VALIDATION SHEET

Writers,

Aldona Jasa Prima P. Lia Khairun Nisa

NIS. 08 54 06113 NIS. 08 54 06229

Parents,

Japansus Purba Wateno

Bogor, 29 April 2010

Teacher of subject,

Rusman, M.Si

NIP 19781113 200502 1 001

i

PREFACE

Firstly we would like to deliver great gratitude to God Almighty for the chance given to finish this kind of paper. We also would like to deliver thanks to our beloved teacher, Mr. Rusman, M.Si as the organic subject teacher who has given his belief for us to finish this duty. Great thanks also delivered to all of our friends who have supported us to finish this duty.

As we all know, organic matters or materials are always near with us. As chemical students knowledge of those organic materials is necessary to know, especially if the organic materials is included to the dangerous ones. There are actually plenty benefits given by the organic compounds for human. That is why by knowing all the organic materials properties, preparation, presence; etc people can exploit the materials to develop useful necessity for them.

This paper- Cyclopropane is one result of an effort of searching the knowledge and understanding to organic compound. The writers include the properties, presence, preparation, functions, and dangers of the cyclopropane. Those kinds of information are obtained from several literature and sources which the writers try to deliver to the readers and to make the understanding and knowledge about cyclopropane summarized in one kind of paper.

After reading this paper the writers hope that the reader will get beneficial information about cyclopropane and also the readers can give suggestions and comments about this paper in order the writers can always improve the ability of writing information.

The writers,

ii

Table of Contents

VALIDATION SHEET................................................................................................................................. i

PREFACE................................................................................................................................................. ii

Table of Contents.................................................................................................................................. iii

Table of Figure.................................................................................................................................. iv

List of Attachment............................................................................................................................v

List of table........................................................................................................................................vi

Physical and Chemical Properties..........................................................................................................1

Physical properties.............................................................................................................................1

Chemical Properties..........................................................................................................................3

Preparation of Cyclopropane.................................................................................................................5

Synthesis Reactions...........................................................................................................................5

Synthesis Reaction of Cyclopropanes............................................................................................5

Preparation from Natural Source................................................................................................15

The Presence of Cyclopropane............................................................................................................17

The Usage of Cyclopropane.................................................................................................................19

The Usage Case of Cyclopropane.........................................................................................................22

ATTACHMENTS....................................................................................................................................30

iii

Table of Figure

Figure 1 1...............................................................................................................................................1Figure 1 2...............................................................................................................................................1Figure 1 3.............................................................................................................................................19Figure 1 4.............................................................................................................................................19

iv

List of Attachment

v

List of Table

vi

Physical and Chemical Properties

Physical propertiesCyclopropane

   

Cyclopropane is a cycloalkanemolecule with the molecular formula C3H6,

consisting of three carbonatoms linked to each other to form a ring, with each

carbon atom bearing two hydrogen atoms. Cyclopropane and propene have the

same empirical formula but have different structures, making them structural

isomers.

The bonds between the carbon atoms are considerably weaker than in a

typical carbon-carbon bond, yielding reactivity similar to or greater than alkenes.

Baeyer strain theory explains why: the angle strain from the 60° angle between

the carbon atoms (less than the normal angle of 109.5° for bonds between atoms

with sp3hybridised orbitals) reduces the compound's carbon-carbon bond energy,

making it more reactive than other cycloalkanes such as cyclohexane and

cyclopentane. The molecule also has torsional strain due to the eclipsed

conformation of its hydrogen atoms. It is somewhat stabilized by some pi

character in its carbon-carbon bonds, indicated by the Walsh orbital description

whereas it is modeled as a three-center-bonded orbital combination of methylene

carbenes.

Cyclopropane is included to cyclic aliphatic hydrocarbons (Table. 1.2)

resemble those of the corresponding open-chain hydrocarbons, although the

boiling points and densities of compounds are somewhat higher. Being non polar

or weakly polar compounds, cyclic hydrocarbons dissolve in non polar or weakly

polar solvents like carbon tetrachloride, ligroin, or ether, and do not dissolve in

the highly polar solvent water.

Molecular weight  42.08 g/mol

1

Figure 1 1Figure 2 1

Figure 3 : Line Structure

Figure 1Figure 2 : Molecular

StructureFigure 1. 1Figure 1 : Complete Structure

Critical point

Critical temperature 

Critical pressure 

125.1 °C

55.8 bar

Gaseous phase

Specific gravity (air = 1) (1.013 bar and 21 °C (70

°F))

Specific volume (1.013 bar and 21 °C (70 °F

1.45

0.574 m3/kg

Miscellaneous

Solubility in water (1.013 bar and 21 °C (70 °F))

Autoignition temperature

0.308

vol/vol

495 °C

Name Melting

point 0C

Boiling

Point 0C

Density

at 200C

Cyclopropane -127 -33

Cyclobutane -80 13

Cyclopentane -94 49 0.746

Cyclohexane 6.5 81 0.778

Cycloheptane -12 118 0.810

Cyclooctane 14 149 0.830

Methyl

cyclopentane

-142 72 0.749

2

Table 1 1

Cis-1,2-

dimethylcyclopentane

-62 99 0.772

Trans-1,2-

dimethyl cyclopentane

-120 92 0.750

Methylcyclohexa

ne

-126 100 0.769

Cyclopentane -93 46 0.774

1,3-

cyclopentadiene

-85 42 0.798

Cyclohexene -104 83 0.810

1,3-

cyclohexadiene

-98 80.5 0.840

1,4-

cyclohexadiene

-49 87 0.847

Chemical Properties

Cyclopropane can also undergo certain addition reactions. These addition

reactions destroy the cyclopropane ring system and yield open-chain products

A C-C bond in cyclohexane is about as strong as

an interior bond in butane, but the ring strain in cyclopropane provides a C-C

bond strength that is somewhat weaker than one of the bonds of a double bond .

