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Advances in the Chemistry of Aliphatic N-Nitrosamines

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1971 Russ. Chem. Rev. 40 34

(http://iopscience.iop.org/0036-021X/40/1/R04)

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34 Russian C h e m i c a l Reviews, 4 0 ( 1 ) , 1 9 7 1

U.D. C. 547.231 + 547.233:547.495.41

Advances in the Chemistry of Aliphatic N-Nitrosamines

A.L.Fridman, F.M.Mukhametshin, and S.S.Novikov

The review gives for the first time a systematic account of the extensive literature data on the chemistry of aliphaticnitrosamines. A separate chapter summarises the work on the physical properties, structure, and spectra of N-nitroso-derivatives. The chemical behaviour of the nitrosamines is determined largely by the characteristics of the p-

π-conjugation in the N-N-0 fragment. The principal chemical reactions of nitrosamines are treated from this standpoint:

the denitrosation reaction, the formation of complexes, the cyclisation to sydnones and sydnoneimines, and the synthesis oflactams. In conclusion, certain aspects of the practical applications of nitrosamines are considered.The bibliography includes 272 references.

CONTENTS

I. IntroductionII. Nitrosating agents and nitrosation

III. Methods of synthesis of iV-nitrosaminesIV. Physical properties, structure, and spectraV. Chemical properties

VI. Certain aspects of practical application

343435384046

I. INTRODUCTION

Λ- Nitrosamines occupy an important place in the largeclass of nitroso-compounds. The reason for this i s notonly the high chemical reactivity of the nitroso-group butalso the valuable products formed as a result of variousreact ions. It is sufficient to say that jV-nitroso-compoundsa r e widely used in the synthesis of diazo-derivatives anddialkylhydrazines, and a r e employed to prepare ni t ramines,sydnones, sydnoneimines, and complex compounds. TheN-nitrosation reaction is closely related to the chemistryof carbonium ions. N-Nitrosamines a r e excellent objectsfor the investigation of ^-^-conjugation, n-v* and v-ir*transi t ions, and rotational i somerism.

Despite the large number of studies that have been madeon nitrosamines and their theoretical and pract icalimportance, we were unable to find any reviews on thisfield of chemistry. The existing reviews deal mainly witharomatic ni trosamines, or deal with highly specificp r o b l e m s 1 " 5 .

The present review i s the first attempt to fill this gap,and covers the fundamental studies on aliphatic ni t ros-amines up to 1968-1969.

The study of the chemistry of aliphatic nitrosaminesbegan in 1863, when Geuther obtained JV-nitrosodiethyl-amine by the reaction of diethylamine hydrochloride withsodium n i t r i t e 6 ' 7 . Subsequently the JV-nitrosation r e a c -tion was employed by many investigators, who improvedand developed it. A number of interesting studies on thechemistry of ni trosamines have been made by Sovietchemists . Significant advances in the understanding ofthe s t ructure of nitrosamines were made in the 1950'sand 1960's. During this period, many new reactions ofnitrosamines were discovered.

II. NITROSATING AGENTS AND NITROSATION

It is believed that nitrosation is achieved by agentsrelated to nitrous acid having the s t ructure NOX, whereX = OAlk, NO2, NO3, halogen, orOH 2

+ . Depending on theexperimental conditions, any member of this se r ies maybecome the main nitrosating agent.

In the reaction of alkali metal nitrites with inorganicacid, nitrous acid is formed, its subsequent fate beingdetermined by the reaction conditions. Thus two nitrousacid molecules can be converted via a stage involving"self-protonation" and nucleophilic attack by the nitriteion into nitrogen trioxide, which is 6-10 times weakerthan protonated nitrous acid8 '9:

2HONO

HaO

· NO + NO7

N,O, + H2O

If a halide ion serves as the nucleophilic agent,nitrosyl halides a r e formed. This happens when thenitrosation is carr ied out in hydrogen halide solut ion 1 0 ' 1 1 .

In a highly acidic medium, nitrogen trioxide andnitrous acid cannot exist in a free form, and, for examplein 70-80% sulphuric acid, a r e converted into the nitroso-nium salt NO+HSO4. 1 2 Nitrosyl sulphate acid readilydissociates with formation of a nitrosonium cat ion 1 3 :

NaO, + 3HaSO4 -• 2NO+ + 3HSO7 + Ηβ+.

The nitrosonium cation is one of the most activenitrosating agents. Nitrosonium tetrafluoroborate is aninteresting nitrosating substance w . Recently nitrosyl -sulphuric anhydride HOSO2ONO was proposed as aneffective nitrosating compound 1 5 .

Certain investigators 1 6 explain the nitrosating activityof nitrogen tetroxide by the existence of the la t ter in thenitrosyl nitrate form NO.ONO2, which serves as a sourceof nitrosonium cations, like the nitrosonium salt ofsulphuric acid already mentioned. The nitrosonium cationis present at high concentrations only a t high acidities.In a weakly acidic medium or in the presence of an activenucleophilic agent, for example hydroxide ions, thenitrosonium cation is converted into nitrous acid andfurther into nitr i te ions 1 3:

NO+ + OH" •£ HNO2 ·£ H+ + NO7 .

At pH > 7 the equilibrium in the reaction is completelydisplaced to the right.

Depending on changes in the acidity in the reactionzone, various nitrosating agents a re present , which can bearranged in the following s e r i e s in t e r m s of increasingactivi ty 1 1 : NO.NO2, NOCl(Br, F ) , NO.OH2

+, NO+. Nitrous

Russian C h e m i c a l Reviews, 4 0 ( 1 ) , 1 9 7 1 35

acid and alkyl nitrites are absent from this series becausefree nitrous acid does not exhibit nitrosating activity u .In addition nitrous acid salts of primary and secondaryamines have been described in a number of papers 1 7 '1 8.Alkyl nitrites are as a rule rarely recommended forJV-nitrosation reactions.

In its simplest form the nitrosation of amines includeselectrophilic attack by the nitrosating species on the lonepairs of sp3 electrons of the nitrogen atom and subsequentdeprotonation of the alkylnitrosimmonium cation n . In thecase of secondary dialkylamines the reaction may berepresented by the following scheme:

R \ RV/" R\NH + NO—X 7 - * \\ + X " — £ > - Ν—NO .

R'/ R'/^-NO "" R'/

The amine participates in the reaction in a non-protonated form and therefore it is desirable to carry outthe nitrosation of highly basic amines in a weakly acidicmedium. Under these conditions, the comparativelyinactive nitrogen trioxide or at best a nitrosyl halide willfunction as the nitrosating agent. With amines having alow electron density at the nitrogen atom, nitrogen tri-oxide proved to be less effective than the nitrosoniumcation. This makes it necessary to carry out the reactionin a highly acidic medium.

Thus the acidity of the medium plays a dual role in thenitrosation of amines. Its increase enhances the concen-tration of the more powerful nitrosating agent (H2O

+.NO,NO+), but lowers the concentration of the active (non-protonated) form of the amines, i.e. the excess acid hasan inhibiting effect, which is shown particularly clearlyin the case of highly basic aliphatic amines. When thebasicity of the amine is low, part of it may exist as thenon-protonated species even in the presence of a consider-able excess of the acid u and this species is in fact actedupon by the powerful nitrosating agent.

These factors must be taken into account in the nitro-sation of various types of secondary amines.

III. METHODS OF SYNTHESIS OF iV-NITROSAMINES

The methods of preparation of JV-nitrosamines may bedivided into three principal groups: 1) nitrosation ofsecondary amines in an acidic medium, which shouldinclude also the nitrosation of the hydrochlorides,hydrogen nitrates, and hydrogen sulphates of secondaryamines by metal nitrites; 2) nitrosation with the aid ofNOC1, N2O3, and N2O4; 3) nitrosation by cleaving tertiaryamines. In addition, several methods of nitrosation havebeen described which are not of general importance at thepresent time.

1. Reaction of Alkali Metal Nitrites with Solutions ofAmines in Acids

After the discovery of ΛΓ-nitrosodialkylamines 6 theefforts of investigators were concentrated on the develop-ment of a convenient and reliable method for their syn-thesis. As early as 1865, Fischer found that, whendimethylamine hydrochloride acidified with sulphuric acidis treated with sodium nitrite in an aqueous medium,JV-nitrosodimethylamine is formed in a high yield19.Subsequently acetic 2 0" 2 5 or nitric 2 6 " 2 9 acid was employedin addition to sulphuric acid, but hydrochloric acid in factfound the widest application 51.

Various modifications of Fischer's method are dis-tinguished by the procedures employed to isolate thedesired products or by the temperature conditions.Nitrosamines have been extracted from the reactionmedium by steam distillation1 9'5 2"5 4, extraction by differ-ent solvents2 0 '2 1 '3 0 '3 7 '5 0, and other methods 6 ' 2 0 ' 2 1 ' 3 1" 3 6.Some investigators carried out the nitrosation reactionwith cooling (usually to 0 -5 o C), 2 0 ' 2 7 ' 3 6 ' 4 0 ' 4 1 ' 4 5 " 5 1 ' 5 5 - 5 8 whileothers heated the reaction mixture 6 ' 2 2 ' 3 1 ' 3 6 ' 3 8 ' 5 2 ' 5 4 ' 5 9 " 6 1 .However, temperature is in fact an important factor in thereaction. In an acidic medium it is desirable to carry outthe process at a low temperature to avoid denitrosation,which is acid-catalysed. If the acidity in the reaction zoneis low, the process usually takes place at an elevatedtemperature 60>61

f which has a favourable effect on the yieldof the final product and reduces the duration of the reac-tion. It is not fortuituous that, in the synthesis of nitros-amines, many investigators treated secondary aminehydrochlorides with an excess of sodium or potassiumnitrite at room or higher temperature without additionalacidification6 '2 1 '3 7 '5 5 '5 9 '6 2"6 9.

