ammonia eros ra094

AMMONIA

Ammonia

[7664-41-7]

(MW 17.03)

InChI = 1/H3N/h1H3
InChIKey = QGZKDVFQNNGYKY-UHFFFAOYAF

(weak base;

essential nonaqueous solvent medium for dissolv-

ing metal reactions;

precursor of organic nitrogen compounds

including amines,

unsubstituted amides,

heterocycles

1,6

)

Physical Data:

mp −78

◦

C; bp −33.3

◦

C/760 mmHg; d liq. NH

0.682 g cm

−

(−33.3

◦

C/760 mmHg).

Solubility:

very sol water (47.8% w/w, 0

◦

C), methanol, ethanol;

also sol chloroform, ether.

Form Supplied in:

although gaseous at room temperature, anhy-

drous NH

is usually supplied as the liquified form in stainless

steel cylinders which are sometimes fitted with an eductor tube
to permit convenient and rapid extraction of liquid NH

when

the cyclinder is inverted or tipped on its side. NH

is also read-

ily available as aqueous solutions (‘ammonium hydroxide’) in
various concentrations.

Drying:

commercial ‘anhydrous’ NH

can be used as supplied

in many applications though in some cases drying is required
to ensure optimum yield. Gaseous NH

can be dried by passing

through a column of NaOH pellets, whereas liquid NH

can

be dried using sodium metal (sufficient to obtain a persistent
deep-blue coloration) or CaH

followed by distillation under

nitrogen directly into the reaction vessel.

Handling, Storage, and Precautions:

since NH

is highly corro-

sive, cylinders must be equipped with the appropriate stainless
steel valves and fittings. As a consequence of its comparatively
high enthalpy of vaporization (23.5 kJ mol

−

), reactions in-

volving liquid ammonia can be carried out on laboratory scale
without the need for external cooling since an insulating layer of
ice quickly builds up around the outside of the reaction vessel.
NH

is highly toxic; inhalation of the vapor can cause edema

of the respiratory tract, spasm of the glottis, and asphyxia. All
reactions involving anhydrous ammonia must be conducted in
a well-ventilated fume hood.

As a consequence of the lone pair of electrons on the nitrogen,

ammonia is both a weak base (K

1.8 × 10

−

) and a nucleophile,

two properties which account for most of its reagent chemistry.

Ammonia reacts readily and reversibly with mineral and organic
acids to form salts (eq 1) which, being stable solids, are often used
as convenient sources of ammonia. Since ammonia is an extremely
weak acid (pK

estimated to be ∼38),

the amide anion is a very

strong base.

(1)

–

Ammonia in Dissolving Metal Reactions.

In addition to

dissolving a wide range of organic compounds and inorganic
salts, anhydrous liquid NH

can act as a solvent for the Group

1 and 2 metals, producing deep-blue colored solutions which
conduct electricity and are strongly reducing. The physical and
chemical properties of such solutions are usually attributed to

solvated electrons.

3,8

In the presence of a catalyst such as an-

hydrous Fe(NO

)

, solutions of sodium and potassium in liquid

are conveniently converted into the amide salts (M

−

which are very strong bases.

Solutions of Li, Na, and K metals in liquid NH

, usually in the

presence of a proton source like ethanol, have been extensively
used for the partial reduction of a variety of benzene derivatives
and polyfused aromatic compounds (the Birch reduction);

typi-

cally, benzene gives 1,4-cyclohexadiene (eq 2) whereas naphtha-
lene is reduced to the tetrahydro derivative. o-Methoxybenzoic
acid (also its salts and esters) can be converted to 2-alkylcyclo-
hexenones (eq 3).

Similar reaction conditions have been uti-

lized for the ring opening of cyclopropanes,

the transformation

of conjugated enones to the saturated carbonyl compounds

their 2-substituted derivatives,

the stereospecific reduction of

disubstituted alkynes to (E)-alkenes,

the hydrodehalogenation

of gem-dihalides,

and the reductive cleavage of polysulfides to

thiols.

(2)

Na/liq. NH

EtOH

(3)

OMe

1. Na/liq. NH

2. RX
3. H

Alkylation of Ammonia. Direct reactions between ammonia

and alkyl halides are complex and generally produce mixtures of
the salts of the primary, secondary, and tertiary amines, and also
quarternary salts (eqs 4–7). The final composition of the product
mixture depends on the relative initial concentrations of the reac-
tants, the nature of the reaction solvent, and the steric requirements
of the alkyl groups. The reactions generally exhibit the character-
istics of S

2 type displacements (reaction rate with respect to the

alkyl group: primary > secondary > tertiary) and the ease of halo-
gen displacement follows the expected order I > Br > Cl > F.

Reactions carried out in liquid ammonia tend to give mixtures of
primary and secondary amines, whereas in methanolic ammonia
more complex mixtures of the primary, secondary, and tertiary
amines are obtained.

Separation of the various amine products

by distillation is usually easier for higher alkyl substituents, e.g.
n

-octyl.

(4)

RNH

–

RNH

–

(5)

(6)

–

(7)

–

With dihaloalkanes, intramolecular cyclization will occur to

form five- to seven-membered heterocyclic compounds as appro-
priate, though even in favorable cases, over reaction can occur
(eq 8).

Tribromoalkanes have also been used to synthesize novel

azabicyclic systems (eq 9),

and l-azaadamantane (eq 10).

(8)

–

Avoid Skin Contact with All Reagents

AMMONIA

(9)

(CH

)

(CH

)

(10)

Amination of Aromatic and Heteroaromatic Compounds.

Although amination of simple aryl halides to yield anilines by
ipso

substitution of the halo group is more usually carried out

using Potassium Amide in liquid NH

, NH

itself can also be

used but requires elevated temperatures and pressure, and a copper
catalyst.