As a result , cleavage of one of the cyclopropane bonds is much more exothermic

than cleavage of a normal single bond. However, not all relief of ring strain is

obtained at the transition state and cyclopropyl rings are generally substantially

less reactive than alkenen double bonds. Cyclopropane is unaffected by cold

potassium permanganate or ozone , whereas alkenes react immediately with

both reagents.

Cyclopropane and alkylcyclopropane undergo ring opening with

hydrogenation catalyst under e that are somewhat more vigorous than the

condition necessary to reduce alkenes.

3

Table 2 1

Reaction :

Reaction with aquaeous acids, such as hydrobromic acid, is relatively fas

to give n-propyl compounds.

Reaction:

These reactions are probably of the carbonium ion type. In the case of

substituted cyclopropanes, the mode of ring opening is that which gives the most

stable carbonium ion, but the reaction has little practical use. Cylopropane reacts

with hydrogen in the presence of a catalyst to form propane , with bromine to

form 1,3-dibromopropane, and with hydriodic acid to form n-propyl iodide.

Reaction :

By contrast cyclopropane undergoes normal photochemical chlorination to

give cyclopropyl chloride.

Reaction:

+ Cl2

4

H2(1 atm)

50 O

Pt/C

CH3CH2CH3

aq. HBr

CH3CH2CH2Br

CH3

H+

h.v

CH3CH2CHBrCH3

Cl+HCl

5

Preparation of Cyclopropane

Synthesis Reactions

The synthesis of chiral cyclopropane remains a considerable challenge,

especially due to the fact that Organic chemist have always been fascinated by

the cyclopropane subunit which has played and continues to play prominent role

in organic chemistry. It is strained structure, interesting bond characteristics and

value as internal mechanistic probe have attarced the attention of the physical

organic community.

For example they constitute a common structural motif in phyretroids, the

anti depressant, tranylcypromine, papain, and cystein protease inh

The industrial and laboratory preparation of cyclopropane occurs in the

synthesis of some compounds to produce the cyclopropane as the product.

Despite the high ring strain can be constructed with relative ease, primarily

because the two functional groups involved in ring formulation are close

neighbors.

Synthesis Reaction of Cyclopropanes

Basic Reaction

1. Cyclopropane itself can be prepared by treating 1,3-diromopropane

with zinc. The reaction probably involves the formation of an

intermediate organozinc compound.

Reaction :

BrCH 2CH 2CH2Br Zn , ALCOHOL∆→

[Br CH2CH 2CH 2ZnBr ]→

2. Simmons-Smith Reaction

6

+ ZnBr2

A generally better method for accomplishing this ring closure starts with

an alkene and the Simmons-Smith reagent, a material that appears to

be an iodomethylzinc. The reagent was developed in 1959 by DuPont

chemist , Howard E. Simmons and Ronald D. Smith, and is prepared as

needed by treating zinc dust with cupric sulfate solution to give a zinc

copper copule. A suspension of the couple in ether is refluxed with the

alkene and methylene iodide. Variations of this general procedure have

since been developed.

Reaction:

CH 2 I 2+Zn (Cu )→ICH 2ZnI

C=C + I CH 2ZnI ether∆→

This reaction is applicable to many kinds of double bonds. The yields are

generally only fair (30%-70%) but the products are often difficult to

prepare y alternative routes.

CH 3 (CH 2 )4CH=CH 2Zn (Cu )

CH2 I2 , ether→

CH 3 (CH 2)4CHCH 2CH 2

3. Wurtz Reaction (intramolecular modification)

7

CH2-CH2

I CH2ZnI+ ZnI2

30%

pentylcyclopropane1-hepetene

4. Corey-Chaykovsky Reaction

Reaction from Recent Literature

1.

Suitable conditions enable the Suzuki-Miyaura coupling reaction of

potassium cyclopropyl- and cyclobutyltrifluoroborates in moderate to

excellent yield with electron-rich, electron-poor, and hindered aryl

chlorides to give various substituted aryl cyclopropanes and

cyclobutanes.

G. A. Molander, P. E. Gormisky, J. Org. Chem., 2008, 73, 7481-7485.

8

2.

The palladium-catalyzed cross-coupling reaction of tricyclopropylbismuth

with aryl and heterocyclic halides and triflates tolerates numerous

functional groups and does not require anhydrous conditions. The

method was successfully extended to the cross-coupling of

triethylbismuth.

A. Gagnon, M. Duplessis, P. Alsabeh, F. Barabé, J. Org. Chem., 2008,

73, 3452-3459.

3.

A class of zinc reagents (RXZnCH2Y) is very effective for the

cyclopropanation of olefins. The reactivity and selectivity of these

reagents can be regulated by tuning the electronic and steric nature of

the RX group. A reasonable level of enantioselectivity was obtained for

the cyclopropanation of unfunctionalized olefins with chiral

(iodomethyl)zinc species.

J. C. Lorenz, J. Long, Z. Yang, S. Xue, X. Xie, Y. Shi, J. Org. Chem.,

2004, 69, 209-212.

4.

