonies.

2.3 Bioassays

The first step in the study of a new pheromone is the observation of a behavioral or

physiological response that appears to be mediated by semiochemicals. A bioassay

is then developed as a repeatable experiment for measuring this response. A

bioassay must first be as simple as possible, and at the same time be able to

measure the type of behavior that has been observed in the field. You need to select

an answer that is easy to record and can predict the outcome. Most of the methods

used involves the recording of behavioral changes; Other recorded changes in

physiological activity

One of the simplest bioassays apply it Butenandt in his initial studies of the sex

pheromone of the moth, Bombyx mori and consisted in bringing the male moth a

glass rod with a small amount of the fraction to be tested and observe the motor

response moth.

Other widely used electrophysiological bioassays are the most used being the

electroantennogram that was developed by Schneider in 1957.


16

Fig 3. Electroantennogram schedule

2.4 Using semiochemicals: applications of pheromones

The importance of smell in the natural behavior of animals has long been recognized

and, long before it was known what semiochemicals were, people used them to

manipulate the behavior of animals.. The clear potential for applications of

pheromones was an early encouragement for research. At the turn of the twentieth

century and in its first few decades, the potential of synthetic chemical signals to

control insect pests was anticipated both in North America and in Europe. There is

now increasing use of an understanding of semiochemicals to affect the behavior of

domesticated animals, from bees to sheep, as well as use as “greener” alternatives

to pesticides, largely for the control of insect pests but also potentially for vertebrate

pests.


17

2.4.1 Pheromones in pest management

Currently the most successful applications of pheromones are for insect pest

management, with significant cost and environmental benefits to the farmer, the

consumer, and society. There are many successful schemes using pheromones, at

least as or more effective than the conventional pesticides they have replaced, for

the direct control of insect pests over millions of hectares. Pheromones for many

insect pests have been identified. A major strength of pheromones is their low

toxicity, which makes them ideal as part of integrated pest management (IPM)

schemes, which include biological control agents and other beneficial invertebrates

such as bees and spiders (van Lenteren 2012; Witzgall et al. 2010). Pheromones fit

neatly into the virtuous spiral, for example in greenhouse IPM, where the use of

bumblebees for pollination or one biological control agent such as a predatory spider

mite encourages (or requires) ending the use of conventional pesticides for other

pests.The main, and sometimes overlapping, ways of using pheromones to control

pests are monitoring, mating disruption, “lure and kill” or mass trapping, and other

manipulations of pest behavior. Some of these techniques have also been used to

control vertebrate pests.

2.4.1.1 Monitoring

An important use of pheromones is for baiting traps for monitoring populations of

insect pests of stored .Pheromone-based monitoring provides one of the most

effective survey methods for detecting the presence and density of pest and/or

invasive species. Thanks to the specificity of insect pheromones, almost all animals

attracted to the trap will belong to that species


18

2.4.2 Mating disruption

Mating disruption is one of the most successful uses of insect pheromones covering

around one million hectares worldwide. The aim of mating disruption is to prevent

adult males and females finding each other, thereby stopping fertilization of eggs and

thus the caterpillars that cause the damage. For most moths, which rely on

pheromones for the sexes to find each other, this can be achieved by flooding the air

in the host crop with synthetic pheromone. Area-wide treatments that involve every

farmer over a region are the most effective. A variety of slow-release formulations

has been developed to release small quantities of volatile pheromone over the

months of the insect pest. The potential mechanisms for mating disruption include:

(1) desensitization (sensory adaptation of the olfactory sensory neuron or habituation

in the central nervous system); (2) false-plume following (competition between

natural and synthetic sources); (3) camouflage of natural plumes by ubiquitous high

levels of synthetic pheromone; (4) imbalance in sensory input by massive release of

a partial pheromone blend; and (5) the effects of pheromone antagonists and

mimics). Another, complementary, way in which mating disruption reduces crop

damage is by reducing or eliminating the need for pesticides, thereby keeping more

natural enemies alive, so the few caterpillars present have a greater chance of being

killed by predators or parasites. In addition, pollinating insects are unharmed, which

increases fruit set.


19

.

Fig 4 Mating disruption action

2.4.3 ”Lure and kill” (attracticide) and mass trapping

The aim of “lure and kill” or mass trap pest control is to reduce the pest population by

attracting pests with pheromones and then either trapping, sterilizing, or killing

responding individuals. With lure and kill (also called attracticide), pest animals are

attracted to the pheromone source and pick up an effective dose of insecticides,

sterility, or insect pathogens. Mass trapping method confines the animals in a specific

trap with also specific chemical signal .Pheromones may be combined with visual

targets and other semiochemicals such as host plant odors. Much less synthetic

pheromone is required than for mating disruption and this may sometimes be a

crucial financial factor. Both lure and kill and mass trapping rely on the specificity of

pheromones to attract only members of the target pest species This means that the

whole crop or forest does not need to be sprayed, thus helping to save beneficial

insects that would normally be killed with area-wide pesticide sprayings. Effective

attracticide or mass trapping depends on highly attractive synthetic pheromone lures,

low initial population densities, ideally attraction of females, a slow rate of population


20

increase (longer lived species), ability to attract a high proportion of the population,

and limited dispersal Large curculionid weevils have all the characteristics.

2.4.4 The mango white schale Aulacaspis tubercularis

Between the subtropical crops in the Iberian Peninsula, the avocado is the most

widespread, occupying a total of 9,400 hectares, 9,000 of them in the provinces of

Granada and Malaga. The annual production of Andalusia avocados is around

73,000 tones. It is noteworthy that in our community is concentrated 87% of the

surface of avocado cultivated in Spain.

Nowadays, white mango and avocado Aulacaspis tubercularis Newstead (Hemiptera:

Diaspididae) is the main pest of this crop. The difficulty in its treatment with synthetic

pesticides makes it necessary to implement new tools for the biotechnical control of

the white mango mealybug based on the use of its sexual pheromone.