By virtue of its simplicity, nitrosation in an acidicmedium has been more widely used than other methods70"72.The considerable range of applications of "acid" nitrosationis shown by its employment to synthesise many nitros-amines containing various substituents in the alkyl residue:aryl groups 2 3 ' 3 5 ' 3 6 ' 3 9 ' 5 7 ' 6 3 ' 7 3" 7 5 halogens2 1 '5 9 '7 6 '7 7 andketo- 2 2 ' 4 1 ' 6 4, ester 3 2" 3 4 ' 6 2 ' 7 8 ' 7 9; carboxy-3 7 '4 0 '4 5 '5 0 '5 6,hydroxy-21'57'61'73, alkoxy- 2 0 ' 5 3 , nitrile 2 6 ' 4 6 " 4 9 ' 5 1 ' 7 8 ' 8 0 ,nitrate2 7, sulphate81, and nitro-groups 55. Nitrosation inan aqueous solution of an inorganic acid has been used tosynthesise dinitroso-compounds based on JV-alkyl-sub-stituted ethylenediamines30'68 and nitrosamines containingan olefinic residue at the nitrogen atom2 2 '8 2. In aceticacid a number of labelled [14C]-./V-nitrosodialkylamineshave been synthesised83.

Taylor and Price 8 4 attempted to determine the concen-tration of nitrous acid necessary for successful reaction.They showed for dimethylamine that, when equimolaramounts of the reagents (0.05 Ν amine + 0.05 iVHNO2) aremixed, the reaction does not occur. With increase ofthe concentration of nitrous acid to 0.1 N, an adduct withthe composition [(CH3)2NH2]

+.[NO2]".[HNO2] is formed,but the formation of iV-nitrosodimethylamine was notobserved.

The formation of nitrous acid salts in the reactionbetween secondary o--arylamine hydrochlorides andsodium nitrite in ethanol was observed even earlier byCurtius 1 7>8 5 '8 6. On prolonged refluxing in ethanol, thenitrite salt of the amine is converted into the correspond-ing nitrosamine:

RCH, . NaNO, R C H SNiNH2 · ΙΛ >

RCH,/ RCH2

Δ RCH, V

• N O " • > N - N O + H2OR C H , 7

Ring-substituted JV-nitrosodibenzylamines have beensynthesised in this way. Some investigators employedsilver nitrite instead of sodium nitrite 8 7 ' 8 8. The resultsof the studies quoted1 7 '8 4"8 8 confirm that in the nitrosatio·.?.of fairly basic amines the reaction must be carried out atcomparatively high temperatures.

The dependence of the reaction conditions on the basicityof the amine is also illustrated, for example, byiV-nitrosodi-(2-bromo-2,2-dinitroethyl)amine, which wasobtained by treating di-(2-bromo-2,2-dinitroethyl)aminewith sodium nitrite in concentrated sulphuric acid29:

BrC (NO2)2 CH 2 S^

BrC (NO2)2

BrC (NO2)2 CH,X

BrC (NO2), C I V

36 Russian Chemica l Reviews, 4 0 (1) , 1971

In trifluoroacetic acid and trifluoroacetic anhydride,iV-nitrosodi-(2,2,2-trinitroethyl)amine was obtained fromdi-(2,2,2-trinitroethyl)amine89.

In contrast to the work of Curtius and Taylor, in thestudies quoted above the nitrosation of weakly basicamines was investigated and the reaction carried out in astrongly acidic medium.

2. Reaction of Nitric Oxide, Nitrogen Trioxide, NitrogenTetroxide, and Nitrosyl Chloride with Secondary Amines

The first studies where the application of nitrogentrioxide as the nitrosating agent in the series of aliphaticamines was reported were carried out towards the end ofthe nineteenth century. Paulman90, who investigated theproperties of sarcosine, found that it reacts readily with"gaseous nitrous acid", forming a nitroso-derivative.Subsequently nitrosiminodiacetic acid91'92 anddi-(2-azapro-pyl-2-nitroso-3-phenyl)methanol93 were synthesised in asimilar way. The reaction was carried out in anaqueous medium:

(HOOCCH2)2 NHN,OS; H,0

(HOOCCH2)2 N-NO

The dinitrile and the dimethyl esters of nitrosiminodiaceticacid were obtained with nearly quantitative yields inether94.

Brookes and Walker95, who allowed nitrogen trioxideto react with ar-aminoacetonitriles, observed that theformer is not only a nitrosating agent but also promotesthe cyclisation of the intermediate iV-nitrosoacetonitrilesto sydnoneimines:

R—CH—CN

R1—NH

R—CH—CN

R1—N—NO " Ho

R'N

Despite the fact that the method of introduction of thenitroso-group with the aid of nitrogen trioxide gives as arule good results, it has not found as wide an applicationas "acid" nitrosation. This is probably because theprocess is complicated by the necessity to obtain nitrogentrioxide. The latter is usually obtained from sodiumnitrite and sulphuric acid95 or by the reaction of nitricacid with arsenic oxides 94.

Above its boiling point nitrogen trioxide readily decom-poses into NO and NO2. This property constitutes thebasis of the synthesis of nitrosamines. Thus iV-chloro-dialkylamines are readily converted into JV-nitrosodialkyl-amines when acted upon by nitric oxide in solutionscontaining the redox system Fe3+/Fe2+ or Cu2+/Cu+.96

Similarly iV-nitrosodi(trifluoromethyl)amine was syn-thesised from A/-bromodi(trifluoromethyl)amine 9?. Aradical mechanism was proposed for the reaction:

R2N—Hal -> R2N- + Hal' ,

Hal" + NO -» NO ,

RjN* + NO — R2N—NO .

The gas-phase or liquid-phase nitrosation of secondaryalkylamines probably takes place by a radical mech-anism 98'99. The reaction is performed in an autoclaveat a high temperature, after mixing nitrogen oxides and theamine. Judging from patent data, N-nitrosodialkylaminesare formed when nitric oxide reacts with secondary aminesunder pressure in the presence of transition metal salts,metallic nickel, palladium, or rhodium100, itf-nitroso-diethylamine is formed when the adduct of diethylamine withnitric oxide is decomposed in the presence of oxygen 101.The kinetics of the reaction of diethylamine with nitric

oxide have been investigated. The reaction is of firstorder with respect to diethylamine and proceeds via theintermediate adduct (C2H5)2NH.N2O2, which reacts with asecond molecule of nitric oxide and then with diethyl-amine. The activation energy for the reaction is12 kcal mole"1.102

The use of nitrogen tetroxide and nitrosyl chloride asnitrosating agents has been insufficiently investigatedalthough they have been known for a long time and areused for the nitrosation of amines and amides 16»89»103

:

[(NO2)3CCH2]2

C H ' C O O H + C H ' C O ° K ^ [(NO2)3CCH2]2N-NO+HNO3

Et2NH2 · NO3 + NO · NO3 - E t 2 N-NO + 2HNO3 .

The reaction of nitrosyl chloride with secondary amineswas investigated by Solonina When nitrosyl chloridewas passed into a solution of the amine in ether,iV-nitroso derivatives of dipropyl-, di-isobutyl-, anddipentyl-amines were synthesised. Later it was shownthat the reaction of nitrosyl chloride with diethylaminehydrochloride results in a quantitative yield of theJV-nitroso-derivative:

Et2NHa · Cl + NOC1 — Et 2 N-NO + 2HC1 .

The synthesis of JV-nitroso-di-t-butylamine in 23%yield from di-t-butylamine and nitrosyl chloride has beendescribed105.

3. Cleavage of Tertiary Amines Accompanied by Nitro-sation. Syntheses of Nitrosamines from Primary Amines

Until recently there has been no unanimous view on thecleavage of tertiary amines with nitrous acid. Not until1967 was it shown convincingly that tertiary amines canbe converted into nitrosamines by nitrous acid106,although examples of this reaction were known in the pastcentury. Geuther 107 obtained JV-nitrosodiethylamine fromtrie thy lamine, but Heintz 108 was unable to reproduce hisresults and arrived at the erroneous conclusion thattertiary amines do not react with nitrous acid. Thisinitiated the controversy which continued for more than onehundred years. Subsequently the validity of Geuther'sresults was confirmed by Solonina109, who investigated thecleavage of forty nitrite salts of amines and in all casesobserved the formation of nitrosamines, and also by otherinvestigators110"112. The cleavage of tertiary amines bynitrous acid is discussed in detail in the literature 106>112.

The most probable mechanism of the cleavage includesattack by the nitrosating agent on the free electron pair ofthe nitrogen atom and the formation of the nitrosimmoniumion. The latter splits off the "nitroxyl" (HNO) andhydrolyses under the reaction conditions to a secondaryamine. A ketone or an aldehyde is formed as a sideproduct106:

R 2N-CHR 2 R 2N=CR 2+HNO ,

R 2 N-NO ,

2HN0 -^ H2N2O2 — H20 + N20

The degree of conversion of the tertiary amine into thenitrosamine reaches 50-70%.

The cleavage of tertiary amines with nitrous acid andnitrosyl chloride has been described103. Thus, on reflux-ing in alcohol with nitrous acid, tribenzylamine is smoothlyconverted into JV-nitrosodibenzylamine and benzaldehyde.

Russian C h e m i c a l Reviews, 4 0 ( 1 ) , 1 9 7 1 37

The results obtained with nitrosyl chloride are contra-dictory. In an early study Solonina noted that tri-isobutyl-amine is cleaved with nitrosyl chloride to iV-nitrosodi-isobutylamine104. According to these data1 1 4, when cyclo-hexyldimethyl- and dicyclohexylmethyl-amines are actedupon by nitrosyl chloride, Λ-nitrosocyclohexylmethyl- andiV-nitrosodicyclohexyl-amines are formed respectively.In another publication115 it was noted that the reaction oftrimethylamine with nitrosyl chloride gives only the hydro-chlorides of di- and tri-methylamines: the reaction withtribenzylamine results in the formation of the hydrochlor-ides of tribenzylamine and dibenzylamine and of benz-aldehyde 106. The same products are formed in the reac-tion of tribenzylamine with nitrosonium tetrafluoroborate106.Probably the basicity of the nitrogen atom is importantfor the cleavage of tertiary amines to the correspondingiV-nitroso-compounds. For example, triglycineamine,the basicity of the nitrogen atom in which is reduced, isincapable of undergoing cleavage with nitrosation116.Diethylaminotrimethylsilane is readily cleaved by nitrosylchloride U 7 :

(CJHjJ.NSiiCHjOa + NOCl -* ( Q H 5 ) 2 N - N O + (CH3)3 SiCl .