Thus, for example, aniline is obtained from chloroben-

zene (200

◦

C, Cu cat.),

3,4-dimethylaniline from 4-bromo-

-xylene (195

◦

C, Cu/CuCl),

and p-trifluoromethylaniline from

-chlorotrifluoromethylbenzene (200

◦

C, CuCl/KF).

The amination reaction proceeds more smoothly if the ben-

zene ring is activated by strongly electron-withdrawing groups,
particularly NO

, in the o- and p-positions. The ease of halide

displacement follows the sequence F > Br > Cl > I.

22b

Nitro

groups have also been displaced from 2,3-dinitrotoluene.

Naphthol derivatives can be transformed to the correspond-

ing amines by treatment with aqueous ammonia in the presence
of sulfite or bisulfite ion at elevated temperatures (the Bucherer
reaction) (eq 11);

the analogous transformation with phenols is

known, but is less common.

(11)

Heteroaromatic compounds, particularly pyridines and diazines,

are more susceptible to amination with NH

than arenes. Al-

though the amination reactions generally proceed under milder
conditions, they may also be catalyzed by Cu salts. Typical exam-
ples include the Cu-catalyzed conversion of 3-bromopyridine to
3-aminopyridine, and 2-chloro-3-aminopyridine to 2,3-diamino-
pyridine,

the aminolysis of fluoro-

and chloropyrazines

treatment with aqueous NH

at room temperature and 180

◦

C re-

spectively, the displacement of the methoxy group in 4-metho-
xypyrimidone to give cytosine on treatment with methanolic
ammonia at 100

◦

C (eq 12),

and the selective transformation of

2,6-dichloropurine to the corresponding 6-amino-2-chloro deriva-
tive under similar conditions (eq 13).

Treatment of solutions of

3-halo-2-alkylisothiazolium salts in acetonitrile with excess am-
monia yields exclusively the N-monosubstituted 3-isothiazoles via
a ring opening/recyclization process (eq 14).

Irradiation of so-

lutions of 6-phenyl- and 6-t-butyl-4-halopyrimidines in liq NH

with UV light affords the corresponding 4-amino derivatives.

OMe

(12)

, MeOH

100 °C

(13)

, MeOH

100 °C

(14)

NHR

, MeCN

25 °C

–

Highly π-electron deficient nitroaza heterocycles (including

pyridines, diazines, and their respective benzo compounds) react
with Potassium Permanganate in liq NH

to give amino com-

pounds via an S

H mechanism involving the initial formation

of a σ-adduct with NH

which is subsequently oxidized by the

permanganate.

The reactions can be highly regioselective and

give high product yields (>80%) (eq 15).

For less π-electron de-

ficient compounds, the combination KNH

/liq NH

/KMnO

has

been used.

(15)

X = Cl, Br

[O]

-Amino Acids.

Ammonia reacts readily with α-halo car-

boxylic acids to yield the corresponding α-amino acids (eq 16).
The reactions are conveniently carried out using a large excess
of ammonia with either ammonium chloride

or formaldehyde

present to suppress further alkylation. The displacement normally
proceeds with inversion of configuration

unless the adjacent

-position is substituted.

(16)

, NH

∆

Ring-opening of Epoxides and Aziridines. Epoxides, pos-

sessing a relatively high degree of ring strain, readily open on
treatment with ammonia to give 1,2-amino alcohols, usually with
a high degree of regio- and stereoselectivity.

Consistent with

an S

2 mechanism, nucleophilic attack by the ammonia occurs

at the sterically least hindered carbon center of the epoxide, e.g.
with propene,

butene,

and styrene

45,46

oxides (eq 17). The ring

opening proceeds in a trans fashion with concomitant inversion
of configuration, e.g. trans-2-butene oxides give erythro-amino
alcohols, whereas the cis compounds afford the diastereoisomeric
threo

-amino alcohols (eq 18).

Aminolysis of cyclopentene

and cyclohexene

oxides produces the corresponding trans-

amino alcohols; the cyclohexane derivative is also obtained from
the reaction of trans-chlorohydrin with aqueous ammonia at room
temperature.

Substitution at the 3-position directs the incoming

ammonia to the more distal carbon center (eq 19).

With epox-

ides derived from six-membered ring compounds which have rigid

A list of General Abbreviations appears on the front Endpapers

AMMONIA

geometries, the amino and hydroxy groups in the resulting product
are normally trans diaxially related, an important consideration in
the stereoselective syntheses of amino sugars.

43,51

(17)

(18)

(19)

X = OMe, OPh

Ring opening of aziridines by anhydrous NH

in the presence

of ammonium chloride proceeds smoothly at 100

◦

C to give 1,2-

diamines.

The regio- and stereochemical preferences of this

reaction have been shown to be similar to those observed for
epoxides.

-Amino Nitriles. These key intermediates in the Strecker

synthesis of amino acids (see below) can be prepared from the re-
action of cyanohydrins with ammonia.

-Amino nitriles (yields

80–95%) can be conveniently prepared from α-silyloxy nitriles
on treatment with ammonia in methanol (eq 20).

R C

OTMS

′

R C

′

(20)

Amidines.

Formamidine Acetate, a relatively nonhygro-

scopic salt, is conveniently obtained in high yield from the reaction
of Triethyl Orthoformate with ammonia in acetic acid at 115

◦

(eq 21). The corresponding acetamidine salt is prepared in a
similar fashion using NH

Cl in ammonia.

R C

OEt

(21)

OAc

–

2 NH

AcOH

Primary Amides. Nucleophilic substitution by ammonia at

the carbonyl carbon of a carboxylic acid or a related derivative
provides

general

synthetic

route

unsubstituted

primary amides (eq 22).