2.4.5 Aulacaspis spp semiochemicals

Mango -Mangifera indica L. (Anacardiaceae) - is one of the main tropical fruit

produced in Malaga (South Andalucía, Spain); but it is damaged by the white mango

scale (WMS) Aulacaspis tubercularis Newstead (Hemiptera: Diaspididae) which

produce losses higher than 50%, meanwhile until now the pest is not controlled. The

usual scale damage consisting in heavy leaves desiccation and finally the death of

the tree. Due to this problem, knowledge about its chemical ecology and

semiochemical compounds implied in chemical communication between scales is

required for management purposes. To date, just six pheromones have been

identified from other Diaspidid scale species, and all of these pheromones are esters

of mono- or sesquiterpene alcohols. The unsaturated ketone (R)-Solanone (1),

(5R,6E)-5-Isopropyl-8-methyl-6,8-nonadien-2-one, was identified as a female-specific

attractant of the scale insect, Aulacaspis murrayae Takahashi (Hsiao-Yung Ho et al.

2014) but to date, it is the only identified pheromone in the genus Aulacaspis and


21

after that (R)-Solanone was identified as semiochemical, the interest about it

synthesis had been increasing.

The (S)-Solanone ketone is yellow clear oil isolated from tobacco leaves headspace

that occurs as a trace amounts. The first racemic synthesis was done by Johnson

and Nicholson (1965) and the chiral synthesis (R enantiomer) was reported Hsiao-

Yung Ho et al.

Fig 5 Solanone structure.

The aim of this study was to plan a synthetic pathway to obtain racemic Solanone

and then isolating both enantiomers using a -cyclodextrin column chromatography.

Cyclodextrins (CDs) adsorbent are cyclic oligosaccharides composed of seven D-

glucose units that are linked by α (1, 4)-glucosidic bonds and are usually used as

chiral chromatography for enantiomers separation

Fig 6.Beta- cyclodextrin column chromatography structure


22

2.5 Review

The following revision attempts to show the method on which was based our

synthesis of the racemic Solanone, provided by John Nicholson (1965) together with

another synthesis model which however, ends in R-Solanone enantiomer, designed

by Hsiao-Yung Ho (et al. 2014). After this, main stages and characteristics of both

methods of synthesis will be presented also explaining, with reasoning accompanied

by a series of explanatory tables why just one of these methods is availed for our

aims.

2.5.1 Method HO: Synthesis of racemic Solanone

As previously mentioned, the design of this strategy of synthesis was carried out by

John Nicholson (1965) who, in addition, identified and cataloged the Solanone as a

sexual semiochemical.

The initial reagent of this synthetic strategy is a commercial product, 3-

methylbutyraldehyde (1), which was purchased from Sigma Aldrich for an average

price 30€/100 mg.

The first reaction consists of a Wittig reaction for the formation of an alkene from an

aldehyde. This type of reaction allows anticipating with total certainty the position of

the double bond, an advantage that this one has in front of, for example the

elimination reactions. The product of this first reaction is an enamine intermediate

which is then alkylated in CH3CN, followed by a breakdown of bonds in aqueous

solvent. The next reaction step is performed with a phosphorus ylide prepared from

triphenylphosphine and 3-chloro-2-methylpropene, both commercial reagents which

can be obtained, for example, from the same commercial house mentioned above. In

the third and last stage we used a Grignard reagent (MeBr in this case) in an inert

atmosphere, using BuLi as strong base. The reaction finishes with an aqueous

hydrolysis to give racemic Solanone as product.

Some positive points of this method are the small steps number and all reagents

except the phosphonium yilde are commercial.

All these stages are reflected in the following scheme:


23

CH3

CH3

OCH

O

CH3 CH3

aN

CH3 CH3

CH3

CH2

b

c CH3

O

CH3 CH3

CH3

CH2

A B C

D

Fig 7. Synthesis of Solanone. Reaction conditions: a (i) pyrrolidine, toluene,

273 K, 2 hr, moleculas sieves ; (ii) acrylonitrile, CH3CN, aqueous acid buffer

solution, 288 K, 24 hr ; b methallyltriphneylphosponium chloride , n-BuLi, THF ;

c methylmagnesium bromide, toluene, reflux, 24 hr; aqueous workup.

2.5.2 Method HO: Synthesis of RSolanone

Here, there is a second method to review. This has been designed by South Korean

scientist Hsiao-Yung Ho et al. (2014) who used Solanone as a sexual attractant for

the insect Aulacaspis murrayae Takahashi. In the case of Dr. Hsiao, the enantiomer

R-Solanone was used because is known from previous studies for its attractive

power for this species of insect.

One of our objectives is the enantiomer separation by β-Cyclodextrins, however the

following reaction method only has the formation of a single enantiomer as final

product. For this reason the reaction here has a greater number of stages, time of

reaction and difficulty, besides requiring a greater number of solvent, more specific

reaction conditions and more expensive reagents.


24

O NH

Bn

O

O NCH3

CH3O

Bn

CH2

O

CH3

CH3Bn

CH2

CH2

O

OAcO

CH3

CH3

O

OH

OO

CH3

CH3CH3 CH3

CH3

CH3 CH3

OO

CH3

CH3

CH2

CH3

OH

CH3 CH3

CH2

CH3

CH3 CH3

N

CH2

CH3 CH3

O

CH3 CH3

CH2

a b

c d

e f

g h

1 2 3

4 5

6 7

8 9

Fig 8.. Synthesis of (R)-Solanone. Reaction conditions: a n-BuLi, THF, - 78 ºC,

3-METHYLBUTYRIL CHLORIDE, 3h ; b LiHMDS, THF, -78 ºC, allyl bromide, 18 h;

c i) OsO4 , NMO, CH3CN, rt, 15h ; ii) Ac2O, pyridine, DMAP, 0ºC, 2h, d i) LiBH4 ,

THF, rt, 12 h; ii) 2,2-dimethoxypropane, p-TsOH , DMF, rt, 15 h ; e i) DMSO,

oxalyl chloride, Et3N, CH2Cl2, rt 1h ; ii) diethyl( 2-methylallyl)phosphonate, n-

BuLi, HMPA, THF, 12 h ; f i) NaIO4, 80% aq AcOH, 4h; ii) NaBH4 , MeOH, 30 min;

g i) p-tosyl chloride, Et3N, DMAP, CH2Cl2 , 2h; ii) NaCN, DMSO, rt, 14 h ; h i)

CH3MgBr, toluene, reflux, 24 h ; ii) H2O, 4 h.