In 1920 a method for the preparation of JV-nitrosodialkyl-amines by the cleavage of tertiary amines with tetranitro-methane was discovered. The reaction takes place whenalcoholic solutions of tertiary amines are heated withtetranitromethane in the presence of pyridine 1 1 8:

RiR2NCH2R + C5H5N + C (NO2)4 — RiR2N—NO + RCHO + C5H5N · HC (NO2)8 .

A large series of JV-nitrosodiaryl-, A/-nitrosoarylalkyl-,and iV-nitrosodialkyl-amines was synthesised by thisprocedure. Subsequently a similar cleavage was achievedin the absence of pyridine in acetic acid u 9 . Nitroformis formed as a side product.

In connection with the nitrosating activity of tetranitro-methane, it is interesting to note that this compoundexhibits nitrosating and nitrating properties in relation to

1 2 0 1 2 2

Although the method of preparation of the nitrosaminesfrom primary amines has no preparative importance, itis interesting from the theoretical standpoint. Since themechanism of the denitrosation of amines is presumed toinvolve the formation of an intermediate carbonium ion u ,the results described above can be accounted for by thealkylation of the primary amine by the carbonium ion:

RNH2 - £ ^ R-N=N-OH S R+ ,

RNH2 + R+ -» RNH2 τ ^ 1 - » R.N-NO .

R

Cleavage of amines accompanied by nitrosation is ofpreparative interest as a method for the purification ofsecondary amines. Thus, when a mixture of primary,secondary, and tertiary amines is treated in successionwith a nitrosating agent and potassium permanganate, onlythe iV-nitrosodialkyl-amine remains 134. A method for thesynthesis of pure iV-nitrosodialkylamines by the nitrosationof a mixture of di- and trialkylamines has also beendescribed104'110.

4. Other Methods

The preparation of JV -nitrosodipropylamine from thenitrite salt of dipropylamine by fusing the latter or heatingit in water has been described 135. JV-Nitrosodimethyl-and N-nitrosodiethyl-amines are formed when nitrite 18

and nitrate salts of dimethyl- and diethyl-amines areheated 136, via the following mechanism:

(CH3)2 NH · HNO3 Λ (CH3)2 NH · HONO - (CH3)2 N - N O + H2O + Ο .

JV-Nitrosodibenzylamine was isolated when tetrabenzyl-

with nitric acid

(CeH5CH2)2 N - XHNO,

(C,H5CH2)2 N - N O ; X=OH; Ν (CH2C eH5)2

exhibits nitrosating and nitrating properties in relation toaromatic compounds 1 2 0" 1 2 2, a nitro-group can be replaced hXd^a2:ine and^iV-dibenzylhydroxylamine were treatedby a halogen 123>124 or an alkyl residue in polar aproticsolvents 1 2 5, and is tetranitromethane capable of a numberof other extremely interesting reactions1 2 6"1 2 8.

Cleavage of tertiary amines accompanied by nitrosationtakes place also under the action of bromonitroform inchloroform. This is accompanied by the bromination andnitration of the benzene ring. Thus the reaction of bromo-trinitromethane with dimethylaniline leads to the formationof JV-methyl-iV-nitroso-/>-bromoaniline and JNN- dimethyl -/>-nitroaniline 129.

In his study of the reaction of silver nitrite with thehydrochlorides of n-propyl- and n-butyl-amines, Meyerobserved that, together with other products, low yields ofiV-nitrosodipropyl- and iV-nitrosodibutyl-amines areformed in this process 130>131. Deamination of n-propyl-amine gave a mixture of propanol, 2-propanol, andJV-nitrosodipropylamine x 2.

Under thermolysis conditions, the nitrite salts ofmethyl- and ethyl-amines tend to undergo similar reac-tions 18.

When ethyl- and isobutyl-amines were treated withnitrosyl chloride in ether, JV-nitrosodiethyl- andiv-nitroso-di-isobutyl-amines were formed together with corres-ponding alkyl chlorides. It is interesting that the authorexplained "their formation (nitrosamines) via the prelimi-nary synthesis of secondary amines by the action of thealkyl chlorides on the primary amines". Seconday aminesare then converted into nitroso-compounds ***.

It has been reported that JV-nitrosodibenzylamine isformed when isopentyl nitrite reacts with dibenzylamine138.Titov employed benzyl nitrite to nitrosate diethylamine 1 3 9;a continuous method for the synthesis of JV-nitrosodimethyl-amine with a yield in excess of 90% by the nitrosation ofdimethylamine in alcohol with methyl nitrite has beendescribed140.

The formation of JV-nitrosodi-isopropyl-, JV-nitroso-dibutyl-, and JV-nitrosodi-03-nitroxyethyl)amines has beenobserved in the catalytic nitration of the correspondingamines in the presence of zinc chloride 2 7 > 1 4 1. in thisconnection, one may note that the catalytic effect of Cu2+

ions in the nitrosation of diethylamine in methanol withnitric oxide under pressure has also been investigated142'143.The effects of temperature, pressure, and the concentra-tion of nitrogen oxides on the mode of reaction have beenstudied. The optimum yield of iV-nitrosodiethyl-amine(93.8%) is attained in the reaction carried out at 30°C at apressure of 1 atm. The reduction of temperature to-30°C, an increase of pressure, and an increase of theconcentration of nitric oxide leads to a fall of the yield ofthe nitrosamine to 11-15% owing to the formation of methylnitrite. The nitrosating species is CuNO2+. The kineticsof the reactions were investigated.

38 Russian C h e m i c a l Reviews, 4 0 ( 1 ) , 1 9 7 1

According to patent data, when l,l,l,6-tetranitro-3,6-diazaheptane is nitrated with a mixture of acetic anhydrideand nitric acid, l,l.l,6-tetranitro-3-nitroso-3,6-diaza-heptane is formed . We believe that this result is mostprobably "fortuituous". It is likely that the authorsemployed nitric acid containing a high content of nitrogenoxides, which were in fact responsible for the nitrosationof the amine.

Nitration of a ternary mixture of ammonium chloride,the ammonium salts of nitroform and di-(2,2,2-trinitro-ethyl)amine, formed in the condensation of methylene-diamine hydrochloride with 2,2,2-trinitroethanol, andnitric acid in acetic anhydride leads to the formation ofJV-nitrosodi-(2,2.2-trinitroethyl)amine with an admixtureof the nitramine . The authors attribute the appearanceof the Λ-nitroso-derivative to the catalytic effect of thechloride ions. The capacity of a mixture of aceticanhydride and nitric acid to behave as a nitrosating agentwas noted by Wright and coworkers 2 ?. However, thenitrosation of di-(2,2,2-trinitroethyl)amine in this mixturecan also take place in the absence of chloride ions underthe action of N2O4.

The formation of JV-nitrosodi-(2,2,2-trinitroethyl)aminewas observed in the condensation of 2,2,2-trinitroethanolwith hydroxylamine and also in the reaction of nitroformwith formaldoxime in the presence of sulphuric acid89.The mechanism of the reaction was not established:

2 HC (NO2)3 + 2 CH 2 =NOH [(NO2)3)CCH2]2N-NO.

IV. PHYSICAL PROPERTIES, STRUCTURE, ANDSPECTRA

1. General Characteristics

In the wide class of JV-nitro sodialky lam ines, the proper-ties of the simplest members (ΛΓ-nitrosodimethyl- andiv-nitrosodiethyl-amines) were most fully investigated.The lower JV-nitrosodialkylamines are yellow or yellow-green non-hygroscopic liquids, which are partially solublein water and readily soluble in organic solvents. Theirboiling points increase with the increasing size of thealkyl substituents and lie in the range 150-220°C. As arule, substituted nitrosamines are yellow crystallinecompounds. In this connection, it is important to notethat TV-nitrosopolynitroalkylamines are colourless, whichis undoubtedly due to the effect of the polynitroalkyl sub-stituents on the p-v conjugation in the nitrosamines.Compared with the related nitramines, iV-nitrosodialkyl-amines have lower boiling and melting points. Thedensities of the majority of nitrosamines are relativelylow and lie in the range 0.9-1.2 g cm"3, increasing withthe molecular weight.

The dipole moments of i\T-nitrosodialkylamines areevidence of a considerable polarity of the molecules.For example, the dipole moment of JV-nitrosodimethyl-amine is 3.98 D, 1 4 5 while that of JV-nitrosodibutylamine is4.32 D. 1 4 6 The introduction of electron-accepting sub-stituents into the molecule leads to a decrease of thedipole moment. Thus the dipole moment of iV-nitroso-iV-phenylaminoacetic acid is 3.18 D 147 and those of JV-nitroso-methylaniline and iST-nitrosodiphenylamine are 3.62 and3.39 D respectively The replacement of each methyl

believe that it is of interest to investigate the dipolemoments of nitrosamines with other electronegative sub-stituents such as trifluoro-, trichloro-, and trinitro-methyl groups, which will make it possible to trace theireffect on the conjugation in the nitrosamino-group by thedipole moment method.

The average refraction of the N-N bond in iV-nitroso-dialkyl-amines hardly differs from the value in asym-metric dialkyl-hydrazines and amounts to 1.99. Therefraction of the >N-N=O fragment is 7.748 and slightlyexceeds the group refraction in dialkylhydrazines 5 4>" 9.The parachors of the N=O and >N-N=O groups in anumber of JV-nitrosodialkylamines have been determinedand the average values of these quantities have been foundto be 53.4 and 68.0 respectively i 4 ' 1 4 9 .