9

A mixture of ZnI2, EtZnI·2OEt2 and CHI3 produces a gem-

dizinccarbenoid that is an efficient cyclopropanating reagent, which

shortens reaction times and leads to cleaner reactions, particularly with

less reactive substrates. Mechanistic aspects of the reaction are

discussed.

J.-F. Fournier, A. B. Charette, Eur. J. Org. Chem., 2004, 1401-1404.

5.

A new class of anionic, boron-bridged analogues of the box ligands was

developed. These borabox ligands showed a considerable potential for

asymmetric cyclopropanation and desymmetrizations of mesodiols.

C. Mazet, V. Koehler, A. Pfaltz, Angew. Chem. Int. Ed., 2005, 44, 4888-

4891.

6.

A new nucleophilic isopropyl transfer reagent,

triisopropylsulfoxoniumtetrafluoroborate, converts after deprotonation

10

with NaH a range of electron deficient alkenes, including several

chalcone analogues, α,β-unsaturated ketones, dienones and quinones,

plus α,β-unsaturated esters, nitrile, sulfone and nitro examples into the

corresponding gem-dimethylcyclopropane compounds.

M. G. Edwards, R. J. Paxton, D. S. Pugh, A. C. Whitwood, R. J. K.

Taylor, Synthesis, 2008, 3279-3288.

7.

In a Rh-catalyzed procedure for the cyclopropanation of alkenes with α-

alkyl-α-diazoesters, sterically demanding carboxylate ligands serve to

avoid β-hydride elimination. The use of triphenylacetate (TPA) as ligand

also imparts high diastereoselectivity.

P. Panne, A. DeAngelis, J. M. Fox, Org. Lett.,2008, 10, 2987-2989.

8.

A samarium-promoted cyclopropanation can be carried out on

unmasked (E)- or (Z)-α,β-unsaturated carboxylic acids. In all cases the

process is completely stereospecific and stereoselective. A mechanism

has been proposed.

J. M. Concellón, H. Rodríguez-Solla, C. Simal, Org. Lett., 2007, 9, 2685-

2688.

9.

11

Efficient, simple, cheap, and environmentally benign preparations of

cyclopropanes were achieved. One method is based on a 3-exo-trig

cyclisation of various electron-deficient 2-iodoethyl-substituted olefins

with zinc powder in a mixture of t-butyl alcohol and water, and the other

on a 3-exo-tet cyclisation of various 1,3-dihalopropanes with zinc powder

in ethanol.

D. Sakuma, H. Togo, Tetrahedron, 2005, 61, 10138-10145.

10.

D. Sakuma, H. Togo, Tetrahedron, 2005, 61, 10138-10145.

11.

Methyl 1-aryl-2-amino-cyclopropane carboxylates have been readily

synthesized in high yields by Rh-catalyzed decomposition of

aryldiazoacetates in the presence of N-vinylphthalimide. The reaction is

highly trans-selective.

T. Melby, R. A. Hughes, T. Hansen, Synlett, 2007, 2277-2279.

12.

12

The first Corey-Chaykovskyepoxidation and cyclopropanation using

trimethylsulfonium iodide/trimethylsulfoxonium iodide and KOH as base

in the recyclable ionic liquid, (bmim)PF6 are described.

S. Chandrasekhar, Ch. Narasihmulu, V. Jagadeshwar, K. Venkatram

Reddy, Tetrahedron Lett.,2003, 44, 3629-3630.

13.

(S)-(-)-indoline-2-yl-1H-tetrazole readily facilitates the

enantioselectiveorganocatalyticcyclopropanation of α,β-unsaturated

aldehydes with sulfur ylides, providing cyclized product in excellent

diastereoselectivities and enantioselectivities.

A. Hartikka, P. I. Arvidsson, J. Org. Chem., 2007, 72, 5874-5877.

14.

Three highly enantio- and diastereoselective one-pot procedures for the

synthesis of cyclopropyl and iodocyclopropyl alcohols with up to four

contiguous stereocenters are reported. Route 1 and 2 involve

asymmetric addition of an alkylzinc reagent to an enal followed by

13

diastereoselectivecyclopropanation using either diiodomethane or

iodoform to generate the zinc carbenoid, leading to cyclopropyl or

iodocyclopropyl alcohols, respectively. Route 3 entails asymmetric

vinylation of an aldehyde with divinylzinc reagents and subsequent

diastereoselectivecyclopropanation.

H. Y. Kim, A. E. Lurain, P. Garcia-Carcia, P. J. Carroll, P. J. Walsh, J.

Am. Chem. Soc., 2005, 127, 13138-13139.

15.

H. Y. Kim, A. E. Lurain, P. Garcia-Carcia, P. J. Carroll, P. J. Walsh, J.

Am. Chem. Soc., 2005, 127, 13138-13139.

16.

An organocatalytic asymmetric cascade Michael reaction of α,β-

unsaturated aldehydes with bromomalonates, efficiently catalyzed by

chiral diphenylprolinol TMS ether in the presence of base 2,6-lutidine,

gives cyclopropanes in high enantio- and diastereoselectivities. Using

NaOAc as base, a spontaneous ring-opening of cyclopropanes leads to

(E) α-substituted malonate α,β-unsaturated aldehydes.

14

H. Xie, L. Zu, H. Li, J. Wang, W. Wang, J. Am. Chem. Soc., 2007, 129,

10886-10894.

17.

The reaction of 1-aryl-2,2,2-trifluorodiazoethanes with alkenes provides

trifluoromethyl-substituted cyclopropanes with high diastereoselectivity

and enantioselectivity in the presence of an adamantylglycine-derived

dirhodium complex Rh2(R-PTAD)4 as catalyst.