There are more method for Solanone synthesis (example: Park, Oee Sook 1993),

however they have been chosen because their detailed decryption in the article

already named and also, in both, initial reagents are commercial products.


25

But nevertheless the strategic chosen in this work was the first one (Fig 7) and

chosen by Hsiao-Yung had been the other option. Some reasons for this choice

were:

2.5.3 Number of reaction steps and reaction timing

Reaction A (Fig 7) B (Fig 8)

Steps number 3 8

Reaction time (h) 50 126,5

Table 1. “Comparison” between the steps number and reaction time of both

methods.

Without taking into account the ease or difficulty of this reaction steps, it is clear that

the reaction B requires a large number of steps and time in comparison with reaction

A. The objective of this work is the synthesis of a product with plague control

applications so an easy developed and short time reaction product is really important

factors to take account.

2.5.4 Number of reaction steps with temperature changes

Reaction A includes two temperature changes: first in the Witting reaction between A

and pyrrolidine in benzene at 273 K, and second, the addition of the formed enamine

to acrylonitrile, at 378 K. The rest steps react at room temperature.

On the other hand however, reaction B requires more temperature changes and also,

some steps react at 295 K using probably, liquid nitrogen or other instruments,

increasing the difficulty of the reaction and its time

2.5.5 Solvent amount

This reason is connected with the first one. Bigger amount of reaction steps include

usually bigger amount of solvents that should be avoid or decrease because of an

economic and environmental point of view.


26

2.5.6 Reagents price

Reagent A 1

Purity (%) 97 100

Quantity 25 mL 1 g

Price ($) 17 93,50

Table 2. Prices in Sigma Aldrich website comparing the lowest amounts

availed to buy.

Economically the difference between the first reagents is a clear example that

Reaction B is much more expensive in reagents cost than Reaction B. It is a clear

disadvantage not just in this academic work, also as synthetic method as plague

control product.

2.5.7 Enantiomer

Reaction B is designed specifically for a enantiomeric reaction giving (R)- Solanone

as product that it is known for sure as sexual attractive pheromone. However one of

the aims of this work is checking if it is possible use racemic Solanone without a big

attractive field lose.

This reasons shown Reaction B inappropriate for the aims of this works. In

conclusion, the synthetic schedule that was used as base for this work is Reaction

(Fig 7).


27

3 OBJECTIVES

The objectives of this work are multiple:

In the first place, a method of synthesis of the racemic Solanone that is capable of

being produced for an effective pest control is sought. For this, it is very important, as

explained above, a not very high number of reagents or solvent and preferably, that

these are not very polluting. The method should also be based on a synthesis of few

steps and all of them are easily reproducible and controllable. Once this method is

designed, the work has a second aim

This second objective is the corresponding bioanalysis that is, testing the

semiochemical synthesized with the insect species Aulacaspis Murrayae

tubercularis, the target pest. Check if the efficacy of the Solanone is affected by the

enantiomer used. In case of biological activity, next step would be an enantiomeric

separation; this will be carried out by a B-cyclodextrin column.

Fig 9. Aulacaspis Murrayae Takahasi. Photo from Digital Insect of Taiwan Agriculture Research Institute.


28


29

4 METHODS AND MATERIALS

4.1 General

The reagents and solvent used for this work were purchased and used without

further purification-by the chemical companies Sigma Aldrich, VWR Chemicals and

Panreac SLU.

Reactions were monitored by thin layer chromatography (TLC) (……) and the

visualization of the developed TLC was performed by UV at 256 nm, or

phosphomolybdic acid staining.

For preparation of pyrrolidine 1-(3-methylbut-1-enyl) were used the next reagents:

3-methylbutyraldehyde 99%

Toluene HPLC quality

Pyrrolidine 98%

Diethyl ether

Sodium sulphate anhydrous

Reagents used in alkylation of pyrrolidine 1-(3-methylbut-1-enyl) were:

Acrylonitrile 99%

Acetonitrile 99%

Acetic Acid 99%

Sodium Acetate 99%

Diethyl


30

And finally for the preparation of methallyltriphenylphosphonium chloride

Triphenylphosphine 99%

Acetonitrile

3-chloro-2-methylpropeno

For the tests was also used dichloromethane

4.2 Instrumental

Nuclear Magnetic Resonance (MRN). The spectras of 1H-MRN and 13C-MRN

were obtained with Bruker Advance-400, from CICT in Jaén University.

Melting points were obtained by Brostead Electrothermal 9100.

GC-Quadrupole mass analyzer. The equipment is a Thermo mass

spectrometer model DSQ II attached to a Trace GC Ultra gas chromatograph

with quadrupole ion analyzer.

IR spectra were recorded in the region 4000-400 cm−1 on a NICOLET

spectrometer

All chemical shifts (δ) are given in parts per million (ppm) with reference to solvent

residues in CDCl3 and coupling constant (J) are reported in Hertz (Hz). Multiplicities

are abbreviated as follows: s: singlet, d: doublet, dt: double triplet, t: triplet, dt: double

triplet, dc: double quadrupole m: multiplete.

Mem

4.3 Ex

4.3.1

Fig 10.