The order of reactivity is carboxylic

acids < esters < anhydrides < acyl chlorides.

(22)

X = OH, OR, Cl, OCOR, OCO

Since direct reaction between a carboxylic acid and NH

requires vigorous reaction conditions (reaction temperatures

170–200

◦

C), excess NH

, and continuous removal of the water

formed, this method is only suitable for amides derived from ther-
mally stable acids; at higher temperatures, nitrile formation com-
petes. Nonetheless, the primary amides from a series aliphatic car-
boxylic acids (C

–C

) have been prepared by this approach.

56,57

Under similar reaction conditions, cyclic imides (favorable for
ring sizes 5 and 6) can be obtained from diacids and NH

Although esters react cleanly with ammonia to give the corre-

sponding amides, the reported conditions to effect the transforma-
tion are still reasonably vigorous, e.g. excess conc aq NH

/NH

at 100

◦

or liq NH

at 165–180

◦

Ethyl cyanoacetate

affords cyanoacetamide on shaking with aqueous NH

As an

alternative method, esters are transformed to primary amides
under mild conditions (CH

/T < 40

◦

C) using Me

AlNH

(2 equiv), generated in situ from AlMe

and NH

The ammonolysis of acyl chlorides has been used extensively

as a standard laboratory procedure for the preparation of primary
amides, the reactions are rapid and exothermic and usually carried
out in solvent.

5,60,63

To ensure completion of reaction, a minimum

of a twofold excess of ammonia is required since it reacts with the
HCl liberated. Instead of ammonia, ammonium acetate in acetone
can be used with acyl chlorides.

Carboxylic acid anhydrides readily undergo ammonolysis

to give the corresponding primary amide.

With cyclic anhy-

drides, cyclic imides are formed, e.g. phthalic anhydride gives
phthalimide.

Treatment of mixed anhydrides, generated in situ from car-

boxylic acids and Ethyl Chloroformate, with anhydrous ammonia
provides primary amides under mild conditions;

5,65

product yields

are claimed to be superior to those obtained using acyl chlorides.

Reactions conditions for the ammonolyses of substituted

esters and acyl chlorides can usually be adapted to be compatible
with a range of functionality including unsaturation,

halo,

68,69

hydroxyl,

amino,

and acetal groups.

For example, α-halo-

carboximides can be obtained from the corresponding acid
chlorides

or esters

with conc aq NH

by maintaining the re-

action temperature below 0

◦

Aromatic or allylic aldehydes can be converted into primary

amides by reaction with NH

using either Nickel(II) Peroxide in

dry Et

O at −20

◦

or Sodium Cyanide and Manganese Di-

oxide in isopropanol at 0

◦

Amination of aliphatic

and aryl aldehydes has also been accomplished using N-
Bromosuccinimide with AIBN as an initiator in the presence of
NH

; radical substitution of the aldehydic hydrogen by Br gener-

ates an acyl bromide which reacts rapidly with the NH

present.

Primary amides are obtained from the thermal,

76a

photo-

chemical,

76b

or metal ion (e.g. Ag

) catalyzed

rearrangement

of α-diazo ketones in the presence of ammonia (Wolff rearrange-
ment). In cases where the required diazo ketone can be gener-
ated in situ from an acyl chloride and Diazomethane, the overall
transformation is an homologation (the Arndt–Eistert synthesis)
(eq 23).

(23)

RCH

∆

aq. NH

The Ugi Reaction.

Ammonia, usually in the form of an

ammonium salt of a carboxylic acid, reacts with a mixture of

Avoid Skin Contact with All Reagents

AMMONIA

isocyanides and aldehydes to give bis-amides in moderate yield
(∼50%) (the Ugi reaction) (eq 24).

The scope of the reaction is

considerably more limited with ammonia than with amines.

– +

(24)

CHO

≡N–R

80% aq. MeOH

Addition of Ammonia to Alkenes and Alkynes.

Since it

is intrinsically nucleophilic, NH

does not form adducts readily

with simple alkenes. Under high temperature (200

◦

C) and pres-

sures (800–1000 atm), and in the presence of Na metal, ethy-
lene, propene, isobutene, and cyclohexene react with NH

give the corresponding amines in low yield (15–30%).

Simi-

larly, 2-phenylethylamine is obtained from styrene in 8% yield.

does, however, undergo nucleophilic addition to Pd

and

complexes derived from 1,5-dienes; subsequent reduction of

the adducts with Sodium Borohydride releases the amines, e.g.
2-aminohexane (93%) and cyclooctylamine (57%) are obtained
from 1,5-hexadiene and 1,5-cycloocatdiene, respectively.

Simple alkenes undergo aminosulfenylation on treatment

in turn with Dimethyl(methylthio)sulfonium Tetrafluoroborate
followed by ammonia (eq 25).

(25)

SMe

1. MeS–SMe

–

2. NH

Alkenes with electron withdrawing substituents (carbonyl,

nitrile, alkoxycarbonyl) are susceptible to Michael addition to
form, at least initially, the β-amino adducts. With systems un-
substituted at the β-position, multiple addition usually occurs af-
fording the di- and triadducts even with a large excess of ammonia
(eq 26). Thus, the diadduct is the major product from the addition
of NH

to acrylonitrile at 30

◦

C even with a significant excess of

. When the reaction is carried out with a large excess of NH

(>threefold) at 110

◦

C for short reaction times, the monoadduct

is the major component of the reaction mixture.

Ethyl acrylate

reacts readily with NH

to give the corresponding di- and

triadducts which are separable by distillation.

3–n

(26)

Substitution at the β-position of α,β-unsaturated systems in-

hibits multiple addition. Thus crotonic acid,

ethyl crotonate,

and mesityl oxide

all form the corresponding β-amino com-

pounds. 1-Nitropropene and butene also form monoadducts with
ammonia which tend to be unstable.

