1.2. FORMULACIÓN DEL PROBLEMA
2.1.2.1. Incidencia de las redes sociales en el rendimiento académico
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3 . 0 . R e a c t i o n s of T r i b u t v l t i n H v d r i de
3.1 RESULTS
As already m entioned, the reaction of 1 7 a -e th y n y le s tra d io M with tributyltin hydride yields a m ixture of Z and E vinyltin isomers.
In order to study the p ro file of the reaction and the isom er c o m p o s itio n , a m odel co m p o u n d , 2 -m e th y l-3 -b u ty n -2 -o l, w as studied to see if pure Z and E isomers could be obtained.
3 . 1 . 1 2 - M e t h y l - 3 - b u t y n - 2 - o l \ . _ / 7 AIBN 80“ C H . ' ” — H ^SnBu Toluene Z ^ E 3 R = C(0H)(CH3)2 BuaSn^ Scheme 3.1.1
The re a c tio n of 2 -m e th y l-3 -b u ty n -2 -o l w ith trib u ty ltin hydride in the presence of AIBN in toluene at 80°C was carried out over a two hour period. The reaction was follow ed by tic and the pure products were isolated by distillation at 84°- 8 6°C /0.05 mmHg in yields of 75 - 80%.
The products were then separated by hpic and identified as the Z and E isomers (Scheme 3.1.1) by proton NMR spectroscopy, which show s characteristic patterns in the olefinic region. Previous work on the a ddition of organotin hydrides to a l k y n e s , 2 . 3 , 4 w hich is
H-3
11 OH SnBuq C^ = C4 H\
Z -isomerH-4
JULU iU JL
-p ii i | m i] m n :iiq iiii|iiii|in n r nT|Tm | i i i i | ii i ij m i 6. 6 . 6 6 . 4 6 . 2 6 . 0 5 . 8 PPMI
\ ui 111111II11II11111111'l I'l 11111111111111T| III11 M 1111II11 11111111 i I 111111 M 11
7 6 5 4 3 2 1 PPM o"
F igure 1 400 M H z^H N M R spectr«/nof (Z )- 4 - tr ib u ty ls ta n n y l- 2 -m G lh y l-3 -b u te n > -
OH SnBu E -isomer
H-3
H-4
o 1 1 7 / 1 1 9 1 1 7 /1 1 9 — oo <£) <r T T T T T 7 I 6 ?0 6 15 6 iC . nr ppF ig u r e 2 P a rtia l 400 M H z ^H NMR sp e ctru m o f (E) -4- t r ib u t y ls t a n n y - 2 - m e t h y l- 3 - b u t e n - 2 - o l, sho w in g 1 1 7 /1 1 9 ^ ^ co upling to the o le fin ic re g io n .
a d d u cts have c h a ra c te ris tic coup lin g co n sta n ts fo r the o le fin ic protons. These range from 12 - 13 Hz, 137 - 114 Hz and 65 - 68 Hz for 3JH-H, ^Jsn-H and 2Jsn-H in the Z-isom er, and from 18 - 19 Hz, 73 - 78 Hz and 63 - 68 Hz for 3j|_|_|_|, and ^Jsn -H in the E- isomer. The a-isom er shows 2Jh-h 0 - 3 Hz and ^Jsn-H 67 - 164 Hz.
The proton NMR spectrum (Figure 1) of the Z-isom er which was isolated shows two doublets at;
ÔH 6.58 (1H, d, 3Jh 13.4 Hz, 3 j l l 7 g ^ 136.6 Hz, 3 jl1 9 g n 143.1 Hz; H-3); 5.75 (1H, d, 3Jh 13.4 Hz, 2 j l l 7 g ^ 65.5 Hz, 2 j l l 9 g ^ 68.6 Hz; H-4).
These coupling constants fall close to the range for Z isomers as given above in the introduction and as obtained by Ensley.2
The carbon-13 NMR spectrum of this com pound showed peaks at:
6c 72.44 (3Jsn 57.4 Hz; C-2); 124.90 (1j117sn 393.2 Hz, 411.3 Hz, C-3); 152.80 (C-4).
The proton NMR spectrum of the E-isom er (Figure 2) showed peaks centred at:
ÔH 6.07 (1H, d, 3Jh 19.2 Hz, 2 j l l 7 g ^ 75.2 Hz, Z jllS g ^ 78.5 Hz; H-4); 6.14 (1H, d, 3Jh 19.2 Hz, 3 j l i 7 g ^ 68.6 Hz; 3 j i i 7 g ^ 71.8 Hz; H-3).
The carbon-13 NMR spectrum of the E isom er shows peaks which can be assigned as follows:
The 13Q spectrum was interpreted by com parison with those of other vinyltin com pounds such as tetravinyltin.5
A further experim ent was carried out in which the progress of the reaction of 2 -m e th y l-3 -b u ty n -2 -o l w ith trib u ty ltin hydride in the presence of AIBN was followed by proton NMR spectroscopy in a sealed NMR tube. The significant signals to observe were at 5 2 .2 - 2.5 for the acetylenic proton and 6 5.8-6.8 for the olefinic protons.