A 100-

mmol)

reactio

pyrolid

latest m

stirring

conclud

mixture

100 mL

and dr

evapor

experim

methyl

1H NM

H) 2.19

J=13.8

1 The proenamine

moria Tr

xperimen

General pr

.Enamine

-mL round

and dried

n tempera

dine (2) (2

mixture w

. After 2 h

de that re

e was extra

L separato

ried with s

rator. Theo

mental pe

lbut-1-eny

R (400 MH

9 - 2.34 (m

5 Hz, 1 H)

oduct is pyrro(3) for conven

rabajo F

ntal

ocedure for

product (3

d-bottomed

d or hplc q

ature: 273

21 mmol)

was slowly

of reactio

eaction wa

acted first

or funnel. T

sodium su

oretical pe

erformance

yl) (3)1 was

Hz, CHLOR

m, 1 H) 2.8

.

lidine 1‐(3‐menience.

in de Gr

r the synth

3): pyrroli

d flask was

quality tolu

K. Parall

with solut

dropwise

n and che

as ended,

1x10 mL

The comb

ulphate an

erformance

e ratio wa

s character

ROFORM-

8 - 2.99 (m

ethylbut‐1‐eny

ado Ale

esis of pyrr

idine 1-(3-

s charged

uene (10

el a dropp

ion of sam

added to

cking by T

which als

water and

bined organ

nhydrous.

e ratio of

as 83% o

rized by 1H

-d) δ ppm

m, 5 H) 4.1

yl) however in

ejandro J

rolidine 1(

-methylbu

with 3-me

mL) sunke

ping funne

me toluene

o the abo

TLC (60:40

so agrees

d 3x10 mL

nic extract

The prod

f this rea

of pure p

H-NMR.

0.97 - 1.00

13 (dd, J=1

n the rest of t

José Rom

(3methylb

t-1-enyl)

ethylbutyr

en in an i

el 250 mL

e (10 mL)

ve one co

0, hexane:

with the

with cold

ts were dr

uct was p

ction is 9

product. P

0 (m, 7 H)

13.75, 6.93

he work this p

mero Mu

ut1enyl)

raldehyde

ce bath to

L with solu

is prepare

onstant m

ethyl acet

bibliograph

diethyl eth

ried, conce

purified by

95%. The

Pyrrolidine

1.76 - 1.8

3 Hz,1 H) 6

product will b

uñoz

31

(1) (20

o reach

ution of

ed. The

magnetic

tate) we

hy. The

her in a

entrated

y rotary

lowest

e 1-(3-

86 (m, 5

6.15 (d,

be named


32

CH3 CH3

O

+NH

CH3CH3

Nmolecular sieves

Toluene0 °C4 h

1 3

Fig 11.Enamine (3) production reaction

4.3.2 Alkylation of pyrrolidine 1(3methylbut1enyl)

CH3 CH3

ON

Fig 124-isopropyl-5-oxo-pentanenitrile

The equimolar amount of enamine (3) (just true if we suppose 100% ratio reaction)

was added to a solution of acrylonitrile (4) (20mmol) in acetonitrile (20 mL) with

continue stirring at 288 K for the appropriate time until consumption of enamine (3)

(TLC monitoring). The bibliographic reaction time is 18 h. Acidic buffer solution (

made up of AcOH 0,5 g , AcONa 0,5 g ) and water (1mL) was added and the mixture

continue at same temperature for separated and purified using first 1x10 mL water

portion and 3x10 mL diethyl ether washing aqueous portions. Finally the solid was

filtered and the solvents removed in a rotary evaporator to obtain the 4-isopropyl-5-

oxo-pentanenitrile.


33

CH3

CH3

N+

CH3 CH3

ONCH2

N CH3CN288 K18 h

Acid buffer solution

3 4

Fig 13. Alkylation of (3) reaction

4.3.3 Preparation of methallyltriphenylphosphonium chloride

Cl-

P+

CH3

CH2

Fig 14. Methallyltriphenylphosphonium chloride

This phosphonium ylide has been prepared from triphenylphosphine (5) (20 mmol)

was added to another solution 3-chloro-2-methylpropeno (6) (20 mmol) in 10 mL

CH3CN. Experiment continued with the dropping of both solutions into a round

bottomed 150 mL flask. The reaction temperature was 323 K that was controlled by

dry heater system moreover with magnetic stirring. Reaction time: 24 h. When the

reaction ended, it was observable a white precipitate on the surface of the round

bottom flask. This solid was extracted by using vacuum filtration with a kitasato and

Buchner funnel, using as cleaner solvent cold CH3CN. Finally, the solid had been

collected and let it in open air in order to eliminate solvent remains. In the other step,


34

it was characterized according to its melting point. However more products were

obtained later drying the aqueous phase using rotary evaporator. The second portion

of product was different colour if we compare with the first product portion. First

portion colourless, second portion colour: pink. It could mean that in second portion

there are impurities. Theoretical yield of this reaction is 66%. If we consider both

portions of product experimental performance yield was 81, 87%.

1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.44 - 1.67 (m, 3 H) 4.77 (d, J=15.51 Hz, 2 H) 4.88 (d, J=5.17 Hz, 1 H) 5.03 (dt, J=5.07, 1.19 Hz, 1 H) 7.63 -7.70 (m, 6 H) 7.73 - 7.79 (m, 3 H) 7.82 - 7.89 (m, 6 H)

Theoretical melting point: 491 K

Experimental melting point 1º portion: 485 K

Experimental melting point 2º portion: 482 K

CH2

Cl

CH3+PCH3CN

Cl-

P+

CH3CH2

Fig 15. Formation of methallyltriphenylphosphonium chloride


35

5 RESULTS AND DISCUSSION 2

5.1.1 Preparation of pyrrolidine 1(3methylbut1enyl)

The initial reaction begins with 3-methylbutyraldehyde (1) using toluene as the

solvent and by dropwise addition the pyrrolidine, also with the same amount of

toluene as solvent. For this purpose, the followed conditions were described

according to John Nicholson (1965), summarized in Fig. 7, focus on obtain the

product racemic Solanone with an optimum yield.

These reaction conditions were that the reaction would be carried out at 0 ° C,

achieved by the use of ice, by dropwise addition, with magnetic stirring and using

pre-dried molecular sieves. The study of the reaction point was performed by TLC,

which shows two separations (AR1 and AR2) corresponding to the mixture before

and after 2 hours reaction time. It can be clearly seen how, despite being reactive at

first, the reaction can be carried out. The TLC technique was used to measure the

progress of reactions and to perform a qualitative analysis of the reaction.

Next there is an image (Fig TLC1.) corresponding to a TLC that was made to analyze

the progress of the reaction. It shows two initial signals: AR1 corresponding to

pyrrolidine diluted in dichloromethane and AR2 corresponding to the sample also

diluted in dichloromethane. It is observed the progress of the reaction and the

appearance of a new signal with different Rf to the source signal despite the fact that

in AR2 the pyrrolidine signal still appears but it is found in less quantity than the new

one.

2 In this section and its subsections will be referred to a series of spectra that are in the annexes


36

Fig TLC 1. TLC in which the signal obtained by the pyrrolidine can be compared with the signal obtained after a certain reaction period

After completion of the reaction at 2 h, and also after an extraction and purification

process, the product is analyzed by H-NMR.

However, in later experiments, the suitability of the use of molecular sieves was

questioned so they were removed, which bring to a change in the reaction conditions

comparing with designed by John Nicholson (1965). After subjecting the result of this

reaction to the same process as the previous product.


37

8

7

CH39

CH310

6

N2

53

4

Fig 16. Enamine different 1H. Each number corresponds with one signal however because of

symmetry there are equivalent signals.3

1H-RMN (CDCl3 )

Compound 10-9

8

7

6

2-5

3-4

Enamine

(3) 0.97 - 1.00

(m, 6 H)

2.19 -2.34

(m, 1 H)

4.13 (dd, J=13.75, 6.93 Hz,1 H)

6.15 (d,

J=13.85

Hz, 1 H)

2.88 -2.99

(m, 5 H)

1.76 - 1.86 (m,4

H)

δ in (ppm), multiplicity (s: singlet, d: doublet, dt: double triplet, t: triplet, dt: double triplet, dc: double quadrupole m: multiplete)

Table 3. Assignment of proton signals. The numbers correspond to the signals according to

the numbering in Fig. 16.

3 Anex I


38

5.1.2 Preparation of methallyltriphenylphosphonium chloride

In parallel with the previous reaction, the reaction of phosphonium ylide, which starts

with triphenylphosphine (5), was carried out, with a solid salt which was atomized

with 3-chloro-2-methylpropene (6) at 50 ° C for 24 h with magnetic stirring. The

result is a white precipitate which is extracted by vacuum distillation using CH3CN as

washing water. The characterization was carried out by measuring the melting point

of the two portions which were obtained and by 1 H-NMR of the first portion, yielding

the following results:

C l-

P+

21

2019

22

1514

13

12

16

5

4 3

2

6 8

CH310

CH223

Fig 17. Methallytriphenylphosphonium different 1H signals. Each number corresponds with

one signal however because of symmetry there are equivalent signals4

4 Anex II


39

Table 4. Assignment of proton signals. The numbers correspond to the signals according to

the numbering in Fig. 17.

5.1.3 Alkylation of pyrrolidine 1(3methylbut1enyl)

The alkylation reaction of the enamine product of the first reaction is carried out with

an equimolar reaction of this enamine with acrylonitrile in acetonitrile for 18 h for

subsequent acid work-up. However, this last stage turned out to be a critical stage of

the reaction and the expected results were not obtained (expecting results in table 6.)

so that different reaction conditions were changed and the results were observed:

1H-RMN (CDCl3 )

Compound

10

23

8

5-3-14-

15-19-21

4-20-13

2-6-12-16-

22

Methallyltriphenylphos

phonium

1.44 - 1.67 (m, 3

H)

4.77

(d,

J=15.51

Hz, 2 H)

4.88 (d,

J=5.17 Hz,

1)

5.03 (dt,

J=5.07,

1.19 Hz, 1

HH)

7.63 - 7.70 (m, 6

H)

7.73-

7.79 (m,

3 H)

7.82 - 7.89

(m, 6 H)

δ in (ppm), multiplicity (s: singlet, d: doublet, dt: double triplet, t: triplet, dt: double triplet, dc: double quadrupole m: multiplete)


40

Solvent Temperature Molecular

Sieves

Acid

work-

up

Acid

work-up

timming

Results

Acetonitrile 50 º C Yes Water 3 h Anex III

Acetonitrile Room-

Temperature

Yes Water

with

HCL

1h

Annex IV

Acetonitrile 75 º C No Water

with

HCL

3h Annex V

Acetonitrile Room-

Temperature

No Water

with 0,5

g

AcOH.0

,5g

AcONa

1h Annex VIII

Dichloromet

hane

Room-

Temperature

No Water 3h Annex VII

Without Room-

Temperature

No Water 3h Annex VI

Table 5. Example of different results obtained in the alkylation of enanime (3)


41

8

7

63

2

4

CH35

CH310

ON

Fig 18 . 4-Isopropyl-5-oxo-pentanenitrile different 1H signals. Each number corresponds with one signal however because of symmetry there are equivalent signals5

1H-RMN (CDCl3 )

Compound 8 7 6 3 2 4 5‐10

4-Isopropyl-

5-oxo-

pentanenitrile

2,4‐3( d, 1H) 2,3‐3

(d, 1H)

2,4‐3

(t,1H)

2,3‐2,6(Q, 1H)

9‐10

(d,1H)

1,9‐2,5

(dq, 1H)

1‐1,13

(d,6H)

δ in (ppm), multiplicity (s: singlet, d: doublet, dt: double triplet, t: triplet, dt: double

triplet, dq: double quadrupole m: multiplete)

Table 6. Theoretical 1H-RMN assignation of 2-Isopropyl-5-cyano-butanal. The numbering expressed in this table corresponds with numbering in Fig 18.

5 Anex III‐VIII


42


43

6. CONCLUSION

During the period in which this work was carried out it was possible to reach a series

of objectives that are summarized as follows:

1º. First, a study on the role of semiochemicals in the communication between living

beings and their uses in different interdisciplinary fields.

2º .A search and comparative of different methods of synthesis of the semiochemical

Solanone depending on the use that it has later.

3º. The synthesis and characterization of pyrrolidine 1-(3-methylbut-1-enyl) using the

method John Nicholson (1965) and a later optimization to obtain a better result.