Sorbic acid undergoes dou-

ble addition of NH

to give 3,5-diaminohexanoic acid.

As with alkenes, reactions between simple alkynes and NH

generally take place under forcing reaction conditions, producing
complex product mixtures containing 1,2-diamines, piperidines,
etc.

Conjugated dialkynes react with NH

in the presence of

CuCl catalyst to give pyrroles (eq 27).

CuCl

(27)

Addition of Ammonia to Heterocumulenes.

adds

across the carbon–carbon double bond of ketenes to give primary
amides, usually in good yield (cf. the Wolff rearrangement men-
tioned above) (eq 28).

•

′

(28)

With isocyanates and isothiocyanates, the addition of NH

takes

place specifically across the carbon–nitrogen double bond, pro-
ducing ureas

and thioureas, respectively (eq 29).

R N C X

(29)

X = O, S

Amidines. Alkyl and aryl nitriles react with ammonia in the

presence of ammonium salts to give amidine salts, usually in yields
of the order of 80% (eq 30).

The reaction between nitriles and

MeAl(Cl)NH

, generated in situ from AlMe

and NH

Cl, pro-

vides an alternative general synthetic route to amidines.

Dini-

triles of suitable chain length give cyclic imidines on treatment
with NH

in methanol at 100

◦

C (eq 31).

R C N

(30)

/NH

120–150 °C

–

C N

(31)

/MeOH

100 °C

(CH

)

(CH

)

= 2, 3

Addition of Ammonia to Carbonyl Compounds.

Nucle-

ophilic addition of NH

to an aldehyde or ketone affords ini-

tially a hemiaminal which subsequently dehydrates to an imine
(eq 32). Imines which are not readily isolable except those
derived from perfluoroalkyl

or diaryl ketones

usually react

further. Condensations of ammonia with (a) formaldehyde yield
the polycyclic adduct hexamethylenetetramine (eq 33),

100

(b)

-alkanals and arylacetaldehydes form the trimeric hexahydrotri-

azines (eq 34),

101

and (c) aromatic aldehydes give hydrobenza-

minidines (eq 35).

102

′

(32)

– H

(33)

6 H

C=O

4 NH

(34)

3 RCHO

3 NH

N=CHAr

(35)

3 ArCHO

3 NH

A list of General Abbreviations appears on the front Endpapers

AMMONIA

Reductive Amination. Catalytic hydrogenation (Ni, Pt, Rh)

of mixtures of aldehydes or ketones (usually in ethanol) and NH

affords primary amines, presumably by hydrogenation of the in-
termediate imine (eq 36).

103

Aliphatic carbonyl compounds with

at least five carbon atoms (lower molecular weight compounds are
too reactive) or aromatic aldehydes are found to be most suitable.
Since the primary amines formed initially are potential substrates
for reaction, further alkylation may occur giving secondary and
tertiary amines.

′

R´

′

/cat

(36)

Treatment of aromatic aldehydes or aliphatic ketones, which

are not soluble in water, with either NH

/Formic Acid or Ammo-

nium Formate yields the corresponding primary amines (Leuckart
reaction).

104

Mannich Reaction. The product mixtures from condensation

reactions between ketones which possess at least one α-hydrogen
atom, Formaldehyde, and NH

are generally more complex than

those obtained from the corresponding reactions in which the NH

is replaced by a secondary amine such as dimethylamine.

105

Thus

acetophenone affords a mixture of the di- and triadducts rather than
the expected β-amino ketone (Mannich base) (eq 37).

106

Mannich

reactions involving dibenzyl ketones with formaldehyde and NH

in a relative molar ratio of 1:5:2 respectively give adamantane-like
diaza ketones in good yields (eq 38).

107

(37)

(38)

Strecker Synthesis of α

-Amino Acids. Aldehydes react with

Hydrogen Cyanide in the presence of ammonia to yield an α-
amino nitrile which on subsequent hydrolysis is converted to
an α-amino acid (eq 39).

108

-Substituted α-amino acids can be

prepared from ketones.

109

-Silyloxy nitriles offer an alternative

route to the required intermediate amino nitriles (see eq 20).

(39)

HCN

Willgerodt Reaction. Heating mixtures of alkyl aryl ketones

with ammonium polysulfide (or sulfur and dry NH

) affords

primary amides or the ammonium salts of the carboxylic acid
(eq 40).

110

Side reactions become more pronounced as the chain

length increases.

(CH

)

–1

(CH

)

(40)

With acyclic and cyclic aliphatic ketones (2 equiv), sulfur, and

-thiazoline derivatives can be obtained. In addition, treat-

ment of methyl ketones, which can only be thiolated on the methyl
group (e.g. acetophenone and pinacolone), with a large excess of
sulfur (∼eightfold) affords

-imidazoline-5-thiones.

111

Nitriles.

Gas phase co-pyrolyses of (a) aliphatic mono- or

dicarboxylic acids over silica gel at 500

◦

112

or (b) primary al-

cohols over a 15% Cu/alumina catalyst at 300

◦

113

with NH

afford mono- or dinitriles as appropriate in good yield.

Benzaldehydes are converted to the corresponding benzoni-

triles on treatment with NH

in the presence of either Iodine

114

or Lead(IV) Acetate.

115

Miscellaneous Reactions Involving Ammonia. Liq NH

found to be a convenient medium and a mild base for the de-
protection of FMOC-protected amino acids (eq 41).

116

Removal

of Nα-benzyloxycarbonyl protecting groups for sulfur-containing
peptides by Pd-catalyzed hydrogenolysis proceeds smoothly in
liq NH

because poisoning of the catalyst is substantially dimi-

nished.

