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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5852_Библиотеки_им_академика_М_И_Перельмана.pdf
C H a P T e r 7 Cycloalkanes
CH
2
reduction
—CO
2
CH
2
CH
2
CH
2
H2C
H
2
C
CH
2
H2C
H
2
C
∆
Zn–Hg/HCl
CH
COOH
CH
2
H2C
H
2
C
CO
CO
Ni, 200°C
+ 3H
2
Benzene Cyclohexane
Ni, 200°C
+ 3H
2
OH
P
Phenol Cyclohexanol
OH
Zn dust
Cyclohexane
+ H2C
Hydrolysis; —2C
2H5
OH
Cyclopropane
carboxylic acid
Cyclopropane
NaOC2H
5
—2HBr
CH2Br COOC2H
5
CH2Br COOC2H
5
C
COOC
2H5
H2C
COOC
2H5
H2C
∆
−CO
2
∆
−CO
2
C
COOHH
2
C
COOHH
2
C
CHCOOH
H
2
C
H
2
C
CH
2
H2C
H
2
C
5. From aromatic compounds: By the catalytic reduction of benzene and its derivatives, we can
easily obtain six-membered cyclo compounds:
291
6. a. Condensation of α,ω-dihalide with malonic ester (Perkin’s method): α,ω-Dihalide is
condensed with malonic ester in the presence of naOC2H5. alicyclic carboxylic ester thus
obtained is hydrolysed and decarboxylated to yield cycloalkane.
b. In general, any other suitable α, ω-dihalide can be condensed with malonic ester in presence of
sodium ethoxide to get the desired cycloalkane.
292
NaOC2H
5
—2HBr
Hydrolysis; —C2H5OH
(CH2)
n
+ H2C
CH
2
Br
CH
2
Br
(CH2)
n
C
CH
2
CH
2
COOC2H
5
COCH
3
COOC2H
5
COOC2H
5
∆
−CO
2
(CH2)
n
C
CH
2
CH
2
COOH
COCH
3
(CH2)
n
CHCOCH
3
CH
2
CH
2
NaCH(COOC2H5)
2
NaCH(COOC2H5)
2
+
CH2Br
CH2Br
CH
2
CH(COOC2H5)
2
—2NaBr
—2NaI
CH
2
CH(COOC2H5)
2
I
2
(i) Hydrolysis
(ii) Decarboxylation
2NaOC2H
5
C(COOC2H5)
2
H2C
C(COOC2H5)
2
H2C
Cyclobutane
CH
2
H2C
CH
2
H2C
CH2C Na(COOC2H5)
2
CH2C Na(COOC2H5)
2
CH –CH Br Na
32
+
—
CH –CH Br Na
22
+
+
C
2–
COCH
3
COOC H
25
CH
H
2
O; – C2H5OH
– 2NaBr
–CH
22
—
CH –CH
22
C
COCH
3
COOC H
25
CH –CH
32
—
CH –CH
22
CH
COCH
3
CH –CH
22
—
CH –CH
22
C
COCH
3
COOH
—
Soda lime
Heat
Cyclopentyl
methyl ketone
Disodioaceto acetic ester
PHarMaCeuTiCaL OrGaniC CHeMiSTry
c. Condensation of 1,2-dibromoethane with monosodiomalonic ester yields cyclobutane according
to the following sequence of steps:
7. From disodio acetoacetic ester and dihalogenated parafns: Disodio derivative of acetoacetic
8. Addition of carbene to olens—Synthesis of cyclopropane derivatives: Highly reactive bivalent
ester condenses with dihalogenated parafn to form an ester which on hydrolysis and decarboxylation gives cycloparafns. Cyclobutane cannot be obtained by this method.
carbon species, carbenes, add on to alkane molecules forming cyclopropane derivatives. For example,
C H a P T e r 7 Cycloalkanes
Butene-2
Dichlorocarbene
1,1-Dichloro-2,
3-dimethylcyclopropane
+ [ :CCl
2
]
CH
3
H3C
CH
CH
CH
CH
CH
3
H3C
CCl
2
LiN(C2H5)
2
Acid
hydrolysis
(CH2)
n
CH2CN
CH
2
CN
NH(CH2)
n
C
CH
CH
2
CN
∆
− CO
2
Zn–Hg
Cycloalkane
HCl
(CH2)
n
CH
2
CH
2
(CH2)
n
CH
2
CH
2
CH
2
(CH2)
n
CO
CH
2
CH
COOH
CO
+
C
C
RR
RR
C
C
RR
RR
RR
RR
RR
RR
hν
dichloro or dibromocarbenes, obtained by the reaction of potassium tertiary butoxide on chloroform or
bromoform, when treated with alkenes undergo cis-addition to form cyclopropane derivatives.
9. Thorpe–Ziegler reaction: When aliphatic α,ω-dinitriles are treated with bases such as metal salts
of secondary amines (e.g. Lin(et)2), an intramolecular cyclization occurs resulting in the formation
of cyclic imino compounds, which on hydrolysis furnish the corresponding cyclic ketone in good
yield.
293
10. Photochemical [2+2] cycloaddition reactions: [2+2] Cycloaddition reaction refers to an addition
The mechanism of the reaction is similar to that of Dieckmann cyclization, Lin(et)2, acting as
a strong base. Large dilution is required to ensure intramolecular reaction. at present, this is the
appropriate method for the synthesis of macrocycle compounds.
of two alkene molecules using two π electrons each to form a cyclobutane ring. A convenient
method for the synthesis of cyclobutane derivatives is photodimerization reaction between two
alkenes. These reactions take place in a concerted manner involving a cyclic transition state.
294
+
CH
2
CHCHO
Acrolein1,3-Butadiene
CHO
+
Maleic
anhydride
Tetrahydrophthalic
anhydride
Butadiene
C
O
O
C
O
O
C
O
O
C
+
cis-Dimethyl-1,2,3,
6-tetrahydrophthalate
Butadiene Dimethyl
maleate
COOCH
3
COOCH
3
COOCH
3
H
H
COOCH
3
PHarMaCeuTiCaL OrGaniC CHeMiSTry
Some suitable substituted alkenes such as r2C CF2 or CH2 CH X (X COr, Cn,
COOr, etc.) yield cyclobutane derivatives under thermal conditions.
11. Diels–Alder reaction [4+2] Cycloaddition: The [4+2] cycloaddition reaction between a
conjugated diene (4π-electron system) to form an adduct is known as Diels–Alder reaction
named after the two German chemists, who received the noble Prize for chemistry in 1950. a
typical example is the addition of 1,3-butadiene with acrolein at 100ºC to form tetrahydrobenzaldehyde.
Similarly, the addition of maleic anhydride to butadiene gives tetrahydrophthalic anhy-
dride.
The reaction is highly stereospecific and used for the synthesis of a variety of adducts
having diverse type of ring structures. For example, dimethyl maleate, a cis-dienophile, reacts
with butadiene to give cis-dimethyl-1,2,3,6-tetrahydrophthalate whereas dimethylfumarate,
a trans-dienophile, on reaction with butadiene yields the corresponding trans product, i.e.
trans-dimethyl-1,2,3,6-tetrahydrophthalate. Thus,
C H a P T e r 7 Cycloalkanes
+
trans-Dimethyl-1,2,3,
6-tetrahydrophthalate
Butadiene Dimethylfumarate
H3COOC
COOCH
3
COOCH
3
H
H
COOCH
3
OH
Cyclobutylcarbinol
Cyclopentanol
Cyclopentene
Methylene
cyclobutane
Cyclobutylmethylamine
(i) H2O
(ii) − H
⊕
(i) H2O
HNO
2
(ii) − H
⊕
− H
⊕
− H
⊕
C
⊕
CH2NH2 CH2CH
CH2CH
2
⊕
CH
2
CH2CH
CH2CH
2
CH2OHCH2CH
CH2CH
2
CH
2
CH
2
C
CH
2
CH
2
CH
CH2CH
CH
2
CH
2
CH
2
CH2CH
CH
2
CH
2
CH
2
CH2CH
CH
2
CH
2
12. Demjanov rearrangement: The rearrangement has been used for ring expansion or contraction of
alicyclic ring. The reaction of nitrous acid on cycloalkymethylamines is a general method for ring
expansion. Cyclobutylmethylamine will illustrate the behaviour of this class of amines. in general
four products are formed; in this instance they are cyclopentanol, cyclopentene, cyclobutylcarbinol
and methylene cyclobutane. The mechanism of ring expansion is indicated in the following sequence
of reactions:
295
Cyclobutylamine gives both cyclobutanol and cyclopropylcarbinol.
7.4 PHYSICAL PROPERTIES
1. The rst two members cyclopropane and cyclobutane are gases, the next three members are liquids
and higher members are solid.