The literature quotes certain thermochemical param-eters for iV-nitrosodimethylamine: heat of combustion(382 ± 1.5 kcal mole"1), heat of formation in the standardstate (-10.7 ± 1.5 kcal mole"1), heat of evaporation(9.9 ± 0.5 kcal mole"1), and heat of formation in the gasphase (-0.8 ± 2 kcal mole"1). 15°

The dissociation energy of the N-N bond in JV-nitroso-dimethylamine, determined by the electron impactmethod, is 43 kcal mole" 1, 1 5 1 while according to otherdata it is 32 kcal mole"1. This quantity was recentlyestimated more accurately in a study already quoted 15°and was found to be 55.2 kcal mole" . Thus, contraryto earlier data, the N-N bond in iV-nitrosodimethylamineproved to be stronger than in iV~-nitro-di-methylamineto the extent of 14.1 ± 5.2 kcal mole"1 according to thermo-chemical data and 11.3 ± 3.0 kcal mole"1 according tokinetic data1 5 0. These data appear to be the most correct,since they are consistent with the hypothesis of p-n con-jugation in the nitrosamine group, as a result of whichthe amount of N-N multiple bond character in nitros-amines is enhanced (about 49%) compared with that innitramines (about 15%).153"155

2. Structure and Spectra

The molecules of aliphatic nitrosamines have coplanarstructures in the gaseous and crystalline states. Bothnitrogen atoms are in the state of sp2 hybridisation,which is confirmed by the C'-N-N (120.3°), C'-N-N(116.4°), and N-N-0 (113.6°) valence angles in JV-nitroso-dimethylamine. The bond lengths in JV-nitrosodimethyl-amine are as follows: 1.235 Afor N-O, 1.344 Afor N-N,1.461 Afor C-N, and 1.129 Afor C-H. It is interestingthat the N-N bond in JV-nitrosodimethylamine is shorterby 0.04 A than in JV-nitrodimethylamine, which has beenattributed to the greater electron-accepting activity of thenitroso- group compared with the nitro-group 156. TheN-N bond length in iV-nitrosodimethylamine agrees wellwith its enhanced multiplicity and strength compared withthose in JV-nitrodi-methylamine.

The planar disposition of the nitrosoamino-group hasbeen established by an X-ray diffraction study of theadduct of iNT-nitrosodimethylamine with copper chloride.The bond between the copper atom and the nitrosamine isformed via the oxygen atom of the nitro so-group. Thenitrogen atom of the nitroso-group is located at equaldistances from the neighbouring copper atoms. Theconsiderable difference between the Cu-O and Cu-Ndistances may be due to the fact that the copper atom isdisplaced by 0.2 A from the plane passing through the

group by a phenyl group leads to a decrease of the dipolemoment of the nitrosamine by 0.3 D. 1 4 8 Therefore we

chlorine atoms The shortening of the N-N bond inthe complex compared with the free nitrosamine can be

Russian C h e m i c a l Reviews, 4 0 ( 1 ) , 1971 39

accounted for by the transfer of electron density from the156dimethylamino-group to the nitroso-group :

The disposition of the atoms in the nitrosamino-groupin one plane naturally facilitates the overlapping of thep orbital of the amino-nitrogen atom with the ir-electroncloud of the N*"O bond. The force constant of the №«0bond in nitrosamines is 6.8 mdyn A"1.1 5 8 According tothis value, the multiplicity of the Ν—Ο bond in nitros-amines is between 1 and 1.5:

In a number of studies the internal rotation about theN-N bond with partial double bond character was investi-gated. The barrier to rotation about this bond isestimated as approximately 24 kcal mole ' 1 . 1 5 9 " 1 6 1 Thisleads to the appearance of s-cis-trans isomerism in nitros-amines. The presence of the isomers of a large numberof iV-nitroso-derivatives has been demonstrated by NMRspectroscopy162>163:

,/

Only the «s-methyl isomer has been detected forJV-nitrosomethylphenylamine. Both isomers have beenfound for JV-nitrosoethylphenylamine and JV-nitrosoisopro-pylphenylamine. The conformations of the alkyl substi-tuents in JV-nitrosoisopropylmethyl-, ΛΓ-nitroso-t-butyl-methyl-, and JV-nitrosodi-isopropyl-amines are discussedin the same paper. The following conformations arecharacteristic of iV-nitrosodi-isopropylamine:

CH, CH, CH 3 OH, Η C H , CH C H 3

isomers of benzyl-2,6-dimethyl-JV-nitrosoanilines wereseparated by thin-layer chromatography. The bulky2,6-dimethylphenyl group evidently stabilises the isomers.Both substances are stable in the crystalline state 162.Rotational isomerism has also been observed for N-nitroso-benzylisopropylamine 1 6 4> 1 6 5. The equilibrium mixture ofthe isomers was separated into its components by crystal-lisation from carbon disulphide 1 6 5. The ratios of theareas of proton signals for certain cis- and trans-isomershave been investigated as a function of the bulk of the alkylsubstituents. The screening of the protons of the cis-isomers is more pronounced than that of the protons of theirons-isomers, owing to the diamagnetic anisotropy of theN=O bond 1 6 6 .

In a study of the optical rotatory dispersion it wasobserved that an intense cotton effect is characteristicof various nitrosamines in the range 350-400 n m . 1 6 7 Then-v* and n-v* transitions are active in the nitroso-chromophores 1 6 8 " 1 7 1 . For example, in aqueous solutionof JV-nitrosodimethylamine the π-ττ* transition is shown inthe region of 228 nm and the η-π* transition in the regionof 332 n m . 1 6 9 The studies on the optical circular dichro-ism of nitrosamines have been reviewed in a monograph 172.The sector rule for nitrosamines and its correlation withthe stereochemistry of these compounds have beendescribed Ι β 1 .

Although a large number of infrared spectra of nitros-amines have been described in the l iterature, few syste-matic accounts of the assignments of the absorptionfrequencies are available1"»159»173-180. in One of the firstdetailed studies of the infrared spectroscopy of nitros-amines, Haszeldine and Jander drew attention to theinconsistency between the absorption bands of the N=Obond in nitrosamines and those for nitramines, nitrites,and C-nitroso-compounds. They observed in the infraredspectra of nitrosamines three relatively intense bands inthe region of 7.1-7.4, 7.6-8.6, and 9.15-9.55 μιη. Thefirst two were assigned to the vibrations of the N=O bondand the last to the vibrations of the N-N bond. Theappearance of the 7.6-8.6 μιη band was attributed by theauthors to the resonance of the following limiting struc-tures:

RjN—N=O <-• R,N=N-0 .(I) (ID

To confirm these conclusions, a study was made of theeffect of various solvents and the state of aggregation onthe nature of the spectral changes77>175. it was foundthat the spectra of nitrosamines in the liquid state differfrom those recorded in solvents (carbon tetrachloride andchloroform), particularly in the range of frequenciescharacteristic of the N=O bond. The authors attributethese changes to three causes: (a) dipole-dipole inter-action between molecules, (b) intramolecular binding ofthe alkyl hydrogen by the oxygen atom of the nitroso-group,and (c) dimerisation of the molecules:

+δ -βR2N—Ν—Ο

Ι ΙR2H

HC2< ^NR2

ΔΗ for the cis- trans isomerisation of iV-nitrosobenzyl-methyl-amine is less than 1 kcal mole" \ 1 5 8 The cis- trans

-—N+—NR2

(a) ' N H ( b ) (C)

The predominance of a particular type of interactiondepends on the conditions under which the nitrosamineexists. In the gaseous states the molecules are of coursenot associated and therefore the N=O absorption band iscloser to that in the spectra of nitramines. In the liquidstate monomer-dimer equilibrium obtains and the N=Oabsorption band is displaced towards longer wavelengths(6.74 and 6.93 μιη respectively for JV-nitrosodiethylamine).

40 Russian Chemical Reviews, 4 0 (1), 1971

Polar solvents have a similar effect. The N-N absorptionband varies in exactly the same way. For example, in thespectrum of gaseous ΛΓ-nitrosodiethylamine it is in theregion of 9.55 μΐη and in that of the liquid substance it isdisplaced to 9.35 μπι. The idea of a monomer-dimerequilibrium in nitrosamines was supported by Tarte 1 7 6

and by Piskorz and Urbanski l tT.An interesting observation was made in a study of the

infrared spectrum of JV-nitrosodi-(2,2,2-trifluoroethyl)-amine, one of the few JV-nitroso-derivatives containingelectron-accepting substituents7T. In this substance theN=O absorption bands are displaced under the influenceof the trifluoroalkyl groups towards shorter wavelengthsand are located in the region of 6.45 μπι for the gaseousnitrosamine and in the region of 6.60 μπι for the liquidsubstance. The displacement of the bands was attributedby the authors to a decrease of the polarity of theiV-nitrosodi-(2,2,2-trifluoroethyl)amine molecule, whichreduces sharply the interaction between the individualmolecules. It is interesting that the N-N bond vibrationfrequencies in is/-nitrosodi-(2,2,2-trifluoroethyl)aminein solution, or following a change in the state of aggrega-tion, are displaced less than for unsubstituted nitros-amines.

Williams et al. 1 7 8, who postulated the occurrence ofmesomerism in nitrosamines, suggested that, when thespectra are recorded in polar solvents, the absorptionbands associated with the N=O bond vibrations (6.6-6.7μπι)should be displaced towards longer wavelengths. On theother hand, the N-N absorption band should be shown atlower wavelengths. This hypothesis was confirmedexperimentally. In the spectra of iV-nitrosodimethylaminein carbon tetrachloride and methylene bromide XN=O is6.85 and 6.94 μΐη, the corresponding values for the N-Nabsorption band (XN-N) being 9.66 and 9.52 μπι. An ana-logous situation was found in the spectra of other nitros-amines.

The wavelength corresponding to the N=O bond in thenitrosamines is much higher than for C-nitroso-derivativeswhich can be accounted for by the greater contribution tothe structure of nitrosamines of the canonical form (II).1 7 8

The hypothesis of the dimerisation of nitrosamines putforward by Haszeldine and coworkers was rejected byWilliams 1 7 8 and other investigators m>1 7 9>1 8 0.

The Table summarises the principal literature data onthe infrared spectra of nitrosamines.

Comparison of the infrared spectra of N-nitrosodi-(2,2,2-trifluoroethyl)amine with those of unsubstitutedanalogues demonstrates that electron-accepting substitu-ents have a significant influence on the structure of thenitrosamino-group, probably by reducing the degree ofp-τι conjugation. This conclusion has been confirmedexperimentally in a study of the chemical properties ofJV-nitrosopolynitroalkylamines. It is significant that inthe infrared spectrum of JV-nitrosodi-(2-bromo-2,2-dinitro-ethyl)amine and iV-nitrosodi-(2,2,2-trinitroethyl)amine,bands with i>NO = 1490 and 1520 cm"1 and I^N_N = 980 and1020 cm"1 respectively are characteristic of the nitros-amino-group t.