At 25°, 35° and 50°C no reaction was observed, w hilst at 75°C we observed that the acetylenic proton signal reduced in intensity and the Z-isom er was formed and had started to convert into the E- isom er; after five minutes the Z/E ratio was 4:1. After 10 minutes the Z/E ratio was 2:1 with further reduction of the acetylenic peak. A fter 20 m inutes the Z/E ratio was 3:2 and eventually reached a steady 1:1 ratio after 35 - 40 minutes, when the acetylenic proton had been lost.
HPLC of the sample showed that three rather than two isomers were present. Two of these were identified as the E and Z isomers by the values of Jh-h and Jsn-H- The third isomer which was present in ca. 20% of the total adducts showed two doublets centred at:
ÔH 5.12 (1H, s, 3 J h 1.5 Hz, 3Jsn 67.7 Hz; H-4B) and at Ô 5.70 (1H, s, 3 J h 1 . 5 Hz, 3Jsn 164.6 Hz; H-4A). This sm all am ount might go undetected by NMR spectroscopy
T hese va lu e s su g g e st th a t th e re are tw o clo s e -c o u p le d protons, one c is to the tin and the other tra n s to the tin. From this, and from com parisons with values obtained by Leusink,3 for other a - adducts we conclude that this is the a -is o m e r (S ch e m e 3 .1 .1 ), where the tin is attached to C-3.
3 . 1 . 2 3 , 3 - D i m e t h y 1 - 1 - b u t y n e
To investigate the influence of the hydroxyl group on the reaction we decided to study the reaction of the above compound for com parison. •02= 0' — H \ = o : ; ; f ^ + A IB N 8 0 °C N g „B u3 Toluene E Z R = C(CH3)3 Scheme 3.1.2
3 ,3 -D im e th y 1-1 -b u ty n e re acte d w ith trib u ty ltin h y d rid e at 80°C in toluene with AIBN as radical initiator to give a 100% yield o f E-1 -tr i b u ty l Stan ny 1-3,3-d im e th y I- 1 -b u te n e (S c h e m e 3 .1 .2 ), w hich was purified by distillation at 140°C/0.08 mmHg.
The proton NMR spectrum of the product showed characteristic ole fin ic protons at:
ÔH 5.75 (1H, d, 3Jh 19.4 Hz, 2 jll7 g ^ 67.4 Hz, 2 jll9 g n 70.5 Hz; H-1); 5.71 (1H, d, 3Jh 19.4 Hz, 3 jii7 g ^ 75.6 Hz, 3 jii9 s n 79.2 Hz; H-2).
The carbon-13 NMR spectrum of the E-isomer sim ilarly showed the expected vinyl carbons with associated values of J sn -0 as fo llo w s :
The form ation of the Z and E-isomers with tim e was monitored by NMR spectroscopy. We observed that now the formation of the E- isom er was im m ediate with only 33% Z-isom er being present, and after 40 m inutes of reaction only the E-isom er was present. This confirm s that the Z-adduct, in this instance, isom erizes to the E- a d d u c t fa s te r than does (Z )-4 -trib u ty ls ta n n y l-2 -m e th y l-3 -b u te n -2 - ol, presum ably because there is no oxygen atom present to form a sta b ilizin g tin-oxygen linkage.
3 . 1 . 3 2 - M e t h y l - 2 - ( t r i m e t h y l s i l y l o x y ) - 3 - b u t y n e
Silylation of the oxygen at the C-2 position would be expected to reduce the Lewis basicity of the oxygen and thus the extent of S n < -0 a ssociation which m ight affe ct the isom eric ratio of the p rod u cts. AIBN
eo“C
h'
*S(iBu3
Toluene H H Z R =Me2COSiMe3 Scheme 3.1.3The reaction was carried out as previously and the proton NMR spectrum , after the first hour of reaction, showed that the E and Z isom ers w ere present in a ratio of 2:1, but after three hours of reaction there was 100% of the E isomer. This was then purified by co lu m n c h ro m a to g ra p h y . P roton NMR s p e c tro s c o p y show ed c h a ra c te ris tic signals at:
ÔH 6.09 (1H, d, 3Jh 19.4 Hz, 3 j l l 7 77.5 Hz, 3 j l l 9 g ^ 81.1 Hz; H-3); 5.95 (1H, d, 3Jh 19.4 Hz, 2 j1 l7 g ^ 70.1 Hz, Z jllS g n 73.4 Hz; H-4).
The proton NMR spectrum of the Z-isom er showed signals at: Ô 5.86 (1H, d, 3Jh 13.4 Hz); 6.91 (1H, d, 3Jh 13.4 Hz);
The am ount of the Z-isom er which was available was too small for Jsn-H to be observed clearly.
The 3j^_|_| and v a lu e s o b ta in e d c o m p a re favourably with the range of values obtained for E and Z-isom ers by ourselves and other w orkers.2 . 3
3 . 1 . 4 2 , 7 - D i m e t h y l - 3 , 5 - o c t a d i y n e - 2 , 7 - d i o l
1 7 a - T rib u ty ls ta n n y lv in y le s tra d io l re a c ts w ith ra d io a c tiv e iodine to give the iodovinyl adducts, w hich are then used in the radio-im aging of certain lym phatic cancers. It w as hoped that a diyne at the 17a position w ould increase the potential for radio im aging at the cancer site by perhaps form ing a bis-adduct with B uaS nH , and thus the reaction of 2 ,7 -d im e th yl-3 ,5 -o cta d iyn e -2 ,7 - diol was studied with this end (Scheme 3.1.4).