4º. The formation and characterization of methallyltriphenylphosphonium chloride

with a better yield than bibliographical.

5º. Planning different reaction conditions for the alkylation of 1-(3-methylbut-1-enyl).

However, it has not been possible to complete all the initial objectives for this work

because it has not been possible to find the necessary conditions for the alkylation

reaction to be our critical stage.

To end this work I would like to use the following sentence:

“I did not fail. I have found 10000 ways that do not work"

Thomas Edison

7. BIBLIOGRAPHY

Butenandt, A, Beckmann, R, Stamm, D & Hecker, E (1959) Uber den sexual-lockstoff

des seidenspinners Bombyx mori – reindarstellung und konstitution. Zeitschrift Fur


44

Naturforschung Part B-Chemie Biochemie Biophysik Biologie Und Verwandten

Gebiete 14: 283–4.

Cummins, S F & Bowie, J H (2012) Pheromones, attractantsand other chemical cues

of aquatic organismsand amphibians. Nat Prod Rep 29: 642–58.

Ho, H.-Y., Kuarm, B.S., Ke, C.-H., Ma, Y.-K., Lee, H.-J., Cheng, C.-C., Liu, K.K., and

Millar, J.G. 2014.Identification of the major sex pheromone component of the scale

insect, Aulacaspis murrayae Takahashi. J. Chem. Ecol. 40:

Karlson, P & Lüscher, M (1959) ‘Pheromones’: a new term for a class of biologically

active substances. Nature 183: 55–6

Nordlund, D A & Lewis, W J (1976) Terminology ofchemical releasing stimuli in

intraspecific interspecific interactions. J Chem Ecol 2: 211–20.

van Lenteren, J C (ed.) (2012) IOBC Internet Book ofBiological Control, 6th edn.

Wageningen, theNetherlands: Available fromwww.iobc-

global.org/publications_iobc_internet_book_of_biological_-control.html.

Tristam.D.Wyatt.2014. Pheromones and Animal behavior. Chemical signals and

signature mixture


45

8. ATTACHEMENTS

Annex I pyrrolidine 1(3methylbut1enyl)

Annex II methallyltriphenylphosphonium chloride

Annex IIIVIII Alkylation of pyrrolidine 1(3methylbut1enyl) with reaction conditions appear in Table 5.

15/01/2017 11:12:47 p.m.

Acquisition Time (sec) 3.3114 Comment =1H CDCl3 D:\\ d2arm00102 19 Date 18 Jul 2016 12:31:28Date Stamp 18 Jul 2016 12:31:28 File Name C:\Users\usuario\Desktop\TFG\AR16 ENAMINA\1\pdata\1\1rFrequency (MHz) 400.13 Nucleus 1H Number of Transients 16 Origin spect Original Points Count 22435Owner bruker Points Count 32768 Pulse Sequence zg30 Receiver Gain 25.40 SW(cyclical) (Hz) 6775.07Solvent CHLOROFORM-d Spectrum Offset (Hz) 3000.9736 Spectrum Type STANDARD Sweep Width (Hz) 6774.86Temperature (degree C) 27.060

This report was created by ACD/NMR Processor Academic Edition. For more information go to www.acdlabs.com/nmrproc/

1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.97 - 1.00 (m, 7 H) 1.76 - 1.86 (m, 5 H) 2.19 - 2.34 (m, 1 H) 2.88 - 2.99 (m, 5 H) 4.13 (dd, J=13.75, 6.93 Hz,1 H) 6.15 (d, J=13.85 Hz, 1 H)

VerticalScaleFactor = 1AR16 ENAMINA.001.001.1r.esp

6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)

0

0.25

0.50

0.75

1.00

Nor

mal

ized

Inte

nsity

0.266.430.300.254.420.311.134.481.000.91

M01(m)

M06(d) M05(dd)

M02(m)M04(m)

M03(m)

0.920.93

0.950.

970.

980.99

1.09

1.11

1.11

1.19

1.721.73

1.80

1.80

1.81

1.82

1.83

1.85

2.16

2.24

2.26

2.26

2.28

2.94

2.942.

952.

952.

97

3.424.

104.

124.

144.

156.13

6.17

No. (ppm) (Hz) Height1 0.92 366.4 0.02472 0.93 373.8 0.03483 0.95 380.2 0.03984 0.97 386.6 0.08865 0.98 391.4 0.97406 0.98 393.2 0.09897 0.99 398.0 1.00008 1.09 437.7 0.05389 1.11 444.3 0.050910 1.11 444.7 0.0520

No. (ppm) (Hz) Height11 1.17 467.2 0.047912 1.19 474.3 0.049913 1.72 689.5 0.020714 1.73 693.2 0.035015 1.74 696.1 0.020616 1.80 718.9 0.023517 1.80 721.6 0.027018 1.81 725.5 0.143519 1.82 728.6 0.145320 1.83 732.1 0.3585

No. (ppm) (Hz) Height21 1.84 735.6 0.132622 1.85 738.7 0.137823 2.16 865.7 0.101424 2.16 866.1 0.110225 2.17 866.5 0.079526 2.23 890.9 0.028227 2.23 891.5 0.028228 2.24 897.5 0.047329 2.26 904.3 0.045330 2.26 905.0 0.0447

No. (ppm) (Hz) Height31 2.28 911.0 0.027632 2.94 1174.6 0.137033 2.94 1177.3 0.091534 2.95 1178.7 0.121335 2.95 1181.2 0.287936 2.96 1183.7 0.107437 2.96 1185.3 0.082338 2.97 1187.8 0.121039 3.42 1367.1 0.032040 4.10 1641.8 0.0632

No. (ppm) (Hz) Height41 4.12 1648.9 0.062242 4.14 1655.7 0.065343 4.15 1662.5 0.063144 6.13 2454.2 0.082945 6.17 2468.1 0.0801