In the ultraviolet spectra of nitrosamines there aretwo absorption bands in the region of 235 and 365 nm, 1 7 4

230 and 374 nm, 1 7 7 230 and 365 nm, 7 7 and 228 and332 nm 1 6 9 (in water). The first of these is more distinctthan the second. The bands were assigned by comparing

the spectra of nitrosamines with those of nitrites andnitramines. In the ultraviolet spectra of nitramines,there is a strong absorption in the region close to 235 nmand in the spectra of nitrites in the region of 375 to380 nm. 7 7 ' Therefore the absorption band in theregion of 230-235 nm in the spectra of nitrosamines char-acterises the N-N bond and the absorption in the region oflonger wavelengths is due to the N=O bond 1 7 5.

The positions of the bands in the ultraviolet as well asinfrared spectra, depend greatly on the nature of thesolvent. For example, on passing from a non-polarsolvent to water, the 365 nm band is displaced to 331 nm.This shows that the N=O bond is sensitive to externaleffects. A similar observation was made in a study ofthe ultraviolet spectrum of JV-nitrosodi-(2,2,2-trinitro-ethyl)amine 89.

Infrared spectra of certain

R

CH 3

C 2 H 6

n-C 9 H,1S0-C3H7S-C4H9n-C 5 H u

CeH5CH2C«Hi3

F3CCH2

Liquid

V N=Ocm"1

144514481455

—1460

—.14601515

V N — N 1

cm' 1

104810691069

—1084

—10901052

nitrosaminesSoln. in CC14

v N = o ·

cm'1

14601459146014381437

1463—

1528

VN—N.

cm"1

104110611067113911351082112010851046

R2N-NO.

πVN=O"

cm"1

148814851486

——

——

1550

ap

V N-N

cm"1

101510481049

—————

1046

tThe absorption frequencies were assigned by theauthors of the review on the basis of the spectra quotedby Grimes et al . 8 9

Electron-accepting substituents have an appreciableeffect on the absorption by the nitroso-group. Whereasthe absorption by the N=O bond in JV-nitrosodiethylamineoccurs in the region of 360 nm, in the JNT-nitroso-deriva-tives of di-(2,2,2-trinitroethyl)-, di-(2-bromo-2,2-dinitro-ethyl)-, and di-(2,2,2-trifluoroethyl)amines it is displacedto the region of 380 nm. Information about these effectsof the nature of the substituent on the >N-N=O fragmentis also provided by mass spectrometric data. Forexample, JV-nitrosodimethylamine dissociates with forma-tion of C2H4N

+ as the major ion (19.2%), while iV-nitroso-di(trifluoromethyl)amine gives the CF3 major ion(37.8%).181

V. CHEMICAL PROPERTIES

Aliphatic nitrosamines are highly reactive. Thereason for their reactivity is that the nitrosamino-grouphas four lone pairs of electrons, which make nitrosaminespotential Lewis bases. The occurrence of p-n conjuga-tions with the withdrawal of the electron cloud towards theoxygen atom is responsible for many interesting reactionsof nitrosamines. In the first place these are the complex-formation reactions, reaction with inorganic acids,reduction to NN-substituted hydrazines, oxidation andnitration, cyclisation to sydnones, and sydnoneimines,and photochemical reactions.

Russian Chemical Reviews, 40 (1). 1P71 41

2. Reaction with Inorganic Acids, Hydrogen Bonds, andComplex-formation Capacity of Nitrosamines

When inorganic acids act upon nitrosamines, thenitroso-group is split off with formation of amine salts.In one of the first studies6 it was already noted that, whenhydrogen chloride is passed into an emulsion of iST-nitroso-diethylamine in water, the nitroso-derivative rapidlydissolves. When an ethereal solution of JV-nitrosodiethyl-amine is treated with hydrogen chloride, a salt with thecomposition (CsHs^NNO.HCl is formed, and then readilydecomposes on addition of water or alcoholΆ.

iV-Nitrosodimethylamine decomposes on heating withhydrochloric acid into dime thy lanune hydrochloride andnitrous acid. Hydrochloric acid acts similarly onN-nitrosodibutylamine31, JV-nitrosomethylallylamine82,JV-nitrosodibenzylamine, and others 4 3 ' 5 5 ' 1 8 2 :

RtR,N-NO HC1 + HNO2

Hydrogen chloride has a more pronounced denitrosatingactivity6 '4 2 '1 1 3 '1 3 4. Some investigators have also proposeda method for the preparation of pure secondary aminesinvolving the treatment of nitrosamine solutions in etheror toluene with hydrogen chloride42>134.

It is interesting that the denitrosation takes place morereadily than the hydrolysis of the nitrile group. Thus,in an attempt to hydrolyse the dinitrile of i\i-nitrosimino-diacetic acid, Curtius9 4 isolated as the main product thehydrochloride of the dinitrile of iminodiacetic acid.

The carbonyl group has a significant influence on theresult of the denitrosation. When the nitroso-derivative(III) is treated with hydrochloric acid, ethylene and mesityloxide are formed41. In contrast to hydrochloric acid,hydrogen chloride has only a denitrosating effect:

ON ^

οII

^(CH^jCHaCCHi,

CH2CH3

(III)

ΟII

( C H 3 ) a C = C H - C C H 3 + C H 2 = C H 2 + H2O + N 2

ΟII

CH3CCH2C (CH 3) 2

yNH-HCl .

CHaCH2

It has been noted that, when JV-nitrosopolynitroalkyl-amines are denitrosated, it is impossible to isolate thesalts of polynitroalkylamines or the free amines.Evidently in this case a more profound degradation of themolecule takes place, owing to the reduced basicity of theamino-nitrogen in polynitroalkylamines89'183.

Apart from hydrochloric acid and hydrogen chloride,bromine and sulphuric acid have been used as denitrosat-ing agents 1 1 3 ' 1 8 4:

(C eHBCH 2) 2 N - N O _ (BrCeH4CH2)2 NH · HBr

The study of the kinetics of the cleavage of aliphaticnitrosamines by acids led to the hypothesis that the split-ting off of the nitroso-group is preceded by the occurrenceof an equilibrium between the nitrosamine and its pro-tonated form. The protonated nitrosamine then splits offthe nitroso-group in the form of the nitrosonium cationand is itself converted into the corresponding amine:

R'RN—N=O+H+ ^ R'RNH—N=O ,

R'RNH—N=O -• R'RNH + NO (slow) .

The hydrolysis is easier the more electrophilic is theR or R' group. In hydrochloric acid the denitrosationtakes place more readily than in sulphuric or perchloric

acid. The authors explain this by the nucleophilic reac-tion

NH + NOC1 .

The rate of hydrolysis obeys the Hammett equation 1 8 5>1 8 6

:

= const.

According to the data of Porai-Koshits and co-workers 187~ 90, the denitrosation of aliphatic-aromaticnitrosamines takes place by a "push-pull" mechanism.Preliminary protonation of the nitrosamino-group was notobserved. The splitting off of the nitroso-group ispromoted by the additional polarisation of the N-N bondowing to the formation of a hydrogen bond involving thenitrogen atom of the amino-group. The formation of thenew N-H bond takes place simultaneously with the splittingoff of the nitroso-group.

The presence of electron-accepting substituents in thepara -position of the aromatic ring lowers the basicity ofthe amino-nitrogen in the nitroso-derivative and in thiscase the nucleophilic attack by the acid anions plays adecisive role. However, acid anions participate in thesplitting off of the nitroso-groups only in the presence ofhydrogen ions. On the basis of the results obtained, thefollowing reaction mechanisms have been proposed as afunction of the structure of the nitrosamine:

Alk

H---N—N=O

Alk Alk

Ν—Ν=Ο AH--N—N=O φ**X

HNAlk

f L N 0

~ Alk

H—N---N=O

The results of studies on the formation of hydrogenbonds in aliphatic nitrosamines and also their chemicalbehaviour show that the reaction centre is located at theoxygen atom of the nitroso-group, which is inconsistentwith the above hypothesis concerning the denitrosation ofnitrosamines.

We believe that a more correct mechanism of thedenitrosation of aliphatic nitrosamines involves electro-philic attack on the oxygen atom of the nitroso-group.The latter is readily eliminated as a result of the genera-tion of partial positive charges at the nitrogen atom 157:

Ν^^Ν'-^^Ο »-H —^>- NH-HA + NO.

The reaction of nitrosamines with trichloroacetic acidin cyclohexane takes place with formation of one or twohydrogen bonds and may be described by the followingstructures1 6 8:

(A)

R—N^^l

(B)

A number of changes takes place in the ultraviolet spec-trum of ΛΓ-nitrosodimethylamine in aqueous sulphuric acidsolution due to acid-base interaction :

R2NNO . . .

RaNNO . .

R2NNO . . .

R2NNO . . . (H2O)X

H,SO.^ = ί RjNNO

x t5 R2NNO . . .

HSOi j i R2NNOH+ . . . (H2O)X ,

O; ϊ ; R2NNO . . . (H2O)X (H2SO«)2

R2NNO . . . (H 2O) xHSOi ^ R2NNO . . . (HSO4)2

42 Russian Chemica l Reviews, 4 0 ( 1 ) , 1971

The attempts to isolate the salts of the nitrosamine andsulphuric acid were unsuccessful, but unstable white 1:1crystalline adducts of 72% perchloric acid with JV-nitroso-di-n-heptylamine, JV-nitrosodi-n-octylamine, andJV-nitrosodi- (2-ethylhexyl)amine were obtained, whichindicates the possibility of proton transfer to the oxygenatom of the nitroso-group.