117

(41)

RNH

liq NH

NHR

-Acetyl-β-keto esters are readily deacylated on treatment with

gaseous NH

in dry Et

O (eq 42).

118

COMe

(42)

is a participating solvent in ozonolysis reactions; ozonol-

yses of indene and indole in the presence of NH

afford isoquino-

line and quinazoline, respectively.

119

Diamines are obtained in

50–60% yield from cyclic alkenes by a sequence involving ozonol-
ysis in methanol and partial reduction of the resulting reaction
mixture followed by catalytic hydrogenation over Rh or Raney
Nickel at 200–400 psi/50

◦

120

The Borane–Ammonia complex, prepared in situ from NH

and diborane or available commercially, reduces carbonyl com-
pounds rapidly; aldehydes are selectively reduced in the pres-
ence of aliphatic and aromatic acyclic ketones.

121

Moreover,

the NH

–BH

complex reacts faster than NaBH

with hindered

ketones.

Ammonia in the Synthesis of Nitrogen-containing Hetero-

cycles. Ammonia has been used extensively for the introduction
of nitrogen atoms into heterocyclic ring systems. Space does not
permit an adequate discussion of the various methods. For fur-
ther details, see the general overview by Jeyaraman

and special-

ist monographs and reviews for systems such as pyridines,

6a,b

pyrroles,

6c,d

and diazines.

122

Avoid Skin Contact with All Reagents

AMMONIA

Jeyaraman, R., Synth. Reagents 1983, 5, 9.

Smith, P. A. S. The Organic Chemistry of Open-Chain Nitrogen
Compounds

; Benjamin: New York, 1965; Vol. 1, p 1.

(a) Birch, A. J., Q. Rev., Chem. Soc. 1950, 4, 69; (b) Birch, A. J.; Smith,
H., Q. Rev., Chem. Soc. 1958, 12, 17. (c) Smith, H. In Organic Reactions
in Non-aqueous Ionizing Solvents

; Jander, G.; Spandau, H.; Addison,

C. C., Eds.; Wiley: New York, 1963; Vol. 1, Part 2. (d) Birch, A. J.
and Rao, G. S., Adv. Org. Chem. 1972, 8, 1. (e) House, H. O. Modern
Synthetic Reactions

, 2nd ed.; Benjamin: Menlo Park, 1972; p 145.

(a) Methoden Org. Chem. (Honben-Weyl) 1958, XI/1, XI/2. (b)
Schneider, W.; Hoyer, J.; Ehrenstein, W.; Haller, R.; Hänsel, W.;
Lehmann, K.; Roth, H. J.; Schönenberger, H.; Camerino, B.; Cainelli,
G. F.; Ferles, M. Methodicum Chimicum; Zymalkowski, E., Ed.;
Academic: New York, 1975; Vol. 6, p 439. (c) Gibson, M. S., Chem.
Amino Group 1968

, 37.

Beckwith, A. L. J., Chem. Amides 1970, 73.

(a) Brody, F.; Ruby, P. R. Pyridine and Its Derivatives; Klingsberg,
E., Ed.; Wiley: New York, 1960; Vol. 14, Part 1, p 272. (b) Sausicns,
A.; Duburs, G., Heterocycles 1988, 27, 269. (c) Katritzky, A. R.;
Ostercamp, D. L.; Yousaf, T. I., Tetrahedron 1987, 43, 5171. (d) Bean,
G. P. Pyrroles; Jones, R. A., Ed.; Wiley: New York, 1990; Vol. 48,
Part 1, p 105.

Buncel, E.; Menon, B., J. Organomet. Chem. 1977, 141, 1.

(a) Dye, J. L., Ann. China. (Rome) 1968, 1, 306. (b) Dye, J. L., Prog.
Inorg. Chem. 1984

, 32, 327.

(a) Vaughn, T. H.; Vogt, R. R.; Nieuwland, J. A., J. Am. Chem. Soc.
1934, 56, 2120. (b) Leffler, M. T., Org. React. 1942, 1, 99.

10.

(a) Taber, D. F., J. Org. Chem. 1976, 41, 2649. (b) Taber, D. F.; Gunn,
B. P.; Chiu, I.-C., Org. Synth., Coll. Vol. 1990, 7, 249. (c) Hook, J. M.;
Mander, L. N.; Woolias, M., Tetrahedron Lett. 1982, 23, 1095.

11.

(a) Fraisse-Jullien, R.; Frejaville, C., Bull. Soc. Chem. Fr. 1968, 4449.
(b) Dauben, W. G.; Wolf, R. E., J. Org. Chem. 1970, 35, 374.

12.

(a) Caine, D., Org. React. 1976, 23, 1. (b) Mueller, R. H.; Gillick, J. G.,
J. Org. Chem. 1978

, 43, 4647.

13.

Caine, D.; Chao, S. T.; Smith, H. A., Org. Synth., Coll. Vol. 1988, 6,
51.

14.

(a) Campbell, K. N.; Eby, L. T., J. Am. Chem. Soc. 1941, 63, 216. (b)
Dobson, N. A.; Raphael, R. A., J. Chem. Soc. 1955, 3558. (c) Schwarz,
M. Waters, R. M., Synthesis 1972, 567. (d) Boland, W.; Hansen, V.;
Jaenicke, W., Synthesis 1979, 114.

15.

Schweizer, E. E.; Parham, W. E., J. Am. Chem. Soc. 1960, 82, 4085.

16.

(a) Parham, W. E.; Wynberg, H., Org. Synth., Coll. Vol. 1963, 4, 295.
(b) Parham, W. E.; Wynberg, H.; Ramp, F. L., J. Am. Chem. Soc. 1953,
75

, 2065.

17.