2. These are nonpolar and hence are soluble in alcohol or acetone but insoluble in water.
3. as we move down the series, both density and molecular weight increase. Because density of
cyclohexane is lower than that of water, cyclohexane oats over it.
4. The boiling point is higher than their corresponding alkenes and alkanes. The boiling points
increase with increase in molecular weight.
PH arM a C euT i CaL OrG aniC CH eM iSTry
296
109.5° bond angles
60° bond angles
h
ν
1-ChlorocyclopropaneCyclopropane
+ Cl
2
CH
2
CH
2
H2C
CH
2
CH ClH2C
+ Cl
2
Cyclohexane Chlorocyclohexane
CH
2
CH
2
CH
2
CH
2
H2C
H
2
C
CH
2
H2C
H
2
CCH
2
H
2
CH
Cl
C
h
ν
7.5 CHEMICAL PROPERTIES
Cycloalkanes are very akin (same) to the alkanes in relation
Learning Plus
Cycloalkanes are almost similar to alkanes,
but they have higher van der Waals forces
because the ring shape allows for a greater area
of contact. Van der Waals forces may be the
attractive or repulsive forces. For cycloalkanes,
these forces refer to the repulsive forces
between the molecules that causes ring strain.
to reactivity, excluding for the very small ones—in particular
cyclopropane. Cyclopropane is very reactive than expected
because of the ring strain. in general, carbon compounds are
tetrahedral and the bond angles are of 109.5°. But in case of
cyclopropane, they are 60°.
as the electron pairs are very close, the repulsion between
the bonding pairs, which keep the carbon atoms together,
makes the bond easier to break. Therefore because of the angle
strain, cyclopropane and cyclobutane are comparatively less stable and more reactive (following Baeyer’s
strain theory). The cycloalkanes then form cyclopentane and after that show notable similarity with alkanes
because of their stability. Higher alkanes are less reactive due to less strain in the ring and the bond angle is
very close to 109.5o. Hence higher cycloalkanes do not easily react with acids, alkalies, etc.
Following are some important reactions of cycloalkanes.
1. Free radical substitution: Cycloalkanes are halogenated in presence of sunlight or uV light like
alkane.
C H a P T e r 7 Cycloalkanes
Br
2
BrH2CCH2CH2Br
CH
3CH2CH2
Br
CH
3CH2CH2
OH
CH
3CH2CH3
1,3-Dibromopropane
Propyl bromide
Propanol-1
Propane
HBr
(i) Conc. H
2SO4
(ii) H
2
O
H
2
, Ni
80°C
Cyclopropane
H
2
CCH
2
CH
2
Cyclobutane n-Butane
H2, Ni
120°C
CH3CH2CH2CH
3
H2C
H
2
C
CH
2
CH
2
CH2CH2COOH
CH
2CH2
COOH
Adipic acid
CH
2
CH
2
[0]
Alk. KMnO
4
CH
2
CH
2
CH
2
CH
2
2. Addition reactions:
a. Due to the strained ring, cyclopropane (bond angle 60°) is very reactive and undergoes addition
reactions like alkenes.
b. Cyclobutane (bond angle 90°) is relatively less reactive because of less ring strain and
therefore does not undergo addition reactions under normal conditions.
297
3. Oxidation: Dicarboxylic acids are formed when cycloalkanes are oxidized by alkaline potassium
permanganate.
298
HC
2
CH
2
60º
109º28
′
24º64
′
24º64′
CH
2
PHarMaCeuTiCaL OrGaniC CHeMiSTry
7.6 RELATIVE STABILITY OF CYCLOALKANES (BAEYER’S STRAIN THEORY)
in 1885, adolf von Baeyer proposed a theory to enlighten the relative stability of the cycloalkanes.
The postulates of the theory are as follows:
1. The carbon atoms constituting the ring lie in the same plane and thus all the cycloalkanes are planar.
2. a strain in the ring is caused by the deviation of bond angle from the normal tetrahedral angle
(109°28′) and this is called angle strain.
3. Greater the angle strain, greater is the instability of the ring.
4. Higher the stability of the ring, greater would be its ease of formation.
The angle strain in various cycloalkanes is calculated by Baeyer. in cyclopropane, the three carbon atoms
occupy the corners of an equilateral triangle and hence C C C bond angle is 60°. The normal tetrahedral
angle is 109°28′. During the formation of cyclopropane, the normal angle of 109°28′ has been reduced to
60°. Hence, the angle strain in cyclopropane is calculated as ½ (l09°28′ – 60°) = 24°64′ (Fig. 7.1).