J. R. Denton, D. Sukumaran, H. M. L. Davies, Org. Lett.,2007, 9, 2625-

2628.

18.

An efficient lithium amide-induced intramolecularcyclopropanation of

bishomoallylic and trishomoallylic epoxides is described. The

methodology is

used in an

asymmetric

synthesis of

sabina ketone.

15

D. M. Hodgson, Y. K. Chung, J.-M. Paris, J. Am. Chem. Soc., 2004, 126,

8654-8655.

19.

Exposure of enynes containing a hydroxyl group at one of the

propargylic positions to catalytic amounts of either PtCl2 or

(PPh3)AuCl/AgSbF6 results in a selective rearrangement with formation

of bicyclo[3.1.0]hexan-3-one derivatives. A total synthesis of the

terpenessabinone and sabinol is described.

V. Mamane, T. Gress, H. Krause, A. Fürstner, J. Am. Chem. Soc., 2004,

126, 8654-8655.

20.

V. Mamane, T. Gress, H. Krause, A. Fürstner, J. Am. Chem. Soc., 2004,

126, 8654-8655.

21.

The reaction of various 1,6-enynes with N2CHSiMe3 in the presence of

RuCl(COD)Cp* as catalyst precursor leads to the general formation of

alkenylbicyclo[3.1.0]hexanes at room temperature in good yield with high

stereoselectivity. The catalytic formation of alkenylbicyclo[3.1.0]hexanes

also takes place in the presence of  N2CHCO2Et or N2CHPh.

F. Monnier, C. Vovard-Le Bray, D. Castillo, V. Aubert, S. Dérien, P. H.

16

Dixneuf, L. Toupet, A. Ienco, C. Mealli, J. Am. Chem. Soc., 2007, 129,

6037-6049.

22.

F. Monnier, C. Vovard-Le Bray, D. Castillo, V. Aubert, S. Dérien, P. H.

Dixneuf, L. Toupet, A. Ienco, C. Mealli, J. Am. Chem. Soc., 2007, 129,

6037-6049.

23.

A new Pd-catalyzed oxidation reaction for the stereospecific conversion

of enynes into cyclopropyl ketones proceeds with net inversion of

geometry with respect to the starting olefin. This result is consistent with

a mechanism in which the key cyclopropane-forming step involves

nucleophilic attack of a tethered olefin onto the PdIV-C bond.

L. L. Welbes, T. W. Lyons, K. A. Cychosz, M. S. Sanford, J. Am. Chem.

Soc., 2007, 129, 5836-5837.

17

Preparation from Natural Source

A Simple Produce for Detecting the Presence of Cyclopropane Fatty

Acids in Bacterial Lipids.

Materials and methods

Cultural conditions

Cultures of E.coli strain B, S.marcescens,P.fluorescens, and V.cholerae

strain NIH 41 were maintained by monthly transfer on Trypticase Soy Agar (BBL)

slants. A 1-ml amount of an 18-hr (37o C) broth culture (pH 7,3) was inoculated

into each of two Roux flaks containing 100 ml of Trypticase Soy Brothand 3%

agar. Flaks were incubated for 24 hr at 37o C. cells harvested with 10 ml of 0,85%

NaCl were centrifuged for 30 min at 4,500 x g. All tests were conducted in

duplicate.

Lipid extraction and esterification of acids

Wet bacteria were suspended 20 ml of CHCl2-CH3OH (2:1, v/v) and

allowed to stand overnight. The suspension was filtered, and the solvent was

evaporated in astream of nitrogen. Fatty acids were esterified with 5 ml of BCl3-

CH3OH. CHCl3 (10ml) and water (3ml) were added, the mixture was shake in a

separatory funnel, and the lower phase was evaporated with nitrogen.

Elimination procedures

After gas-liquid chromatography of methyl esters from extracted lipids,

unsaturated components were hydrogenated for 15 min in 5% Pt on charcoal.

This procedure is selective in that unsaturated acids are converted to saturated

ones, although cyclopropane acids are not affected.

After gas-liquid chromatography of Hydrogenated samples

Remaining methyl eters (approximately 10 mg) were diluted in 2 ml of

diethyl ether (anhydrous, reagent grade) and cooled to 0o C. A1-ml amount of

18

bromine (reagent grade) in ether (1:5,,v/v) was added to each sample. Ether and

excess bromine were evaporated at 50oC with N2.

Gas-liquid chromatography. Gas-liquid chromatography was performed

wth an aerograph (Varian Associates, Palo Alto, Calif; model 204-1B) gas

chromatograph with flame ionization detectors. Columns (10 ft x 0,125 inch or 3

m x 3mm) containing 20% diethylenegycol succinate (DEGS) polyester on

Chromosorb W (60/80 mesh) were operated at 180o C. Detector and injector

temperatures were 210 o C, and the N2 flow was 20 ml/mi

19

The Presence of Cyclopropane

Cyclopropanes are a class of organic compounds sharing the common

cyclopropane ring, in which one or more hydrogens may be substituted. These

compounds are found in biomolecules; for instance, the pyrethrum insecticides

(found in certain Chrysanthemum species) contain a cyclopropane ring.