Spielberger, G. Methodium Chemicum; Zymalkowski, E., Ed.;
Academic: New York, 1975; Vol. 6, p 24.

18.

Westphal, O.; Jerchel, D., Chem. Ber. 1940, 73, 1002.

19.

Braun, J. V.; Lotz, R.; Warne. K. C.; Pinkernelle, W.; Rohland, W.;
Pohl, A.; Dengel, F.; Arnold, H., Chem. Ber. 1937, 70, 979.

20.

Mosby, W. L. Heterocyclic Systems with Bridgehead Nitrogen Atoms;
Wiley: New York, 1961; Part II, p 1267.

21.

Lukes, R.; Galik, V.; Bauer, J., Collect. Czech. Chem. Commun. 1954,
19

, 712.

22.

(a) Ullmann, F., Chem. Ber. 1905, 38, 2120. (b) Bunnett, J. F.; Zahler,
R. E., Chem. Rev. 1951, 49, 273. (c) Lindley, J., Tetrahedron 1984, 40,
1433.

23.

Quick, A. J., J. Am. Chem. Soc. 1920, 42, 1033.

24.

(a) Wisansky, W. A; Ansbacher, S., Org. Synth., Coll. Vol. 1955, 3, 307.
(b) Wisansky, W. A.; Ansbacher, S., J. Am. Chem. Soc. 1941, 63, 2532.

25.

Seiwell, L. P., J. Org. Chem. 1979, 41, 4731.

26.

(a) Kenner, J.; Parkin, M., J. Chem. Soc. 1920, 117, 852. (b) Ibbotson,
K.; Kenner, J., J. Chem. Soc. 1923, 123, 1260.

27.

Drake, N. L., Org. React. 1942, 1, 105.

28.

(a) Lantz, R.; Michel, E., Bull. Soc. Chem. Fr. 1961, 2402. (b) Lantz,
R.; Michel, E., Bull. Soc. Chem. Fr. 1962, 353. (c) Lantz, R., Bull. Soc.
Chem. Fr. 1964

, 538.

29.

Brooks, W.; Day, A. R., J. Heterocycl. Chem. 1969, 6 759.

30.

Rutner, H.; Spoerri, P. E., J. Heterocycl. Chem. 1966, 3, 435.

31.

Cheeseman, G. W. H., J. Chem. Soc. 1960, 242.

32.

Holý, A., Collect. Czech. Chem. Commun. 1979, 44, 2846.

33.

Brown, G. B.; Weliky, V. S., J. Org. Chem. 1958, 23, 125.

34.

Rokach, J.; Hamel, P., J. Heterocycl. Chem. 1978, 15, 695.

35.

de Bie, D. A.; van der Plas, H. C.; Geurtsen, B., J. Chem. Soc., Perkin
Trans. 1 1974

, 1363.

36.

Wo´zniak, M.; van der Plas, H. C., Acta Chem. Scand. 1993, 47, 95.

37.

Wo´zniak, M.; Bara´nski, A.; Szpakiewicz, B., Liebigs Ann. Chem. 1991,
875.

38.

Van der Plas, H. C; Wo´zniak, M., Croat. Chem. Acta 1986, 59, 33.

39.

Cheronis, N. D.; Spitzmueller, K. H., J. Org. Chem. 1941, 6, 349.

40.

Kulikova, G. N.; Strukov, I. T., Khim. Farm. Zh. 1969, 3, 30 (Chem.
Abstr. 1969

, 71, 102 208).

41.

Brewster, P.; Hiron, F.; Hughes, E.; Ingold, C. K.; Rao, P. A. D. S.,
Nature 1950

, 166, 179.

42.

Stammer, C. H.; Webb, R. G., J. Org. Chem. 1969, 34, 2306.

43.

Parker, R. E.; Isaacs, N. S., Chem. Rev. 1959, 59, 737.

44.

Leffler, M. T.; Adams, R., J. Am. Chem. Soc. 1937, 59, 2252.

45.

McManus, S. P.; Larson, C. A.; Hearn, R. A., Synth. Commun. 1973,
3

, 177.

46.

Emerson, W. S., J. Am. Chem. Soc. 1945, 67, 516.

47.

Dickey, F. H.; Fickett, W.; Lucas, H. J., J. Am. Chem. Soc. 1952, 74,
944.

48.

McCasland, G. E.; Smith, D. A., J. Am. Chem. Soc. 1950, 72, 2190.

49.

Godchot, M.; Mousseron, M., Bull. Soc. Chem. Fr. 1932, 51, 1277.

50.

Bannard, R. A. B.; Casselman, A. A.; Langstaff, E. J.; Moir, R. Y., Can.
J. Chem. 1968

, 46, 35.

51.

Foster, A. B.; Horton, D., Adv. Carbohydr. Chem. 1959, 14, 213.

52.

Clapp, L. B., J. Am. Chem. Soc. 1948, 70, 184.

53.

Methoden Org. Chem. (Honben-Weyl) 1958

, XI/1, 183.

54.

Mai, K; Patil, G., Tetrahedron Lett. 1984, 25, 4583.

55.

(a) Taylor, E. C.; Ehrhart, W. A., J. Am. Chem. Soc. 1960, 82, 3138.
(b) Taylor, E. C.; Ehrhart, W. A.; Kawanisi, M., Org. Synth., Coll. Vol.
1973, 5, 582.

56.

Mitchell, J. A.; Reid, E. E., J. Am. Chem. Soc. 1931, 53, 1879.

57.

Ralston, A. W.; Hoerr, C. W.; Pool, W. O., J. Org. Chem. 1943, 8, 473.

58.

(a) Wheeler, O. H.; Rosado, O., Chem. Amides 1970, 335. (b)
Hargreaves, M. K.; Pritchard, J. G.; Dave, H. R., Chem. Rev. 1970,
70

, 439. (c) Buckles, R. E.; Probst, W. J., J. Org. Chem. 1957, 22, 1728.