Nitrosamines form hydrogen bonds with formic,acetic, and trifluoroacetic acids and with alcohols,phenols, and amines1 7 1 191~193. The proton-donatingactivity of alcohols in the formation of the hydrogen bondincreases in the series primary > secondary > tertiary.The equilibrium constants for the hydrogen-bonded com-plexes of nitrosamines and phenols increase linearly withthe pAa of the phenols 1 9 \

A detailed study of the protonation of JV-nitrosodimethyl-and JV-nitrosodiethylamines and also JV-nitrosopiperidineby NMR spectroscopy was undertaken194. The charac-teristic signal associated with the interaction of theproton with the nitrosamine occurs only in fluorosulphonicacid at 0°C and below. In other acids the spectra alsoshow changes characteristic of structure (A); the dialkyl-amino-group is not protonated. The spectra shows thatthe formation of the hydrogen bond or protonation involvesthe oxygen atom of the nitrosamino-group. A structurewith a delocalised positive charge has been proposed forthe adducts of nitrosamines with fluorosulphonic acid:

The delocalisation of the positive charge probably preventsfurther protonation of the molecule.

A study of the competing protonation of iNT-nitroso-dimethylamine and dimethylformamide by trifluoroaceticacid in 2-nitropropane showed that the nitrosamine is aweaker base 1 9 .

The basic nature of the oxygen atom is shown by thecapacity of nitrosamines to give rise to brightly colouredstable complexes with bromoplatinic acid, the compositionof which corresponds to the formula [R2NNO.H]2PtBr6.195

Complexes of nitrosamines with boron trifluoride areformed when equimolar amounts of the nitrosamine andboron trifluoride-ether are mixed or when an etherealsolution of the nitrosamine is treated with boron tri-fluoride 1 9 6:

R^N—N=O + BF, — RtR2N ^ N r . o.~-—BFS .

The stability of the complexes increases with theelectron-donating capacity of the substituent linked to thenitrogen atom. The complex with iV-nitrosodiphenylaminecould not be isolated. It is interesting that in the adductof boron trifluoride and JV-methyl-iV-nitrosoaniline theN-N bond is so much weakened that rapid rearrangementto iV-methyl-/>-nitrosoaniline takes place:

remains in a state of spz hybridisation. Consequently theacceptor is linked to the oxygen atom This structure

<<s>" O N \ O / N H C H 3 B F 3

The r e s u l t s of spectroscopic analys i s showed that theoxygen atom of the ni t rosamino-group behaves a s theelectron donor in these complexes, although the possibi l i tyof the involvement of the am in o-nitrogen in the formationof the donor-acceptor bond has a l so been suggested 1 8 8 .

The NMR s p e c t r a of the adducts of .N-nitrosodimethyl-amine with B F 3 , P C 1 5 , SbCl5, AICI3, and ZnBr 2 showedthat the methyl groups a r e non-equivalent, a s in the freen i t r o s a m i n e . The η on- equivalence of the methyl groupsis evidence that the amino-nitrogen in the complexes

is also confirmed by the high dipole moments (7.3 and7.5 D) of the complexes of JV-nitrosodiethyl- and JV-nitroso-dipropyl-amines with boron trifluoride.

JV-Nitrosodiethylamine forms a 2 :1 complex withnitrogen tetroxide, which was confirmed by studies of thephase diagram, viscosity, and electrical conductivity ofnitrosamine-N2O4 mixtures103'198»199. On the basis ofultraviolet spectroscopic data, structure (TV) was attri-buted to the complex , but, in the light of the aboveconcepts concerning the structure of nitrosamines,structure (V), where the oxygen atom of the nitrosamino-group functions as the electron donor, is evidently morelikely:

r(C2H5)2NNO -1+ r<C,H»), Ν—Ν-0 n +

N,O«+2 (CH.), NNO G )*NO · NO7; )}NO . N O 7 .

L(C2H5)2 NNO J L(C2H5)2N^-N-O J

(IV) (V)

Recently it was discovered that JV-nitrosodialkylaminesreadily form complexes with di(trinitromethyl)mercury inwater °°"2Qe. The compounds are stable on storage andcan be readily purified:

R2NNO + H g [ C ( N O 2 ) 3 ] - 2 R2NNO - Hg[C (NO2)3]2 .

JV-Nitrosopolynitroalkylamines, for example N - n i t r o s o -di-(2,2,2-tr initroethyl)amine, do not r e a c t with d i ( t r in i t ro-ethyl jmercury, in contras t to their unsubstituted ana-logues. This finding can be accounted for by a weakeningof the electron-donating activity of the oxygen atom of thenitroso-group owing to a d e c r e a s e of the degree of p-%conjugation caused by the polynitroalkyl groups.

The react ions of n i t r o s a m i n e s with other e lectrophi l icagents a r e based on the complex-forming capacity of theformer . F o r example, on heating to 60°C, JST-nitroso-dimethylamine r e a c t s with methyl iodide 2 0 3:

(CH3)2 NNO + 2 CH,I -» [(CH3)4 N]+ I" + NO + Vi h •

The react ion with triethyloxonium hexachloroantimonatein the cold r e s u l t s in the formation of ethoxy dim ethyl-diazonium hexachloroantimonate 2 < E '2 0 3;

(CH3)2NNO + (C2H6),OSbCl, - [(CHS)2 NNOC 2H 6]+SbClf .

O-Alkylnitrosimmonium salts are formed in high yieldswhen nitrosamines are allowed to react with triethyl-oxonium fluoroborate or a mixture of alkyl iodide andsilver perchlorate 2 0 4 ' 2 0 5

:

R 2 N - N = O + (C 2 H 6 ) 3 OBF 4 - ]R2N - ^ N i ^ - O C 2 H 5 ] + B F 7 + (C 2H 6) 2 Ο ,

R a N — N = O + C H S I + A g C 1 0 4 - • [ R 2 N ^ - N I ^ J O C H S ] + C l O f + A g l .

The study of the chemical behaviour of the salts and theirinfrared spectra showed that they are O-derivatives.

Dimethyl sulphate alkylates ΛΓ-nitrosodimethylaminewith formation of trimethylnitrosimmonium methyl sul-phate. It is interesting that this adduct readily reacts withsodiocyclopentadienyl, forming the monomeric hydrazoneof cyclopentadienone 2 :

( C H s ) 2 N - N O + ( C H , ) a S O 4 - > [ ( C H 3 ) 2 N ^

2. Reduction to NN- Substituted Hydrazines

The reduction of the nitroso-group to the amino-groupis one of the characteristic reactions in the nitrosamineseries. It was discovered by Fischer in the synthesis ofdimethylhydrazine The reaction takes place when anacetic acid solution of JV-nitrosodimethylamine is treated

Russian Chemical Reviews, 4 0 ( 1 ) , 1971 43

with zinc dust. Apart from dimethylhydrazine, ammoniaand dimethylamine were isolated. Later diethylhydra-zine 2 0 7, piperidylhydrazine 2 0 8, isobutylmethylhydrazine 2 0 9,etc. were synthesised in this way; dimethylhydrazine wasobtained in a higher yield58.

When JV-nitrosodiethylamine is reduced with the zincand acetic acid, the formation of tetraethyltetrazenetogether with diethylhydrazine was observed210. A simi-lar reaction was noted in the reduction of nitrosamineswith hydrogen in the presence of palladium deposited oncalcium carbonate211:

2 (C2H5)2 N - N O + H 2 - (C2HB)2 N - N = N - N (C2H5)2 .

Several ring-substituted dibenzyl derivatives ofhydrazine were described by Curtius 1 7>2 1 2 '2 1 3 and otherinvestigators87'88. Using a modified method of reductionin ethanol and milder reaction conditions, they increasedthe yields of the desired products to 75%. A number ofarylalkyl and dialkyl derivatives of hydrazines weresynthesised by the same method 137>214>215.

Apart from zinc and acetic acid, sodium amalgam7 8 '1 1 3

and also tin and hydrochloric acid u 3 were employed toreduce nitrosamines. In the latter case hydrazine isnot formed but the nitrosamine decomposes with elimina-tion of the nitroso-group. The available data on thereduction with sodium amalgam are contradictory.Hydrazinoacetic acid and its dimethyl ester are formedfrom the corresponding nitrosamines in low yields, whileJV-nitrosodibenzylamine is converted into ammonia anddibenzylamine u .

The method of reduction of JV-nitrosodialkylamineswith zinc in acetic acid is effective only for methyl-,ethyl-, and propyl-substituted nitrosamines Startingwith the η-butyl derivative, secondary amines appear asthe main reaction product. A general method of reductionwith lithium aluminium hydride, developed for the syn-thesis of di-n-propyl-, di-n-butyl-, and di-n-pentyl-hydrazines as an example215, has been proposed for thehigher JV-nitrosodialkylamines. Subsequently it wasestablished that the result of the reaction depends on thenitrosamine: lithium aluminium hydride molar ratio.Thus for the reduction of JV-nitrosodimethylamines themolar ratio of the components must be 1: 2,2 1 6 and in thecase of JV~nitrosodiphenylamine the ratio must be 1:1. 2 1 7

The yield of the desired product is affected also by theorder of mixing of the components.

It is interesting that in the first stage of the reactionof the nitrosamine with lithium aluminium hydridescoloured complexes are formed, which are converted intodialkylhydrazines only on treatment with water2 1 7 '2 1 8:

2 R 2 N-NO + 2 L1AIH4 -* (R 2N-N)j AlLi + LiA10a + 2 H2 ,

(R2N—N)2 AlLi + 2 H2O — 2 R2N—NHa + Li AIO2 .

The appearance of side products in the case of aromaticnitrosamines can be explained by the decrease of thepolarity of the N-O bond owing to conjugation with thebenzene ring. The reduction of JV-methylpiperidine-nitrosyl fluoroborate with lithium aluminium hydride leadsto the formation of JV-methylpiperidine-borane106:

BF7V B H 3

The catalytic hydrogenation of nitrosamines on thepalladium catalyst in the presence of iron salts underpressure 2 1 9, reduction with zinc and aluminium in thepresence of mercury salts or reduction with zinc in hydro-chloric acid2 2 0, and other reduction processes2 2 1 havebeen described. The reaction of JV-nitrosodialkylamines

with zinc dust in formic acid in the presence of mercury(II)chloride results in the formation of an interesting classof compounds-JV-isocyanodialkylamines 2 2 2.