Cyclopropane rings are often found in a variety of natural products and biological

active compounds.Cyclopropane ring is a highly strained entity, it is nonetheless

found in a wide variety of naturally occurring compounds including terpenes,

pheromones, fatty acid metabolies and unsual amino acids. Cyclopropane

subunits also occur in many natural products of primary and seconday

metabolism. Indeed, the prevalence of cyclopropane containing compounds with

biological activity, whether isolated from natural sources or rationally designed

pharmaceutical agents.

Fatty acids containing one or more cyclopropane rings are present in

may bacteria. Mycobacteria are rich in cyclopropane ring-containing fatty acids.

These mycolic acids are major components of the cell walls and may account for

30% of the dry weight cells. The most abundant mycolic acid of M. tuberculosis

of C52fatty acid containing two cyclopropane rings joined via a claisen-type

condensation with C26 carboxylate fatty acid. A similar mycolic acid formed by

M..smegmatis has double bonds instead of cyclopropane rings as indicated.

Four gram-negative bacterial species, including Escherichia coliB,

Serratiamarcesnen, Pseudomonas fluorescens, and Vibrio cholera (comma)

strain NIH 41, were investigated for fatty acid content by gas-liquid

chromatography involving a preparatory technique which facilitated detection of

cyclopropane fatty acids. Methyl esters of fatty acids were subjected to mild

catalytic hydrogenation to eliminate unsaturates. Hydrogenation was followed by

bromination which removed cyclopropane acids from chromatographic profile

patterns. Lactobacillic acid (cis-11,12-methyleneoctanoate) and cis-9,10-

methylenehexadecanoate, previously reported in lipids of E.coli and

S.marcescens, were found in small amounts in P.fluorescens but were not

detected in V.cholerae.

20

Reports of lactobacillicacid (cis-11,12-mthyleneoctanoate) in lipids of

Lactobacillus arabinosus , Lactobacillus casei, Agrobacterumtumefaciens,

Escherichia coli, and Clotridiumbutyricum were followed by detection of both

lactobacillic and cis-9,10-methylenehexaddecanoic acids in lipids of E.coli,

A.tumefaciens, Serratiamarcescens, and Aerobacteraerogenes.

The methods usually employed for identification of cyclopropane fatty

acids include mild hydrogenation for selective removal of unsaturated acids,

infrared spectroscopy of isolated acids, and strong catalytic hydrogenation of the

ring structure, followed by analyses of resulting branched chain products.

Hydrogenation of the cyclopropane ring is difficult and results in additional peaks

when mixed fatty acid methyl esters are analyzed by gas-liquid chromatography.

The present study involves an investigation of a new and simple

procedure for detection of bacterial cyclopropane acids. Two organism known to

contain these acids, E.coli and S.marcescens, were compared with two

organism, Vibrio cholera (comma) and Pseudomonas fluorescens, in which such

acids have not been reported. Cultural conditions which favored production of

cyclopropane acids were used.

21

The Usage of Cyclopropane

Naturally occurring and synthetic cyclopropanes bearing simple or

complex functionalities are endowed with large spectrum of biological properties,

including enzyme inhibition, and insecticidal, antifungal, herbidical, antimicrobial,

antibiotic, anticacterial, anti tumor, and antiviral activities. ihibitors,potential

antipsychotic substances, anti HIV-agents, and marine lactones. So far,

thousands of natural compound and their derivatives carrying a cyclopropane

group have been synthetised and described in the literature. Indeed, with

represantion in more than 4000 natural isolates and 100 thereapeutic agents, the

cyclopropane motif has long been established as a valuable platform for the

development of a new asymmetric technologies.

Cyclopropane is an

anesthetic when inhaled. In modern

anaesthetic practice, it has been

superseded by other agents, due to

its extreme reactivity under normal

conditions.Colourless gas-

cyclopropane(C3H6 ) used in

medicine since 1934 as a general

anesthetic. Cyclopropane is

nonirritating to mucous membranes

and does not depress respiration.

Induction of and emergence from

cyclopropaneanesthesia are usually

rapid and smooth. A mixture of about

5 to 20 percent cyclopropane in

oxygen is administered by inhalation. Because of the flammability and expense of

cyclopropane, it is usually used in a closed (rebreathing) system, in which an

absorbent chemical, such as soda lime, removes exhaled carbon dioxide, and

the anesthetic is recirculated.

22

Figure iFigure 1.44Figure 1 3 Figure 4 : Anesthesia

The Disadvantages and Dangers of Cyclopropane

Hazards of Cyclopropane

Explosion

Because of the strain in the carbon-carbon bonds of cyclopropane, the

molecule has an enormous amount of potential energy. In pure form, it will break

down to form linear hydrocarbons, including "normal", non-cyclic propene. This

decomposition is potentially explosive, especially if the cyclopropane is liquified,

pressurized, or contained within tanks. Explosions of cyclopropane and oxygen

are even more powerful, because the energy released by the formation of

propene is compounded by the energy released via the oxidation of the carbon

and hydrogen present.

23

Table 3 1

HAZARDS

Major hazard : Asphyxiant

Toxicity (Am. Conf. Of Gov.

Ind. Hygienists ACGIH 2000 Edition) :

None Established

Flammability limits in air (STP conditions) : 2.4-

10.4 vol%

Odour : Petroleum Ether

UN Number : UN1027

EINECS Number : 200-847-8

DOT Label (USA) : FG

DOT Hazard class (USA) :

Flammable Gas

At room temperature, sufficient volumes of liquifiedcyclopropane will self-

detonate. To guard against this, the liquid is shipped in cylinders filled with

tungsten wool, which prevents high-speed collisions between molecules and

vastly improves stability. Pipes to carry cyclopropane must likewise be of small

diameter, or else filled with unreactive metal or glass wool, to prevent explosions.