59.

Davey, D. D., J. Org. Chem. 1987, 52, 4379.

60.

Roe, E. T.; Scanlan, J. T.; Swern, D., J. Am. Chem. Soc. 1949, 71, 2215.

61.

Corson, B. B.; Scott, R. W.; Vose, C. E., Org. Synth., Coll. Vol. 1941,
1

, 179.

62.

(a) Basha, A.; Lipton, M.; Weinreb, S. M., Tetrahedron Lett. 1977, 18,
4171. (b) Lipton, M. F.; Basha, A.; Weinreb, S. M., Org. Synth., Coll.
Vol. 1988

, 6, 492. (c) Levin, J. I.; Turos, E.; Weinreb, S. M., Synth.

Commun. 1982

, 12, 989.

63.

(a) Sonntag, N. O. V., Chem. Rev. 1953, 52, 237. (b) Kent, R. E.;
McElvain, S. M., Org. Synth., Coll. Vol. 1955, 3, 490.

64.

Finan, P. A.; Fothergill, G. A., J. Chem. Soc. 1962, 2824.

65.

Fischer, H. P.; Grob, C. A., Helv. Chim. Acta 1964, 47, 564.

66.

Almond, M. R.; Stimmel, J. B.; Thompson, E. A.; Loudon, G. M., Org.
Synth. 1988

, 66, 132.

67.

Mowry, D. T.; Butler, J. M., Org. Synth., Coll. Vol. 1963, 4, 486.

68.

Truitt, P.; Richardson, E. E.; Long, L. M.; Middleton, W. J., J. Am.
Chem. Soc. 1949

, 71, 3479. (b) Stevens, C. L., J. Am. Chem. Soc. 1948,

, 165.

A list of General Abbreviations appears on the front Endpapers

AMMONIA

69.

Jacobs, W. A.; Heidelberger, M., Org. Synth., Coll. Vol. 1941, 1, 153.

70.

(a) Kleinberg, J.; Audrieth, L. F., Org. Synth., Coll. Vol. 1955, 3, 516.
(b) Audrieth, L. F.; Sveda, M., Org. Synth., Coll. Vol. 1955, 3, 536.

71.

Yang, P. S.; Rising, M. M., J. Am. Chem. Soc. 1931, 53, 3183.

72.

(a) McElvain, S. M.; Clarke, R. L., J. Am. Chem. Soc. 1947, 69, 2661.
(b) Israel, M.; Zoll, E. C.; Muhammad, N.; Modest, E. J., J. Med. Chem.
1973, 16, 1.

73.

Nakagawa, K.; Onoue, H.; Minami, K., J. Chem. Soc., Chem. Commun.
1966, 17.

74.

Gilman, N. W., J. Chem. Soc., Chem. Commun. 1971, 733.

75.

Markó, I. E.,; Mekhalfia, A., Tetrahedron Lett. 1990, 31, 7237.

76.

(a) Wolff, L., Justus Liebigs Ann. Chem. 1912, 394, 23. (b) Eaton,
P. E.; Jobe, P. G.; Reingold, I. D., J. Am. Chem. Soc. 1984, 106, 6437.

77.

(a) Bachmann, W. E.; Struve, W. S., Org. React. 1942, 1, 38. (b) Burger,
A.; Avakian, S., J. Org. Chem. 1940, 5, 606.

78.

Ugi, I.; Steinbrückner, C., Chem. Ber. 1961, 94, 2802.

79.

Howk, B. W.; Little, E. L.; Scott, S. L.; Whitman, G. M., J. Am. Chem.
Soc. 1954

, 76, 1899.

80.

Wegler, R.; Pieper, G., Chem. Ber. 1950, 83, 1.

81.

Palumbo, R.; de Renzi, A.; Panunzi, A.; Paiaro, G., J. Am. Chem. Soc.
1969, 91, 3874.

82.

Trost, B. M.; Shibata, T., J. Am. Chem. Soc. 1982, 104, 3225.

83.

Bruson, H. A., Org. React. 1968, 5, 79.

84.

McElvain, S. M.; Stork, G., J. Am. Chem. Soc. 1946, 68, 1049.

85.

Fischer, E.; Roeder, G., Chem. Ber. 1901, 34, 3755.

86.

Adamson, D. W., J. Chem. Soc. 1950, 885.

87.

Haeseler, P. R., Org. Synth., Coll. Vol. 1941, 1, 196.

88.

Heath, R. L.; Rose, J. D., J. Chem. Soc. 1947, 1486.

89.

(a) Fischer, E.; Raske, K., Chem. Ber. 1905, 38, 3607. (b) Fischer, E.;
Scholotterbeck, F., Chem. Ber. 1904, 37, 2357.

90.

Chekulaeva, I. A.; Kondrat’eva, L. V., Russ. Chem. Rev. (Engl. Transl.)
1965, 34, 669.

91.

Schulte, K. E.; Reisch, J.; Walker, H., Chem. Ber. 1965, 98, 98.

92.

Hill, C. W.; Senter, G. W.; Hill, M. E., J. Am. Chem. Soc. 1950, 72,
2286.

93.

(a) Maugin, C., Ann. Chim. Phys. 1911, 22, 297. (b) Sasse, K., Synthesis
1978, 379.

94.

Moore, M. L.; Crossley, F. S., Org. Synth., Coll. Vol. 1955, 3, 617.

95.

(a) Oxley, P.; Partridge, M. W.; Short, W. F., J. Chem. Soc. 1948, 303.
(b) Schaefer, F. C.; Krapcho, A. P., J. Org. Chem. 1962 27, 1255.