Numerous modifications of the methods of hydrogena-tion of JV-nitrosodialkylamines are quoted in the patentliterature Compared with catalytic hydrogenation,the reduction of nitrosamines with sodium in liquidammonia or alcohol234 gives lower yields of dialkyl-hydrazines.

Nitrosamines can be reduced electrochemically to thecorresponding hydrazines2 3 5"2 3 7 or amines with eliminationof one nitrogen atom in the form of ammonia. NN-Sub-stituted hydrazines are formed via the mechanism

R2NNO + 4 H+ + 4e ^ R2NNH, .

The studies on the electrochemistry of nitrosamineshave recently been reviewed in a monograph238 andtherefore they will not be discussed here.

When JV-nitrosodialkylamines are hydrogenated insulphuric, hydrochloric, nitric, acetic, or oxalic acidsin the presence of Group VIII elements on charcoal orsilica gel under pressure, hydroxylammonium salts areformed239.

Nitrosamines undergo far-reaching cleavage on treat-ment with sodium hydrosulphite in an alkaline medium orwhen acted upon by lithium in liquid ammonia. This isknown as the Overberger-Lombardino reaction and takesplace via the intermediate formation of JV-nitrenes, whichreadily decompose with evolution of nitrogen:

(RCH 2) 2N-NO Na,s,o,;OH- > ( R C H l ! ) a N-NHOH - r ^ o ~ * (RCH 2 ) a N-N - z ^

-(CH 2 R) 2 .

The Overberger-Lombardino reaction has been discussedin detail in monographs 2 4 0 ' 2 4 1 .

3. Oxidation and Nitration

Nitrosamines are important starting materials for thesynthesis of secondary JV-nitramines. According to theexisting hypotheses, this reaction is based on the oxidationof the nitroso-group to the nitro-group.

The use of hydrogen peroxide with nitric acid for theoxidation gives low yields of nitramines and the desiredproduct is contaminated 2 4 2. Best results were obtainedwhen nitric acid mixed with ammonium persulphate wasemployed 2 7. Trifluoroperacetic acid proved to be a veryconvenient oxidising agent for nitrosamines' Thesimplicity of the process and the purity and high yields ofthe final products made the oxidation of nitrosamines withtrifluoroperacetic acid a valuable preparative method forthe synthesis of secondary nitramines. For example,when JV-nitrosodiethyl- and JV-nitrosodibutylamines wereacted upon by a mixture of trifluoroacetic acid in 90%hydrogen peroxide, the corresponding JV-nitramines wereobtained in 80% yield. When 30% hydrogen peroxide wasemployed, the yield of nitramines fell. A mixture ofhydrogen peroxide and trifluoroacetic anhydride in methyl-ene chloride may serve as a source of trifluoroperaceticacid2 4 4. This modification of the oxidation reactionyields pure nitramines in yields of 90% and above. Themechanism of the conversion of nitrosamines into nitra-mines under the influence of trifluoroperacetic acid hasnot been investigated:

R2NNO C F . C O O O H ; R 2 K N O 3 .

When JV-nitrosodiethylamine was oxidised with nitro-nium pyrosulphate, acetaldehyde and acetic acid were

44 Russian C h e m i c a l Reviews, 4 0 ( 1 ) , 1 9 7 1

formed. The oxidation of JV-nitrosodiethylamine withnitrogen pentoxide is very vigorous. The reaction maybe controlled only by diluting the reactants 1 9 9:

NNO + N 2O 5 - 2 C2H6NOa + 2 CHsCOOH + HNO2 + HNOa ,

C2H6NO2 + HNO2 -> CHiC (NOH) NOa + H2O .

Until recently the reaction of nitrosamines with nitricacid was investigated only for aromatic compounds 2 4 5 ' 2 4 6 .It has been shown247 that ethyl JV-isobutylcarbamatereacts with fuming nitric acid at -80°C to give a mixtureconsisting of 90% of ethyl JV-isobutyl-iV-nitrosocarbamateand 10% of ethyl iV-isobutyl-iV-nitrocarbamate. When theiV-nitroso-derivative is subsequently treated with 100%nitric acid, the iV-nitrated product is formed. The reac-tion was not investigated in detail. In other studies2 9 '1 4 4

it was shown that certain JV-nitrosopolynitroalkylaminesare readily converted into the corresponding nitraminesunder the influence of nitric acid or a mixture of nitricand sulphuric acids:

[BrC (NO2)2 CH 2 ] 2 N - N O [BrC (NO2)2 CH 2 ] 2 N - N O 2

It is important to note that iV-nitrosopolynitroalkyl-amines are resistant to oxidation by trifluoroperaceticacid8 9 '2 4 8. If the oxidation of nitrosamines with trifluoro-peracetic acid is assumed to be analogous to the hydroxy-lation of olefins, the negative results obtained in theoxidation of iV-nitrosopolynitroalkylamines can probablybe accounted for by the deficiency of electrons in the>N**»N"*O system owing to the electron-accepting influenceof the substituents.

On the other hand, in JV-nitrosopolynitroalkylaminesthe N-N bond should be weakened compared with theunsubstituted analogues. This leads to the possibility ofan electrophilic substitution of the nitroso-group by anitro-group in compounds of this kind. We believe thata convincing proof of the substitution of the nitroso-groupis provided by the reaction of JV-nitrosopolynitroalkyl-amines with nitrourea in sulphuric acid, leading to theformation of iV-nitro-derivatives248. Nitrourea in sul-phuric acid is known to be a source of nitronium cations249:

ON—Ν•CH2C (NO2)2 R

CH2 C(NO2)2 R

ο

Ο,ΝΗΝΟΝΗ,+Η,βΟ,O2N-N.

,CH 2C (NO2)2 R

SCH,C (NO2)2 R.

4. Cyclisation of a-Nitrosaminocarboxylic Acids and TheirNitriles into Sydnones and Sydnoneimines

In 1935 Earl and Mackney250 obtained by treatingJST-nitroso-iV-phenylglycine with acetic anhydride a cycliccompound, which was called sydnone (in honour of theplace where it was first synthesised). Later it provedpossible to introduce into the cyclisation reaction thenitriles of α-nitrosaminocarboxylic acids6*, whichresulted in the formation of sydnoneimines. The initialdiscoveries were followed by an intense investigation ofthe methods of synthesis and properties of this interestingclass of compounds. Two reviews dealing with thechemistry of sydnones and sydnoneimines were published2'3

the second of which appeared comparatively recently andtherefore we shall only mention the methods for themechanism of the cyclisation of nitrosamines into thesecompounds.

Usually acetic anhydride is employed for the cyclisation.However, trifluoroacetic anhydride, thionyl chloride,and iW-di-isopropylcarbodi-imide can also be used forthis purpose2 5 1 '2 5 2. iV-Nitrosodicarboxylic acids, forexample nitrosiminodiacetic acid, are cyclised similarlyto monocarboxylic acids 2 5 3 ' 2 5 4, but cases are known whereonly the carboxy-groups are involved in the reaction95:

/CHjCOOH

\:H2COOH

/—°\•HOOCCH,t/ (±)

\H—c=oC s H 5 CHjN

NO COOH COOH

C,HjCH2N(NO)CHI CHa'

The formation of sydnones is based on the nucleophilicnature of the oxygen atom of the nitroso-group, and takesplace via a mixed anhydride (when anhydrides areemployed as the dehydrating agents), which already at roomtemperature splits off in succession an acetate ion and aproton2 '2 5 2:

Hl+jRNCH2C—OH· -CHgCOOH I

RNCH 2COCCH 3 -OCOCH3

\

The reaction of JV-nitrosopolynitroalkylamines withnitronium perchlorate in sulphuric acid is also accom-panied by the formation of iV-nitrosopolynitroalkylamines a*8.In an organic solvent (carbon tetrachloride) nitration doesnot occur. Since the presence of an acid and a nitroniumcation is essential for the nitration of nitrosamines, thereaction can probably be described in terms of a "push-pull" mechanism:

R

O2N....NrLrN.^i:O . . .

+ NO

R

HS04 + Η+

.N=O....H2SO4—NR 2

Thus the conversion of nitrosamines into nitraminescan be achieved not only by the oxidation of the nitroso-group, but also by its electrophilic substitution by a nitro-group. The latter type of reaction is particularly char-acteristic of nitroso-derivatives containing electron-accepting substituents, for example polynitroalkylderivatives.

In contrast to ethyl-iV-nitrosiminoacetic acid, 2,2,2-trinitroethyl-JST-nitrosiminoacetic acid does not form asydnone when acted upon by acetic anhydride 2 5 5. This isprobably due to the reduction of the nucleophilicity of theoxygen atom in the >N-N=O fragment under the influenceof the trinitroethyl group. In the cyclisation of poly-nitroalkyl-iV-nitrosaminoacetic acids, it is essential toemploy trifluoroacetic anhydride, which increases theelectrophilicity of the carbonyl carbon atom in the inter-mediate mixed anhydride:

jN CH,CGOH

NO

(F3CC0),0C(NO,),CH,N

The nature of the cyclisation of the nitrile of a-nitro-saminocarboxylic acids to sydnoneimines is determinedby the capacity of the nitrile group to combine with

Russian Chemica l Reviews, 4 0 ( 1 ) , 1971 45

electrophilic agents. The reaction is achieved under theinfluence of hydrogen chloride 2 5 6 or nitrogen oxides 9 6:

H 2 C - G N

N—NO

Η

I -H—C-

- N = O iThe powerful influence of the electron-accepting sub-

stituents on the conjugation in the >Ν*"Ν*-"Ο fragment canbe demonstrated yet again for the nitriles of polynitro-alkyl-JV-nitrosaminocarboxylic acids as an example. Thus,in attempts to cyclise the nitrile of 2,2,2-trinitroethyl-iV-nitrosaminoacetic acid in methanol under the influence ofhydrogen chloride, the imino-ether (VII) was isolatedinstead of the expected sydnoneimine (VI), the structureof (VII) being demonstrated unambiguously by its conver-sion into JV-nitramino-2,2,2-trinitroethylacetic acid2 5 7:

(NO.2),CCHjN CH

ΘfNO2)3CCH_,NCH2CN

NO(VI)

* - (NO,)3CHUNCRjC=NH · HC1

NO OCH, ( V 1 [ ) ,

(VII)—>- C(NO,) 3CH 2NCH,eOOCH 3 £• C(NO ?) 1CH,NCH 2CODCH 3 -^-»-

NO NO2

*- C(NO2)3CH2NCH2COOH .