Even if these precautions are followed, cyclopropane is dangerous to handle and

manufacture, and is no longer used for anaesthesia.Cyclopropane is an

anaesthetic when inhaled. In modern anaesthetic practice, it has been

superseded by other agents, due to its extreme reactivity under normal

conditions.

Effect of Cyclopropane in human health

Damage or injury to the liver caused by exposure to an anesthetic agent

called cyclopropane. Anesthetic agents are a relatively uncommon cause of liver

damage. Symptoms vary depending on the degree of exposure and hence extent

of the liver damage or injury. Mild liver damage may cause few if any symptoms

whereas severe damage can ultimately result in liver failure. Symptoms may be

acute, subacute or chronic depending on the severity of the exposure. Factors

such as age, race, gender, overall health and underlying liver problems may also

influence a person's risk of developing liver problems and the severity of the

symptoms.

Symptoms of Anesthetic agent-induced liver damage –Cyclopropane :

Asymptomatic - mild liver damage

Nausea

Vomiting

Abdominal pain

Loss of appetite

24

The Usage Case of Cyclopropane

Personal History

There are some personal histories obtained from the internet about the

case of Cyclopropane usage in human life, especially for anesthesia.

This one come from : Taunton, Somerset

  The anaesthetists at Musgrove Park Hospital occasionally used

cyclopropane, but not too often, except that is for MrsLailey. The problem was

that the general surgeons always wanted to use the diathermy so explosive

agents were out. In contrast the gynaecologists with whom MrsLailey worked

(including her husband) tied off bleeding points with thick ligatures rather than

‘frying’ them with the diathermy, so she was able to use whatever she wanted to.

‘I like to use nitrous oxide with lots of oxygen and a little cyclo,’ she would

say, ‘that way the patients stay pink and asleep, and the surgeon and I are both

happy.’

It certainly seemed to work well, together with some tubarine, for the

abdominal cases, whom we would ventilate by taking turns at squeezing the bag

of the ‘closed circuit’, which we always used, of course, because cyclopropane

was so explosive and expensive. For minor things, like ‘D & C’s, they just used a

hefty dose of thiopentone, say 400-500mg, followed by nitrous oxide and a small

dose of gallamine. The relaxant would ‘soften the patient up’ but was not enough

to stop them breathing. However, for emergency gynae cases out of hours, like a

D & C for an incomplete abortion when the patient had already lost a lot of blood,

I would often revert to MrsLailey’s mixture of nitrous oxide, oxygen and cyclo, but

without any relaxant, keeping the patients breathing normally while ‘pink and

asleep’.

I liked the gynae lists with MrsLailey. She was a motherly sort of woman

and we shared a deep appreciation of food in general, and of spinach in

particular. When there was a quiet moment during the list the conversation would

always get around to something edible. Also there was the excitement of never

knowing exactly what the surgeon would find inside the abdomen. Strange things

were always cropping up, even if they were only odd-shaped fibroids

25

The patients for hysterectomy always had high blood pressures, or so it

seemed. I used to wonder if treating the blood pressure first might not actually

cure the patient of her heavy periods even before she had her hysterectomy. Still

it would never have worked out that way because the anaesthetists were very

wary of patients on drugs for lowering high blood pressure as these often

interacted with the anaesthetic in an alarming fashion. At least that was the

theoretical worry, though I often found myself having to anaesthetise patients for

emergencies when there was no time to stop these particular drugs and it never

proved to be a problem in practice. Still it was the current teaching that anti-

hypertensives, and also anti-depressant drugs, should be withdrawn two or three

weeks before elective surgery. Occasionally this policy had disastrous results as

when, for example, one patient had a stroke during the waiting period, and

another committed suicide.

Although MrsLailey was the only person to use cyclopropane regularly the

other anaesthetists would at times use it to induce anaesthesia in children in the

way I had seen it used at Guy’s. I grew to enjoy this technique very much, though

in the ENT theatre, which was where I met most of my younger patients, I

continued to use ethyl chloride in the traditional manner. Nevertheless

cyclopropane played a small but useful part in my own practice, and it certainly

served both me and my patients well.

This one come from : Catterick Camp, Yorkshire

  Being on duty as Orderly Medical Officer (OMO) was certainly an

interesting occupation. The weekend started with a complaint from the brigadier

who had had his hernia repaired three days earlier. His supper was cold. He did

not see why he should put up with it. He told the nursing orderly so in no

uncertain manner.

The orderly, a quiet simple man, told the QARANC [1] sister who reported it

to the OMO, who was me. I felt quite unreasonably irritated. I marched down the

corridor to confront the general in a mood and manner that could only belong to a

national serviceman, or to someone who felt himself a national serviceman even

if he had taken a short service commission.

‘I hear that you have been complaining about your supper,’ I said

belligerently. ‘Surely you realise that the more important you are the more

26

important it is that you do not complain. If you do, it all gets blown up out of

proportion. I will have to put it into my report in the morning and some poor cook

will get into trouble. I expect you didn’t know that most of the cooks are off sick

and there are only four of them left to cook for the whole hospital.’ I did not add

that the hospital was nearly empty. That was immaterial.

The brigadier was clearly taken aback by the onslaught, but his wife

sniggered. Clearly she had never heard anyone talking to her husband in this

way. I withdrew before a counter attack could be mounted.