96.

Garigipati, R. S., Tetrahedron Lett. 1990, 31, 1969.

97.

(a) Elvidge, J. A.; Linstead, R. P., J. Chem. Soc. 1954, 442. (b) Elvidge,
J. A.; Linstead, R. P.; Salaman, A. M., J. Chem. Soc. 1959, 208.

98.

(a) Middleton, W. J.; Krespan, C. G., J. Org. Chem. 1965, 30, 1398. (b)
Middleton, W. J.; Carlson, H. D., Org. Synth., Coll. Vol. 1988, 6, 664.

99.

Verardo, G.; Giumanini, A. G.; Strazzolini, P.; Pioana, M., Synth.
Commun. 1988

, 18, 1501.

100.

(a) Sprung, M. M., Chem. Rev. 1940, 26, 297. (b) Richmond, H. H.;
Myers, G. S.; Wright, G. F., J. Am. Chem. Soc. 1948, 70, 3659. (c)
Nielsen, A. T.; Moore, D. W.; Ogan, M. D.; Atkins, R. L., J. Org.
Chem. 1979

, 44, 1678.

101.

(a) Nielsen, A. T.; Atkins, R. L.; Moore, D. W.; Scott, R.; Mallory,
D.; LaBerge, J. M., J. Org. Chem. 1973, 38, 3288. (b) Nielsen, A.
T.; Atkins, R. L.; DiPol, J.; Moore, D. W., J. Org. Chem. 1974, 39,
1349.

102.

(a) Crowell, T. I.; McLeod, R. K., J. Org. Chem., 1967, 32, 4030.
(b) Ogata, Y; Kawaski, A.; Okumura, N., J. Org. Chem. 1964, 29,
1985.

103.

(a) Emerson, W. S., Org. React. 1948, 4, 174. (b) Rylander, P. N.
Catalytic Hydrogenation over Platinum Metals

; Academic: New York,

1967; p 291. (c) Rylander, P. N. Catalytic Hydrogenation in Organic
Syntheses

; Academic: New York, 1979; p 167.

104.

(a) Moore, M. L., Org. React. 1968, 5, 301. (b) Leuckart, R., Chem.
Ber. 1885

, 18, 2341. (c) Lewis, K. G., J. Chem. Soc. 1950, 2249.

105.

Blicke, F. F., Org. React. 1942, 1, 303.

106.

Mannich, C.; Abdullah, S. M., Chem. Ber. 1935, 68, 113.

107.

(a) Chiavarelli, S.; Töffler, F.; Mazzeo, P.; Gramiccioni, L., Farmaco
Ed. Sci. 1968

, 23, 360. (b) Chiavarelli, S.; Töffler, F.; Valsecchi, G. P.;

Gramiccioni, L., Farmaco Ed. Sci. 1969, 24, 622. (c) Misiti, D.; Settimj,
G.; Matovani, P.; Chiavarelli, S., Gazz. Chim. Ital. 1970, 100, 495.

108.

Mowry, D. T., Chem. Rev. 1948, 42, 189.

109.

(a) Reinhold, D. F.; Firestone, R. A.; Gaines, W. A.; Chemerda,
J. M.; Sletzinger, M., J. Org. Chem. 1968, 33, 1209. (b) Steiger, R. E.,
Org.. Synth. 1955

, 3, 66. (c) Steiger, R. E., Org. Synth., Coll. Vol. 1955,

, 84.

110.

(a) Carmack, M.; Spielman, M. A., Org. React. 1946, 3, 83. (b) Brown,
E. V., Synthesis 1975, 358.

111.

Asinger, F.; Offermanns, H., Angew. Chem., Int. Ed. Engl. 1967, 6, 907.

112.

(a) Cope, A. C.; Cotter, R. J.; Estes, L. L., Org. Synth. 1963, 4, 62. (b)
Mitchell, J. A.; Reid, E. E., J. Am. Chem. Soc. 1931, 53, 321.

113.

Card, R. J.; Schmitt, J. L., J. Org. Chem. 1981, 46, 754.

114.

(a) Misono, A.; Osa, T.; Koda, S., Bull. Chem. Soc. Jpn. 1966, 39, 854.
(b) Misono, A.; Tetsuo, O.; Koda, S., Bull. Chem. Soc. Jpn. 1967, 40,
2875.

115.

Parameswaran, K. N.; Friedman, O. M., Chem. Ind. (London) 1965,
988.

116.

Carpino, L. A.; Han, G. Y., J. Am. Chem. Soc. 1970, 92, 5748.

117.

(a) Felix, A. M.; Jimenez, M. H. Meienhofer, J., Organomet. Synth.
1988, 6, 252. (b) Meienhofer, J.; Kuromizu, K. Tetrahedron Lett. 1974,
3259.

118.

(a) Guha, M.; Nasipuri, D., Org. Synth. 1973, 5, 384. (b) Korman, J., J.
Org. Chem. 1957

, 22, 848.

119.

Fremery, M. I.; Fields, E. K., J. Org. Chem. 1964, 29, 2240.

120.

White, R. W.; King, S. W.; O’Brien, J. L., Tetrahedron Lett. 1971, 3591.

121.

(a) Andrews, G. C.; Crawford, T. C., Tetrahedron Lett. 1980, 21, 693.
(b) Andrews, G. C., Tetrahedron Lett. 1980, 21, 697.

122.

(a) Barlin, G. B. The Pyrazines; Wiley: New York, 1982; Vol. 41. (b)
McCullough, K. J. In Rodd’s Chemistry of Carbon; Coffey, S.; Ansell,
M. F., Eds.; Elsevier: Amsterdam, 1989; Vol. IV, p 241.

Kevin J. McCullough

Heriot-Watt University, Edinburgh, UK

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