No. Shift1 (ppm) H's Type J (Hz) Multiplet1 Connections (ppm)1 0.99 7 m - M01 - [0.97 .. 1.00]2 1.82 5 m - M02 - [1.76 .. 1.86]3 2.25 1 m - M03 - [2.19 .. 2.34]4 2.95 5 m - M04 - [2.88 .. 2.99]5 4.13 1 dd 13.75, 6.93 M05 M06, ? [4.08 .. 4.17]6 6.15 1 d 13.85 M06 M05 [6.13 .. 6.17]

No. (ppm) Value Absolute Value Non-Negative Value1[0.9665 .. 0.9710]0.26286003 2.79857640e+7 0.262860032[0.9710 .. 1.0026]6.42515182 6.84062848e+8 6.425151823[1.0866 .. 1.1191]0.29967812 3.19056520e+7 0.299678124[1.1583 .. 1.1929]0.25350040 2.69892780e+7 0.253500405[1.7637 .. 1.8571]4.41985607 4.70566176e+8 4.419856076[2.1298 .. 2.1872]0.31265008 3.32867300e+7 0.312650087[2.1872 .. 2.3379]1.12859082 1.20157008e+8 1.128590828[2.8834 .. 2.9911]4.48456764 4.77455808e+8 4.484567649[4.0840 .. 4.1700]1.00387824 1.06879312e+8 1.0038782410[6.1263 .. 6.1741]0.90682304 9.65461920e+7 0.90682304


15/01/2017 11:36:26 p.m.

Acquisition Time (sec) 3.3114 Comment =1H CDCl3 D:\\ d3jcobo 11 Date 08 Jul 2016 14:11:44Date Stamp 08 Jul 2016 14:11:44 File Name C:\Users\usuario\Desktop\TFG\AR-3 SAL DE FOSFORO\1\pdata\1\1rFrequency (MHz) 400.13 Nucleus 1H Number of Transients 16 Origin spectOriginal Points Count 22435 Owner bruker Points Count 32768 Pulse Sequence zg30Receiver Gain 90.50 SW(cyclical) (Hz) 6775.07 Solvent CHLOROFORM-dSpectrum Offset (Hz) 3000.9736 Spectrum Type STANDARD Sweep Width (Hz) 6774.86 Temperature (degree C) 26.960


1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.44 - 1.67 (m, 3 H) 4.77 (d, J=15.51 Hz, 2 H) 4.88 (d, J=5.17 Hz, 1 H) 5.03 (dt, J=5.07, 1.19 Hz, 1 H) 7.63 -7.70 (m, 6 H) 7.73 - 7.79 (m, 3 H) 7.82 - 7.89 (m, 6 H)

VerticalScaleFactor = 1AR-3 SAL DE FOSFORO.001.001.1r.esp

8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5Chemical Shift (ppm)

0

0.25

0.50

0.75

1.00

Nor

mal

ized

Inte

nsity

3.001.930.980.975.852.905.85

M03(d)

M04(dt)

M06(m)

M05(m)

M02(d)

M07(m)

M01(m)

1.57

1.58

1.58

2.43

4.75

4.79

4.89

5.02

5.035.04

7.297.

647.65

7.66

7.66

7.68

7.75

7.83

7.837.

867.

887.

887.

89

No. Shift1 (ppm) H's Type J (Hz) Multiplet1 Connections (ppm)1 1.58 3 m - M01 - [1.44 .. 1.67]2 4.77 2 d 15.51 M02 - [4.73 .. 4.80]3 4.88 1 d 5.17 M03 M04 [4.86 .. 4.91]4 5.03 1 dt 5.07, 1.19 M04 M03, ? [5.01 .. 5.06]5 7.66 6 m - M05 - [7.63 .. 7.70]6 7.76 3 m - M06 - [7.73 .. 7.79]7 7.86 6 m - M07 - [7.82 .. 7.89]

No. (ppm) Value Absolute Value Non-Negative Value1[1.4428 .. 1.6733]3.00000000 2.39529072e+8 3.000000002[4.7290 .. 4.8004]1.93207288 1.54262544e+8 1.932072883[4.8626 .. 4.9104]0.97782600 7.80725840e+7 0.977826004[5.0066 .. 5.0557]0.97305351 7.76915360e+7 0.973053515[7.6253 .. 7.6961]5.84838533 4.66952768e+8 5.848385336[7.7339 .. 7.7928]2.89774632 2.31364832e+8 2.897746327[7.8186 .. 7.8915]5.84797668 4.66920160e+8 5.84797668

No. (ppm) (Hz) Height1 1.57 629.8 0.82322 1.58 631.0 0.82213 1.58 632.2 0.81824 2.43 972.4 0.25605 4.75 1901.3 0.58856 4.79 1916.8 0.59067 4.88 1951.8 0.24768 4.89 1956.9 0.24999 5.02 2008.8 0.170010 5.02 2010.3 0.202311 5.03 2011.1 0.1765

No. (ppm) (Hz) Height12 5.03 2014.0 0.176813 5.04 2015.3 0.201514 5.04 2016.3 0.167715 7.29 2915.5 0.318016 7.63 3054.8 0.275417 7.64 3055.7 0.398318 7.64 3057.3 0.267519 7.64 3058.3 0.311020 7.65 3059.2 0.422721 7.65 3061.5 0.331722 7.66 3063.1 0.9888

No. (ppm) (Hz) Height23 7.66 3066.4 0.995624 7.67 3069.3 0.364025 7.67 3071.0 0.717426 7.68 3072.8 0.411827 7.68 3074.3 0.690928 7.74 3096.4 0.202529 7.74 3097.6 0.428530 7.74 3098.9 0.392031 7.75 3099.5 0.448032 7.75 3100.7 0.252433 7.76 3103.2 0.1840

No. (ppm) (Hz) Height34 7.76 3105.1 0.642435 7.77 3107.1 0.635736 7.77 3109.2 0.158137 7.78 3111.3 0.134138 7.78 3112.7 0.218139 7.78 3113.3 0.193940 7.78 3114.6 0.214341 7.79 3115.8 0.108342 7.83 3132.2 0.827343 7.83 3133.4 0.967344 7.84 3135.5 0.2364