Ten minutes later they brought in a soldier with ‘the DTs’ who started

wrecking the reception department. I tried to reason with him at first but ended up

injecting paraldehyde into his leg to quieten him, thrusting the needle through the

cloth of his battledress trouser deep into the muscle of his thigh while three men

restrained him. Unusual, but effective The smell of the paraldehyde would

certainly hang around the room for the next two days.

Later in the day I got a call to visit a woman at home; she said she

feverish and unwell, and her husband was away on manoeuvres. This was the

life, I thought. Perhaps I should have been a general practitioner. I had a quick

stitch or two to put into a cut hand and then I was on my way.

I pulled up outside the house, locked the car and walked up the drive.

There seemed to be a sinister quietness about the place. I rang the bell. The

woman who opened the door to me was in a thin pink dressing gown. She looked

terribly ill. Her face was flushed and drawn, and her arms and body were

trembling. She smelt of stale sweat.

‘Thank God you’re here,’ she said. ‘I feel so ill. It’s my own fault. I

shouldn’t have done it. I hope I won’t die.’ She paused, and then ‘I think I am

going to die.’

‘What have you done? Tell me.’

‘I used a knitting needle on myself to get an abortion. I did it this morning.

I boiled it in Dettol first. I did this once before, two years ago, and it was OK then,

but this time I must have done something wrong. ‘

27

I stepped into the hall and followed her into the sitting room. I opened my

bag and got out the thermometer.

‘I’ll take your temperature, ‘ I said, and popped it into her mouth.

A minute later I looked at the thermometer in disbelief... 106.7oF! (we

would measure this as 41.5oC these days). Dear God, I had never seen or heard

of a temperature like that. 106.7oF? Surely it could not be compatible with life. I

looked again. There was no mistake. If I didn’t do something this very moment

the proteins in her brain would coagulate like the white of a boiled egg.

‘You will have to go to the hospital,’ I said, ‘but we will have to get your

temperature down first. It’s very, very high. I think we should put you in a tepid

bath and cool you down. Come on, let’s do that now, straightaway. Come on.’

I led her upstairs where I ran a tepid bath. I helped out of her dressing

gown and into the water and I sponged her down for several minutes.

‘Let’s see if that has done the trick.’

I took her temperature again. 104o. Well, that’s a start. I continue to

sponge her with tepid water until it had dropped another 2o, and then I dried her,

got her back into her dressing gown, bundled her into my car and took her to the

hospital. I wondered if she would need to go to theatre; if so I guessed I would

give her some cyclo; that would be excellent. In the event the gynaecologists

thought that she had not perforated her womb through into her abdomen and

they treated her conservatively with massive doses of antibiotics.

Next there was a Sergeant Major with raging toothache. I said that we

would get hold of the duty dental officer and get him to have a look. I guessed

that I would be asked to give him an anaesthetic in due course.

The dentist proved difficult to contact. He had gone out somewhere but

nobody knew where. We left messages for him everywhere we could think of; two

hours later and we were still waiting for him to ring us back.

‘You’ll have to take this tooth out for me, Doc, if there isn’t a dentist. I can’t

stand it any longer.’

28

The big, burly man looked so wretched that I decided that certainly I

would have to do something for him. Where on earth had the dentist got to? He

seemed to have vanished into thin air. Probably in a pub somewhere, I thought

‘Let me have another look. Just open your mouth wider if you can.’

Yes, the gum was altogether too swollen and inflamed to contemplate

putting local anaesthetic into it. It would have to be a general or nothing.

Almost as though he could read my mind the Sergeant Major said

‘You can just put the forceps on it and pull if you like. The pain couldn’t be

worse than it is now. I know you said you were not keen on giving me an

anaesthetic and taking the tooth out yourself all at the same time. Well, why not

just take it out without an anaesthetic. That’s what they would have done in the

olden days, isn’t it?’

The logic seemed indisputable and anyway with an abscess like that the

tooth might well be surprisingly loose. It was worth a try.

‘O.K., We’ll give it a go. Give me a few moments to find the right forceps

and I’ll see what I can do.’

I went down the corridor to the dental surgery, and rummaged through the

various instruments. There, this pair would do for an upper six, I felt sure. I found

the switches for the overhead light and for the sucker, and worked out how the

chair tipped.

‘O.K.,’ I said to the Nursing Orderly, ‘please go and get him.’

This was it, then. Let’s hope it won’t hurt him too much. Must wipe the

sweat off my hands or they will slip on the handles of the forceps.

‘Come and sit in the chair. That’s right, but just tip your head back a bit

more. Good.’

There’s the tooth..carefully now.. up with the forceps, take a big breath

and grip the tooth firmly.. don’t rush it.. pull It did not budge even the slightest bit.

I knew that it must be excruciatingly painful and I felt desperate for the poor man.

29

I gave it one last totally useless yank and stepped back. There were tears in the

soldier’s eyes and sweat on his brow. He looked reproachfully at me.

‘You didn’t get it, did you?’

‘No, I’m sorry.’

‘Well, thank you for trying.’

I was wondering what to say next, when one of the nursing orderlies came

into the room.

‘The duty dental officer is on the phone. He says do you still want him?’

‘Thank Heavens for that. Yes, I’ll come and talk to him.’

He said he was sorry that he had been so difficult to find but pointed out

that he never held himself instantly available.

‘There are no such things as real emergencies in dentistry,’ he said. ‘I

would never get any peace if I didn’t hide myself away for a few hours every now

and then.’

I thought back to my childhood, when my father used to tell people with

toothache to go Guy’s if they had pain as there was a dentist on duty there. It

would not do for the doctors to take that line, would it?