Figure 7.1 Angle strain in cyclopropane.
angle strain for other cycloalkanes can be calculated in the same way and the values of angle strains are
given in Table 7.1.
Table 7.1 Angle strain in cycloalkanes
Compound Structure Bond angle Angle strain
Cyclopropane 60°
Cyclobutane
Cyclopentane
Cyclohexane
90°
108°
120°
½ (109°28′ – 60°) = 24°44′
½ (109°28′ – 90°) = 9°44′
½ (109°28′ – 108°) = 0°44′
½ (109°28′ – 120°) = –5°16′
C H a P T e r 7 Cycloalkanes
The positive angle strain indicates that the bonds are compressed from the normal tetrahedral angle and
negative sign indicates that the bonds are stretched.
7.6.1 Advantages of Baeyer’s Strain Theory
1. Lower cycloalkanes such as cyclopropane, cyclobutane have higher angle strain and are more
reactive.
2. Cyclopentane is most stable because the angle strain is minimum.
3. The relative stabilities of cycloalkanes up to cyclopentane can be explained satisfactorily.
7.6.2 Limitations of Baeyer’s Strain Theory
299
1. The theory gives planar model of cycloalkanes.
2. according to this theory, cyclohexane is less stable than cyclopentane.
However, cyclohexane and other higher cycloalkanes are found to be
more stable than cyclopentane.
Learning Plus
In 1980, Hermann Sachse proposed the chair conformation
of cyclohexane.
3. Carbon–carbon double bond is easily formed. But according to
Baeyer’s strain theory, it is difcult to form.
7.7 HEAT OF COMBUSTION AND STABILITY OF CYCLOALKANES
every cycloalkane does not have a similar degree of stability. it is determined based on their enthalpies of
combustion values given in Table 7.2. Higher the enthalpy per CH2 group, lower is its stability.
Table 7.2 Enthalpies of combustion per CH2 group in cycloalkanes
S. no. Cycloalkane ∆H combustion in kJ/mol/CH2 group
1. Cyclopropane 697.05
2. Cyclobutane 685.7
3. Cyclopentane 664.0
4. Cyclohexane 658.6
an additional sign, which explains the relative stability, is the ease with which the cycloalkane ring
opens up. Lesser the stability of the ring, more easily it opens up. The following are the conditions for
hydrogenation of cycloalkanes.
PH arM a C euT i CaL OrG aniC CH eM iSTry
300
+ H
2
Ni
Propane
Cyclopropane
Cyclobutane
Cyclopentane
Butane
Pentane
80°C
+ H
2
+ H
2
Ni
200°C
Ni
300°C
CH
3
CH2CH
3
CH
3
CH2CH2CH
3
CH
3
CH
2
CH2CH2CH
3
back
seat
foot
From the above reactions, it is clear that cyclopropane is the most unstable of cycloalkanes. The stability
of cycloalkanes increases with increase in the ring size.
7.8 SACHSE–MOHR THEORY OF STRAINLESS RINGS
Sachse and Mohr proposed a theory of strainless rings to give explanation for the stability of higher cycloalkanes.
This theory says that the ring with six or more carbon atoms becomes free from strain as all the ring carbon
atoms are not forced into one plane. Hence the higher the cycloalkanes, the carbon atoms occupy different
planes so that the normal tetrahedral angle is retained. The rings formed are called strainless rings.
Both these forms are without any angle strain. Hence, they are
strainless rings.
due to the subsequent reasons.
1. in the chair conformation, the adjacent C–H bonds on all
2. Out of the twelve hydrogens, six of them point up or
For example, cyclohexane exists in two puckered conformations. They are (1) chair form and (2) boat form.
Chair form of cyclohexane is more stable than the boat form
Learning Plus
If we visualize chair conformation of cyclohexane
on a chair, it clearly shows foot, seat and back.
the neighbouring carbon atoms are staggered. in the boat
form, the adjacent C–H bonds on C
eclipsed. Hence energy of boat form becomes more than
the chair form.
C3 and C5 C6 are
2
down perpendicular to the plane of the molecule. These are called axial hydrogens. The other six
hydrogens are found either above or below the plane of the molecule. They are equatorial hydrogens.
in the boat form, the two axial hydrogens on C2 and C4 are closer than in the chair form. Hence the
energy of boat form is more than the chair form.