No. (ppm) (Hz) Height45 7.85 3140.6 0.801046 7.85 3141.7 0.619847 7.86 3144.8 0.843548 7.86 3146.2 1.000049 7.87 3148.1 0.246250 7.88 3153.3 0.777851 7.88 3154.5 0.600252 7.89 3156.4 0.0966


08/02/2017 11:12:21

Acquisition Time (sec) 4.8366 Comment Reactor =1H CDCl3 D:\\ d2arm00102 12 Date 28 Jul 2016 02:58:34Date Stamp 28 Jul 2016 02:58:34 File Name C:\Users\dell\AppData\Local\Temp\wz0538\AR1-04-2\1\pdata\1\1rFrequency (MHz) 400.13 Nucleus 1H Original Points Count 32768 Points Count 32768SW(cyclical) (Hz) 6775.07 Solvent CHLOROFORM-d Spectrum Offset (Hz) 3000.9736 Sweep Width (Hz) 6774.86Temperature (degree C) 0.000


VerticalScaleFactor = 1AR1-04-2.001.001.1r.esp

16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)

0

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

0.50

0.55

0.60

0.65

0.70

0.75

0.80

0.85

0.90

0.95

1.00

Nor

mal

ized

Inte

nsity

08/02/2017 11:13:00

Acquisition Time (sec) 4.8366 Comment =1H CDCl3 D:\\ d2arm00102 13 Date 28 Jul 2016 02:58:42Date Stamp 28 Jul 2016 02:58:42 File Name C:\Users\dell\AppData\Local\Temp\wzdb35\AR1-4B\1\pdata\1\1rFrequency (MHz) 400.13 Nucleus 1H Original Points Count 32768 Points Count 32768SW(cyclical) (Hz) 6775.07 Solvent CHLOROFORM-d Spectrum Offset (Hz) 2964.1301 Sweep Width (Hz) 6774.86Temperature (degree C) 0.000


VerticalScaleFactor = 1AR1-4B.001.001.1r.esp

16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)

0

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

0.50

0.55

0.60

0.65

0.70

0.75

0.80

0.85

0.90

0.95

1.00

Nor

mal

ized

Inte

nsity

08/02/2017 11:13:50

Acquisition Time (sec) 4.8366 Comment =1H CDCl3 D:\\ d2arm00102 14 Date 28 Jul 2016 02:59:00Date Stamp 28 Jul 2016 02:59:00 File Name C:\Users\dell\AppData\Local\Temp\wz6ef9\AR1-4C\1\pdata\1\1rFrequency (MHz) 400.13 Nucleus 1H Original Points Count 32768 Points Count 32768SW(cyclical) (Hz) 6775.07 Solvent CHLOROFORM-d Spectrum Offset (Hz) 2965.8628 Sweep Width (Hz) 6774.86Temperature (degree C) 0.000


VerticalScaleFactor = 1AR1-4C.001.001.1r.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 1.5 1.0 0.5Chemical Shift (ppm)

0

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

0.50

0.55

0.60

0.65

0.70

0.75

0.80

0.85

0.90

0.95

1.00

Nor

mal

ized

Inte

nsity

08/02/2017 11:17:39

Acquisition Time (sec) 4.8366 Comment =1H CDCl3 D:\\ g1jcobo 29 Date 25 Oct 2016 00:34:36Date Stamp 25 Oct 2016 00:34:36 File Name C:\Users\dell\AppData\Local\Temp\wzb0bc\Reaccionacrilonitrilo\1\pdata\1\1rFrequency (MHz) 400.13 Nucleus 1H Original Points Count 32768 Points Count 32768SW(cyclical) (Hz) 6775.07 Solvent CHLOROFORM-d Spectrum Offset (Hz) 3070.6233 Sweep Width (Hz) 6774.86Temperature (degree C) 0.000


VerticalScaleFactor = 1Reaccionacrilonitrilo.001.001.1r.esp

10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)

0

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

0.50

0.55

0.60

0.65

0.70

0.75

0.80

0.85

0.90

0.95

1.00

Nor

mal

ized

Inte

nsity

08/02/2017 11:18:51

Acquisition Time (sec) 4.8366 Comment =1H CDCl3 D:\\ d2arm00102 57 Date 28 Jul 2016 02:59:28Date Stamp 28 Jul 2016 02:59:28 File Name C:\Users\dell\AppData\Local\Temp\wzfe26\DCL\1\pdata\1\1rFrequency (MHz) 400.13 Nucleus 1H Original Points Count 32768 Points Count 32768SW(cyclical) (Hz) 6775.07 Solvent CHLOROFORM-d Spectrum Offset (Hz) 2968.7156Sweep Width (Hz) 6774.86 Temperature (degree C) 0.000


VerticalScaleFactor = 1DCL.001.001.1r.esp

10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)

0

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

0.50

0.55

0.60

0.65

0.70

0.75

0.80

0.85

0.90

0.95

1.00

Nor

mal

ized

Inte

nsity

08/02/2017 11:14:49

Acquisition Time (sec) 4.8366 Comment =1H CDCl3 D:\\ d2arm00102 55 Date 28 Jul 2016 02:59:26Date Stamp 28 Jul 2016 02:59:26 File Name C:\Users\dell\AppData\Local\Temp\wz68da\CH3CN\1\pdata\1\1rFrequency (MHz) 400.13 Nucleus 1H Original Points Count 32768 Points Count 32768SW(cyclical) (Hz) 6775.07 Solvent CHLOROFORM-d Spectrum Offset (Hz) 2969.3560 Sweep Width (Hz) 6774.86Temperature (degree C) 0.000


VerticalScaleFactor = 1CH3CN.001.001.1r.esp

10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)

0

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

0.50

0.55

0.60

0.65

0.70

0.75

0.80

0.85

0.90

0.95

1.00

Nor

mal

ized

Inte

nsity

Date post:	17-Aug-2020
Category:	Documents
Upload:	others
View:	1 times
Download:	0 times

New synthesis of solanone...

Documents