Anyway, now we had found him he agreed to come and take the tooth

out. Ten minutes later and the Sergeant Major was back in the chair, and I

slipped a needle into a vein on his forearm.

‘‘Let’s get on with it then,’ I said to him, as I slowly injected 500mg of

Pentothal into his vein.

‘What was it you were saying about Cyprus, sergeant?’ I asked.

‘Well, we were going down this street, and... I.... said..... to....... the.......

cor........poral.....’. His voice faded away and he yawned; a slow extended yawn.

He’ll be asleep in a moment, I thought, but he did not close his eyes; he just

stared straight ahead for a moment or two and then ‘I...... am..... not.... go..ing...

to.. go.. round the corner till I’ve looked with a mirror.’

30

Dear God, I thought, 500mg is enough to put an elephant to sleep and it

has only made him pause in mid-sentence. I injected another 200mgs. He went

off this time; the dentist slipped a prop and a pack into his mouth and picked up

the forceps. I watched him apply it carefully and then he pushed rather than

pulled, squeezing the handles hard as he did so; now he began to rock the tooth

from side to side. A moment later he delivered the tooth sideways from the gum

and dropped with a clang into the bowl.

‘Well, I hope the poor fellow feels a bit better for getting rid of that. It must

have been hell for him when I tried it.’

‘Yes, but sixes can be brutes to move so you mustn’t feel too bad about

it.’

‘Next time we have an extraction to do I’m going to try some cyclopropane

mixed with oxygen in a six litre bag. I’ve been reading about it. It’s the idea of

aanaesthetist from the London called Bourne. He’s the man who has written

about fainting in the dental chair as a problem when patients are anaesthetised in

the sitting position[2]. He’s just got an M.D. from Cambridge University for his

thesis.’

‘It sounds unusual. Tell me more.’

‘Well, he thinks that people can faint when sitting upright in the dental

chair and that there have been one or two cases of delayed recovery from an

anaesthetic because of this, as their brains don’t get enough oxygen during the

faint. He also thinks that nitrous oxide is not necessarily the best thing to use in

the dental surgery. He has been trying out cyclopropane mixed with oxygen, with

some nitrogen added in to make it non-explosive. He puts it all in a six litre bag

and gets the patient to breathe in and out of it. It seems to work really well, but it

only gives a few minutes useful anaesthesia. I’ll read it up when I get a chance

and, as I said, we’ll try it out next time.’

A few nights later I got Dr Bourne’s book[3] down from the shelf. What a

good project it had been. I could visualiseDr Bourne running around the hospital

with his large black rubber bag, filled with his knock-out mixture. I turned to the

chapter on Cyclopropane as I knew that his main thesis was that cyclo was the

best alternative to nitrous oxide.

31

The chapter started by discussing cyclo’s potency as an anaesthetic. Ever

since 1929 it had been considered a powerful agent because it acted so quickly.

Dr Bourne argued that this speed was not due to high potency at all, but to its

great lack of solubility and to the fact that it was non-irritant even when breathed

in high concentration.

This places cyclopropane in a unique position amongst the available

anaesthetics: it is a good deal more powerful than nitrous oxide, but compared

with the other anaesthetics it is weak. Divinyl ether has more than twice its

strength, ethyl chloride and ether about five times it strength, and halothane,

chloroform and trichloroethylene about ten times its strength. Far from being

extremely powerful it is in fact the second weakest anaesthetic. It stands alone in

that wide gap that separates nitrous oxide from the others. Its potency is

intermediate..... In ambulatory work, an anaesthetic of intermediate potency and

very low blood solubility is precisely what is needed.

In the next chapter he described how he had first tried using a six litre

rubber bag filled with 50% cyclopropane and 50% oxygen for a dental extraction

in a large muscular man of 45 years, who was ‘accustomed to considerable

amounts of alcohol’, and how well it had worked. It sounded just like my sergeant

major

He had also studied the flammability of cyclopropane; apparently it was

possible for sparks to be caused by forceps slipping on a tooth. If the

concentration of oxygen was less than 30% it was unlikely that such a spark

would cause an explosion. It was best therefore to wait for the patient to take five

breaths of air after he had breathed the gas mixture before attempting any

extractions. Alternatively the mixture could be made up with 25% oxygen and

25% nitrogen instead of 50% oxygen; this could be done by using two small

disposable bulbs like those used in making soda water.

It was clear from reading the book that Dr Bourne was a man of great

enthusiasm, and I warmed to him and his ideas.

I tried it out the next time I was asked to give ‘a gas’ for a dental

extraction. It worked really well. I am sure that I would have continued using it if

only it had not been quite so explosive.

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REFERENCES

http://www.britannica.com/EBchecked/topic/148134/cyclopropane

http://www.general-anaesthesia.com

http://www.ncbi.nlm.nih.gov

http://journals.lww.com/anesthesiology/Abstract

http://www.ncbi.nlm.nih.gohttp://www.jstor.org

http://www.ncbi.nlm.nih.gov

http://www.springerlink.com

http://www.sciencedirect.com

http://www.biochempress.com

http://www.faqs.org

http://encyclopedia.airliquide.com/Encyclopedia.asp?GasID=78#MajorHazardshttp://

www.organic-chemistry.org/synthesis/C1C/cyclic/alkanes

www.google.com

www.wikipedia.org

Streitwieser, Andrew and Clayton H. Heathcock. 1976. Organic Chemistry. Collier Macmillan Publishers : London

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