NO2

The formation of the imino-ether (VII) is possible onlywhen the nucleophilic properties of the oxygen atom ofthe nitroso-group are weakened, as a result of which theintermediate carboimmonium ion (NO2)3CCH2N(NO)CH2C=NH undergoes methanolysis, which competes with the ring-closure reaction. The removal of the nitro-groups tothe y-position relative to the nitrosamino-group weakenstheir influence on the polarisation of the oxygen atom andpromotes the formation of the sydnoneimine 57:

NOI HC1; CH,OH

(NO2)2C(CH2CH2NCH,CN)2

:—»-

(NO2)3CCH2CH2NCH2CN

NO

N2O3; HNO3

Ν

(NO 2) 2C\CH 2CH,N

(NO2)3CCH2CH2N

\c=

/

-CH

Ν C = N H · HNO3

Sydnones and sydnoneimines are reactive mesoionicaromatic compounds. The hydrogen atom in the 4-positionin the ring is readily substituted by halogens, nitro-groups,sulpho-groups, etc. Sydnones may be employed tosynthesise hydrazines 45. They undergo the 1,3-dipolar-cycloaddition reaction with unsaturated compounds,forming pyrazoline derivatives' In contrast tosydnones, sydnoneimines undergo ring opening under con-ditions of alkaline hydrolysis, the amides of a-nitros-aminocarboxylic acids being formed95. Sydnoneiminesform readily e*o-JV-nitroso- and nitro-derivatives.

When JV-nitrososarcosine is heated with acetic anhydridein the presence of acetylenedicarboxylic acid esters,carbon dioxide is evolved and a cycloadduct (VHI) isformed259:

type of cyclisation is characteristic of N-nitroso-com-pounds. When JV-nitrosodi-(4-methoxycarbonyl-2,2-dinitrobutyl)amine and JVJV-dinitrosodi-(4-methoxycarbon-yl-2,2-dinitrobutyl)ethylenediamine were treated with amixture of acetic and hydrochloric acid, A/-(4-carboxy-2,2-dinitrobutyl)-yy-dinitro-6-valerolactam and ethylene-di(yy-dinitro-6-valerolactam) were isolated260:

ο ο

" - C H 2 N C H 2 C (NO,), CH2CH2COOCH,1 HCI-.CH.COOH

NO

H 2 c / ^ N C H , -

H2C CHa

— C H . N / ^C

HjCI

CH

C(NO,).

The reaction is accompanied by vigorous evolution ofnitrogen oxides. The nature of closure to the lactamring shows that the nitroso-group is split off as the nitro-sonium cation with transfer of the bonding electron pairto the nitrogen atom of the amino-group. The presence ofacid promotes the elimination of the nitroso-group andthe protonation of the carbonyl carbon atom, while thepresence of a five-membered carbon chain at the nitrogenatom creates favourable steric conditions for ring closure.The mechanism of the formation of the lactam ring can berepresented as follows:

NO

NK .OCH·,

( N O 2 > 2 C

\ /OCH3

X3H

5. Photochemical Reactions of Nitrosamines

Several years ago reports appeared about a new reac-tion in the nitrosamine series: photolytic decompositionin the presence of acids 2 6 1 ' 2 6 2. On ultraviolet irradiationin methanol or water in the presence of hydrochloric acid,nitrosamines are converted into amidoximes, secondaryamines, alkylideneimines, and other compounds. It issuggested that in the first reaction stage a complex (IX)is formed, which decomposes to the imine (X) and anitroxylina solvent cage via an excited triplet radical-ion7r-complex. The amidoxime (XI) is formed as a result ofthe recombination of (X) and NOH. The recombination ispossible either via the addition of the monomer of hypo-nitrous acid and a proton to the C=N double bond of (X) orvia the intermediate formation of N-hydroxyaziridine (XII)with subsequent rearrangement of the latter to theamidoxime:

R"

R N C H - R '

R* H 2N 2O 2

I tRN=CR' + [NOH]

(X) | H +

r τ "fRN C—R'

|>N/

Ι (ΧΠ)"

(XIII)

3 N — CH,COOH

NO

(CH3CO)2O (=C—COOR)2

oosi

N—CH,

(VIJJ)

Recently it has been established for esters of poly-nitroalkyl-JV-nitrosaminocarboxylic acids that yet another

In this case, when the carbon atom of the C=N bond of(X) does not split off a proton (R"# H), for example in thephotolysis of iV-nitrosodicyclohexylamine, the OH group islost and a C-nitroso-compound (ΧΙΠ) is formed. Elimina-tion of NOH from (XIII) again leads to the alkylideneimine(X). Therefore the retardation of the nucleophilic attack

46 Russian C h e m i c a l R e v i e w s , 4 0 ( 1 ) , 1 9 7 1

on NOH is accompanied by the hydrolysis or polymerisa-tion of the primary photolysis product. It is evident thatthe steric factor plays an important role in the photo-elimination reaction and therefore trans-anU eliminationof NOH from the photoexcited nitrosamine-proton complextakes place. The intermolecular mechanism of thephotoisomerisation of JV-nitrosodialkylamines has beendiscussed263.

The photolytic decomposition of nitrosamines leadsultimately to the formation of aldehydes and ketones.For example, JV-nitrosodibutylamine gives a high yield ofbutyraldehyde after the hydrolysis of the amidoxime (XI),while JNT-nitrosodicyclohexylamine gives rise to cyclo-hexanone 264.

In the presence of acids the photolytic addition ofJV-nitrosamines to various olefins takes place smooth-ly2 6 5"2 6 7. Formally the photoaddition reaction takes placevia the dissociation of the N-N bond with subsequent addi-tion of the nitroso- and amino-groups to the C=C bond andformation of a C-nitroso-compound as the primary reac-tion product. The latter undergoes secondary reactions,which lead to the final product265.

JV-Nitrosodibutylamine adds to cyclohexene withformation of the oxime of 2-di-n-butylaminocyclohexanonein 38% yield267:

C H ^ C H , ) ^

CH3 (CH,),/ N-NO+

NOH

\ /

The nitroso-group adds as a rule to the most hydro-genated carbon atom. This observation made it possibleto achieve the photolytic addition of nitrosamines to amultiple bond with subsequent dissociation of the C-Cbond 66. Thus irradiation of a mixture of tetramethyl-ethylene and nitrosopiperidine leads to the formation ofacetone and acetoxime:

(CH3)j C=C (CH3)2 + ^ N -

. C=NOH + (CH8)2 C = N /

(CH3)2 C = N ^ + H2O - (CSH)2 C=O + HN/

Similarly α-methylstyrene forms acetophenone and di-(l-piperidinyl)methane. When the carbon atom bound tothe nitroso-group is combined with a hydrogen atom, thereaction stops at the stage involving the isomerisation ofthe C-nitroso-derivative to the oxime and the C-C bond isnot ruptured. Sometimes intramolecular proton transfercan be faster than the isomerisation to the oxime.JV-Nitrosodimethylamine reacts with 1-methylcyclohexene,forming predominantly 6-oxoheptanal265:

(CHr,)2N-NOH 3

^=NOH

CH3 CH., | l l 2 o

tCH ,CO(CH2),CHO

N(CH 3) 2

The addition of N-nitrosopiperidine to pent-1-ene isaccompanied by the formation of a dimer of the C-nitroso-derivative via the mechanism265:

0 + C 3 H 7 C H = C H 2

Η Λ Η « J .

<v ; o N = \

where R = C3H7CHCH2•PWhen JST-nitrosodimethyl- and N-nitrosodiethylamines

were photolysed in the vapour phase, hydrogen, nitrogen,alkanes, secondary amines, and nitrogen oxides weredetected in the reaction products 152. These resultssuggest that, in contrast to the low-temperature photolysis,the process has a radical mechanism:

(CH,),, NNO + Av -» (CH,)a N" + NO , (CHs)a N+NO -» Ο,Η, + H20 + Ν, ,

2 (CH3)a Ν' - (CH3)2NF + CHj N-CHj , Η + NO - HNO' ,

(CH8)a NH -* (CHJ,, Ν + Η , (CH,)2 NH + HNO' - 2 CH3 + N, + H 2 0 .

VI. CERTAIN ASPECTS OF PRACTICAL APPLICATION

The lower ΛΓ-nitrosodialkylamines, in particularJV-nitrosodimethylamine, are largely employed in the syn-thesis of asymmetric dialkylhydrazines. Dimethyl-hydrazines are one of the most important components ofrocket fuels 268>269. A mixture of dime thy lhydrazine,dimethylamine, and ammonia, obtained by the hydrogena-tion of JV-nitrosodimethylamine in the vapour of liquidphase, has been recommended for guided rockets andmissiles2 2 8 '2 2 9.

It has been noted in the patent literature that nitros-amines may be employed as antioxidants in fuels, lubricat-ing oils, and rubbers 98. There is an interesting pros-pect of the employment of nitrosamines as special fuels,stabilisers for aromatic halogeno-compounds, fungicides,insecticides, and bactericides and also as intermediatesin the manufacture of medicinal preparations 61»98»270.

JV-Nitrosodimethylamine is employed in the form ofaqueous solutions or powders as a nematocide. In a doseof 112 kg per hectare it protects tomatoes from thenematode Meloidogyne incognita and in doses of 56 to112 kg per hectare it is non-phytotoxic for carrots,tobacco, cabbage, and the cotton plant; however, itinhibits to some extent the growth of flimal beans andpeas 2 7 0.

JV-Nitrosodimethylamine has been recommended as asolvent in the manufacture of fibre from polyacrylo-nitrile2 7 1.

However, the high toxicity of nitrosamines should benoted. For example, JsT-nitrosodimethylamine has beenincluded in the group of carcinogenic and irritant sub-stances. It is recommended that the possibility of thecontamination of air by this compound be completelyprevented272.

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Zelinskii Institute ofOrganic Chemistry,USSR Academy of Sciences,Moscow

Perm State PharmacologicalInstitute