ne.

26.! Reacrions of Aqdamtnes lOAl

'larnides also pro-r.rv-acetylaniiine

rone in g0?o yietd

OH

",*{}$_L<lL-,/ l1 N-oSulfatbiazole

NH,

)'.

V-'o

NH"t"

a:?:oN&

26.4 Account for the fact that an amido substituent (_NHCOR) is ortho- and para_direct_ing, by drawing resonance structures that share the niirogen lone-pair electronswith the aromatic ring.

robenzophenone$O.qa)

of amino-sub_rne that allow_.rzied out thatration of sulfa

26.5 Propose syntheses of these compounds from benzene:(a) N,N-Dimethylaniline (b) p-Chloroaniline(c) m-Chloroaniline (d)

-2,a_limethylaniiine

DIAZONIUM SALTS: THE SANDMEYER REACTTON

Primary aromatie amines react with nitrous acid, HNo2, to yield stabieareaed.iazorium salts, Ar-fr=N X-. This diazotization reaction is com-patible with the presence of a wide variety of substituents on the aromaticring.

/->(*'' ,4'---.rirz*(/ + HNo, + Hzso4

- (/" Hso4- + 2H2o

Alkylamines also react with nitrous acid., but the products of these reactions,alkanediazonium salts, are too reactive to isolaL since they lose nitrogeninstantly to yield carbocations.

R * 'r * H2Soa + [n . -HSo4] __--., R* -HSo4 +

Arenediazonium sarts are extremely usefur in synthesis, because thediazonio group (N2+) can be replaced by nucleophiles:

.r'',-u;u-'*(}" HSon- + :Nu- +

0*" . N2

Many different nucleophiles react with arenediazonium salts, and manydifferent substituted benzenes can be prepared with this reaction. The ovei-all sequence of(L) nitration, (2) reduclion, (A) diazotization, and (4) nucleo_phile replacement is probably the single most versatile method of aromaticsubstitution (Figure 26.3). Although the details aren,t fully understood,, the

tarmaceuticalhave largell-

Ia drugs wererofthousand_.'osulfonationzenesulfonvlnide, Hydro_drolysis caneuse suifon-

fouilamidetulfa drugr

1008 CHAPTER 26 Arylamines and Phenols

mechanism by which these substitutions occur is a radical, rather than ,polar, one.

,4-'-zB'(/

(\'\-/

,4-"-/cl(/+

,4t--r'HU,Z-\1oH

U

C=N

H,C

p-Bromotoluene

Figure 26.3 Preparation of substituted aromatic compounds by

di azonio replacement reactions.

Aryl chlorides and bromides are prepared by reaction of an

azonium salt with the corresponding cuprous halide, CuX, a process

the sandmeyer2 reaction. Aryi iodides can be prepared by direct reac:.

with sodium iodide without using a cuprous salt. Yieids generally fa--

the 60-80% range.

*.-cr*'' # 1,,",(rn=NHSo4- ]

*p-Methylaniline

Cr"" # l er-=NHSoa' l -'- er'Iodobenzene (677o)

zTraugott Sandmeyer (L854-1922'l; b. Wettingen, Switzerland; Ph.D. Heidelberg

mann); Geigy Company, Basel, Switzerland.

\ "'-"' ""-'''=""" *n=,,,,-J

,ffi

iffi

26,g Reactions of Arytamines I OO9

similar treatmelt of an arenediazonium salt with cuprous cyanideyields the arenenitrile, ArcN. This re-ac-tion is partic,rruriy .r"-"r,rr, becauseit altows the replacement of a,ritrogenl-ub"s;,il;; ;;;;i#i substituent.The nitrite can then be further .;";;;;J into orher i"il;;;i groups suchas carboxvl, -coo*. For example, hvdroivsi. "f

;-*;;;il;;;onitriie, pro_duced by sandmeyer reac'ion oi r--"tirytbenzenediazonium bisurfate withcuprous cyanide, yierds. o-methyrbenzoic acid. This product could not beprepared from o-xyrene by the usuai side-chain oxidaiion.""r", since bothmethyl groups would be oxidized

HNO,H2SOl

+

Y=N Hso4-

CH,

HNO,H2SOI

KCN

CUCN

,,-Methylaniline o-Methylbenzene- o_Methylbenzonitrilediazonium bisulfate o-Methyltrenzoic

acid

The diazonio group can arso be replaced by -oH to yierd phenols andby -H to yield ,..nuJ. phenors u.r.r'.rruitv prepared by addition of thearenediazonium salt to hot aqueous u.ia. mo ,";;i;; ['"riiiurry impor_tant, since few other general methods exist ro. i.riroir.irrg-'"" -orr grouponto an aromatic ring.

NI{"

2',\A*o,

7x-f{if,1'6*nilins

OH

-tHso' (' \

-lllVwo,

m.Nitrophenol (86Va)

NO,

Y=N Eso4-

Arenes are oroduced by reduction of the diazonium salt with hypo-phosphorous acid' H3po2. rlir ."r.iirn i. ro, particularry usefu], however,uniess there's u .r""ifo, i"*p*;;iylri.oor.,"* an amino substituenr ontoa ring to take advantage of it" *"iirrutlng etrect. The preparation of B,s-dibromotoluene from p-methylanili"e [-161,ridine) i1]usiraies how this canbe done. Dibromination ofp-ioluiJi* ot"r. ortho to the strongry directingamino substituent, and diazotization f;r;*;d il';r;;,#;i,itr, i,rpoprro._phorous acid vields 8,5-dibromot"r"""".-irri. p"oa,r.t .;;;;ilJ p""pared byf,r#:LT:Tination

of toluene, h";";;;, since reaction woutd oecur at posi_

+ 2Brz.'"$"'

CHB CHs

}INO,H2SOI

II3PO2

CH,

3,5-Dibromotoluene

C=N COOH

CH,p.Methytaniline

Br Br

ffij

CH,

#

l: